photosensitization and analytical study on reactive oxygen
TRANSCRIPT
City University of New York (CUNY) City University of New York (CUNY)
CUNY Academic Works CUNY Academic Works
Dissertations, Theses, and Capstone Projects CUNY Graduate Center
6-2021
Photosensitization and Analytical Study on Reactive Oxygen Photosensitization and Analytical Study on Reactive Oxygen
Intermediates: Self-sorting Surface Radicals and “On-off” Intermediates: Self-sorting Surface Radicals and “On-off”
Sensitizer Function Mechanisms Sensitizer Function Mechanisms
Sarah J. Belh The Graduate Center, City University of New York
How does access to this work benefit you? Let us know!
More information about this work at: https://academicworks.cuny.edu/gc_etds/4354
Discover additional works at: https://academicworks.cuny.edu
This work is made publicly available by the City University of New York (CUNY). Contact: [email protected]
i
Photosensitization and Analytical Study on Reactive
Oxygen Intermediates: Self-sorting Surface Radicals and
“On-off” Sensitizer Function Mechanisms
by
Sarah Joann Belh
A dissertation submitted to the Graduate Faculty in Chemistry in partial fulfillment of the
requirements for the degree of Doctor of Philosophy,
The City University of New York
2021
ii
2021
Sarah Joann Belh
All Rights Reserved
iii
Photosensitization and Analytical Study on Reactive Oxygen Intermediates: Self-sorting Surface
Radicals and “On-off” Sensitizer Function Mechanisms
by
Sarah Joann Belh
This manuscript has been read and accepted for the Graduate Faculty in
Chemistry in satisfaction of the dissertation requirement for the degree of
Doctor of Philosophy.
Alexander Greer
Date
Chair of Examining Committee
Yolanda Small
Date
Executive Officer
Supervisory Committee:
Malgorzata Ciszkowska
Alan Lyons
Ryan Murelli
THE CITY UNIVERSITY OF NEW YORK
iv
Abstract
Photosensitization and Analytical Study on Reactive Oxygen Intermediates:
Self-sorting Surface Radicals and “On-off” Sensitizer Function Mechanisms
Advisor: Prof. Alexander Greer
This thesis consists of four chapters which are detailed below. Chapter 1 is an introductory
chapter, which lays out the background and purpose of the research.
Chapter 2 describes a study of the mobility of alkoxy radicals on a surface by detection of
their recombination product. A novel method called symmetrical product recombination (SRP)
utilizes an unsymmetrical peroxide that upon sensitized homolysis recombines to a symmetrical
product [R'OOR → R'O•↑ + •OR → ROOR]. This allows for self-sorting of the radical to enhance
the recombination path to a symmetrical product, which has been used to deduce surface migratory
aptitude. SPR also provides a new opportunity for mechanistic studies of interfacial radicals,
including monitoring competition between radical recombination versus surface hydrogen
abstraction. This is an approach that might work for other surface-born radicals on natural and
artificial particles.
Chapter 3 discusses how photosensitizers rarely function in both light and dark processes
as they usually have no function when the lights are turned off. We hypothesized that light and
dark mechanisms in an α-diketone will be decoupled by dihedral rotation in a conformation-
dependent binding process. Successful decoupling of these two functions is now shown.
Namely, anti- and syn-skewed conformations of 4,4′-dimethylbenzil promote photosensitized
alkoxy radical production, whereas the syn conformation promotes a binding shutoff reaction with
trimethyl phosphite. Less rotation of the diketone is better suited to the photosensitizing function
v
since phosphite binding arises through the syn conformer of lower stability. The dual function seen
here with the α-diketone is generally not available to sensitizers of limited conformational
flexibility, such as porphyrins, phthalocyanines, and fullerenes.
Chapter 4 shows efforts to increase the number of triplet sensitizer sites in
superhydrophobic surfaces, which is key for increasing 1O2 output in aqueous phase oxidations.
Here, mainly theoretical work is shown with some supporting experimental work. Based on
theoretical calculations, the porous particle would provide the highest potential sensitizer
population on the superhydrophobic surface. Experimental approaches were used with chlorin e6
sensitizer adsorbed with porous milliparticles, and nonporous microparticles, and nonporous
nanoparticles to determine the weight of particles loaded onto the superhydrophobic surface.
Desorption of the sensitizer is found to be a key component.
vi
Acknowledgements
I want to acknowledge that two of the chapters have been previous published as follows. Chapter
2: Belh, S. J.; Ghosh, G.; Greer, A. Surface-radical Mobility Test by Self-sorted Recombination:
Symmetrical Product upon Recombination (SPR). J. Phys. Chem. B 2021, 125, 4212-4220. Chapter 3: Belh,
S. J.; N. Walalawela; S. Lekhtman; A. Greer Dark-binding Process Relevant to Preventing Photosensitized
Oxidation: Conformation Dependent Light and Dark Mechanisms by a Dual-functioning Diketone. ACS
Omega 2019, 4, 27, 22623-22631.
I would like to thank Professor Alexander Greer, whose guidance and mentorship has been
invaluable during the process of completing my PhD. Professor Greer accepted me into his group during a
particularly difficult time in my life and I have greatly benefited from his advice, the depth of his knowledge
in the field, and from the discussions we have shared about related research.
I would also like to thank Professor Alan Lyons for graciously allowing me to conduct research in
his laboratory and for his advice on research projects. I am also grateful for Professor Lyons as well as
Professor Ryan Murelli and Professor Malgorzata Ciszowska for their guidance as members of my
dissertation committee.
During my graduate studies I have been fortunate to find myself in a deeply supportive and
enriching environment as a part of Prof. Greer’s group. Dr. Goutam Ghosh has been an amazing friend and
has contributed valuable work on projects that were key to my research. Dr. Niluksha Walalawela was
crucial in my first year in the Greer group, welcoming me into the group and helping me become more
acquainted with equipment we used in the laboratory. Stas Lekhtman was the best undergraduate research
assistant I could have asked for. The rest of Prof. Greer’s group made it a pleasure to work in the lab.
I would like to thank Dr. QingFeng Xu for his work on the project described in chapter 4. I would
like to thank Prof. Lesley Davenport and Prof. Terry Dowd for the use of their equipment. I would also like
vii
to thank Isanna Agrest and Yuri Buzin for their assistance with equipment and supplies for my research. I
would like to thank Leda Lee for their beautiful and highly professional graphic arts work.
I am grateful to Graduate Center of the City University of New York for generous financial support
through CUNY Science scholarship, and Brooklyn College Chemistry department for the rewards and
funding I received. I wish to acknowledge the National Science Foundation (CHE- 1856765). This work
used Comet, the Extreme Science and Engineering Discovery Environment (XSEDE) cluster at the San
Diego Supercomputer Center, which is supported by the NSF (ACI-1548562) through allocation CHE-
200050.
Lastly, I would like to thank my family, particularly my husband John Connelly, for their love and
support through my Ph.D. career. Without their support of my life pursuits I would not have made it to
where I am.
viii
Table of Contents
Page
Chapter 1. Introduction 1
1.1 Background 1
1.2 Purpose of Work 2
Chapter 2. Surface-radical Mobility Test by Self-sorted Recombination:
Symmetrical Product upon Recombination (SPR)
7
2.1. Results and Discussion 10
2.1.1. Products of the Reaction. 10
2.1.2. Radical Mobility Test 12
2.1.3. Radical Self-sorting 13
2.1.4. Radical H-atom Abstraction 16
2.1.5. Mechanism 22
2.2. Conclusion 24
2.3. Experimental 25
2.4. Supportive Studies 28
2.4.1. Compound Desorption, and Detection. 28
2.4.2. Attempts at Estimation of Radical Lifetime on Silica 30
2.4.3. Temperature Study. 33
2.5. References 34
Chapter 3. Dark-Binding Process Relevant to Preventing Photosensitized Oxidation:
Conformation-Dependent Light and Dark Mechanisms by a Dual-Functioning Diketone
42
3.1. Results and Discussion 45
3.1.1. Dihedral Rotation Dependence of Bidentate Binding. 46
3.1.2. Kinetics of Dione Binding to Phosphite. 50
ix
3.1.3. Separating the Light and Dark Paths. 56
3.1.4. Trapping of Photogenerated Cumyloxy Radical. 60
3.1.5. Summary 62
3.2. Conclusion 63
3.3. Experimental 65
3.4. References 68
Chapter 4. Theoretically Enhancing Three Phase Device Performance by Maximizing the
Number of Triplet Sensitizer Sites on the Superhydrophobic Surface
74
4.1. Results and Discussion 75
4.1.1. Effect of Embedded Particle Shape and Size on Surface Area 75
4.1.2. Effect of Embedded particle Size and Shape on Weight and Volume 79
4.1.3. Particle Agglomeration and Sensitizer Desorption 81
4.2. Sensitizer Efficiency 87
4.2.1. Small Bottle Device 87
4.3. Conclusion 88
4.4. Experimental 89
4.5. References 89
x
List of Figures
Page
Figure 2.1. Schematic of alkoxy radical migration on a nanoparticle [R = C(Me2)Ph; R' = Et] 9
Figure 2.2. Proposed paths for the photosensitized homolysis of cumylethyl peroxide at the
gas/nanoparticle interface
10
Figure 2.3. Correlation of dicumyl peroxide 3 with cumyloxy radical migration distance on the
nanoparticles that arose by the sensitized homolysis
13
Figure 2.4. Illustration of the photosensitized reaction 16
Figure 2.5. Calculated energy difference between H-bonded isomers 19
Figure 2.6. Maximum number of SiOH bypassed by the cumyloxy radical as it migrates linearly
on the particle surface
21
Figure 2.7. HPLC trace of compounds formed by the photosensitized homolysis of cumylethyl
peroxide at the gas/nanoparticle interface
23
Figure 2.8. Intensity of methyl peaks of dicumyl peroxide 3 and cumene hydroperoxide in 1H
NMR is plotted against concentration
23
Figure 2.9. A schematic of our air/solid heterogeneous system with a dispersion of R18O18OR
and R16O16OR peroxides on a nanoparticle
25
Figure 2.10. Illustration of a grid depicting compound loading on the nanoparticle surface 27
Figure 2.11. A semilog plot of the observed rate of dicumyl peroxide production versus the
peroxide to peroxide distance on the silica surface
32
Figure 2.12. A plot of temperature in air, of the 5-mL vial, of uncoated nanoparticles, and of
nanoparticles coated with 4,4-dimethylbenzil
34
Figure 3.1. Micelle degradation by singlet oxygen for the release of doxorubicin for combined
1O2 and drug activity
44
Figure 3.2. Conformational switch of dione for photosensitized oxidation activity and binding 44
xi
Activity
Figure 3.3. Proposed mechanism that blends the dark (thermal) and light (Jablonski-like)
processes
45
Figure 3.4. DFT computed energy plot for the 360° rotation of the 1,2-dione group in glyoxal,
and potential energy surface for the reaction of glyoxal with (MeO)3P
48
Figure 3.5. DFT computed HOMO and LUMO of syn-dione, (MeO)3P, and phosphorane 49
Figure 3.6. Plot of the disappearance of 4,4-dimethylbenzil and (MeO)3P, and appearance of
phosphorane over time in CH3CN
51
Figure 3.7. Absorption spectra following the dark reaction of 4,4-dimethylbenzil and
(MeO)3P, which forms phosphorane and by-products in CH3CN
52
Figure 3.8. Partial 1H NMR spectra following the photoreaction of 4,4ꞌ-dimethylbenzil, dicumyl
peroxide, and (MeO)3P in CD3CN
53
Figure 3.9. Partial 1H NMR spectra following the dark reaction between 4,4ꞌ- dimethylbenzil
and (MeO)3P in CD3CN at 5 min, 22 min, 39 min and 56 min
54
Figure 3.10. 31P NMR spectra following the photoreaction of 4,4ꞌ-dimethylbenzil, dicumyl
peroxide, and (MeO)3P in CD3CN compared to an H3PO4 standard
55
Figure 3.11. Unrestricted B3LYP/D95(d,p) calculations for the O–O bond dissociation of
dicumyl peroxide on the singlet surface, and triplet surface
59
Figure 3.12. Schematic of the photoreactor set up. 65
Figure 3.13. Absorption spectra of 4,4-dimethylbenzil, dicumyl peroxide, (MeO)3P,
(MeO)3P=O, and the potassium phthalate filter solution in CH3CN
66
Figure 4.1. Spherical particles fit into a square surface area 75
Figure 4.2. SEM Images of fumed silica at 200× magnification 82
Figure 4.3. SEM Images of fumed silica at 5000× magnification 83
Figure 4.4. SEM Images of Sil-Co-Sil at 200× magnification 84
xii
Figure 4.5. SEM Images of Sil-Co-Sil at 5000× magnification 85
Figure 4.6. Schematic of the small closed-bottle three phase device for the measurement of
singlet oxygen production via photosensitization
86
Figure 4.7. Schematic of a superhydrophobic surface with embedded sensitizer adsorbed
nanoparticles
88
xiii
List of Tables
Page
Table 2.1. Product distribution (%) for the sensitized homolysis of cumylethyl peroxide that
generates oxygen- and carbon-centered radicals and stable products
11
Table 2.2. Radical ionization potential (IP), electron affinity (EA), and H-abstraction 18
Table 2.3. Details of sensitizer and peroxide adsorption to nanoparticles, and other data 29
Table 2.4. Amount dicumyl peroxide desorption in acetonitrile and toluene 30
Table 2.5. Literature values for diffusion coefficients of molecules similar to cumyloxy radical
in various systems
32
Table 3.1. Using trimethylphosphite to track the dicumyl peroxide photodecomposition as a
function of sensitizer to peroxide ratio
58
Table 3.2. Effect of aprotic and protic media in products formed from the 4,4-dimethylbenzil
sensitized photodecomposition of dicumyl peroxide
61
Table 4.1. Equations for the total surface area of particles embedded on a surface 77
Table 4.2. Effect of particle size on the plastron volume 78
Table 4.3. Information on particles A, B, and C 79
1
Chapter 1.
Introduction
1.1. Background
Reactive oxygen intermediates (ROIs, oxygen radicals and singlet oxygen) which are produced in
photooxidative processes, can be destructive in nature and detrimental to materials. While uncontrolled
ROIs can result in disaster, however, under controlled conditions ROIs can be of great use in areas such as
disinfection and synthesis. These species, including ROO∙, RO∙, OH∙, HO2∙, 1O2, and O2∙—,1-5 are produced
in complex mixtures, which complicates the study of ROIs individual primary production and downstream
mechanisms.6,7 The undefined generation events as well as the unknown downstream reactions of many
ROIs causes difficulty in the orderly application of these species. Further complication can arise from
photo-bleaching of the sensitizer required for their production.8 However, the study of specific purified
ROIs can be achieved through the use of phase separation and interfacial chemistry techniques. Here we
approach the deconvolution of ROI reactions, in order to study photosensitized peroxides and their resultant
alkoxy radicals. Such elucidation will help to control the oxidation of natural and synthetic molecules,
reduce toxicity to organisms and damage to materials, and develop new methods for disinfection of bacteria
and water supplies.
While a great deal of photooxidation research has been performed to elucidate the primary processes
which occur upon light exposure and the initial photooxidative products, only a small number of studies
have focused on secondary processes which occur post the production of the initial products which have
shown to be of proportional consequence.9-13 For example, primary reactions often lead to peroxides, which
in secondary reactions can homolyze their O–O bonds and form alkoxy radicals. Some literature has shown
that the secondary products of primarily formed peroxides can highly detrimental to organisms.14-18 Thus,
studying the reactions of primarily formed peroxides provides important new information on the outcomes
of multistage oxidative events. The research described here was on new techniques in the study of sensitized
2
photolysis of peroxides and the subsequent radical reactions. We report some of the first studies on
heterogeneous surfaces with selective ROI type and quantity to help deduce the mechanisms.
1.2. Purpose of Research
We have developed two and three phase devices for phase-separated photosensitization methods to
selectively produce individual ROIs. Methods which utilize our three phase device, such as the sandwich
device we developed for the study of singlet oxygen,19 permit us to examine specific ROI mechanisms.
Interfacial phase separation has allowed us to address the important topics of post-illumination migration
of alkoxy radicals on surfaces, in a newly developed technique described in chapter 2, and dual functioning
photosensitizers binding to shut off ROI production described in chapter 3. These results have multiple
potential applications, such as in synthesis, photochemistry, device development, facile materials and
plastics photodegradation, and enhanced PDT. The further development of our three phase devices is still
ongoing, and some potential means of enhancing these techniques is discussed in chapter 4.
The study of surface radicals has been a large component in the study of particulate matter in air
pollution. Particularly, the long lives measured for many radicals on the particles’ surface.20-31 The current
methods of detecting surface radicals, those methods being electron paramagnetic resonance (EPR)
spectroscopy32-36 and 31P NMR37 in conjunction with phosphite radical traps, have limitations. Specifically,
these methods are unable to distinguish between a single molecular radical lifetime and a radical
propagation lifetime. This distinction is important in determining the specific radical mechanisms, products,
toxicity, as well as potential methods of damage prevention. Thus, we developed the symmetrical product
upon recombination (SPR) method, discussed in chapter 2, to further the study of specific radical
mechanisms on particle surfaces. The SPR method study discussed in chapter 2 studies peroxides and their
resultant alkoxy radicals, both of which can be destructive when produced in natural photooxidative events.
The development of the SPR method is important to the further study and reduction of ROIs damage to
materials and toxicity to organisms.
3
While the uncontrolled production of ROIs can be harmful, ROIs can also be well utilized when
produced in a controlled manner. ROIs can be used for disinfection, as well as in therapeutics such as
photodynamic therapy (PDT). Some dual action approaches have arisen in the field of PDT. Those being
theranostics, and approach which combines therapy and diagnostics, often accomplishing both through the
use of a single compound, and combination chemotherapy and PDT methods accomplished with the use of
multiple compounds to increase resultant killing. In chapter 3 we explore the potential of diketones to
develop a new class of light-dark dual action compounds, which combine photosensitized ROI production
and drug like binding in a single compound.
1.3. References
1. Baptista, M. S.; Cadet, J.; Di Mascio, P.; Ghogare, A. A.; Greer, A.; Hamblin, M. R.; Lorente, C.;
Nunez, S. C.; Ribeiro, M. S.; Thomas, A. H.; Vignoni, M.; Yoshimura, T. M. Type I and II
Photosensitized Oxidation Reactions: Guidelines and Mechanistic Pathways. Photochem. Photobiol.
2017, 93, 912-919.
2. Foote, C. S. Definition of Type I and Type II Photosensitized Oxidation. Photochem. Photobiol.
1991, 54, 659-659.
3. Beeler, A.; Guest Editor. Thematic Issue: “Photochemistry in Organic Synthesis” [In: Chem. Rev.
2016, 116, 9629-10342].
4. Greer, A.; Guest Editor. Symposium-In-Print: “Organic Chemistry of Singlet Oxygen” [In:
Tetrahedron 2006; 62, 10603-10776].
5. Clennan, E. L.; Pace, A. Advances in Singlet Oxygen Chemistry. Tetrahedron 2005, 61, 6665-6691.
6. Cadet, J.; Decarroz, C.; Wang, S. Y.; Midden, W. R. Mechanisms and Products of Photosensitized
Degradation of Nucleic Acids and Related Model Compounds. Isr. J. Chem. 1983, 23, 420-429.
7. Hancock-Chen, T.; Scaiano, J. C. Nonlinear Effects and a Cascade of Radical Events Leading to
Laser-specific Generation of Active Oxygen Species. J. Photochem. Photobiol. A 1998, 67, 174-178.
4
8. Bonnett, R.; Martinez, G. Photobleaching of Sensitizers used in Photodynamic Therapy. Tetrahedron
2001, 57, 9513-9547.
