The Secret

History of DMeOPrPEAlexander J. Kendall

D. R. Tyler Laboratories

Group Meeting 10/15/2014

The Secret

History of DMeOPrPEAlexander J. Kendall

D. R. Tyler Laboratories

Group Meeting 10/15/2014

Outline•Synthesis

• Iron ComplexesN2 activation

N2 reduction intermediates

H2 activation

•Ru ComplexesH2 activation

H2O coordination

H-bonding of H2

•Future of DMeOPrPE

Background: Synthesis

•1,2-bis(bis(methoxypropyl)phosphino)propane

tmepe – tetra(methoxypropyl) bis(phosphino)ethane

• 99mTc complexes

Bidentate for metal-complex stability

Lipophillic and hydrophillic

Herbowski, A.; Deutsch, E. A. J. Organomet. Chem. 1993, 460, 19-23.

Background: Tyler Lab

•1,2-bis(bis(methoxypropyl)phosphino)propane

DMeOPrPE – bis(dimethoxypropylphosphino)ethane

Miller, W. K.; Gilbertson, J. D.; Leiva-Paredes, C.; Bernatis, P. R.; Weakley, T. J. R.; Lyon, D. K.; Tyler, D. R. Inorg. Chem. 2002, 41, 5453-5465.c

Debut in Inorganic Literature

•Precursors to water-soluble dinitrogen carriers

•Water-soluble iron(II) complexes for small molecule activation

RSO3- groups non-innocent

Bidentate only ligands

Miller, W. K.; Gilbertson, J. D.; Leiva-Paredes, C.; Bernatis, P. R.; Weakley, T. J. R.; Lyon, D. K.; Tyler, D. R. Inorg. Chem. 2002, 41, 5453-5465.c

Someone Crystalized This

Miller, W. K.; Gilbertson, J. D.; Leiva-Paredes, C.; Bernatis, P. R.; Weakley, T. J. R.; Lyon, D. K.; Tyler, D. R. Inorg. Chem. 2002, 41, 5453-5465.

DEMeOPrOPE and Dinitrogen

•Heterolysis of H2

•Coordination of N2

Gilbertson, J. D.; Szymczak, N. K.; Tyler, D. R. J. Am. Chem. Soc., 2005, 127, 10184-10185.

Metal-H2 Complexes

•XRD

• IR

• 15N NMR

DEMeOPrOPE and Dinitrogen

Gilbertson, J. D.; Szymczak, N. K.; Tyler, D. R. J. Am. Chem. Soc., 2005, 127, 10184-10185.

“Free N2”: vNN = 2331 cm-1

DEMeOPrOPE and Dinitrogen

•Reductive deprotonation provides

Fe(0)-N2 complex

Gilbertson, J. D.; Szymczak, N. K.; Tyler, D. R. J. Am. Chem. Soc., 2005, 127, 10184-10185.

DEMeOPrOPE and Dinitrogen

Gilbertson, J. D.; Szymczak, N. K.; Tyler, D. R. J. Am. Chem. Soc., 2005, 127, 10184-10185.

DEMeOPrOPE and Dinitrogen

•Protonation of Fe(0)-N2

provides small yields of

NH3

Gilbertson, J. D.; Szymczak, N. K.; Tyler, D. R. J. Am. Chem. Soc., 2005, 127, 10184-10185.

DEMeOPrOPE and Dinitrogen

•Protonation of Fe(0)-N2

provides small yields of

NH3

Gilbertson, J. D.; Szymczak, N. K.; Tyler, D. R. J. Am. Chem. Soc., 2005, 127, 10184-10185.

Speculative Mechanism of N2 Reduction

•Fe(N2)Fe dimer to N2H4

•Fe(N2) to N2H2

Gilbertson, J. D.; Szymczak, N. K.; Tyler, D. R. J. Am. Chem. Soc., 2005, 127, 10184-10185.

N2 Reduction Intermediates: Pathway

Crossland, J. L.; Balesdent, C. G.; Tyler, D. R. Inorg. Chem., 2011, 51, 439-445.

N2 Reduction Intermediates: N2H4

Crossland, J. L.; Zakharov, L. N.; Tyler, D. R. Inorg. Chem., 2007, 46, 10476-10478.

N2 Reduction Intermediates: N2H4

Crossland, J. L.; Zakharov, L. N.; Tyler, D. R. Inorg. Chem., 2007, 46, 10476-10478.