9. Tong, H.; Arangio, A. M.; Lakey, P. S.; Berkemeier, T.; Liu, F.; Kampf, C. J.; Brune, W. H.; Pöschl,
U.; Shiraiwa, M. Hydroxyl Radicals from Secondary Organic Aerosol Decomposition in Water.
Atmos. Chem. Phys. 2016, 16, 1761-1771.
10. Millet, D. B.; Baasandorj, M.; Hu, L.; Mitroo, D.; Turner, J.; Williams. B. J. Nighttime Chemistry
and Morning Isoprene Can Drive Urban Ozone Downwind of a Major Deciduous Forest. Environ.
Sci. Technol. 2016, 50, 4335-4342.
11. Davies, M. J. Protein Oxidation and Peroxidation. Biochem. J. 2016, 473, 805-825.
12. Kroll, J. H.; Ng, N. L., Murphy, S. M., Flagan, R. C., Seinfel, J. H. Secondary Organic Aerosol
Formation from Isoprene Photooxidation. Environ. Sci. Technol. 2006, 40, 1869-1877.
13. Agon, V. V; Bubb, W. A.; Wright, A.; Hawkins, C. L.; Davies M. J. Sensitizer-mediated
Photooxidation of Histidine Residues: Evidence for the Formation of Reactive Side-chain Peroxides.
Free Radical Biol. Med. 2006, 40, 698-710.
14. Geiger, P. G., Korytowski, W., Lin, F. and Girotti, A. W. (1997) Lipid Peroxidation in
Photodynamically Stressed Mammalian Cells: Use of Cholesterol Hydroperoxides as mechanistic
Reporters. Free Radic. Biol. Med. 1997, 23, 57-68.
15. Girotti, A. W. Photosensitized Oxidation of Membrane Lipids: Reaction Pathways, Cytotoxic Effects,
and Cytoprotective Mechanism. J. Photochem. Photobiol. B. 2001, 63, 103-113.
16. Girotti, A. W.; Korytowski, W. (2014) Generation and Reactivity of Lipid Hydroperoxides in
Biological Systems. In: The Chemistry of Peroxides, Vol. 3, Edited by J. F. Liebman and A. Greer,
2014, Ch. 18, pp. 747-767.
17. Girotti, A. W.; Korytowski, W. Cholesterol as a Natural Probe for Free Radical Mediated Lipid
Peroxidation in Biological Membranes and Lipoproteins. J. Chromatogr. B 2016, 1019, 202-209.
18. Choudhury, R.; Greer, A. Synergism Between Airborne Singlet Oxygen and a Trisubstituted Olefin
Sulfonate for the Inactivation of Bacteria. Langmuir 2014, 30, 3599-3605.
5
19. D. Aebisher; D. Bartusik-Aebisher; S. J. Belh; G. Ghosh; A. M. Durantini; Y. Liu; A. M. Lyons; A.
Greer “Superhydrophobic Surfaces as a Source of Airborne Singlet Oxygen Through Free Space for
Photodynamic Therapy” ACS Appl. Bio Mater. 2020, 3, 2370-2377.
20. Jia, H.; Zhao, S., Shi,Y., Zhu, L., Wang, C., Sharma, V. K. Transformation of Polycyclic Aromatic
Hydrocarbons and Formation of Environmentally Persistent Free Radicals on Modified
Montmorillonite: The Role of Surface Metal Ions and Polycyclic Aromatic Hydrocarbon Molecular
Properties. Environ. Sci. Technol. 2018, 52, 5725-5733.
21. Feld-Cook, E.; Bovenkamp-Langlois, G. L.; Lomnicki, S. M. The Effect of Particulate Matter
Mineral Composition on Environmentally Persistent Free Radical (EPFR) Formation. Environ. Sci.
Technol. 2017, 51, 10396-10402.
22. Jia, H.; Nulaji, G., Gao, H., Wang, F., Zhu, Y., Wang, C. Formation and Stabilization of
Environmentally Persistent Free Radicals Induced by the Interaction of Anthracene with Fe(III)-
Modified Clays. Environ. Sci. Technol. 2016, 50, 6310-6319.
23. Pöschl, U.; Shiraiwa, M. Multiphase Chemistry at the Atmosphere–Biosphere Interface Influencing
Climate and Public Health in the Anthropocene. Chem. Rev. 2015, 115, 4440-4475.
24. Fang, G.; Gao, J., Liu, C., Dionysios, D. D., Wang, Y., Zhou, D. Key Role of Persistent Free Radicals
in Hydrogen Peroxide Activation by Biochar: Implications to Organic Contaminant Degradation.
Environ. Sci. Technol. 2014, 48, 1902-1910.
25. Sapiña, M.; Jimenez-Relinque, E.; Castellote, M. Controlling the Levels of Airborne Pollen: Can
Heterogeneous Photocatalysis Help? Environ. Sci. Technol. 2013, 47, 11711-11716.
26. Khachatryan, L.; Dellinger. B. Environmentally Persistent Free Radicals (EPFRs). 2. Are Free
Hydroxyl Radicals Generated in Aqueous Solutions? Environ. Sci. Technol. 2011, 45, 9232-9239.
27. Vejerano, E.; Lomnicki, S., Dellinger, B. Formation and Stabilization of Combustion-Generated
Environmentally Persistent Free Radicals on an Fe(III)2O3/Silica Surface. Environ. Sci. Technol.
2011, 45, 589-594.
6
28. Khachatryan, L.; Vejerano, E.; Lomnicki, S.; Dellinger, B.; Environmentally Persistent Free Radicals
(EPFRs). 1. Generation of Reactive Oxygen Species in Aqueous Solutions. Environ. Sci. Technol.
2011, 45, 8559-8566.
29. Truong, H.; Lomnicki, S.; Dellinger, B. Potential for Misidentification of Environmentally Persistent
Free Radicals as Molecular Pollutants in Particulate Matter. Environ. Sci. Technol. 2010, 44, 1933-
1939.
30. Alaghmand, M.; Blough, N. V. Source-Dependent Variation in Hydroxyl Radical Production by
Airborne Particulate Matter. Environ. Sci. Technol. 2007, 41, 2364-2370.
31. Dellinger, B.; Pryor, W. A.; Cueto, R.; Squadrito, G. L.; Hegde, V.; Deutsch, W. A. Role of Free
Radicals in the Toxicity of Airborne Fine Particulate Matter. Chem. Res. Toxicol. 2001, 14, 1371-
1377.
32. Sim, S.; Forbes, M. D. E. Radical–triplet Pair Interactions as Probes of Long–range Polymer
Motion in Solution. J. Phys. Chem. B 2014, 118, 9997-10006.
33. Forbes, M. D. E.; Dukes, K. E.; Myers, T. L.; Maynard, H. D.; Breivogel, C. S.; Jaspan, H. B.
Time-resolved Electron Paramagnetic Resonance Spectroscopy of Organic Free Radicals Anchored
to Silica Surfaces. J. Phys. Chem. 1991, 95, 10547-10549.
34. Forbes, M. D. E.; Myers, T. L.; Dukes, K. E.; Maynard, H. D. Biradicals and Spin-correlated
Radical Pairs Anchored to SiO2 Surfaces: Probing Diffusion at the Solid/Solution Interface. J. Am.
Chem. Soc. 1992, 114, 353-354.
35. Forbes, M. D. E.; Ruberu, S. R.; Dukes, K. E. Dynamics of Spin-polarized Radical Pairs at the
Solid/Solution Interface. J. Am. Chem. Soc. 1994, 116, 7299-7307.
36. Chiesa, M.; Giamello, E.; Che, M. EPR Characterization and Reactivity of Surface-Localized
Inorganic Radicals and Radical Ions. Chem. Rev. 2010, 110, 1320-1347.
37. Ghosh, G.; Greer, A. A Fluorinated Phosphite Traps Alkoxy Radicals Photogenerated at the
Air/solid Interface of a Nanoparticle. J. Phys. Org. Chem. 2020; e4115.
7
Chapter 2.
Surface-radical Mobility Test by Self-sorted Recombination:
Symmetrical Product upon Recombination (SPR)
2.0. Introduction
Nanoparticle surfaces can have advantages over homogeneous solution for the control of radical
reactions. For example, surfaces may be tuned to selective reactions by controlling radical mobility.
However, mechanistic studies on surface-bound radicals, such as alkoxy radicals, are still challenging.
While such information is typically sought with EPR trapping1-4 and 31P NMR spectroscopy,5 the goal to
expand on methods to measure radical migratory aptitude is a needed area of research. Here, we report a
symmetrical product recombination (SPR) method that allows the determination of alkoxy radical surface
mobility by a symmetrical product from an unsymmetrical substrate [R'OOR → R'O• + •OR → ROOR]
(Figure 1). This approach is demonstrated here for alkoxy radicals, but might also work for other radicals.
Radicals can form on artificial6-8 and natural surfaces.9-11 Some environmental reactions take place
with particulate formation of persistent radicals.12-15 Thus, developing a trapping system that can assess
surface migration is desirable.
Researchers have developed various methods for monitoring of radical reactions on surfaces. One
method is EPR spectroscopy16 by analyzing the hyperfine tensor for the interaction between the radical and
surrounding magnetic nuclei. A second approach is theoretical, for example a H3Si• diffusion activation
barrier on silicon was found to be 3.7 kcal/mol by DFT and MD simulations.17 A third approach is the use
of 31P NMR spectroscopy with phosphite traps5,18 due to their oxophilicity to trap alkoxy radicals. In the
third approach, alkoxy radicals on silica nanoparticles were trapped by phosphites to form phosphates. In
8
the present article, the SPR method can help to advance the field to deduce the migratory aptitude of radicals
on a particle surface.
We now report on a new concept for generating a scrambled product that probes the lateral diffusion
of alkoxy radicals on a silica nanoparticle. A photoexcited 4,4ꞌ-dimethylbenzil sensitizer 1 is used to
homolyze an unsymmetrical peroxide 2 (Figure 2). The resulting homolysis leads to alkoxy radicals that
can recombine to a symmetrical peroxide 3. We find that the symmetrical product 3 formation depends on
the loading quantity of substrate 2 that is used. We find that radical migration distance reaches a maximum
of 2.9 nm on the nanoparticle surface, suggesting the usefulness of this approach for surface diffusion
studies of alkoxy radicals. A self-sorting preference is also predicted by DFT calculations and mathematical
deductions.
The SPR approach fulfills two functions in this nanoparticle reaction. First, it ensures migration of
a molecular radical. This enables assessment of the radical ability to translocate on the surface, rather than
propagate as in L• (location 1) + LH (location 2) → LH (location 1) + L• (location 2), as is needed to assess
migration patterns of molecular radicals. Second, the chain termination of radicals provides a way to
promote signal intensity within a symmetrical compound by 1H NMR spectroscopy, as used to advantage
in structure determination of natural products bearing molecular bilateral symmetry.19,20 Furthermore, the
SPR approach is a novel peroxide scrambling strategy that provides insight to both the translation and
volatility of radicals.
A mechanism is proposed in Figure 2, in which photosensitization triggers the unsymmetrical
peroxide 2 to homolyze, with the higher molecular weight PhC(Me)2O• radical of the pair remains adsorbed,
and thus generating a symmetrical peroxide 3 to monitor. This supports a mechanistic hypothesis that
radical recombination is detected from PhC(Me)2O• radical pairing on the nanoparticle surface. Further, it
shows that the product signal is symmetry increased for 1H NMR spectroscopy, and not obscured by chain
propagation products, as is often seen in homogeneous solution. The SPR method that we developed can
potentially be used in combination with EPR methods for better insight into mobility and reactions of
radicals on surfaces.
9
Figure 2.1. Schematic of alkoxy radical migration on a nanoparticle [R = C(Me2)Ph; R' = Et]. The radical
production is via cumylethyl peroxide’s photosensitized O–O homolysis, including alkoxy radical
migration, and formation of a symmetrical ROOR product. Symmetrical ROOR product formation is
favored, whereas chain propagation processes, for example H-atom transfer are disfavored.
10
Figure 2.2. Proposed paths for the photosensitized homolysis of cumylethyl peroxide 2 at the
gas/nanoparticle interface. Concentrations of alkoxy radicals forming a symmetrical peroxide product 3
increase at the air/solid interface as EtO• and CH3• fragments volatilize away from the surface. A two-phase
sensitized photolysis of a lighter peroxide, which induces this combination of heavier alkoxy radicals to
provide mechanistic details to radical mobility on a surface. An additional scheme with structure drawings
is shown in Figure 2.4.
2.1. Results and Discussion
2.1.1. Products of the Reaction. Nanoparticles co-adsorbed with 4,4′-dimethylbenzil (sensitizer
1) and cumylethyl peroxide 2 were irradiated with (280 < λ < 700 nm) light in a N2-degassed glass vessel.
Five products were detected in the photoreaction (Table 2.1). The products were dicumyl peroxide 3, cumyl
alcohol 4, and acetophenone 5, as detected upon desorbing products from the particle surface. Ethanal 6
and methane 7 can be detected when analyzing the headspace or in a solution-phase photoreaction
containing dissolved sensitizer 1 and cumylethyl peroxide 2. Diethyl peroxide 8 was not detected with our
HPLC and 1H NMR analyses. Reversible dimerization from primary products 3 and 8 does not yield 2 in
3sens*
hn
(migration distance <2.9 nm)
(sens to 2 distance 6-9 Å)
nanoparticle surfa
ce
11
high yields, apparently because the EtO• is sufficiently volatile to disconnect from the surface. The reaction
allows for a radical mobility test because it forms the bilaterally symmetrical dicumyl peroxide 3 from
recombination of cumyloxy radicals. This is somewhat reminiscent to bilaterally symmetric 1,2-di-p-
tolylethane and 1,2-bis(4-methoxyphenyl)ethane from the radical combination of p-xylene radical and 1-
methoxy-4-methylbenzene radical, respectively, in the photolysis of silica-adsorbed l-(4-methylphenyl)-3-
(4-methoxyphenyl)-2-propanone.21
Table 2.1. Product distribution (%) for the sensitized homolysis of cumylethyl peroxide 2 that generates
oxygen- and carbon-centered radicals and stable products.a
a Selective irradiation of 4,4ꞌ-dimethylbenzil sensitizer 1 (330 µmol/g silica) with (280 < λ < 700 nm) light
was carried out in the presence of cumylethyl peroxide 2 co-adsorbed on particles. b Relative yields
determined by HPLC or 1H NMR and were based on their integrated peak areas without the use of an
relative yields b,c
conditions A condition B d
entry
peroxide 2
adsorbed
(µmol/g)
dicumyl
peroxide 3
cumyl
alcohol 4
acetophenone
5
ethanal
6
methane
7
1 108 25.2±0.5 12.7±0.1 12.4±0.02 12.4 37.3
2 53.2 18.2±1.0 14.9±0.1 13.8±0.1 13.3 39.8
3 27.1 11.8±0.8 15.9±0.2 15.3±0.2 14.6 43.7
4 13.4 9.8±0.6 14.9±0.4 17.6±1.3 14.4 43.2
5 6.78 4.0±2.4 13.2±1.6 16.7±0.7 16.5 49.6
12
external standard. Relative yields of product at the air/solid interface relative to solution-phase conditions.
c Condition A: air/solid interface; condition B: homogeneous photoreaction of sensitizer 1 (0.01 mM) and
peroxide 2 (0.1 mM) in acetonitrile-d3 irradiated in an NMR tube. d The experimental error in condition B
is ±5%.
2.1.2. Radical Mobility Test. Here, sensitizer 1 was used to homolyze 2, where we use radical
recombination to symmetrical product 3 was used as a test for radical mobility on the nanoparticle surface.
Eq 1 shows the calculated number of 1 or 2 molecules adsorbed on the particle surface using Avogadro’s
number (NA). Eq 2 shows the average distance between adsorbed 1 or 2 molecules. Eq 3 is used in
conjunction with eq 2 to deduce the radical migration distance upon recombination to symmetrical 3,
estimating the shape of cumyloxy radical as a rectangle (0.71 nm × 0.43 nm) sitting parallel to the particle
surface. Eq 4 shows the calculation for the percent particle coverage of 1 or 2. Cumyloxy radicals were
generated and recombined to 3 in amounts ranging from a high of 25.2% to a low of 4.0% yield (Table 2.1,
entries 1 and 5). This led to the calculated surface migration distance of cumyloxy radical on the
nanoparticle of 0.27 nm up to a maximum of 2.9 nm (Figure 2.3). The selectivity is not caused by heating
of the reaction. The nanoparticle photoreactions were carried out at 26 °C. During the photolysis, the
particles increased in temperature by ~10 °C, where this rise is insufficient to cause the thermolysis of 2 or
3, based on control reactions, where thermolysis temperatures of 130 °C would have been required.22 A
weaker peroxide, benzoyl peroxide, requires heating above 80 °C to split into benzoyl radicals, which in
turn form phenyl radicals and CO2.23 Next, we compute the difference in O−O bond strength of 2 relative
to 3 to help rationalize selectivity for the high yields of the product 3.
molecules of 1 or 2 = moles of 1 or 2 × 𝑁𝐴………………………………………………….………….(2.1)
13
molecule to molecule distance (nm) = √particle surface area (nm2/g)
molecules of 𝟏 or 𝟐 …………...……………..…….(2.2)
radical migration distance (nm) =𝟑−to−𝟑 distance(nm)
2− 𝟑 length (nm)…………..……….…….…(2.3)
percent particle coverage of 1 or 2 = moles of 𝟏 or 𝟐/g
SiOH groups (moles) g⁄…………….................…………...……..….(2.4)
Figure 2.3. Correlation of dicumyl peroxide 3 with cumyloxy radical migration distance on the
nanoparticles that arose by the sensitized homolysis of 2.
2.1.3. Radical “Self-Sorting”. Unrestricted M06-2X/6-31G(d,p) calculations are used to
help explain the selective formation of the O–O bond in dicumyl peroxide 3. The DFT method
0
0.5
1
1.5
2
2.5
0 0.5 1 1.5 2 2.5 3
dic
um
yl p
ero
xid
e 3
pro
du
ce
d (
µm
ol/g)
cumyloxy radical migration distance (nm)
14
employed here is found to reproduce experimental O–O bond dissociation energies of organic
peroxides.24 Our DFT study was designed to assess the geometries and bonding based on the
influence the PhC(Me)2 and Et groups impart on peroxides 2, 3, and 8 , and radicals PhC(Me)2O•
and EtO•, and also rationalize possible interfacial effects.
Peroxides 2, 3, and 8, and their corresponding alkoxy radicals PhC(Me)2O• and EtO•
optimized to minima. The calculated torsion angle (C–O–O–C) of 3 is increased (178.0°) when
compared to 2 (124.8°) and 8 (109.9°). As the size of the substituent of the peroxide increases (8
< 2 < 3), then rotation about this torsion energy is increased, as we will see. To explore the
energy associated with rotation around the torsion angle, minima and transition structures (TS)
were located on the potential energy surface. Rotation around the torsion angle among gauche
and anti geometries changed the energy by 3.5 kcal/mol (for 3), whereas it only changed by 0.63
kcal/mol (for 2), and 0.43 kcal/mol (for 8). The larger PhC(Me)2 substituent at the O−O bond
increases the activation barrier that yields full rotation. Rotating the torsion angle where they
adopt a syn TS geometry was large 28.0 kcal/mol for 3 (due to destabilizing PhC(Me)2/PhC(Me)2
interactions, whereas the TS is 19.3 kcal/mol for 2 (due to modestly destabilizing PhC(Me)2/Et
interactions), and even less at 11.2 kcal/mol for the TS of 8 (due to less destabilizing Et/Et
interactions). The substituent effects that influence the structures can also influence the bond
energies.
Thus, next we investigated the energetics for O–O bond homolysis. The O–O bond in
peroxides is weak due in part to electronic repulsion of lone pairs on the adjacent oxygen atoms.
The π MO is strong between the two oxygen atoms, and the antibonding π* is destabilizing.
Endothermicity increases for 3 (due to a stronger O–O) than in 2 and 8. The endothermicity of 3
relative to 2 PhC(Me)2O• (39.2 kcal/mol) is greater than PhC(Me)2OOEt 2 relative to PhC(Me)2O•
15
and EtO• (37.4 kcal/mol), and EtOOEt 8 relative to 2 EtO• (37.6 kcal/mol). The presence of
electron delocalization of 3 may explain its greater stability that peroxides 2 and 8 with one or two
ethyl groups. Literature noted that substituting the R group Et for Ph (slight electron withdrawing
group)25 in Me3CO–OC(Me)2R leads to a 0.1 kcal/mol stabilization of the peroxide bond.26
Similarly, substituting the R group Et for CF3 (the latter is a strong EWG) in RO–OR leads to a
15.9 kcal/mol stabilization of the peroxide bond.26,27 Also, substituting the p-X-substituent (X =
MeO for X = NO2) in p-X-C6H4-C(Me)2O–OCMe3 leads to a 0.4 kcal/mol stabilization of the
peroxide bond.26 Further details underlying the stabilities of peroxides has been recently
rationalized in detail.28
The above computed data suggests self-sorting capacity in higher thermal O–O bond
energy in 3 than 2 or 8, is complementary to volatility in terms of binding affinity and selective
binding. Namely, dicumyl peroxide 3 is adsorbed more tightly to the particle surface than 2 and 8
due to its two phenyl rings. Our computed show the formation of a OH∙∙∙π bond between
(HO)3SiOH and benzene in the gas phase is 6.0 kcal/mol, and has a perpendicular orientation to
the plane of the aromatic ring, at the point of plane interaction by a lengthened O–H bond. The
DFT prediction is that the phenyls of PhC(Me)2O•, 2 and 3, are bonded in a -hydrogen bond to
the surface SiOH groups, has been confirmed experimentally for naphthacene.29 This is known to
be stabilizing with a decreased HOMO-LUMO energy gap and an increased dipole moment. These
-hydrogen bonds are often comparable in strength to conventional H-bonding.30 Our DFT results
indicate that the EtO• is weakly bonded to the SiOH group. We suggest that the SiOH∙∙∙π(aromatic
ring) hydrogen bonding will increase the adsorption energy, that along with the increased
molecular weight underlie the lower volatilization of PhC(Me)2O• compared to EtO•, thereby
facilitating self-sorting to reach 3. The RO• •OR binding process was shown to be barrierless,
16
while the desorptive volatility process has a barrier of ~2 kcal/mol for low molecular weight
compounds. But what about to the competition with H abstraction?
Figure 2.4. Illustration of the photosensitized reaction. (a) Peroxide 2 and sensitizer 1 are
adsorbed to the nanoparticle surface (the latter not depicted). (b) The photosensitized homolysis
of 2 at the O–O bond leads to cumyloxy and ethoxy radicals (the latter volatilizes). (c) The
cumyloxy radicals are retained on the surface and migrate prior to recombination to dicumyl
peroxide 3. The brown squares are representing places of former cumyloxy radical residence prior
to migration. This cumyloxy radical migration distance is estimated by the percent yield of dicumyl
peroxide 3.
2.1.4. Radical H-atom Abstraction. The radicals can abstract from the SiOH groups or
adsorbed water on the nanoparticle surface. Here, we draw on a relationship between
electronegativity of radicals and whether they abstract H or dimerize, a concept borrowed in a
b. Peroxide homolysis
and radical formation
a. Peroxide adsorbed on a
silica surface
c. Radical migration and
recombination
17
different vein to the context of H-abstraction versus alkene addition.33-36 Table 2.2 shows that the
electronegativity can be used to assess the paths of radicals as measured by calculation of (IP +
EA)/2. PhC(Me)2O• and (MeO)3SiO• are relatively electropositive radicals that are expected to H-
abstract. On the other hand, as the electronegativity of EtO• and Me• increases, the H-abstraction
ability is predicted to decrease, where their higher volatility must also play a major role in their
fate.
As the electronegativity of EtO• is greater than that of PhC(Me)2O•, it follows that H abstraction is
observed experimentally in the latter, but not former. This can be compared to the literature,37 where more
electronegative t-BuO• favors H abstraction compared to MeO•. In our series, the less electronegative
radical, EtO•, does not give recombination or abstraction, but instead only loss of Me•. Demethylation can
be accomplished by alkoxy radical structures bearing flanking methyl groups. A previous report with M06-
2X calculations also showed that methyl radical elimination is the main dissociation mechanism for
peroxides after O−O bond cleavage.38 The Me• proceeds by H abstraction to form CH4. We find that
PhC(Me)2O• abstracts a hydrogen from SiOH on the particle surface. A secondary reaction between SiO•
and PhC(Me)2O• to form SiOOC(Me)2Ph is possible, but was not discerned. EtO• and Me• are noted, as
our trapping does not address the problem of direct detection that follows the radicals themselves on and
off the surface. We assumed a facile volatility and transit off of the surface, where CH4 increase in the
surrounding medium over time. Adsorption of EtO• is lower than PhC(Me)2O• or else there would have
been dimerization to reach 8, which is not observed.
18
Table 2.2. Radical ionization potential (IP), electron affinity (EA), and H-abstraction
radical
electronegativity
(IP + EA)/2 (eV)
H-abstraction comment
PhC(Me)2O 4.49 observed
EtO 5.72
only H-loss
observed
not observed
Me 5.65 observed
(HO)3SiO a 5.08
more H-
abstraction than
EtO, but less
than
PhC(Me)2O
predicted greater
than Et and less
than
PhC(Me)2O
a Model for surface siloxy radical.
A comparison of the DFT calculated energy difference between alkoxy radicals and corresponding
siloxy radical species is instructive. The calculated energy difference between H-bonding of alkoxy radical
and alcohol systems is shown in Figure 2.5. Notice that the RO•∙∙∙HOSi(OH)3 hydrogen bonding is stronger
by 13.7-13.9 kcal/mol compared to the ROH∙∙∙•OSi(OH)3 hydrogen bonding (cf. I and III with II and IV).
There are also similar stabilizing effects for H-bonding arrangements of EtO•∙∙∙HOSi(OH)3 (-8.4 kcal/mol)
and PhC(Me)2O•∙∙∙HOSi(OH)3 (-10.3 kcal/mol) compared to their separated species, respectively.
Although, the PhC(Me)2O• forms a slightly more stable H-bond than EtO• with HOSi(OH)3. The related H
atom transfer of surface SiOH groups, are similarly expected not to proceed at any significant rate.
From a hydrogen bonding point of view, cumyloxy radical is a candidate for both
SiOH∙∙∙(π)PhC(Me)2O• and PhC(Me)2O•∙∙∙HOSi hydrogen bonding. As has been reported, silanol groups
19
or silanols occupied with water can bind to naphthalene by π∙∙∙HOSi bonding.29 Similarly, alkoxy radicals
can form a weak RO•∙∙∙HOR hydrogen bond to alcohols, although the activation energy for H-atom transfer
is high,39-41 which is consistent with our DFT results.
Figure 2.5. Calculated energy difference between H-bonded isomers.
Similar to the H-abstraction analysis in Figure 2.5 and Table 2.2, the reactions were analyzed with
mathematical deductions on the particle surface. What we deduce. next is a facet inhibiting radical
recombination to form the symmetrical product 3, where radicals can abstract an H atom from the SiOH
group (or adsorbed water) on the particle surface. Eq 2.5 shows the calculated number of silanol groups per
gram using the known surface area (200 m2/g) and the known 4 SiOH/nm2 of silica. Eq 2.6 uses Avogadro’s
number (NA) in the conversion of the number of silanol groups per gram of silica found using eq 2.4 to
moles of silanol per gram. The presence of SiOH groups attenuates cumyloxy radical migration due to H-
abstraction reactivity, as we will see next.
SiOH groups per gram particle = surface area (m2/g) (silanol groups present/m2)…………….....(2.5)
SiOH groups (moles)/g particle= number of SiOH groups/g particle
𝑁𝐴…………………….......................(2.6)
Si
O
HOO
OHO
HH
1.678 Å
0.969 Å
Si
O
HOOH
O
H Ph
O
H
2.184 Å
93.7°
0.967 Å
1.678 Å
Si
O
O OH
O
H
H
H
0.974 Å
1.628 Å
O
1.854 Å
1.374 Å
116.4°
Si
O
HOO
HOH
H
O
Ph2.030 Å
0.967 Å
1.380 Å
135.4°
113.0°∆E = 13.9 kcal/mol
∆E = 13.7 kcal/mol
I I I
III I V
20
Figure 2.6 shows that cumyloxy radical can bypass ~2-3 SiOH groups before H-abstraction
becomes competitive. After the 2-3 SiOH groups, there is a shift toward a more equally balanced formation
of the cumyloxy radical recombination and H abstraction processes. Finally, with more than 3 SiOH
encounters, now there is a shift toward the H abstraction reaction being formed. The maximum number of
SiOH groups that the cumyloxy radical encounters over a given distance is shown in eq 2.7. Eq 2.7 shows
that the radical length is taken as 0.66 nm. These calculations would allow for the smallest SiOH value to
be 1 as the estimated area of the radical would be 0.28 nm2, and estimating how many SiOH are in this area
would be 0.28 nm2 × 4 SiOH per nm2 = 0.76 1 SiOH in the radical area. Table 3.1 shows the yield of
cumyl alcohol 4 in the photoreaction. The H-abstraction route to cumyl alcohol 4 was competitive to radical
recombination to 3 at high loadings of 2. Surface SiOH groups to propagate silicate-type SiO∙ radicals are
minimal or else diffusion distances would have been 0.5 nm given the distance between SiOH groups on
the surface. Lower loading of 2 was used in the photoreaction, where it seems possible that the SiOH
position is sterically hindered by the surface of the nanoparticle itself. Polymer studies have provided
information on the cumyloxy radical H-atom abstraction limited by steric hindrance imposed from methyl
substituents on secondary positions within poly(propylene) and poly(isobutylene).37
maximum SiOH groups bypassed by the cumyloxy radical =
radical migration distance × radical length × 4 SiOH per nm2…………………..(2.7)
We find a relationship between migration distance of cumyloxy radical and its tendency to dimerize
or abstract a hydrogen atom from the surface. Cumyloxy radical gives recombination in a 2:1 preference to
abstraction at high loading of 2 (entry 1). On the other hand, when the loading of 2 decreases (entry 5), H
abstraction is observed in an elevated 3.3:1 preference over recombination. These ratios are measured by
the relative yields of 3 and 4. The acetophenone 5 product is also observed by cumyloxy radical’s loss of
Me•. The products from volatile radicals Me• and EtO• were difficult to quantitate. Me• can abstract a H-
atom and be detected as CH4; EtO• loses an H-atom and is detected as CH3CHO. Despite their volatility,
21
detection in a solution-phase reaction (condition B) was more accessible than in the headspace of an
air/particle reaction (condition A), as seen in Table 2.1.
The cumyloxy radical migration on a silica surface is rationalized because or relatively low H-
bonding strength to the surface. For example, the experimental diffusional activation energy was reported
to be 1.9 kcal/mol for 2,2,6,6-tetramethylpiperidine-l-oxyl radical from hydrogen bonding to the surface
SiOH.42 In passing, we also mention a report on longitudinal-field muon spin relaxation showing a diffusion
activation energy to be 2.6 kcal/mol for •CCl2CH3 radical due to association to the surface SiOH.43
Figure 2.6. Maximum number of SiOH bypassed by the cumyloxy radical as it migrates linearly on the
particle surface as deduced by the formation of recombination (3) and abstraction (4) products. The Y-axis
represents a measure of recombination (3 formation) vs H-abstraction (4 formation).
0
0.5
1
1.5
2
0 2 4 6 8
dic
um
yl p
ero
xid
e 3
/cu
myl a
lcoh
ol 4
maximum number of SiOH bypassed
22
2.1.5. Mechanism. Upon irradiation where it excited, nanoparticle-adsorbed 1 transfers energy to
the O−O bond of 2 resulting in its homolysis. Our previous work5 suggested this to be a Dexter (triplet)
energy transfer process. In the present work, we found that (i) the higher percent the nanoparticle was
loaded with 2, a greater amount of 3 was formed selectively by radical recombination. (ii) Cumyloxy
radical migration distance extended as far as 2.9 nm as measured by its recombination, (iii) HPLC (Figure
2.7) and 1H NMR (Figure 2.8) enable the SPR approach, with the latter detection improved due to the
symmetry of product 3 (detection limit, 0.12 mM). The percent coverage of peroxide 3 of the nanoparticle
surface was 0.87-13.8%, which compares favorably to De Mayo and co-worker’s radical combination to
symmetrical products requiring 10-50% coverage of l-(4-methylphenyl)-3-(4-methoxyphenyl)-2-
propanone.44,45 (iv) The results from DFT calculations provide evidence that the O–O bond energy in
symmetrical 3 is increased by 1.8 kcal/mol upon exchange with unsymmetrical 2, which contributes to
enriching to dimerize PhC(Me)2O• to 3 on the particle surface. (v) The reaction disfavors the formation of
SiO• surface radicals due to endothermicity of 17.0-18.2 kcal/mol based on DFT calculations. The H-
atom loss of EtO• to reach 6 and H-atom gain of Me• to reach 4 may occur on the surface or in the gas
phase. Yet under higher energy conditions, SiO• has been detected by 60Co irradiation of SiOH46,47 and
by •OH reactions.48 (vi) The cumyloxy radical recombination increased relative to cumyl alcohol
formation by surface H-atom transfer when bypassing <3 SiOH groups, otherwise cumyl alcohol
formation is competitive. Reduction of radical migration would be expected on a surface with greater
concentration of silanol groups, e.g., on zeosil silica.46
23
Figure 2.7. HPLC trace of compounds formed by the photosensitized homolysis of cumylethyl peroxide 2
at the gas/nanoparticle interface. The compounds were desorbed with acetonitrile and acquired with 80%
(v/v) MeOH/H2O as the mobile phase. The photosensitizer 4,4-dimethylbenzil 1 and cumylethyl peroxide
2 eluted at tR = 8.7 min and 9.2 min, respectively. Products were assigned to dicumyl peroxide 3 (tR = 30.9
min), cumyl alcohol 4 (tR = 4.2 min), acetophenone 5 (tR = 11.7), and α-methylstyrene (tR = 14.3 min). The
peak identities were deduced by spiking of the sample with known compounds.
Figure 2.8. Intensity of methyl peaks of dicumyl peroxide 3 (upper line) and cumene hydroperoxide (lower
line) in 1H NMR is plotted against concentration.
y = 2075.5x + 2064.3
R² = 0.988
y = 4149.1x + 2428.2
R² = 0.9984
0
15000
30000
45000
60000
75000
90000
0 5 10 15 20 25
inte
nsi
ty
concentration (mM)
24
In summary, the SPR strategy is simple, it capitalizes on the retention of the heavier cumyloxy
radical than the lighter volatile radicals to facilitate self-sorting and thus the formation of the symmetrical
product 3. The SPR method described here is appropriate for the detection of a radical migration up to 2.9
nm in the present case. There is increased migration of cumyloxy radical at lower loadings of 2 compared
to higher loadings. But there are competitive paths due to higher loading of 2, one is SiOH H-abstraction
to form cumyl alcohol 4. With a higher O−O bond energy and lower volatility, product 3 enriches itself
since reagent 2 generates the more labile EtO• and Me• upon sensitized decomposition. Over extended
photolysis times Me• formation increases by PhC(Me)2O• demethylation, which attenuates the SPR
assessment, as there is less of the alkoxy radical to dimerize to symmetrical product 3.
2.2. Conclusion
The SPR method that quantifies radical surface migration will have limitations. It requires
detectable recombination product quantities by HPLC and 1H NMR. Despite the limitation, our findings
provide a new approach important to radical migration on nanoparticles. Our conclusion is that SPR is
appropriate for radical migration studies on particle surfaces, suggesting possibilities to this methodology
might work on other radicals, such as free radicals on airborne fine particulate matter.
While there is value for research in control over surface radical delivery and persistence,
especially when radical persistence is detected in airborne particulate matter, the question is what
technology can be developed to make inroads. Current EPR methods detect surface radicals, where
differentiating between radical propagation versus migration presents challenges. Furthermore,
mechanistic understanding of radicals at the air/solid interface lags well behind that of radical
reactions in homogeneous solution.
25
Future mechanistic efforts are needed for analyzing the properties of radicals at interfaces. Particle
designs could include (i) use of a particle system with variable tumbling rates to enhance surface radical
diffusion and facilitate transiting off of volatile radicals. (ii) An alkoxy radical surface migration system
can be studied based on surface silanols with increasing water content to assess effects on the radical
migration distance.49-52 (iii) A complementary SPR/EPR method can be developed for product distribution
by radical recombination, and assist in distinguishing between stationary and migratory surface radicals.
(iv) Radical migration on surfaces by mass spectrometry can be investigated to homolyze R18O18OR and
R16O16OR for recombination to R18O16OR peroxides (Figure 2.9), which is reminiscent of isotope-sorting
recombination that has been achieved.53,54
Figure 2.9. A schematic of our air/solid heterogeneous system with a dispersion of R18O18OR and
R16O16OR peroxides on a nanoparticle. Upon irradiation, the resulting mixed peroxides R18O16OR will
provide indirect evidence of surface alkoxy radical migration.
2.3. Experimental
2.3.1. General. Acetophenone, cumene hydroperoxide, cumyl alcohol, 4,4-dimethylbenzil 1, and
dicumyl peroxide 3 were purchased from Sigma Aldrich and used as received. Acetonitrile, acetonitrile-d3,
chloroform-d, dichloromethane, methanol, and HPLC grade water were purchased from VWR and used as
26
received. Cumylethyl peroxide 2 was synthesized in 74% yield and 82% purity by a literature procedure.5
1H NMR data were collected on a Brucker Avance 400 MHz instrument. HPLC data were collected on an
Agilent Technology instrument (column: ZORBAX Eclipse XDB-C18).
2.3.2. Sample Preparation. Unfunctionalized hydrophilic fumed silica nanoparticles (200-300 nm
diameter, 200 ± 25 m2/g surface area) were purchased from Sigma Aldrich and washed in a Soxhlet
extractor with dichloromethane and methanol prior to use. The nanoparticles were then dried in a furnace
at 110 °C for 24 h. 4,4-Dimethylbenzil 1 and cumylethyl peroxide 2 were co-adsorbed onto the
nanoparticles in a manner similar to that described previously.5,55 The 4,4′-dimethylbenzil 1 (330 µmol) and
cumylethyl peroxide 2 (amounts ranging from a high of 108 µmol to a low of 6.8 µmol) were dissolved in
5 mL dichloromethane and stirred with 1.0 g of nanoparticles for 30 min in a 25-mL Teflon bottle. The
dichloromethane was then evaporated by use of a vacuum leaving the reagents adsorbed, assumed to be
uniformly distributed on the nanoparticles. This equated to percent loading of adsorbed sensitizer 1 and
peroxide 2 in the amounts of 25% and 0.87-13.8%, respectively. Notice that the surface was loaded with
high sensitizer to low peroxide ratios, that is, sensitizer-to-peroxide loading ratios ranging from 3:1 up to
49:1, which is an uncommon practice, although the photophysics of high dye concentrations have been
reported.56 These ratios of sensitizer-to-substrate were high for the photosensitized homolysis of 2, and is
purposely dissimilar to most literature on sensitization reactions that use very low sensitizer quantities.57
This permitted use to maintain an optimal sensitizer-peroxide distance of 7 Å for the triplet sensitized
homolysis (Figure 2.10), as we had previously established.55 Close intermolecular distances afford high
yields of triplet-sensitized O−O homolysis of peroxides. Another paper has been published on such a
reaction.59
27
Figure 2.10. Illustration of a grid depicting compound loading on the nanoparticle surface: (a) zoomed-out
view, and (b) zoomed-in view. Sensitizer molecules (1) are depicted as black squares, and the peroxide
molecules (2) are depicted as red squares, green squares, and white squares: Red squares depict a ratio of
1:2 of 3:1, green squares depict a ratio of 1:2 of 12:1, and white squares depict a ratio of 1:2 of 49:1. There
are few white squares because it represents the lowest amount of peroxide on the surface. Sensitizer-to-
sensitizer distances are shown as black squares and range in distances from 1.0 to 1.4 nm. Peroxide
molecules (e.g., two red squares) show distances relative four closest sensitizer molecules, which tend to
fall within the range of ~0.7 nm, as was found to be the ideal distance for triplet energy transfer from the
excited sensitizer to the repulsive O–O orbital of peroxide 2. All distances displayed are center to center as
shown with white lines connecting white dots.