Barney, B. M.; Laryukhin, M.; Igarashi, R. Y.; Lee, H.; Dos Santos, P. C.; Yang, T.; Hoffman, B. M. Dean, D. R.;

Seefeldt, L. C. Biochemistry, 2005, 44, 8030-8037. : Barney, B. M.; Yang, T.; Igarashi, R. Y.; Dos Santos, P. C.;

Laryukhin, M.; Lee, H.; Hoffman, B. M.; Dean, D. R.; Seefeldt, L. C. J. Am. Chem. Soc., 2005, 127, 14960-14961.

[Fe(P2)2N2H4][2 NaBPh4]

N2 Reduction Intermediates: N2H4

Crossland, J. L.; Zakharov, L. N.; Tyler, D. R. Inorg. Chem., 2007, 46, 10476-10478.

Barney, B. M.; Laryukhin, M.; Igarashi, R. Y.; Lee, H.; Dos Santos, P. C.; Yang, T.; Hoffman, B. M. Dean, D. R.;

Seefeldt, L. C. Biochemistry, 2005, 44, 8030-8037. : Barney, B. M.; Yang, T.; Igarashi, R. Y.; Dos Santos, P. C.;

Laryukhin, M.; Lee, H.; Hoffman, B. M.; Dean, D. R.; Seefeldt, L. C. J. Am. Chem. Soc., 2005, 127, 14960-14961.

[Fe(P2)2N2H4][2 NaBPh4]

First η2 coordination of hydrazine to iron

N2 Reduction Intermediates: N2H4

Crossland, J. L.; Zakharov, L. N.; Tyler, D. R. Inorg. Chem., 2007, 46, 10476-10478.

N2 Reduction Intermediates: Pathway

Crossland, J. L.; Balesdent, C. G.; Tyler, D. R. Inorg. Chem., 2011, 51, 439-445.

N2 Reduction Intermediates: N2H4

Crossland, J. L.; Zakharov, L. N.; Tyler, D. R. Inorg. Chem., 2007, 46, 10476-10478.

N2 Reduction Intermediates: N2H4

Crossland, J. L.; Balesdent, C. G.; Tyler, D. R. Inorg. Chem., 2011, 51, 439-445.

[Fe(H)(P2)2N2H4][NaBPh4]

N2 Reduction Intermediates: N2H2

Crossland, J. L.; Balesdent, C. G.; Tyler, D. R. Inorg. Chem., 2011, 51, 439-445.

N2 Reduction Intermediates: N2H2

Crossland, J. L.; Balesdent, C. G.; Tyler, D. R. Inorg. Chem., 2011, 51, 439-445.

N2 Reduction Intermediates: N2H2

Crossland, J. L.; Balesdent, C. G.; Tyler, D. R. Inorg. Chem., 2011, 51, 439-445.

N2 Reduction Intermediates: N2H2

Crossland, J. L.; Balesdent, C. G.; Tyler, D. R. Inorg. Chem., 2011, 51, 439-445.

N2 Reduction Intermediates: Characterized

Crossland, J. L.; Balesdent, C. G.; Tyler, D. R. Inorg. Chem., 2011, 51, 439-445.

•Mechanism still not well understood

Fe Complexes: H2 Activation in H2O

•Heterolysis of H2 in water

Gilbertson, J. D.; Szymczak, N. K.; Tyler, D. R. Inorg. Chem. 2004, 43, 3341-3343.

pKa(1)= 8.2

pKa(2)= 5.4

Fe Complexes: H2 Activation in H2O

•Heterolysis of H2 in water

Gilbertson, J. D.; Szymczak, N. K.; Tyler, D. R. Inorg. Chem. 2004, 43, 3341-3343.

pKa(1)= 8.2

pKa(2)= 5.4

Metal-H2 Complexes

•Neutron diffraction

• IR

•NMR

0.8 Å < H-H bond < 1.2Å 1.2 Å < H-H bond

0.74 Å = Free H-H bond

Gilbertson, J. D.; Szymczak, N. K.; Tyler, D. R. Inorg. Chem. 2004, 43, 3341-3343.

Gilbertson, J. D.; Szymczak, N. K.; Tyler, D. R. Inorg. Chem. 2004, 43, 3341-3343.