2.3.3. Photosensitization reactions were carried out using a 5-mL airtight vial. The nanoparticles
were tumbled by a stirring paddle during the irradiation, where samples were placed at a distance of ~10
cm midpoint between two 400-W metal halide lamps delivering light (280 < λ < 700 nm). The fluence rate
at a mid-point in between the bulbs was 21.8 ± 2.4 mW/cm2.58 Upon irradiation, the temperature of the
particles was found to rise by ~10 °C, as we had detected in a similar system previously.5 This was measured
by a thermos couple probe attached to an IR thermometer, as is discussed in the temperature study section.
28
After photolysis, compounds were desorbed from the nanoparticle surface by stirring with 2-mL acetonitrile
for 20 min. Particles in the acetonitrile were removed passing through a syringe filter. Acetonitrile was then
completely evaporated and the residue analyzed by HPLC (C-18 reverse phase column, 80% MeOH-H2O
v/v mobile phase, 1-mL/min flow rate) and 1H NMR (with acetonitrile-d3). Even with modest peroxide 2
surface loadings of 0.9-13.8%, and ~15% conversion of the reaction, dicumyl peroxide product 3 was
readily detected by HPLC and 1H NMR. To analyze the volatile products released off the silica surface after
photolysis, head space analysis of 1-mL gas was drawn up in a glass syringe and slowly bubbled into
chloroform-d and analyzed by 1H NMR. For the homogeneous photoreactions, sensitizer 1 (0.01 mM) and
peroxide 2 (0.1 mM) in acetonitrile-d3 were irradiated in an NMR tube for 1 h using the 400-W metal halide
lamp system.
2.3.4. Theoretical Section. DFT calculations were carried out to analyze structural aspects and
reactions of peroxides 2-4, and alkoxy radicals PhC(Me)2O• and EtO•. We used M06-2X along with Pople’s
6-31G(d,p) basis set. The quality of the energetics was reasonable in comparison to M06-2X calculations
with the use of larger basis sets.24 The TS structures were verified with frequency calculations, and by
tracing their internal reaction coordinates (IRC). The endothermicity of peroxides 2-4 relative to their
corresponding alkoxy radicals was computed by comparing optimized energies of the former to the latter
as radical pairs separated by a distance of 3.0 Å. π∙∙∙HO and O•∙∙∙HO hydrogen bonding of PhC(Me)2O•,
EtO•, PhC(Me)2OH, EtOH, or C6H6 with silanol or silanoxy sites representing the air/solid interface were
modeled with (HO)3SiOH and (HO)3SiO• in the gas phase.
2.4. Supportive Studies
2.4.1. Compound Desorption, and Detection. We further demonstrate that the recombination of
cumyloxy radicals to the symmetrical product, dicumyl peroxide 3, has improved sensitivity to detection
via an 1H NMR study. Additions of 3 to solution showed the expected 2-fold higher sensitivity compared
29
to cumyl hydroperoxide at the same concentrations. This higher signal intensity of dicumyl peroxide 3 is
due to twice the number of methyl hydrogens in 3 compared to cumene hydroperoxide. The detection limit
of dicumyl peroxide 3 is 0.12 mM and for cumene hydroperoxide is 0.24 mM.
Table 2.3. Details of sensitizer 1 and peroxide 2 adsorption to nanoparticles, and other data
As the degree of dicumyl peroxide desorption from the silica sample is crucial to its detection a
study was performed for candidate solvents. The degree of dicumyl peroxide desorption from fumed silica
was measured in acetonitrile and toluene. It was found that dicumyl peroxide was able to fully desorb from
a 103 µmol/g silca sample in order to make a 0.1 to 0.2 mmol/L solution, adequate.
entry
cumylethyl
peroxide 2
adsorbed
(µmol/g. SiO2)
% surface
coverage
by peroxide
ratio of surface
silanols to
peroxide
molecules
peroxide 2–
peroxide 2
distance
(nm) a
maximum
cumyloxy
radical
migration
distancea
(nm)
maximum
number of
silanols
bypassed by
cumyloxy
radical
ratio of
dicumyl
peroxide 3
to cumyl
alcohol 4
1 108 13.8 12 1.7 0.27 1 1.98
2 53.2 6.8 25 2.5 0.65 2 1.22
3 27.1 3.5 49 3.5 1.2 3 0.74
4 13.4 1.7 99 5.0 1.9 5 0.66
5 6.78 0.87 196 7.0 2.9 8 0.30
30
Table 2.4. Amount dicumyl peroxide desorption in acetonitrile and toluene
a According the absorbance at the same wavelength as the adsorbates, due to impurities on the silica.
2.4.2. Attempts at Estimation of Radical Lifetime on Silica. Previous studies73,74 have
calculated the half-life of ROIs by determining their degree of decay over various distances. Here we
attempted to calculate the lifetime of the cumyloxy radical on the silica surface in a similar manner.
However, these calculations were unreliable under our method due to the increased complexity.
The typical overall rate for reactions taking place on surfaces must consider the constant for the
adsorption and desorption of the molecules from the surface, but as the adsorption of our molecules is not
a step in our reaction, but rather step in the preparation of our particles before the reaction takes place, and
desorbtion doesn’t occur until after the reaction has taken place, these constants do not need to be considered
into the rate. Rather the surface diffusivity must be considered as our molecules must diffuse across the
surface in order to react.
Therefore, when calculating the lifetime of the radicals on the surface we considered the diffusivity,
radical migration distance, and the reaction rate of the radicals to form our measured product that being the
cumyl radical termination forming dicumyl peroxide. The rate constants for the reaction were found using
the following rate law
d[dicumyl peroxide]/dt = (1/2) d[cumyl radical]/dt = kobs[cumyl radical]2 …… (5)
Sample
Dicumyl peroxide
103 µmol/g adsorbed
Monitored at 209 nm
Solvent Acetonitrile Toluene
Blank
Fumed Silicaa 18±5% 18±6%
Peroxide Only 100±11% 40±15%
31
Where the surface concentration of dicumyl peroxide was experimentally measured at 2 hours or
7200 seconds, and the surface concentration of dicumyl peroxide adsorbed was 0; making the surface
concentration of dicumyl peroxide at 0 seconds (t=0) 0. The rate constant was then found by graphing
1/[cumyl radical] vs time. Where [cumyl radical] is in mol/m2 and time is in seconds.
Pseudo-first-order decay of the radical over the surface due to water molecule and surface silanols
in high concentration. However, This doesn’t consider that two cumyloxy radicals must diffuse over the
surface and meet in order to form dicumyl peroxide. Therefore, the decay of the radicals over the surface
would have to be factored in double, thus the equations from previous studies were not adequate.
The lifetime of the cumyloxy radical on a fumed silica surface was calculated via eqns 1-3.
[dicumyl peroxide]d / [dicumyl peroxide] d=0 = kobs/k(d=0) = e−(ka/2D)d^2 (2.8)
-(ln(kobs/k(d=0))/d2)2D = ka (2.9)
1/ka = τcumyloxy radical (2.10)
ka is the first order rate constant of the radical termination step to create dicumyl peroxide from two
cumyloxy radicals. Figure 2.11 shows a semilog plot in which the slope is taken to be equal to
ln(kobs/kobs(d=0))/d2 and was used to estimate ka and surface lifetime of the cumyloxy radical. However, as
can be seen in Figure 2.11 the semilog plot of the data does not have a linear fit. Ignoring this the following
lifetime of cumyloxy radical on the silica surface was calculated. Using the literature value of D = 5.22 ×
10−5 cm2/s for cyclohexadienyl radical on a silica surface (46), τcumyloxy radical is calculated to be 1.86 × 10−7
ms.
32
Figure 2.11. A semilog plot of the observed rate of dicumyl peroxide production versus the peroxide to
peroxide distance on the silica surface. Used to calculate the ka and cumyloxy radical lifetime on the surface.
As seen the data does not have the necessary linear fit for properly computing the lifetime.
Table 2.5. Literature values for diffusion coefficients of molecules similar to cumyloxy radical in various
systems.
Solute Solvent/Surface Diffusion coefficient Reference
Cyclohexane
carboxylate (anion) Water 7.64 × 10–6 cm2 s-1 70
Phenylacetate (anion) Water 8.15 × 10–6 cm2 s-1 70
Naphthylacetate–
(anion) Water 7.56 × 10–6 cm2 s-1 70
Benzene Activated Carbon
particle 1.6 × 10–7 cm2 s-1 71
Phenol Activated Carbon
particle 4.3 × 10–8 cm2 s-1 71
β-Naphthol Activated Carbon
particle 7.4 × 10–9 cm2 s-1 71
naphthalene Activated Carbon
particle 7.0 × 10–9 cm2 s-1 71
cyclohexadienyl radical Cab-o-sil 5.22 × 10–5 cm2 s-1 72
0
1
2
3
4
5
6
0 2E-18 4E-18 6E-18 8E-18 1E-17
-ln(k
obs/k
(d=
0))
Radical migration distance squared (m2)
33
2.4.3. Temperature Study. We have examined the surface temperature of the vial which contained
the sample during photolysis, the surface temperature of the nanoparticle samples with and without
adsorbed sensitizer, and the air temperature under the photolysis lamps, in a series of experiments with an
IR thermometer.
Vial temperature. An empty glass vial was placed on the rotating paddle between the metal halide
lamps and the base room temperature of the vial was recorded. The vial was then rotated with the lamps on
for inconsecutive periods of time. After each period of time the lamps were shut off and the temperature of
the vial was immediately recorded. The vial was permitted to cool to its base room temperature, and the
temperature was recorded, before turning the lamps back on for the next time interval. This measurement
was performed for durations of 15, 30, 45, 60, 75, 90, 105, and 120 minutes leaving the lamps on.
Air temperature. The temperature of the air between the mercury halide lamps was recorded before
each time the lamps were turned on, and before each time the lamps were shut off to record vial temperature
using the thermocouple probe attachment to the IR thermometer. This temperature is likely most accurate
as the temperature could be recorded while the lamps were still on.
Nanoparticle samples. The temperature of native nanoparticles, and fumed silica nanoparticles
coated with 4,4-dimethylbenzil 1 was examined. The nanoparticles were placed into a vial and the vial
rotated with the lamps on for periods of time (15, 30, 45, 60, 75, 90, 105, and 120 min). After each period
of time, the lamps were shut off and the temperature of the nanoparticles recorded after removing them
from the paddle and uncapping of the vial lids. The temperature was recorded by pointing the IR
thermometer directly through the opening of the vial at the silica nanoparticles in the vial, so is not to record
the temperature of the vial rather than just the silica particles. The vial was permitted to return to room
temperature and a fresh sample of nanoparticles was weighted, and its temperature recorded before
proceeding to the next time interval.
34
Figure 2.12. A plot of temperature in air (black circles), of the 5-mL vial (red squares), of uncoated
nanoparticles (blue diamonds), and of nanoparticles coated with 4,4-dimethylbenzil 1 (yellow triangles)
immediately after irradiation with the metal halide lamps. The standard deviation of all measurements was
~1 °C.
2.5. References
1. Sim, S.; Forbes, M. D. E. Radical–triplet Pair Interactions as Probes of Long–range Polymer Motion in
Solution. J. Phys. Chem. B 2014, 118, 9997-10006.
2. Forbes, M. D. E.; Dukes, K. E.; Myers, T. L.; Maynard, H. D.; Breivogel, C. S.; Jaspan, H. B. Time-
resolved Electron Paramagnetic Resonance Spectroscopy of Organic Free Radicals Anchored to Silica
Surfaces. J. Phys. Chem. 1991, 95, 10547-10549.
3. Forbes, M. D. E.; Myers, T. L.; Dukes, K. E.; Maynard, H. D. Biradicals and Spin-correlated Radical
22
24
26
28
30
32
34
36
0 20 40 60 80 100 120
tem
per
ature
(oC
)
time (min)
35
Pairs Anchored to SiO2 Surfaces: Probing Diffusion at the Solid/Solution Interface. J. Am. Chem. Soc.
1992, 114, 353-354.
4. Forbes, M. D. E.; Ruberu, S. R.; Dukes, K. E. Dynamics of Spin-polarized Radical Pairs at the
Solid/Solution Interface. J. Am. Chem. Soc. 1994, 116, 7299-7307.
5. Ghosh, G.; Greer, A. A Fluorinated Phosphite Traps Alkoxy Radicals Photogenerated at the Air/solid
Interface of a Nanoparticle. J. Phys. Org. Chem. 2020; e4115.
6. Sindt, A. J.; DeHaven, B. A.; Goodlett, D. J.; Hartel, J. O.; Ayare, P. J.; Du, Y.; Smith, M. D.; Brugh,
A. M.; Forbes, M. D. E.; Bowers, C. R., et al. Guest Inclusion Modulates Concentration and Persistence
of Photogenerated Radicals in Assembled Triphenylamine Macrocycles. J. Am. Chem. Soc. 2020, 142,
502-511.
7. DeHaven, B. A.; Goodlett, D. W.; Sindt, A. J.; Noll, N.; DeVetta, M.; Smith, M. D.; Martina, C. R.;
González, L.; Shimizu, L. S. Enhancing the Stability of Photogenerated Benzophenone Triplet Radical
Pairs Through Supramolecular Assembly. J. Am. Chem. Soc. 2018, 140, 13064-13070.
8. DeHaven, B. A.; Tokarski, J. T.; Korous, A. A.; Mentink-Vigier, F.; Makris, T. M.; Brugh, A. M.;
Forbes, M. D. E.; van Tol, J.; Bowers, C. R.; Shimizu, L. S. Endogenous Radicals of Self-Assembled
Benzophenone bis-Urea Macrocycles: Characterization and Application as a Polarizing Agent for
Solid-State DNP MAS NMR Spectroscopy. Chem. Eur. J. 2017, 23, 8315-8319.
9. Chen, Q.; Sun, H.; Wang, M.; Wang, Y.; Zhang, L.; Hand, Y. Environmentally Persistent Free Radical
(EPFR) Formation by Visible-Light Illumination of Organic Matter in Atmospheric Particles. Environ.
Sci. Technol. 2019, 53, 10053-10061.
10. Jia, H.; Zhao, S., Shi, Y., Zhu, L., Wang, C., Sharma, V. K. Transformation of Polycyclic Aromatic
Hydrocarbons and Formation of Environmentally Persistent Free Radicals on Modified
Montmorillonite: The Role of Surface Metal Ions and Polycyclic Aromatic Hydrocarbon Molecular
Properties. Environ. Sci. Technol. 2018, 52, 5725-5733.
36
11. Runberg, H. L.; Mitchel, D. G.; Eaton, S. S.; Eaton, G. R.; Majestic, B. J. Stability of Environmental
Persistent Free Radicals (EPFR) in Atmospheric Particulate Matter and Combustion Particles. Atmos.
Environ. 2020, 240, 117809.
12. Vejerano, E. P.; Rao, G.; Khachatryan, L.; Cormier, S. A.; Lomnicki, S. Environmentally Persistent
Free Radicals: Insights on a New Class of Pollutants. Environ. Sci. Technol. 2018, 52, 2468-2481.
13. Feld-Cook, E.; Bovenkamp-Langlois, G. L.; Lomnicki, S. M. The Effect of Particulate Matter Mineral
Composition on Environmentally Persistent Free Radical (EPFR) Formation. Environ. Sci. Technol.
2017, 51, 10396-10402.
14. Vejerano, E.; Lomnicki, S., Dellinger, B. Formation and Stabilization of Combustion- Generated
Environmentally Persistent Free Radicals on an Fe(III)2O3/Silica Surface. Environ. Sci. Technol. 2011,
45, 589-594.
15. Truong, H.; Lomnicki, S.; Dellinger, B. Potential for Misidentification of Environmentally Persistent
Free Radicals as Molecular Pollutants in Particulate Matter. Environ. Sci. Technol. 2010, 44, 1933-
1939.
16. Chiesa, M.; Giamello, E.; Che, M. EPR Characterization and Reactivity of Surface-Localized Inorganic
Radicals and Radical Ions. Chem. Rev. 2010, 110, 1320-1347.
17. Bakos, T.; Valipa, M. S.; Maroudasa, D. First-principles Theoretical Analysis of Silyl Radical Diffusion
on Silicon Surfaces. J. Chem. Phys. 2006, 125, 104702.
18. Belh, S. J.; N. Walalawela; S. Lekhtman; A. Greer Dark-binding Process Relevant to Preventing
Photosensitized Oxidation: Conformation Dependent Light and Dark Mechanisms by a Dual-
functioning Diketone. ACS Omega 2019, 4, 27, 22623-22631.
19. Voloshchuk, T.; Farina, N. S.; Wauchope, O. R.; Kiprowska, M.; Haberfield, P.; Greer, A. Molecular
Bilateral Symmetry of Natural Products: Prediction of Selectivity of Dimeric Molecules by Density
Functional Theory and Semiempirical Calculations. J. Nat. Prod. 2004, 67, 1141-1146.
20. Bai, W.-J.; Wang, X. Appreciation of Symmetry in Natural Product Synthesis. Nat. Prod. Rep. 2017,
34, 1345-1358.
37
21. Edericlki, B.; Johnston, L. J.; de Mayo, P.; Wong, S. K. Surface Photochemistry: Generation of Benzyl
Radical Pairs on Dry Silica Gel. Can. J. Chem. 1984, 64, 403-410.
22. Fasciani, C.; Alejo, C. J. B.; Grenier, M.; Netto-Ferreira, J. C.; Scaiano, J. High-Temperature Organic
Reactions at Room Temperature using Plasmon Excitation: Decomposition of Dicumyl Peroxide. Org.
Lett. 2010, 13, 204-207.
23. Greer, A.; Balaban, A. T.; Liebman, J. F. In Chemistry of Peroxides; Greer, A.; Liebman, J. F., Eds.,
Wiley: Chichester, UK, 2014; Vol. 3, pp 1-20.
24. Bach, R. D.; Schlegel, H. B. Bond Dissociation Energy of Peroxides Revisited. J. Phys. Chem. A 2020,
124, 4742-4751.
25. Sert, Y.; Puttaraju, K. B.; Keskinoğlu, S.; Shivashankar, K.; Ucun, F. FT-IR and Raman Vibrational
Analysis, B3LYP and M06-2X Simulations of 4-Bromomethyl-6-tert-butyl-2H-chromen-2-one. J.
Mol. Struct. 2015, 1079, 194-202.
26. Tumanov, V. E.; Denisov, E. T., Estimation of Enthalpies of Alkoxy Radical Formation and Bond
Strengths in Alcohols and Ether. Kinet. Catalysis 2004, 45, 621-627.
27. Ireton, R.; Gordon, A. S.; Tardy, D. C. Thermal Decomposition of Perfluoro‐di‐t‐butyl Peroxide. Int.
J. Chem. Kinet., 1977, 9, 769-775.
28. Yaremenko, I. A.; Radulov, P. S.; Medvedev, M. G.; Krivoshchapov, N. V.; Belyakova, Y. Y.;
Korlyukov, A. A.; Ilovaisky, A. I.; Terent′ev, A. O.; Alabugin, I. V. How to Build Rigid Oxygen-Rich
Tricyclic Heterocycles from Triketones and Hydrogen Peroxide: Control of Dynamic Covalent
Chemistry with Inverse α-Effect. J. Am. Chem. Soc. 2020, 142, 14588-14607.
29. Bjarneson, D. W.; Petersen, N. O. Direct Diffusion Measurements of Naphthacene on Silica as a
Function of Silanol Density. J. Am. Chem. Soc. 1990, 112, 988-992.
30. Hema, B. T.; Pant, T.; Dhondiyal, C. C.; Rana, M.; Chowdhury, P.; Joshi, G. C.; Arya, P.; Tiwari,
H. Computational Study of the Intermolecular Interactions and Their Effect on the UV-visible Spectra
of the Ternary Liquid Mixture of Benzene, Ethanol and Propylene Glycol. J. Mol. Model 2020, 26, 268.
38
31. Casu, M. B. Nanoscale Organic Radicals on Surface, Interface, and Spinterface. Acc. Chem. Res. 2018,
51, 753-760.
32. Mas-Torrent, M.; Crivillers, N.; Rovira, C.; Vecianna, J. Attaching Persistent Organic Free Radicals to
Surfaces: How and Why. Chem. Rev. 2012, 112, 2506-2527.
33. Leach, A. G.; Wang, R.; Wohlhieter, G. E.; Khan, S. I.; Jung, M. E.; Houk, K. N. Theoretical
Elucidation of Kinetic and Thermodynamic Control of Radical Addition Regioselectivity. J. Am. Chem.
Soc. 2003, 125, 4271-4278.
34. Yang, Z.; Yu, P.; Houk, K. N. Molecular Dynamics of Dimethyldioxirane C–H Oxidation. J. Am. Chem.
Soc. 2016, 138, 4237-4242.
35. Yang, F.; Deng, F.; Pan, Y.; Zhang, Y.; Tang, C.; Huang, Z. Kinetics of Hydrogen Abstraction and
Addition Reactions of 3-Hexene by OH Radicals. J. Phys. Chem. A 2017, 121, 1877-1889.
36. Heberger, K.; Lopata, A. Assessment of Nucleophilicity and Electrophilicity of Radicals, and of Polar
an Enthalpy Effects on Radical Addition Reactions. J. Org. Chem. 1998, 63, 8646-8653.
37. Garrett, G. E.; Mueller, E.; Pratt, D. A.; Parent, J. S. Reactivity of Polyolefins toward Cumyloxy
Radical: Yields and Regioselectivity of Hydrogen Atom Transfer. Macromolecules 2014, 47, 544-551.
38. Tabriz, M. F.; Cizmeciyan, N.; Birer, O.; Yurtsever, E. Energy Landscapes in Photochemical
Dissociation of Small Peroxides. J. Phys. Chem. A 2019, 123, 1353-1362.
39. Dibble, T. S.; Phama, T. Peroxy and Alkoxy Radicals from 2-Methyl-3-buten-2-ol. Phys. Chem. Chem.
Phys., 2006, 8, 456-463.
40. Dibble, T. S. Intramolecular Hydrogen Bonding and Double H-Atom Transfer in Peroxy and Alkoxy
Radicals from Isoprene. J. Phys. Chem. A 2004, 108, 2199-2207.
41. Davis, A. C.; Francisco, J. S. Hydroxyalkoxy Radicals: Importance of Intramolecular Hydrogen
Bonding on Chain Branching Reactions in the Combustion and Atmospheric Decomposition of
Hydrocarbons. J. Phys. Chem. A 2014, 118, 10982-11001.
42. Golubev V. B.; Lunina E. V.; Selivanovskii, A. K. The Paramagnetic Probe Method in Adsorption and
Catalysis. Russ. Chem. Rev. 1981, 50, 421-431.
39
43. Rhodes, C. J.; Dintinger, T. C.; Reid, I. D.; Scott, C. A. Mobility of Dichloroethyl Radicals Sorbed in
Kaolin and Silica: A Potential Model of Heterogeneous Atmospheric Processes. Magn. Reson. Chem.
2000, 38, 281-287.
44. Bauer, R. K.; Borenstein, R.; de Mayo, P.; Okada, K.; Rafalska, M.; Ware, W. R.; Wu, K. C. Surface
Photochemistry: Translational Motion of Organic Molecules Adsorbed on Silica Gel and Its
Consequences. J. Am. Chem. Soc. 1982, 104, 4635-4644.
45. Edericlki, B.; Johnston, L. J.; de Mayo, P.; Wong, S. K. Surface Photochemistry: Generation of Benzyl
Radical Pairs on Dry Silica Gel. Can. J. Chem. 1984, 64, 403-410.
46. McMillan, G.; Wijnen, M. H. J. Reactions of Alkoxy Radicals. V. Photolysis of Di-t-butyl Peroxide.
Can. J. Chem. 1958, 36, 1227-1232.
47. Kyasa, S.; Meier, R. N.; Pardini, R. A.; Truttmann, T. K.; Kuwata, K. T.; Dussault, P. H. Synthesis of
Ethers via Reaction of Carbanions and Monoperoxyacetals. J. Org. Chem. 2015, 80, 12100-12114.
48. Oyama, R.; Abe, M. Reactivity and Product Analysis of a Pair of Cumyloxyl and tert-Butoxyl Radicals
Generated in Photolysis of tert-Butyl Cumyl Peroxide. J. Org. Chem. 2020, 85, 8627-8638.
49. Dondi, D.; Buttafava, A.; Zeffiro, A.; Bracco, S.; Sozzani, P.; Faucitano, A. Reaction Mechanisms in
Irradiated, Precipitated, and Mesoporous Silica. J. Phys. Chem. A 2013, 3304-3318.
50. Werst, D. W.; Viokur, E. I. Radiation Damage of Alkoxy and Siloxy Ligands Bonded to Silica. J. Phys.
Chem. B 2001, 105, 1587-1593.
51. Konecny, R. Reactivity of Hydroxyl Radicals on Hydroxylated Quartz Surface. 1. Cluster Model
Calculations. J. Phys. Chem. B 2001, 105, 6221-6226.
52. Hasan, G.; Salo, V.-T.; Valiev, R. R; Kubecka, J.; Kurten, T. Comparing Reaction Routes for
3(RO···OR') Intermediates Formed in Peroxy Radical Self- and Cross-Reactions. J. Phys. Chem. A
2020, 124, 8305-8320.
53. Bianchi, F.; Kurtén, T.; Riva, M.; Mohr, C.; Rissanen, M. P.; Roldin, P.; Berndt, T.; Crounse, J. D.;
Wennberg, P. O.; Mentel, et al. Highly Oxygenated Organic Molecules (HOM) from Gas-Phase
40
Autoxidation Involving Peroxy Radicals: A Key Contributor to Atmospheric Aerosol. Chem. Rev.
2019, 119, 3472-3509.
54. Dibble, T. S.; Chai, J. Critical Review of Atmospheric Chemistry of Alkoxy Radicals. Adv. Atmos. Sci.
2017, 185-269.
55. Kurten, T.; Moeller, K. H.; Nguyen, T. B.; Schwantes, R. H.; Misztal, P. K.; Su, L.; Wennberg, P. O.;
Fry, J. L.; Kjaergaard, H. G. Alkoxy Radical Bond Scissions Explain the Anomalously Low Secondary
Organic Aerosol and Organonitrate Yields From α-Pinene + NO3. J. Phys. Chem. Lett. 2017, 8, 2826-
2834.
56. Yeh, G. K.; Clafin, M. S.; Ziemann, P. J. Products and Mechanism of the Reaction of 1-Pentadecene
with NO3 Radicals and the Effect of a -ONO2 Group on Alkoxy Radical Decomposition. J. Phys. Chem.
A 2015, 119, 10684-10696.
57. Verdaguer, A.; Weis, C.; Oncins, G.; Ketteler, G.; Bluhm, H.; Salmeron, M. Growth and Structure of
Water on SiO2 Films on Si Investigated by Kelvin Probe Microscopy and in situ X-ray
Spectroscopies. Langmuir 2007, 23, 9699-9703.
58. Gun’ko, V. M.; Turov, V.V.; Pakhlov, E. M.; Krupska, T. V.; Borysenko, M. V.; Kartel, M.
T.; Charmas, B. Water Interactions with Hydrophobic versus Hydrophilic
Nanosilica. Langmuir 2018, 34, 12145-12153.
59. Leung, K.; Nielsen, Ida M. B.; Criscenti, L. J. Elucidating the Bimodal Acid−Base Behavior of the
Water−Silica Interface from First Principles. J. Am. Chem. Soc. 2009, 131, 18358-18365.
60. Liu, C. C.; Maciel, G. E. The Fumed Silica Surface: A Study by NMR. J. Am. Chem. Soc. 1996, 118,
5103–5119.
61. De Lima Batista, A. P.; Zahariev, F.; Slowing, I. I.; Braga, A. A. C.; Ornellas, F. R.; Gordon, M. S.
Silanol-Assisted Carbinolamine Formation in an Amine-Functionalized Mesoporous Silica Surface:
Theoretical Investigation by Fragmentation Methods. J. Phys. Chem. B 2016, 120, 1660-1669.
62. Buchachenko, A. L.; Dubinina, E. O. Photo-oxidation of Water by Molecular Oxygen: Isotope
Exchange and Isotope Effects. J. Phys. Chem. A 2011, 115, 3196-3200.
41
63. Buchachenko, A. L.; Yasin, L. L.; Belyakov, V. A. Magnet and Classical Oxygen Isotope Effects in
Chain Oxidation Processes: A Quantitative Study. J. Phys. Chem. 1995, 99, 4964-5969.
64. Walalawela, N.; A. Greer Heterogeneous Photocatayltic Deperoxidation with UV and Visible Light. J.
Phys. Org. Chem. 2018, e3807.
65. Rodríguez, H. B.; Mirenda, M.; Lagorio, M. G.; San Román, E. Photophysics at Unusually High Dye
Concentrations. Acc. Chem. Res. 2019, 52, 110–118.
66. Beeler, A. B. Introduction: Photochemistry in Organic Synthesis. Chem. Rev. 2016, 116, 9629−9630.
67. Scaiano, J. C.; Wubbels, G. G. Photosensitized Dissociation of Di-tert-butyl Peroxide. Energy Transfer
to a Repulsive Excited State. J. Am. Chem. Soc. 1981, 103, 640-645.
68. Mohapatra, P. P.; Chiemezie, C. O.; Kligman, A.; Kim, M. M.; Busch, T. M.; Zhu, T. C.; Greer, A. 31P
NMR Evidence for Peroxide Intermediates in Lipid Emulsion Photooxidations: Phosphine Substituent
Effects in Trapping. Photochem. Photobiol. 2017, 93, 1430-1438.
69. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani,
G.; Barone, V.; Petersson, G. A.; Nakatsuji, H., et al. D. J. Gaussian 16, Revision C.01; Gaussian, Inc.:
Wallingford, CT, 2016.
70. Vany´sek, P. In CRC Handbook of Chemistry and Physics. Haynes, W. M., Eds., CRC Press: Boca
Raton, FL, USA, 2012; 93rd revised, pp. 577-579.
71. Suzuki, M.; Kawazoe, K. Effective Surface Diffusion Coefficients of Volitale Organics on Activated
Carbon During Adsorption from Aqueous Solution. J. Chem. Eng. Japan, 1975, 8, 379-382.
72. Schwager, M.; Dilger, H.; Roduner, E.; Reid, I. D.; Percival, P. W.; Baiker, A. Surface diffusion of the
cyclohexadienyl radical adsorbed on silica and on a silica supported Pd catalyst studied by means of
ALC-,6R. Chem. Phys. 1994, 189, 697-712.
73. Skovsen, E.; Snyder, J. W.; Lambert, J. D. C.; Ogilby, P. R. Lifetime and Diffusion of Singlet Oxygen
in a Cell. Phys. Chem. B 2005, 109, 8570–8573.
74. Naito, K.; Tachikawa, T.; Cui, S.-U.; Sugimoto, A.; Fujitsuka, M.; Majima, T. Single-Molecule
Detection of Airborne Singlet Oxygen. J. Am. Chem. Soc. 2006, 128, 16430−16431.
42
Chapter 3.
Dark-Binding Process Relevant to Preventing Photosensitized
Oxidation: Conformation-Dependent Light and Dark Mechanisms
by a Dual-Functioning Diketone
3.0. Introduction
Dual-functioning compounds, such as those which perform as both imaging agents as well as
photosensitizers, are an increasing class of compounds.1-3 Dual functioning has been approached from many
different angles.4,5 In one case, singlet oxygen (1O2) was used to photodegrade micelles for the delivery of
the doxorubicin for combined 1O2 and drug activity (Figure 3.1).6
However, there is a way to go before photosensitizers can also serve simultaneously as
chemotherapeutic drugs. Here, we describe an -diketone sensitization that responds as a conformational
switch to binding may bring that goal a step closer.
Conformationally-dependent binding of drugs that shut off the photosensitization pathway are
generally not exploited in photodynamic therapy (PDT). The reason that conformational twisting is usually
not available to sensitizers is they are often cyclic structures. In the case of porphyrins and phthalocyanines,
a flat shape is largely retained upon excitation. Sensitizers that can adopt flat and also twisted conformations
are in need of greater study in the context of dual function. Tools from the conformational binding side can
then influence the outcome of the photooxidation. The two functions can come together to influence each
other in competitive light/dark reactions.
The potential for such dual-functioning compounds could be realized with -diketones (diones)
that are now explored for chemical binding vs photosensitization processes. We hypothesized that a dione
will act as a sensitizer as the anti isomer and undergo chemical binding as the syn isomer in a “give and
43
take” to the sensitization process (Figure 3.2). That compounds may be decoupled from sensitization
through drug binding would be of fundamental interest.
Dione compounds have been shown to act well as binding agents.7 For example, benzils bind to
tubulin proteins in a similar manner as stilbenes, such as combretastatin A-4.8 Furthermore, diones have
been shown to be important in chelation reactions with phosphites,9,10 and have been used in the synthesis
of phosphoranes.11 Diones such as 4,4′-dimethylbenzil (9) and mono-carbonyl compounds have been used
as photosensitizers in photooxidation reactions,12-15 but not in the terms of dione conformational binding
and photosensitization as we describe here. Indeed, the dual functionality of diones for photosensitization
and subsequent binding has not been previously explored.
We report on a conformational switch between dione-sensitized peroxide decomposition and dione
binding to phosphite. Tuning the dione conformation is desired not only to thermally chelate, but control
peroxide sensitization to alkoxy radicals, in which Light Path A and Dark Path B are competitive (Figure
3.3). The dione sensitization is permanently shut off by a conformational switch in phosphite binding. We
now demonstrate that anti and syn-skewed conformations of 9 promote sensitization, whereas the syn
conformation promotes phosphite binding. The following presentation only considers 4,4′-dimethylbenzil
9 and glyoxal 11; the former in experimental and theoretical work, the latter only in theoretical work. The
mechanism in Figure 3.3 is consistent with the data collected, as we will see next.
44
Figure 3.1. Micelle degradation by singlet oxygen for the release of doxorubicin for combined 1O2 and
drug activity.
Figure 3.2. Conformational switch of dione for photosensitized oxidation activity and binding activity. The
dione acts as a photosensitizer (Path A) and binds to a phosphite shutting off the sensitization (Path B). It
will be shown how paths A and B are competitive. Dione concentrations and the proticity of the surrounding
environment is tested. Here, “X” represents a chelating agent such as protein binding site or a phosphite
molecule as is examined in the current work
45
Figure 3.3. Proposed mechanism that blends the dark (thermal) and light (Jablonski-like) processes. The
1,2-dione sensitizer is competitive in photodecomposition of dicumyl peroxide 11 (Path A) and binding of
syn dione with (MeO)3P (Path B). Aprotic and protic media influence the reaction of the alkoxy radical.
The alkoxy radical also competes with the 1,2-dione for the (MeO)3P trapping agent. Phosphorane 12 (R =
pCH3C6H4); phosphorane 13 (R = H). “Y” is the C6H5C(Me2) group on dicumyl peroxide 11.
3.1. Results and Discussion
The results are presented in the following four subsections: (1) the computed binding process
between dione 10 and (MeO)3P; (2) analysis of the kinetics of the binding; (3) the sorting out of light and
dark dependent reactions; and (4) product distribution upon photosensitized homolysis dicumyl peroxide
11.
(MeO)3P
hn
Path B
Path A
triple
t ene
rgy
tran
sfe
r
light
dark
anti syn skewed syn
via cis dione
Y O O Y
Y O2
R
O R
O
sens0
1sens*
ISCR
O R
O3sens*
O
R
O
R
O
R
O
R
O
R
R
O
O
P
MeOMeO
O
OMe
R R
70
60
50
40
30
20
10
0
che
latio
n
BDE = 36 kcal
kcal/m
ol
(R = H)
4 or 5
46
3.1.1. Dihedral Rotation Dependence of Bidentate Binding. Some details of the dione rotation
and phosphite binding can be obtained from DFT calculations. Glyoxal 10 was used as a model system to
mimic the 1,2-dione portion of 4,4′-dimethylbenzil 9 due to lower computational cost of the former. Dione
10 serves as a model for the DFT calculations, but is not a good sensitizer. Figure 3.4A shows the
B3LYP/D95(d,p) energies for the rotation of glyoxal 10 around the dihedral angle (θ for O=C–C=O), which
was constrained to 10° increments. The anti rotamer is the global minimum, and the syn rotamer is 5.6
kcal/mol less stable. The syn rotamer is reached by a syn-skewed transition structure with a barrier height
of 7.5 kcal/mol. For the larger dione (dimethylbenzil, 9), a pure syn geometry of 9 cannot be transposed on
its core, and therefore a syn-skewed minimum is favored due to a buttressing of the nearby aryl groups,
which destabilize the syn geometry. It appears that the ortho-aryl hydrogens disable dione 9 from adopting
a pure syn geometry. Nonetheless, 10 served as a good model for the 1,2-dione segment of 9. Relatedly,
Allonas et al.16 have shown that diones in the syn orientation have a lower ET by a couple of kcal/mol than
diones flexible to rotated about their central C–C bonds. In our case, a computed rotational profile is
featured for a syn and anti dione, where both are stable, however the syn dione reacts with (MeO)3P based
on the Curtin-Hammett principle.
Next, we computed the cyclization path of dione 10 with (MeO)3P. This chelation reaction arises
from the syn dione. The transition structure for the cyclization is shown in Figure 3.4B, where the resultant
dihedral angle (θ is O=C–C=O) is approximately planar for TS2/3 is 0.9°. The phosphorane product 13
possesses a trigonal bipyramidal geometry, where the apical P–O bond distance (2.37 Å) is onger than the
equatorial P–O bond distance (2.18 Å). The activation energy for the association of dione 2 with (MeO)3P
is predicted to be ∆E‡ = 15.3 kcal/mol. Only a transition structure for a concerted process from the syn dione
was found. Transition structures for a step-wise addition could not be located. We also did not find an
energy minimum for a monodentate binding between dione 10 and (MeO)3P. Formation of phosphorane 11
is exothermic by 9.1 kcal/mol compared to the reagents 9 and 10. The decomposition of phosphorane is a
47
high-barrier process so that it irreversibly ‘‘masks’’ dione 10, where the energy barrier for the release of
phosphite from the phosphorane is 30.0 kcal/mol. An assessment of molecular orbitals (MOs) was as also
informative to understanding the free form of the dione and the phosphite binding process.