Isotopologue Measurement: 1JHD

•Through-bonding interaction

• 1JHH is 0; H-H magnetically equivalent nuclei

•Smaller J values = longer bond; weaker bond

Claridge, T. D. W. High-Resolution NMR Techniques in Organic Chemistry, Volume 27, Second Edition; 2 edition.; Elsevier Science, 2004.

HD(g) 43.2 Hz

Gilbertson, J. D.; Szymczak, N. K.; Tyler, D. R. Inorg. Chem. 2004, 43, 3341-3343.

Gilbertson, J. D.; Szymczak, N. K.; Tyler, D. R. Inorg. Chem. 2004, 43, 3341-3343.

T1 Correlation Times

•T1 = spin-lattice relaxation time

The average lifetime of nuclei in the higher energy

state

Dependent on the gyromagnetic ratio of the nucleus

and the mobility of the lattice

As mobility increases, the vibrational and rotational

frequencies increase

Claridge, T. D. W. High-Resolution NMR Techniques in Organic Chemistry, Volume 27, Second Edition; 2 edition.; Elsevier

Science, 2004.

Hamilton, D. G.; Crabtree, R. H. J. Am. Chem. Soc., 1988, 110, 4126-4133.

Desrosiers, P. J.; Cai, L.; Lin, Z.; Richards, R.; Halpern, J. J. Am. Chem Soc.1991, 113, 4173-4184.

Gilbertson, J. D.; Szymczak, N. K.; Tyler, D. R. Inorg. Chem. 2004, 43, 3341-3343.

T1 Correlation Times

•T1 = spin-lattice relaxation time

The average lifetime of nuclei in the higher energy

state

Dependent on the gyromagnetic ratio of the nucleus

and the mobility of the lattice

As mobility increases, the vibrational and rotational

frequencies increase

Claridge, T. D. W. High-Resolution NMR Techniques in Organic Chemistry, Volume 27, Second Edition; 2 edition.; Elsevier

Science, 2004.

Hamilton, D. G.; Crabtree, R. H. J. Am. Chem. Soc., 1988, 110, 4126-4133.

Desrosiers, P. J.; Cai, L.; Lin, Z.; Richards, R.; Halpern, J. J. Am. Chem Soc.1991, 113, 4173-4184.

Gilbertson, J. D.; Szymczak, N. K.; Tyler, D. R. Inorg. Chem. 2004, 43, 3341-3343.

T1 Correlation Times

T1 Minimum

“T1 will go through a minimum when the

Brownian motion (measured by a

rotational correlation time, τc) is

matched with the Larmor frequency,

ω… If we can observe the T1 minimum

experimentally we will know τc at that

temperature.”

Hamilton, D. G.; Crabtree, R. H. J. Am. Chem. Soc., 1988, 110, 4126-4133.

T1 (min) Correlation Times in ms

•H2 = 1600

• (H)2Fe(CO)4 = 3000

•Os(H)4(P(p-Tol)3)3 = 820

• [IrH(H2)(bq)(PPh3)]+ = 30, 390

•Fe(H2)H2(PEtPh2)3 = 24

Claridge, T. D. W. High-Resolution NMR Techniques in Organic Chemistry, Volume 27, Second Edition; 2 edition.; Elsevier

Science, 2004.

Hamilton, D. G.; Crabtree, R. H. J. Am. Chem. Soc., 1988, 110, 4126-4133.

Desrosiers, P. J.; Cai, L.; Lin, Z.; Richards, R.; Halpern, J. J. Am. Chem Soc.1991, 113, 4173-4184.

Gilbertson, J. D.; Szymczak, N. K.; Tyler, D. R. Inorg. Chem. 2004, 43, 3341-3343.

M(H2)

T1 ~ 4-100 ms

M(H)(H)

T1 >> 100 ms

Gilbertson, J. D.; Szymczak, N. K.; Tyler, D. R. Inorg. Chem. 2004, 43, 3341-3343.

Fe-H2 Activation

•DMeOPrPE complexes of Fe(II)

Hetrolysis of H2 in water (2 e- from H2)

Activate N2 for reduction

Non-classical H2 ligand

Szymczak, N. K.; Braden, D. A.; Crossland, J. L., Yevgeniya, T.; Zakharov, L. N.; Tyler, D. R. Inorg. Chem., 2009, 48, 2976-2984.

Ruthenium H2 Activation

Ru-H2 Mechanism: Top Route

Szymczak, N. K.; Braden, D. A.; Crossland, J. L., Yevgeniya, T.; Zakharov, L. N.; Tyler, D. R. Inorg. Chem., 2009, 48, 2976-2984.