DFT computations show that the HOMO of dione 10 has zero nodes and an n-type orbital on the
oxygen lone pair electrons, and a LUMO with antibonding * character due to two nodes on the p orbitals
of the C=O groups (Figure 3.5). The chelation of (MeO)3P to the dione alters the electronic transition of the
dicarbonyl group. In contrast, the HOMO of phosphorane 13 is of character with two nodes on the p
orbitals of the C=O groups and a C=C bond. The LUMO of 13 has antibonding * character with p
orbitals on the C=O and C=C groups. The computations are consistent with experimental results showing
that -diketones bear strong n,* character,16 where our DFT results now show that the n,* character in
dione 10 is lost and replaced with the ,* character in the phosphorane 13. Next, we present experimental
evidence for a cyclization of dione 9 with (MeO)3P to reach phosphorane 12.
48
Figure 3.4. DFT computed (A) energy plot for the 360° rotation of the 1,2-dione group in glyoxal 10, and
(B) potential energy surface for the reaction of glyoxal 10 with (MeO)3P. is the dihedral angle for O=C–
C=O of the dione. Oxygen atoms are red, carbon atoms are gray, and hydrogen atoms are white.
-9.1 kcal/mol
20.9
kcal/mol
(q = 0.9°)
TS2
5.6 kcal/mol
trans dione 2
(q = 180°)
(MeO)3P
ene
rgy (
kca
l/m
ol)
7.5 kcal/mol 7.5 kcal/mol
cis skewed
dione 2 (q = 80°)
phosphorane 5 TBP structure
extent of reaction rotational profile (deg.)
cis skewed
dione 2 (q = 260°)
syn dione 2
(q = 0°)
transition state
OPMeO
MeO
O
OMeapical
apical
equatorial
trans syn phosphorane
(major) (minor)
Curtin-Hammett Principle
dione dione
0 50 100 150 200 250 300 350
0
5
10
15
20
25
10
10
10
10
13
49
Figure 3.5. DFT computed HOMO and LUMO of syn-dione 10, (MeO)3P, and phosphorane 13. Oxygen
atoms are red, carbon atoms are gray, and hydrogen atoms are white.
OMeOMeMeO
PH
O O
H O
P
OMe
MeO
O
OMe
HOMO
LUMO
optimized structure
syn dione 2 phosphorane 5 10 13
50
3.1.2. Kinetics of Dione Binding to Phosphite. We sought experimental evidence for the
formation of phosphorane 12 since dione 9 is a sensitizer. Figure 3.6 shows a first-order fit for the reaction
of dione 9 and (MeO)3P over time. Due to the sparing stability of phosphorane 12, kinetics for its
disappearance do not fit a first order plot. Phosphorane 12 is an intermediate and exists for ~10 minutes as
a mixture in the reaction. Notice the absorptivity of dione 9 decreases significantly when chelated to
(MeO)3P upon formation of the phosphorane 12 (Figure 3.7). The phosphorane absorption is attributed to
a ,* transition that appears at a shorter wavelength (λmax = 235 nm) in comparison to dione 9 (λmax = 270
nm). Thus, phosphorane 12 has little to no overlap with the light source (300 < λ < 700 nm). We are
confident to the existence of transient phosphorane 12 in our system based on the evidence to follow. 1H
NMR data show the phosphorane 12 doublet “b” is located at 3.66 and 3.69 ppm and increases with time
(Figure 3.8), where its location is similar to POCH3 peaks in phosphorane compounds previously reported.11
A similar increase over time can be seen in the peak assigned to the phorphorane 12 p-substituted methyls
(Figure 3.9). The 31P NMR data show that phosphorane 12 bears a chemical shift of -49.6 ppm (Figure
3.10), indicating that the phosphorus atom is covalently bound to five oxygen atoms, which is also similar
to a previous report. Similar negative chemical shifts have been observed for other phosphoranes.12
51
R Square Values in Fitting of the Kinetic Data
Compound Zeroth order
fit
First
order fit
Second
order fit
Half
order fit
Dione 9 0.9457 0.9765 0.9946 0.9626
Trimethylphosphite 0.9290 0.9926 0.9893 0.9685
Phosphorane 12 0.9323 0.7734 0.5339 0.8675
Figure 3.6. (A) Plot of the disappearance of 4,4-dimethylbenzil 1 () and (MeO)3P ( ), and appearance of
phosphorane 12 ( ) over time in CH3CN. (B) Near-linear pseudo-first order fits are observed for the
disappearance of 9 () and (MeO)3P ( ), whereas phosphorane 12 appearance does not fit first order
kinetics, presumably due to its simultaneous decomposition. Table shows R square values resulting from
various fittings of the kinetic data.
0
20
40
60
80
100
120
0 2000 4000 6000
Co
nce
ntr
atio
n (
mM
)
Time (sec)
2.0
2.5
3.0
3.5
4.0
4.5
5.0
0 2000 4000 6000
ln[C
on
cen
trat
ion
]
Time (sec)
A B
52
Figure 3.7. Absorption spectra following the dark reaction of 4,4-dimethylbenzil 9 (λmax = 270 nm) and
(MeO)3P, which forms phosphorane 12 (λmax = 235 nm) and by-products in CH3CN. Spectra were recorded
after 1, 11, and 41 min. At 41 min, the mixture contains 4,4-dimethylbenzil 9 and phosphorane 12 in a ratio
of about 1:1.
53
Figure 3.8. Partial 1H NMR spectra following the photoreaction of 4,4ꞌ-dimethylbenzil 9, dicumyl peroxide
11, and (MeO)3P in CD3CN. Spectra were recorded after irradiation times of 5, 22, 39 and 56 min. The
(MeO)3P peaks “a” at 3.48 ppm and 3.51 ppm (d, J = 10.6 Hz, 9H) are found to recede with time, whereas
the phosphorane 12 peaks “b” at 3.66 ppm and 3.69 ppm (d, J = 13.2 Hz, 9H) increase with time. The peak
marked “x” is due to an impurity.
54
Figure 3.9. Partial 1H NMR spectra following the dark reaction between 4,4ꞌ-dimethylbenzil 9 and (MeO)3P
in CD3CN at 5 min (red), 22 min (green), 39 min (blue) and 56 min (purple). The p-substituted methyls
were assigned to the 4,4ꞌ-dimethylbenzil 9 peak “a” at 2.451 ppm and the phosphorane 12 peak “b” at 2.350
ppm.
55
Figure 3.10. 31P NMR spectra following the photoreaction of 4,4ꞌ-dimethylbenzil 9, dicumyl peroxide 11,
and (MeO)3P in CD3CN compared to an H3PO4 standard. Spectra were recorded after irradiation times of 7
and 64 min. The (MeO)3P peak “a” at 140.8 ppm is found to recede with time, whereas the phosphorane 12
peak “b” at -49.6 ppm and the (MeO)3P=O peak “c” at 2.25 ppm increase with time. Peaks marked “x” are
due to impurities.
The appearance of trimethylphosphate [(MeO)3P=O] is a consequence of the phosphorane 12
decomposition via aryl migration, a side reaction leading to ketene. Based on the literature of ketenes,11
phosphorane 12 cleavage is expected to lead to (p-MeC6H4)2C=C=O and (MeO)3P=O, and by-products,
although we did not analyze these downstream reactions. Next, we sought to examine the competitive
binding of dione 9 with (MeO)3P (Dark Path B) and the photooxidation activity in cumyloxy radicals
generated in dicumyl peroxide 11 photodecomposition (Light Path A).
56
3.1.3. Separating the Light and Dark Paths. In addition to phosphite chelation to dione (Path
B), we show that phosphite can be used to indirectly monitor the photodecomposition of dicumyl peroxide,
by trapping the resultant cumyloxy radicals (Light Path A) (Table 3.1). The use of phosphite as alkoxy
radical traps is reported in the literature.17,18 Table 3.1 shows the dione 9 sensitized dicumyl peroxide 11
decomposition as a function of the sensitizer to peroxide ratios. The ratios correspond to concentrations of
100 mM 9 and 0.5 to 100 mM 11. Data are shown for (MeO)3P=O formed from Light Path A, Dark Path
B, and combined Paths A + B. Samples were irradiated (300 < λ < 700 nm) for 1 hour under anaerobic
conditions. The sensitizer/peroxide ratio of 1:1 showed an 9% increase in peroxide homolysis compared to
the 1:10 ratio (entries 1 and 2). Thus, the photosensitized decomposition of 11 was about 3 times more rapid
in the 1:1 ratio sensitizer/peroxide compared to the 1:10 ratio. As we see, the sensitized 11 decomposition
was shown to require a high sensitizer to peroxide ratio. Ratios of 1:40 or lower (entries 3-5) show no
detectable sensitized decomposition of dicumyl peroxide 11.
Path B clearly is significant since Path A values are lower by comparison. In the absence of
sensitizer, direct irradiation (300 < λ < 700 nm) leads to no detectable photodecomposition of dicumyl
peroxide 11 (entry 6). Indeed, the poor excitation wavelength overlap of the dicumyl peroxide 11 with the
light source provides an explanation for dicumyl peroxide’s stability without sensitizer. While dicumyl
peroxide 11 is photochemically unstable with UVC light (data not shown), our light source is mainly UVA
and visible light with some UVB, and thus we demonstrate that dione sensitizer 9 leads to the photolability
of dicumyl peroxide 11. The extent of peroxide decomposition due to direct irradiation (280 < λ < 700 nm)
is negligible for dicumyl peroxide 11 (~0%) under our conditions. Thus, it follows that the fragility of
peroxide O–O bonds needs to be negligible for quantitation of any sensitized contribution to the
decomposition. Next, we carried out DFT studies to probe the dicumyl peroxide O–O bond dissociation
further.
Since the dicumyl peroxide 11 is not excited, we conducted ground-state DFT calculations rather
than TD-DFT calculations to predict the energetics for O–O bond dissociation on the singlet and triplet
potential energy surfaces (PESs). The O–O bond was elongated and optimized at each distance with the
57
resulting potential energy curves shown in Figure 3.11. It is readily seen that on the singlet surface, O–O
bond separation is endothermic with a barrier to O–O bond homolysis of ~60 kcal/mol. In contrast on the
triplet surface, the O–O bond separation is exothermic and that the forming cumyloxy radical pair are
strongly repulsive. The singlet surface in Figure 3.11A shows the separated cumyloxy radicals are found
oriented in an anti-conformation. On the singlet surface, the homolysis would is high in energy to unveil
alkoxy radicals. On the other hand, the triplet surface in Figure 3.11B shows the separated cumyloxy
radicals remains in a cis skewed conformation even up to a separation distance of 3.5 Å. Based on these
DFT results (Figure 3.11), and keeping in mind the O–O bond dissociation energy (BDE) of dicumyl
peroxide 11 is 34 kcal/mol,19,20 we surmise that the photosensitized O–O bond homolysis occurs on the
triplet manifold via energy transfer to a repulsive orbital of the O–O bond. For releasing the cumyloxy
radicals beyond their contact-pair as free species, a small amount of heat would then be required.
58
Table 3.1. Using trimethylphosphite to track the dicumyl peroxide photodecomposition as a function of
sensitizer to peroxide ratioa-c
entry
dicumyl
peroxide
concentration
(mM)
sensitizer 9
concentration
(mM)
sensitizer 9 to
peroxide 11
ratio
% reduction
of 11 from
light path Ad
% phosphate
formed from
dark path Bd
% phosphate
formed from
paths A + Bd
1 100 100 1:1 14 37 51
2 100 10 1:10 5 15 20
3 100 2.5 1:40 0 12 12
4 100 1 1:100 0 14 14
5 100 0.5 1:200 0 15 15
6 100 0 0:1 0 0 0
a Trimethylphosphite concentration was 100 mM. b Amount of phosphite and phosphate monitored by 1H
NMR (corresponding methyl peaks). c Amount of peroxide and products (cumyl alcohol and
acetophenone) monitored according to HPLC. d Standard deviation is ±1%.
11
9
9
13
59
Figure 3.11. Unrestricted B3LYP/D95(d,p) calculations for the O–O bond dissociation of dicumyl peroxide
11 on the (A) singlet surface, and (B) triplet surface. The structures were optimized with the O–O bond was
constrained by increases in 0.05 Å increments. Relative energies in kcal/mol.
60
3.1.4. Trapping of Photogenerated Cumyloxy Radical. As dicumyl peroxide 11 can be
photosensitized to homolytically cleave, we turned to an evaluation of the effect of reaction medium on the
product distribution to seek further evidence of the existence of cumyloxy radical. Table 3.2 show data
which determine the effect of the surrounding media on the products formed in the 4,4′-dimethylbenzil 9
sensitized decomposition of dicumyl peroxide 11. Here, acetophenone (14), 2-phenylpropan-2-ol (15), and
-methylstyrene (16) were detected as products, where the distribution depended on the presence or absence
of an H-atom source.
In wet acetonitrile-d3, irradiating with light from 300 < λ < 700 nm, the products formed were
acetophenone 14 (2%) and 2-phenylpropan-2-ol (7) (98%) (Table 3.2, entry 1). Somewhat similarly, a
literature plasmon-excitation reaction in methanol showed dicumyl peroxide 11 decomposition to 14 (50%)
and 15 (50%) (entry 2).19 In contrast, in dry acetonitrile-d3, products were favored in the opposite direction
with the near exclusive formation of acetophenone 14 (99%), with 2-phenylpropan-2-ol 7 (<1%) and a trace
amount of -methylstyrene 16 (entry 3). Solution-free conditions on silica with unfiltered UV light (280 <
λ < 700 nm) or with direct irradiation of 11 with 254 nm light led to a slightly reduced yield acetophenone
14 (67-70%), with 2-phenylpropan-2-ol 7 (4-5%), and -methylstyrene 16 (1-2%) (entries 4 and 5). For the
solution-free reactions on silica, the mass balance of the reaction was ~75% due to evolution of volatile
species, such as CH3• and CH4. A literature plasmon-mediated reaction in acetonitrile also showed the main
product to be 14 (98%) with a minor amount of 15 (2%) (entry 6).19
We attribute these results to cumyloxy radicals formed in the sensitized homolysis of dicumyl
peroxide 11, which abstracts H atoms from water (in wet acetonitrile) or silanol (SiOH) groups on the silica
surface. The cumyloxy radical may also be reacting with water on adsorbed to the silica surface leading to
increased percent yields of 15. The heterogeneous experiment was carried out on silica with high relative
amounts of SiOH groups for H-atom abstraction. Our results are consistent with literature reports of H-
atom abstraction by cumyloxy radicals in polymer crosslinking and other reactions.21,22
61
Table 3.2. Effect of aprotic and protic media in products formed from the 4,4-dimethylbenzil 9 sensitized
photodecomposition of dicumyl peroxide 11.
entry reaction
medium condition
% yield of
acetophenone 14 g
% yield of
cumyl alcohol
15 g
% yield of α-
methylstyrene
16 g
ref.
1
wet
acetonitrile-
d3
solutiona,b,c
dione 9
photosensitized 2 98 <0.01
this
work
2 methanol
solution
plasmon
excitation 50 50 - 19
3
dry
acetonitrile-
d3
solutiona,b
dione 9
photosensitized 99 <1 <0.01 this
work
4 gas/solid
interfacea,d
dione 9
photosensitized 70 4 1 17
5 gas/solida,e,f
interface 254 nm light 67 5 2
this
work
6 acetonitrile
solution
plasmon
excitation 98 2 - 19
a An average of 3 runs with a standard deviation of ±3. b Irradiation at 300 < λ < 700 nm. c Acetonitrile
containing <1% H2O. d Irradiation at 280 < λ < 700 nm. e Solid phase is fumed silica. f Irradiation at 254
nm. g Sensitizedf homolysis of dicumyl peroxide 11 leads to cumyloxy radical, which adds to (MeO)3P,
and subsequently cleaves a methyl radical in reaching (MeO)3P=O based on the following proposed
reaction: dione 9 + Ph(Me2)COO(Me2)Ph 11 + h → 2Ph(Me2)CO•; Ph(Me2)COO(Me2)Ph ←
[2Ph(Me2)CO•] + (MeO)3P → (MeO)3P=O; [2Ph(Me2)CO•] → MeCOPh + Me•; [2Ph(Me2)CO•] + H-atom
source → ROH.
O
OH
O
+
6 8
7
protic media
(SiOH, wet CD3CN,
aprotic media
(dry CD3CN)
or MeOH)
cumyloxy radical
hnO O
3sens 1
11
9
15
16
15
14
15
62
3.1.5. Summary. We show that a Curtin-Hammett process of the less stable syn conformer of a
dione binds to (MeO)3P irreversibly. The facility of this increases with the syn dione conformation. Since
diones have been used as protein binding drugs,7,8 there is a potential for their use in rotation tuning for
binding from the syn form to sensitization from the anti form. That is, the function of the dione would be
more photodestructive in the anti form, but more effective in protein binding for example in the syn form.
The competition for chemical selectivity (modulation response) emerges through a Curtin-Hammett process
involving the less stable syn conformer. The transition state and formation of phosphorane arises from the
syn dione according to the DFT calculations.
The photosensitized decomposition of dicumyl peroxide 11 requires relatively high concentrations
of dione 9 and is proposed to take place on the triplet manifold. Cumyloxy radicals are formed and scavenge
H-atoms from surface silanols, water adhered to silica, as well as methanol and water producing cumyl
alcohol as the major product. In the peroxide-sensitized homolysis, H-atom abstraction of protic media by
the cumyloxy radical is an important process that competes with methyl radical loss and formation of
acetophenone as a major product in the dicumyl peroxide photodecomposition reaction. Dione 9 is not
likely to photoreduce in the presence of water, but would be susceptible to photoreduction with H atom
donors such as triethylamine or a phenol substituted with an electron donating substituent.16 In terms of
product formation, produced acetophenone (ET = 74 kcal/mol) may also serve as a photosensitizer, although
4,4-dimethylbenzil 9 has a fairly low-lying triple state (ET = ~51 kcal/mol) is expected to be the main
photosensitizer over the course of the peroxide 11 homolysis reaction. Also, for comparison O2 degassed
conditions were used otherwise a competing process would include dione sensitization to O2 and formation
of singlet oxygen. Our work is also part of a growing body of work17,27-33 examining sensitization reactions
by peroxide O–O bond homolysis, where the reaction is also relevant to the more commonly studied
sensitization of 3O2 to 1O2.
Porphyrins have been studied and act well as 1O2 sensitizers, but usually bind to membranes rather
than within enzymatic pockets.23 Porphyrin distortion away from planarity can lead to a shut off of their
63
sensitizer activity,24-26 however, porphyrins’ large size mostly disallow competing processes, such as
binding in a protein pocket. Here, we report on a dione that can bind a phosphite, an observation similar to
the dione binding at metal active sites in enzymes (e.g., tropolones and hydroxy-tropolones), where the
relative size of dione 9 and derivatives can facilitate binding. The effectiveness of the dione as a
photosensitizer is suggested but only prior to binding, which suggests a potential advantage to dione-
sensitized reactions in PDT applications.
3.2. Conclusion
We present a new concept for dark conformational dependence in connection with attenuating a
photooxidation reaction. Namely, the ability of an -diketone (4,4′-dimethylbenzil) to act as a
photosensitizer for alkoxy radical production, and to bind to a trialkyl phosphite was studied in homogenous
and heterogeneous systems. Upon binding to phosphite, the 4,4′-dimethylbenzil decreased in its alkoxy
radical photoproduction, acting as a shut-off mechanism. This opens the avenue of -diketones for
prospective dual action in sensitization and in drug binding activity.
Diones such as 9 can serve as photosensitizers, but also have dark binding opportunities. The light
and dark paths are competitive paths due to the rotational dependence about the two carbonyl groups, with
the syn enhancing dark binding and the anti or syn-skewed increasing the light-dependent route. The
system is a step toward the dual action goal, in which the design can be tailored to selected binding site to
enhance cooperative dialog between phototherapy-to-drug binding. Such a collective mode of reaction is
generally not available to sensitizer macrocycles with restricted conformational freedom.
64
3.3. Experimental
3.3.1. Computations. Calculations were carried out using Gaussian 09 (revision D.01)36 with the
B3LYP functional and the D95(d,p) basis set in gas phase. Molecules were visualized with GaussView
5.0.37 The transition state structure TS2 was verified as transition states by frequency calculations.
Calculations were also carried out by scanning of bond rotations for dione 10 and the O–O bond
dissociations of dicumyl peroxide 3 in the singlet and triplet surfaces by constraining compound geometries.
3.3.2. General. Reagents used include: 4,4-dimethylbenzil 9, dicumyl peroxide 11,
trimethylphosphite [(MeO)3P], trimethylphosphate [(MeO)3P=O], and triisopropylphosphate [(n-
C3H7O)3P=O] purchased from Sigma Aldrich and used as received. Potassium hydrogen phthalate from
Fisher Scientific was used as received. Acetonitrile, acetonitrile-d3, dichloromethane and methanol were
purchased from VWR and used as received. The hydrophilic fumed silica particles used were 200-300 nm
in diameter, with 200 ± 25 m2/g surface area.
3.3.3. Photolysis Method. Figure 3.12 shows a schematic of irradiations that were conducted with
samples placed in a 1-cm filter solution of 0.5 w/v% potassium hydrogen phthalate in water to collect light
from 300 < λ < 700 nm at the midpoint between two 400-W metal halide lamps, which delivered light (280
< λ < 700 nm). A handheld UV 254 nm light source was also used. Rises in temperature of ~2-3 °C were
observed for the sample solution under irradiation after 1 h. We have previously measured the fluency rate
at a mid-point in between the bulbs to be 21.8 ± 2.4 mW/cm2.34 The tail of the absorption of dione 9 (280-
310 nm) overlaps with the output of the metal-halide light, but this overlap is poor and nearly nonexistent
with dicumyl peroxide 11, phosphorane 12, (MeO)3P, and (MeO)3P=O (Figure 3.13). The compound, (n-
C3H7O)3P=O, was used as an internal standard. Photolyses of dione 9 and dicumyl peroxide 11 were done
in N2-sparged solutions and heterogeneous samples, as described next.
65
a b
Figure 3.12. Schematic of the photoreactor set up. A metal-halide lamp system was used for the irradiation
of homogeneous solution (a) or silica particles tumbling inside of a vial (b). Light was filtered through a
potassium hydrogen phthalate filter solution (300 < λ < 700 nm) for the homogeneous studies and unfiltered
(280 < λ < 700 nm) for the heterogeneous studies.
66
Figure 3.13. Absorption spectra of 4,4-dimethylbenzil 9 (black trace), dicumyl peroxide 11 (red trace),
(MeO)3P (magenta trace), (MeO)3P=O (green trace), and the potassium phthalate filter solution (gray trace,
it is a cutoff filter 310 nm) in CH3CN (path length = 1.0 cm). The inset shows the absorption of the
compounds and filter solution in the 310 to 350 nm range.
67
Figure 3.14. Absorption spectrum (black trace; λmax = 270 nm) and fluorescence spectrum (blue
trace; λex = 270 nm) of 4,4-dimethylbenzil 9 in CH3CN. Path length = 1.0 cm.
3.3.4. Homogeneous Method. Typically, acetonitrile solutions were used containing dicumyl
peroxide 9 (0.1 M) in the presence or absence of sensitizer 4,4-dimethylbenzil 9 (0.01 M) and (MeO)3P
(0.1 M). The solutions were sparged with N2 for 15 min prior to irradiation, where the headspace was filled
with N2. Oxygen free conditions were needed otherwise the sensitizer 9 produces singlet oxygen under
aerobic conditions.15 Phosphorous trapping agents such as trimethyl phosphite have been reported to trap
the alkoxy radicals,35 and thus were used here. The product (MeO)3P=O was monitored by GC/MS and 1H
and 31P NMR spectroscopy. The peroxide decomposition yields did not vary by more than 1% between the
68
two methods: GC/MS and 1H NMR spectroscopy. The use of 31P NMR spectroscopy produced higher error
(~2-3%). GC/MS and 1H NMR spectroscopy were also used to characterize the hydrocarbon products.
3.3.5. Heterogeneous Method. The preparation of 4,4-dimethylbenzil 9 and dicumyl peroxide 11
co-adsorbed onto fumed silica has been described previously.17 Briefly, fumed silica was immersed in a
dichloromethane solution of solvated 9 and 11. After stirring, the dichloromethane was evaporated with a
stream of N2 gas leaving reagents adsorbed on the silica. The silica particles were further dried under
vacuum. Compound adsorption was assumed to be uniform. We used a 20-cm3 glass container containing
100-mg silica particles adsorbed with 9 and 11 that form a two-phase system that was N2-degassed. This
container was rotated by its attachment to a stirring paddle where the silica particles tumbled during the
irradiation for 1 h. Once the photolysis was completed after 1 h, products 14–16 were detected upon
desorption from the silica surface with dichloromethane or methanol and filtered with a syringe-loaded
filter. Here, we monitored the consumption of dicumyl peroxide 11 over time and quantitated the products
formed based on GC/MS and NMR. The possible formation of volatile products was not explored.
3.4. References
1. Celli J. P.; Spring B. Q.; Rizvi I.; Evans C. L.; Samkoe K. S.; Verma S.; Pogue B. W.; Hasan
T. Imaging and Photodynamic Therapy: Mechanisms, Monitoring, and Optimization. Chem.
Rev. 2010, 110, 2795–2838.
2. Rai P.; Mallidi S.; Zheng X.; Rahmanzadeh R.; Mir Y.; Elrington S.; Khurshid A.; Hasan
T. Development and Applications of Photo-triggered Theranostic Agents. Adv. Drug Delivery
Rev. 2010, 62, 1094–1124.
3. Amirshaghaghi A.; Yan L.; Miller J.; Daniel Y.; Stein J. M.; Busch T. M.; Cheng Z.; Tsourkas
A. Chlorin e6-Coated Superparamagnetic Iron Oxide Nanoparticle (SPION) Nanoclusters as a
Theranostic Agent for Dual-Mode Imaging and Photodynamic Therapy. Sci. Rep. 2019, 9, 2613.
69
4. Sainuddin T.; Pinto M.; Yin H.; Hetu M.; Colpitts J.; McFarland S. A. Strained Ruthenium Metal–
Organic Dyads as Photocisplatin Agents with Dual Action. J. Inorg. Biochem. 2016, 158, 45–54.
5. Albani B. A.; Peña B.; Leed N. A.; de Paula N. A. B. G.; Pavani C.; Baptista M. S.; Dunbar K. R.;
Turro C. Marked Improvement in Photoinduced Cell Death by a New Tris-heteroleptic Complex with
Dual Action: Singlet Oxygen Sensitization and Ligand Dissociation. J. Am. Chem. Soc. 2014, 136,
17095–17101.
6. Brega V.; Scaletti F.; Zhang X.; Wang L.; Li P.; Xu Q.; Rotello V. M.; Thomas S. W. III Polymer
Amphiphiles for Photoregulated Anticancer Drug Delivery. ACS Appl. Mater. Interfaces 2018, 11,
2814–2820.
7. Hirsch D. R.; Schiavone D. V.; Berkowitz A. J.; Morrison L. A.; Masaoka T.; Wilson J. A.;
Lomonosova E.; Zhao H.; Patel B. S.; Dalta S. H.; Majidi S. J.; Pal R. K.; Gallicchio E.; Tang L.;
Tavis J. E.; Le Grice S. F. J.; Beutler J. A.; Murelli R. P. Synthesis and Biological Assessment of 3,7-
Dihydroxytropolones. Org. Biomol. Chem. 2018, 16, 62–69.
8. Mousset C.; Giraud A.; Provot O.; Hamze A.; Bignon J.; Liu J.-M.; Thoret S.; Dubois J.; Brion J.-D.;
Alami M. Synthesis and Antitumor Activity of Benzils Related to Combretastatin A-4. Bioorg. Med.
Chem. Lett. 2008, 18, 3266–3271.
9. Bhanthumnavin W.; Bentrude W. G. Photo-Arbuzov Rearrangements of 1-Arylethyl Phosphites:
Stereochemical Studies and the Question of Radical-Pair Intermediates. J. Org. Chem. 2001, 66, 980–
990.
10. Hager D. C.; Bentrude W. G. Triplet-Sensitized Photorearrangements of Six-Membered-Ring 2-
Phenylallyl Phosphites. Reaction Efficiency and Stereochemistry at Phosphorus. J. Org.
Chem. 2000, 65, 2786–2791.
11. Osman F. H.; El-Samahy F. A. The Behavior of 3,3-Diphenylindan-1,2-dione Towards Alkyl
Phosphites. Monatsh. Chem. 2007, 138, 973–978.
12. Mahran M. R.; Abdou W. M.; Khidre M. D. Organophosphorus Chemistry. XII. Reaction of Furil
with Alkyl Phosphites and Ylide-Phosphoranes. Monatsh. Chem. 1990, 121, 51–58.
70
13. Ramasamy E.; Jayaraj N.; Porel M.; Ramamurthy V. Excited State Chemistry of Capsular Assemblies
in Aqueous Solution and on Silica Surfaces. Langmuir 2012, 28, 10–16. 10.1021/la203419y.
14. Ramamurthy V. Photochemistry within a Water-Soluble Organic Capsule. Acc. Chem. Res. 2015, 48,
2904–2917.
15. Natarajan A.; Kaanumalle L. S.; Jockusch S.; Gibb C. L. D.; Gibb B. C.; Turro N. J.; Ramamurthy
V. Controlling Photoreactions with Restricted Spaces and Weak Intermolecular Forces: Exquisite
Selectivity during Oxidation of Olefins by Singlet Oxygen. J. Am. Chem. Soc. 2007, 129, 4132–4133.
16. Malval J.-P.; Dietlin C.; Allonas X.; Fouassier J.-P. Sterically Tuned Photoreactivity of an Aromatic
α-diketone Family. J. Photochem. Photobiol., A 2007, 192, 66–73.
17. Walalawela N.; Greer A. Heterogeneous Photocatayltic Deperoxidation with UV and Visible Light. J.
Phys. Org. Chem. 2018, e3807
18. Ding B.; Bentrude W. G. Trimethyl Phosphite as a Trap for Alkoxy Radicals Formed from the Ring
Opening of Oxiranylcarbinyl Radicals. Conversion to Alkenes. Mechanistic Applications to the Study
of C–C versus C–O Ring Cleavage. J. Am. Chem. Soc. 2003, 125, 3248–3259.
19. Fasciani C.; Alejo C. J. B.; Grenier M.; Netto-Ferreira J. C.; Scaiano J. C. High-Temperature Organic
Reactions at Room Temperature using Plasmon Excitation: Decomposition of Dicumyl
Peroxide. Org. Lett. 2011, 13, 204–207.
20. Lazár M.; Matisová-Rychlá L.; Ďurdovič V.; Rychlý J. Chemiluminescence in the Thermal
Decomposition of Dicumyl Peroxide. J. Lumin. 1974, 9, 240–248.
21. Abd-Alla M. A. Novel Synthesis of Poly(benzoin) and Poly(benzil). Characterization and Application
as Photosensitizer Materials. Macromol. Chem. Phys. 1991, 192, 277–283.
22. Rowe P. D.; Thomas D. K. The Thermal Decomposition of Dicumyl Peroxide in Polyethylene Glycol
and Polypropylene Glycol. J. Appl. Polym. Sci. 1963, 7, 461–468.
23. Callaghan S.; Senge M. O. The Good, the Bad, and the Ugly – Controlling Singlet Oxygen Through
Design of Photosensitizers and Delivery Systems for Photodynamic Therapy. Photochem. Photobiol.
Sci. 2018, 17, 1490–1514.
71
24. Röder B.; Büchner M.; Rückmann I.; Senge M. O. Correlation of Photophysical Parameters with
Macrocycle Distortion in Porphyrins with Graded Degree of Saddle Distortion. Photochem.
Photobiol. Sci. 2010, 9, 1152–1158.
25. Kielmann M.; Grover N.; Kalish W. W.; Senge M. O. Incremental Introduction of Organocatalytic
Activity into Conformationally Engineered Porphyrins. Eur. J. Org. Chem. 2019, 2448–2452.
26. Pistner A. J.; Pupillo R. C.; Yap G. P. A.; Lutterman D. A.; Ma Y.-Z.; Rosenthal J. Electrochemical,
Spectroscopic, and 1O2 Sensitization Characteristics of 10,10-Dimethylbiladiene Complexes of Zinc
and Copper. J. Phys. Chem. A 2014, 118, 10639–10648.
27. Manini P.; Bietti M.; Galeotti M.; Salamone M.; Lanzalunga O.; Cecchini M. M.; Reale S.; Crescenzi
O.; Napolitano A.; De Angelis F.; Barone V.; D’Ischia M. Characterization and Fate of Hydrogen-
Bonded Free-Radical Intermediates and Their Coupling Products from the Hydrogen Atom Transfer
Agent 1,8-Naphthalenediol. ACS Omega 2018, 3, 3918–3927.
28. Shah B. K.; Gusev A.; Rodgers M. A. J.; Neckers D. C. Ultrafast Pump-Probe Studies of tert-Butyl
Aroylperbenzoates and Triplet Energy Interception by the O–O Bond. J. Phys. Chem. A 2004, 108,
5926–5931.
29. Scaiano J. C.; Connolly T. J.; Mohtat N.; Pliva C. N. Exploratory Study of the Quenching of
Photosensitizers by Initiators of Free Radical ″Living″ Polymerization. Can. J. Chem. 1997, 75, 92–
97.
30. Morlet-Savary F.; Wieder F.; Fouassier J. P. Sensitized Dissociation of Peroxides and Peresters in the
Presence of Thiopyrylium Salts. J. Chem. Soc., Faraday Trans. 1997, 93, 3931–3937.
31. Nau W. M.; Scaiano J. C. Oxygen Quenching of Excited Aliphatic Ketones and Diketones. J. Phys.
Chem. 1996, 100, 11360–11367.
32. Engel P. S.; Woods T. L.; Page M. A. Quenching of Excited Triplet Sensitizers by Organic
Peroxides. J. Phys. Chem. 1983, 87, 10–13.
33. Walling C.; Gibian M. J. The Photosensitized Decomposition of Peroxides. J. Am. Chem.
Soc. 1965, 87, 3413–3417.
72
34. Mohapatra P. P.; Chiemezie C. O.; Kligman A.; Kim M. M.; Busch T. M.; Zhu T. C.; Greer A. 31P
NMR Evidence for Peroxide Intermediates in Lipid Emulsion Photooxidations: Phosphine Substituent
Effects in Trapping. Photochem. Photobiol. 2017, 93, 1430–1438.
35. Jiao X.-Y.; Bentrude W. G. A Facile Route to Vinyl- and Arylphosphonates by Vinyl and Aryl
Radical Trapping with (MeO)3P. J. Org. Chem. 2003, 68, 3303–3306.
36. Gaussian 09, Revision D.01; Frisch M. J.; Trucks G. W.; Schlegel H. B.; Scuseria G. E.; Robb M. A.;
Cheeseman J. R.; Scalmani G.; Barone V.; Mennucci B.; Petersson G. A.; Nakatsuji H.; Caricato M.;
Li X.; Hratchian H. P.; Izmaylov A. F.; Bloino J.; Zheng G.; Sonnenberg J. L.; Hada M.; Ehara M.;
Toyota K.; Fukuda R.; Hasegawa J.; Ishida M.; Nakajima T.; Honda Y.; Kitao O.; Nakai H.; Vreven
T.; Montgomery J. A. Jr.; Peralta J. E.; Ogliaro F.; Bearpark M.; Heyd J. J.; Brothers E.; Kudin K. N.;
Staroverov V. N.; Kobayashi R.; Normand J.; Raghavachari K.; Rendell A.; Burant J. C.; Iyengar S.
S.; Tomasi J.; Cossi M.; Rega N.; Millam M. J.; Klene M.; Knox J. E.; Cross J. B.; Bakken V.;
Adamo C.; Jaramillo J.; Gomperts R.; Stratmann R. E.; Yazyev O.; Austin A. J.; Cammi R.; Pomelli
C.; Ochterski J. W.; Martin R. L.; Morokuma K.; Zakrzewski V. G.; Voth G. A.; Salvador P.;
Dannenberg J. J.; Dapprich S.; Daniels A. D.; Farkas Ö.; Foresman J. B.; Ortiz J. V.; Cioslowski J.;
Fox D. J.. Gaussian, Inc.: Wallingford CT, 2009.
37. Dennington R.; Keith T.; Millam J.. Gaussview, version 5; Semichem Inc.: Shawnee Mission KS,
2009.
73
Chapter 4.
Theoretically Enhancing Three Phase Device Performance by
Maximizing the Number of Triplet Sensitizer Sites
on the Superhydrophobic Surface
4.0. Introduction.
Superhydrophobic surfaces exhibit many unique properties, including resistance to soiling,
biofouling, accretion of cells and separation of an embedded sensitizer and the target site.1-3 These unique
properties make them good candidates for use in oxidation of compounds, disinfection, and eradication of
biofilm bacteria and tumor cells.4 Recently, we reported on such a superhydrophobic photosensitizer device
for the delivery of singlet oxygen from the plastron interstices into solution or to bacterial biofilms.5 While
our 2020 study5 showed good proof of concept for this singlet oxygen producing superhydrophobic
photodynamic technique, there remain many engineering details which have yet to be considered in
increasing the functionality of these three phase devices. In particular three phase device size, weight of the
three phase device, and nanoparticle surface area have yet to be fully optimized, and exactly how these
aspects correlate to one another as well as triplet sensitizer sites has yet to be entirely realized.
The three phase devices (Figure 4.7) have a few main changeable components which play a crucial
role in their functionality. One such component is the embedded silica nanoparticles, which can be produced
in a wide variety of shapes and sizes, as well as chemical make ups. Another component is that of the
sensitizer. A variety of sensitizers have been studied for the production of singlet oxygen. One such
sensitizer is pterin, of which we recently studied alkylation patterns and excited‐state properties.6 The pterin
study found that the alkylation occurred at either the N(4) or O(3) site on the pterin. Computations done on
74
the pterins found increased solubility and reduced triplet state energetics, which makes them good
candidates for a 1O2 producing device. We have also reported on sensitizers covalently attached to a
nanoparticle surface,7 rather than adsorbed. Such covalently attached sensitizers are able to be released from
the surface through photo-cleavable groups, such as the ethane group in the sensitizer we reported on.
In the study described here we examined, through theoretical calculations and some minor
experimental data, the effect of the size and shape of the embedded silica nanoparticles on the surface area
and weight of these three phase devices as a way to advance this superhydrophobic technique. These
findings are the first part of a study on enhancing the singlet oxygen output of these superhydrophobic
photodynamic (SHP) devices.
4.1. Results and Discussion
4.1.1. Effect of Embedded Particle Shape and Size on Surface Area. First, the effect of particle
size was theoretically examined considering a few basic 3-dimensional shapes: a sphere, cube and
tetrahedron. Varied packing structures and orientations on the surface were also considered. For these
shapes equations were developed using a flat, square surface area as the surface on which the particles
would be embedded or placed.