Ru-H2 Mechanism: Top Route

Szymczak, N. K.; Braden, D. A.; Crossland, J. L., Yevgeniya, T.; Zakharov, L. N.; Tyler, D. R. Inorg. Chem., 2009, 48, 2976-2984.

Ru-H2 Mechanism: Bottom Route

Szymczak, N. K.; Braden, D. A.; Crossland, J. L., Yevgeniya, T.; Zakharov, L. N.; Tyler, D. R. Inorg. Chem., 2009, 48, 2976-2984.

Ru-H2 Mechanism: Bottom Route

Szymczak, N. K.; Braden, D. A.; Crossland, J. L., Yevgeniya, T.; Zakharov, L. N.; Tyler, D. R. Inorg. Chem., 2009, 48, 2976-2984.

Szymczak, N. K.; Braden, D. A.; Crossland, J. L., Yevgeniya, T.; Zakharov, L. N.; Tyler, D. R. Inorg. Chem., 2009, 48, 2976-2984.

Ruthenium H2 Activation

Aqueous Chemistry of H2

•Why the difference in H2O reactivity?

Szymczak, N. K.; Braden, D. A.; Crossland, J. L., Yevgeniya, T.; Zakharov, L. N.; Tyler, D. R. Inorg. Chem., 2009, 48, 2976-2984.

Thermodynamic Explanation

Kinetic Explanation

“If reacting M-L bond is strengthened, a higher activation

barrier generally results, regardless of the energy of the

products. Accordingly, a more highly donating phosphine

ligand such as DEPE and DMeOPrPE will contribute to a

higher activation barrier for ligand substitution. This may

explain the lack of H2O substitution in the case of the more

electron-donating phosphine ligands.”

•DFT: Near thermodynamic neutrality

Neither favored nor disfavored

Szymczak, N. K.; Braden, D. A.; Crossland, J. L., Yevgeniya, T.; Zakharov, L. N.; Tyler, D. R. Inorg. Chem., 2009, 48, 2976-2984.

H2 Hydrogen Bonding in H2O

•H2 H-bonding accounts for stronger H2 binding

Difficult to quantify due to weak interactions

Ion pairing energies

Crystal packing forces

Solvation

Easy to displace H2 with CO, tBuCN, PMe3

Difficult to displace with H-bonding ligands (OH2)

Stable for months in H2O without H2 atmosphere

Szymczak, N. K.; Zakharov, L. N.; Tyler, D. R. J. Am. Chem. Soc. 2006, 128, 15830-15835.

Measuring a H2 H-Bond

• 1JHD with H-bonding acceptor show no

significant changes

• IR with H-bonding acceptor not sensitive

enough

•T1 (min) measurements

Szymczak, N. K.; Zakharov, L. N.; Tyler, D. R. J. Am. Chem. Soc. 2006, 128, 15830-15835.

Measuring a H2 H-Bond

• 1JHD with H-bonding acceptor show no

significant changes

• IR with H-bonding acceptor not sensitive

enough

•T1 (min) measurements

Szymczak, N. K.; Zakharov, L. N.; Tyler, D. R. J. Am. Chem. Soc. 2006, 128, 15830-15835.

τc of the H-Bond Acceptor

Szymczak, N. K.; Zakharov, L. N.; Tyler, D. R.J. Am. Chem. Soc. 2006, 128, 15830-15835.

•Viscous solvent

• Internal rotational

standard (cyHex-d12)

•H2 isolated as H-bonder

via CO derivative

τc of the H-Bond Acceptor

Szymczak, N. K.; Zakharov, L. N.; Tyler, D. R.J. Am. Chem. Soc. 2006, 128, 15830-15835.

•Viscous solvent

• Internal rotational

standard (cyHex-d12)

•H2 isolated as H-bonder

via CO derivative

Summary and Conclusions

• DMeOPrPEWater soluble, strong sigma-donating ability, innocent ligand

• Fe(II) complexesCoordinate and reduce N2

Intermediate reduction complexes are promising

Heterolysis of H2

• Ru(II) complexesExcellent H2 activation

Inertness to H2O Substitution

H-Bonding to H2O in solution

Invented a new H-bonding detection method

DMeOPrPE

Kendall, A. J. The Secret History of the DMeOPrPE; Reprint edition.; Overlook TP: Woodstock, NY, 2014.