75
a. b.
. .
Figure 4.1. Spherical particles fit into a square surface area. a. linearly positioned particle packing. b.
tight particle packing.
The total surface area of the spheres in a square surface area can be taken as the number of spheres
which fit onto the surface, under the linear packing structure depicted in Figure 4.1A, times the surface area
of a single sphere. The number of spheres which fit on the surface is taken as the length of the surface
divided by the diameter of a particle, giving the following equation.
𝑆𝐴𝑇 = (𝑙𝑆
𝐷𝑃)24𝜋𝑟𝑃
2 .….(4.1)
Where SAT is the total surface area which results from the particles, LS is the length in both
dimensions of the square surface on which the particles are being placed, Dp is the diameter of the spherical
particles, and rP is the radius of the spherical particles. When Dp = 2rp is applied and eq. 1 is simplified eq.
2 is obtained.
𝑆𝐴𝑇 = 𝜋𝑙𝑠2 …..(4.2)
76
Highly notable about eq. 4.2 is the fact that no terms related to dimensions of the particles remain.
This supports the conclusion that the total surface area, which supports sensitizer on these SHP devices,
does not depend on the size of the embedded nanoparticles. To confirm this, a second packing structure for
spherical particles was considered. For the tighter packing structure depicted in Figure 4.1B, the total
surface area of the spheres can once again be taken as the number of spheres which fit onto the surface
times the surface area of a single sphere. However, under this packing structure the number of spheres
which fit on the surface is a slightly more complicated, as shown in eq. 4.3.
𝑆𝐴𝑇 = (𝑙𝑆
𝑟𝑃) (
𝑙𝑆
√3𝑟𝑃) 4𝜋𝑟𝑃
2 …..(4.3)
Here the number of particles which fit on the surface is made up of two factors. The first factor is
the length of one side of the square surface divided by the radius of the particles. Multiplied by that factor
is the length of the side of the square surface divided √3𝑟𝑃 which is the height of rows which contain one
full sphere, considering the overlap of the spheres above and below equates to the overlap of the sphere in
the given row into the other rows.
𝑆𝐴𝑇 =4√3𝜋𝑙𝑠
2
3 …..(4.4)
Once again, in eq. 4.4 is no terms related to dimensions of the particles remain, showing that the
total surface area of the particles depends only on the size of the square surface on which the particles are
placed and not on the size of the particles themselves. If eq. 4.3 were modified for half spheres the sphere
surface area would be divided by two and the area of a circle with a radius equal to that of the sphere
would be added, giving eq. 4.5.
𝑆𝐴𝑇 = (𝑙𝑆
𝑟𝑃) (
𝑙𝑆
√3𝑟𝑃) (4𝜋𝑟𝑃
2
2+ 𝜋𝑟𝑃
2) …..(4.5)
Which simplifies to eq. 4.6, which remains absent of any terms related to the size of the particles.
𝑆𝐴𝑇 = √3𝜋𝑙𝑠2 …..(4.6)
77
Table 4.1 further emphasizes the fact that the total surface area of the particles on embedded on a
given surface does not depend on the size of the particles, by giving equations, as well as their simplified
versions, for cubic particles and tetrahedral particles.
Table 4.1. Equations for the total surface area of particles embedded on a surface.
particle
shape
particle
packing
surface
shape
equation for
total surface area of particlesa
simplified
equation for
SAT
sphere linear square 𝑆𝐴𝑇 = (𝑙𝑆𝐷𝑃)2
4𝜋𝑟𝑃2 𝑆𝐴𝑇 = 𝜋𝑙𝑠
2
sphere tight square 𝑆𝐴𝑇 = (𝑙𝑆𝑟𝑃)(
𝑙𝑆
√3𝑟𝑃)4𝜋𝑟𝑃
2
𝑆𝐴𝑇
=4√3𝜋𝑙𝑠
2
3
half sphere tight square 𝑆𝐴𝑇 = (𝑙𝑆𝑟𝑃)(
𝑙𝑆
√3𝑟𝑃) (4𝜋𝑟𝑃
2
2+ 𝜋𝑟𝑃
2) 𝑆𝐴𝑇 = √3𝜋𝑙𝑠2
cube linear
/tight square
𝑆𝐴𝑇
= (𝑙𝑆
√2𝑠𝑃)
(
𝑙𝑆
√((√2𝑠𝑃)2 − (
√2𝑠𝑃2 )
2
))
6𝑠𝑃2
𝑆𝐴𝑇
= 2√3𝜋𝑙𝑠2
tetrahedron tight square 𝑆𝐴𝑇 = (2
𝑙𝑠𝑠𝑃)(
𝑙𝑠
√𝑠𝑃2 − (
𝑠𝑃2 )
2
)√3𝜋𝑙𝑠2
𝑆𝐴𝑇 = 4𝑙𝑠2
aSp is the length of the edge (i.e. side) of a particle.
By examining the simplified equations in Table 4.1 it becomes apparent each particle shape results
in a different factor times the square area. When comparing these factors we find that the cubic shaped
78
particles result in the highest total surface area factor of 2√3𝜋 or 10.88, which is 3.5 times greater than the
lowest factor, that of the linearly packed spheres which is 𝜋.
4.1.2. Effect of Embedded particle Size and Shape on Weight and Volume. As size of particles
has little to no bearing on the surface area available for sensitizer particle size can be reduced to decrease
volume of plastron filled by particles and decrease weight of the particles embedded. Calculations were
performed to show the effect of particle size on the volume of the empty plastron volume (Table 4.4), which
would be the space through which the singlet oxygen produced on the surface of the particles would diffuse.
Though the distance the oxygen has to travel is the same regardless of the particle size the empty area the
oxygen has to travel through changes. The oxygen has slightly more free space to travel through in the
plastron the smaller the particle. The small amount of more free space may reduce quenching of singlet
oxygen by encountering a wall (silica or PDMS). Though the difference is likely negligible.
Table 4.2. Effect of particle size on the plastron volume.
particle
size
particles in
the plastron
empty plastron
volume (mm2)
plastron volume
filled with particles
(mm2)
average distance
through plastron
(mm)
200 nm 19600000 1.85 × 10-1 4.11 × 10-5 0.55
300 nm 8730000 1.84 × 10-1 6.17 × 10-5 0.55
50 μm 312 1.74 × 10-1 1.02 × 10-2 0.55
150 μm 33 1.75 × 10-1 1.00 × 10-2 0.55
79
Table 4.3. Information on particles A, B, and C.
The surface area per gram of the smooth surface particle A is four orders of magnitude smaller than
that of the porous particle C, despite their similar size. While similar weights of these particles were
embedded on the surface the porous particles would allow for a higher population of sensitizer in the
plastron due to the increased surface area. The smaller smooth surface particles B have a similar surface
area per gram as the larger porous particles C, however less than half the weight of particles B was able to
particle
type
particle
size (µm)
chlorin e6
loading
(µmol/g)
weight of
particles per
micro-carpet
(mg)
silica
surface
area
(m2/g)
silica
density
(g/cm3)
surface-to-
volume
(m2/m3)
porosity
particle
A
sil-co-sil
45-105
1.3
16.3 0.016 2.65 3.98 none
2.6
5.3
10.5
21.1
42.2
particle
B
fumed
silica
0.2-0.3
5.3
8.1 200 0.04 0.08 28%
10.5
21.1
42.2
particle
C
PVG
40-150 5.3 ~20 250 1.50 3.75 none
80
embed on the surface when compared to particles A and C. Therefore, particles B would provide less
sensitized surface area within the plastron than particle C. However, it is of note that, with a 28% porosity,
a significant degree of the surface area of porous particles C is within the pores of the particle, potentially
increasing the quenching of the singlet oxygen as it would have to escape the pores.
4.1.3. Particle Agglomeration and Sensitizer Desorption. An additional influence on the aspect
of particle size and shape is their tendency to agglomerate. The issue of agglomeration was examined
through the use of particle imaging via SEM. Particles A and B were loaded with 0 µmol/g, 10.54 µmol/g,
21.1 µmol/g, and 42.2 µmol/g of chlorin e6 sensitizer and imaged at 200× and 5000× magnification (Figures
4.2-4.5) in order to inspect the effects of sensitizer adsorption on the particle surface. Images showed that
adsorption of sensitizer causes increased agglomeration of particles when compared to blank (0 µmol/g)
particles, for both particles A and B. Particle agglomeration is an issue on two fronts. First, agglomeration
decreases the surface area/g of particles as well as screening the sensitizer adsorbed within the aggregate.
Second, agglomeration can cause adherence of particles to the superhydrophobic surface which are not
properly embedded within the surface. This can cause particles to come detached from the surface during
use of the SHP device; eliminating the contact free sensitization aspect of the SHP device.
It was found during this study that sensitizer desorption from the device had occurred. The
superhydrophbic surface with embedded sensitizer adsorbed particles was placed over an aqueous solution.
The aqueous solution was then tested for singlet oxygen production, which could only occur if sensitizer
had desorbed into the solution. It was found that the singlet oxygen was produced within the aqueous
solution. In order for sensitizer desorption to occur contact between the liquid and sensitizer adsorbed
nanoparticle surface must occur. As the superhydrophobic surface is meant to prevent contact between the
sensitized nanoparticle surface and the liquid there are few possibilities for how desorption of the sensitizer
occurred. The detachment of particles which were not properly embedded into the surface due to
agglomeration would be a major source of sensitizer desorption. Thus, the analysis of particle
agglomeration is important.
81
As can be seen in Figure 4.2 A-D, agglomerates of the fumed silica nanoparticles more than double
in size upon the adsorption of sensitizer, with the largest agglomerates of fumed silica particles B measuring
~ 50 µm increasing to ~150 µm with 21.1 µmol of sensitizer adsorbed per gram of silica. As can be seen in
Figure 4.4 A-D sil-co-sil particles A showed a similar increase in aggregation, which is more notable in the
average size. Figure 4.4 A shows the largest sil-co-sil particle A to measure ~ 75 µm with an average
particle size of ~40 µm. Whereas Figure 4.4 B-D shows the largest sensitizer adsorbed sil-co-sil particle A
agglomerates to measure ~100 µm with an average size of ~ 80 µm.
As can be seen in Figure 4.3 A-D, the fumed silica nanoparticle B agglomerates' surface appears
ruff and individual particles remain distinct on the surface. The fumed silica nanoparticle agglomerates
contain from 150 to 750 nanoparticles depending on the size, based on the size of the agglomerates divided
by the size of the fumed silica nanoparticles B themselves. As can be seen in Figure 4.5 A-D the sil-co-sil
nanoparticles A surface appears smooth with some smaller particles adhered to the surface. The sil-so-sil
nanoparticle agglomerates contain only 2 to 3 individual nanoparticles, based off the size of the
agglomerates divided by the size of the nanoparticles. Thus, embedding of the sil-co-sil nanoparticles into
the superhydrophobic surface should be more efficient, with less particles remaining unembedded on the
surface of agglomerates. Therefore, the fumed silica nanoparticles B would be more likely to have
unembedded particles which could fall off into solution, resulting in sensitizer desorption.
82
A B
C D
Figure 4.2. SEM Images of fumed silica at 200× magnification. A: Blank fumed silica; B: Fumed silica
loaded with 10.54 µmol chlorin e6; C: Fumed silica loaded with 21.1 µmol chlorin e6; D: Fumed silica
loaded with 42.2 µmol chlorin e6
83
A B
C D
Figure 4.3. SEM Images of fumed silica at 5000× magnification. A: Blank fumed silica; B: Fumed silica
loaded with 10.54 µmol chlorin e6; C: Fumed silica loaded with 21.1 µmol chlorin e6; D: Fumed silica
loaded with 42.2 µmol chlorin e6
84
A B
C D
Figure 4.4. SEM Images of Sil-Co-Sil at 200× magnification. A: Blank Sil-Co-Sil; B: Sil-Co-Sil loaded
with 10.54 µmol chlorin e6; C: Sil-Co-Sil loaded with 21.1 µmol chlorin e6; D: Sil-Co-Sil loaded with
42.2 µmol chlorin e6
85
A B
C D
Figure 4.5. SEM Images of Sil-Co-Sil at 5000× magnification. A: Blank Sil-Co-Sil; B: Sil-Co-Sil loaded
with 10.54 µmol chlorin e6; C: Sil-Co-Sil loaded with 21.1 µmol chlorin e6; D: Sil-Co-Sil loaded with
42.2 µmol chlorin e6
86
4.2. Sensitizer Efficiency
4.2.1. Small-bottle device. A novel three phase device (Figure 4.6) was constructed to measure the
production of singlet oxygen using ~5 mg or less of a sensitizing compound. This small closed-bottle device
could be used to quickly and easily measure the efficiency of singlet oxygen production by a sensitizer. The
small bottle device was constructed from a GC/MS sample bottle and insert, the insert was fixed to the
bottle lid which had a hole where the septum was removed.
Figure 4.6. Schematic of the small closed-bottle three phase device for the measurement of singlet
oxygen production via photosensitization. A small amount of solid photosensitizer depicted in green is
placed at the bottom of the bottle. A 9,10-anthracene dipropionate dianion is depicted as the trapping
solution.
Singlet oxygen is produced at the solid photosensitizer surface, transverses through the air, and into
the solution where it is detected via a trapping agent. Aqueous trapping agent is solution is held in tube by
cohesive force as the opening faces the bottom of the bottle. This small bottle device has advantages in that
it is simple, made from inexpensive materials, and a closed system, rather than an open air system. The
87
small bottle device is quick and easy to use and require only a small amount of sensitizer and only half a
milliliter of trapping solution.
In summary, it was found theoretically that the size of embedded nanoparticles does not strongly
impact the available surface area for triplet sensitizer sites, however, the shape of the particles does. Thus,
the porous particle should provide the highest number of triplet sensitizer sites. Agglomeration of the
nanoparticles was found to increase with adsorbed chlorin e6 either tripling or doubling in size depending
on the particle. Desorption of the sensitizer was found to occur, however, it was not determined whether
this was from embedded particles or particles which fell off aggregates. Also, a small bottle three phase
device was developed for quick and easy measure of sensitizer singlet oxygen production efficiency.
4.3. Conclusion
Increases in the exposed surface area of the particles are key in increasing the amount of sensitizer
loaded into the plastron and thus the 1O2 output. While variations in the size of the particle have little to no
impact on the total surface area, and thus the overall sensitizer population on the SHP device, the shape of
the particle has a considerable impact. We find theoretically that a cubic particle provides up to 3asssssss.5
times more sensitized surface area than a spherical particle. Of the real particle examined, porous particles
C provide the greatest sensitized surface area within the plastron, however there is increased potential for
quenching of singlet oxygen produced within the pores. Particles imaging revealed increases in
agglomeration upon sensitizer adsorption. The most dramatic difference was seen in the agglomeration of
sensitized adsorbed fumed silica particles B which were shown to reach triple the size of blank fumed silica
particles B agglomerates. The results discussed would support further study on the singlet oxygen output
of SHP devices. These findings may be of practical importance to help guide further development of these
SHP devices for increasing 1O2 output for water purification and medical devices.
88
4.4. Experimental
4.3.1. Materials and Instrumentation. Chlorin e6, Fumed silica, Sil-co-sil particles, PVG were
obtained from commercial supplers. An AMRAY 1910 Field Emission Scanning Electron Microscope
(SEM) was used to obtain the particle agglomeration images.
4.3.2. Silica Particle Preparation. Chlorin e6 was adsorbed onto silica particles by immersing the
blank particles in dichloromethane with dissolved chlorin e6. The dichloromethane was evaporated leaving
chlorin e6 adsorbed onto the particles.
4.3.3. Fabrication of Superhydrophobic Surfaces. The process for printing superhydrophobic
surfaces was reported previously.8,9 Briefly, PDMS posts, ~ 1 mm tall, were printed in 1 cm × 1 cm arrays
on 0.5 mm pitch on a glass slide. The various silica particles were adsorbed with sensitizer as described
previously. The method for embedding of the silica particles into the SH surfaces was also reported
previously.10
Figure 4.7. Schematic of a superhydrophobic surface with embedded sensitizer adsorbed
nanoparticles. The posts, which are ~ 1 mm tall, are printed from PDMS and the sensitizer adsorbed
nanoparticles are immediately embedded.
4.5. References
1. Nayshevsky, I.; Xu, Q.F.; Newkirk, J.M.; Furhang, D.; Miller, D.C.; Lyons, A.M. Self-cleaning
hybrid hydrophobic-hydrophilic surfaces: durability and effect of artificial soilant particle type. IEEE
J. Photovoltaics 2020, 10, 577-584.
89
2. Zhao, Y.; Liu, Y.; Xu, QF, Barahman, M.; Lyons, A.M. A Catalytic, Self-Cleaning Surface with
Stable Superhydrophobic Properties: Printed PDMS Arrays Embedded with TiO2 Nanoparticles. ACS
Appl. Mater. Interfaces 2015, 7, 2632–2640.
3. Lyons, A.M.; Mullins, J.; Barahman, M.; Erlich, I; Salamon, T. Three-Dimensional Superhydrophobic
Structures Printed using Solid Freeform Fabrication Tools. Int. J. of Rapid Manufacturing 2013, 3,
89-104.
4. Pushalkar, S.; Ghosh, G.; Xu, Q.; Liu, Y.; Ghogare, A. A.; Atem, C.; Greer, A.; Saxena, D.; Lyons, A.
M. Superhydrophobic Photosensitizers: Airborne 1O2 Killing of an In-vitro Oral Biofilm at the Plastron
Interface. ACS Appl. Mater. Interfaces 2018, 10, 25819-25829.
5. Aebisher, D.; Bartusik-Aebisher, D.; Belh, S. J.; Ghosh, G.; Durantini, A. M.; Liu, Y.; Lyons, A. M.;
Greer, A. Superhydrophobic Surfaces as a Source of Airborne Singlet Oxygen Through Free Space
for Photodynamic Therapy. ACS Appl. Bio Mater. 2020, 3, 2370-2377.
6. Walalawela, N.; Vignoni, M.; Urrutia, M. N.; Belh, S. J.; Greer, E. M.; Thomas, A. H.; Greer, A.
Kinetic Control in the Regioselective Alkylation of Pterin Sensitizers: A Synthetic, Photochemical,
and Theoretical Study. Photochem. Photobiol. 2018, 94, 834-844.
7. Ghosh, G.; Belh, S. J.; Chiemezie, C.; Walalawela, N.; Ghogare, A. A.; Vignoni, M.; Thomas, A. H.;
McFarland, S. A.; Greer, E. M.; Greer, A. S,S-Chiral Linker Induced U-Shape with a Syn-facial
Sensitizer and Photocleavable Ethene Group. Photochem. Photobiol. 2019, 95, 293-305.
8. Zhao, Y.; Liu, Y.; Xu, Q.; Barahman, M.; Bartusik, D.; Greer, A.; Lyons, A. M. Singlet Oxygen
Generation on Porous Superhydrophobic Surfaces: Effect of Gas Flow and Sensitizer Wetting on
Trapping Efficiency. J. Phys. Chem. A 2014, 118, 10364-10371.
9. Barahman, M.; Lyons, A. M. Ratchetlike Slip Angle Anisotropy on Printed Superhydrophobic
Surfaces. Langmuir 2011, 27, 9902-9909.
10. Aebisher, D.; Bartusik, D.; Liu, Y.; Zhao, Y.; Barahman, M.; Xu, Q.; Lyons, A. M.; Greer, A.
Superhydrophobic Photosensitizers. Mechanistic Studies of 1O2 Generation in the Plastron and
Solid/Liquid Droplet Interface. J. Am. Chem. Soc. 2013, 135, 18990-18998.