click reaction prp

7/30/2019 Click Reaction Prp

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Supporting Information to

Convergent Synthesis of 2nd Generation AB-Type Miktoarm Dendrimersusing Click Chemistry Catalyzed by Copper Wire.

Carl N. Urbani, Craig A. Bell, Michael R. Whittaker and Michael J. Monteiro*

Australian Institute of Bioengineering and Nanotechnology, University of Queensland, St

Lucia QLD 4072, Brisbane, Australia

e-mail: [email protected]
mailto:[email protected]:[email protected]


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EXPERIMENTAL.................................................................................................................... 3Materials: ............................................................................................................................ 3Synthesis of ATRP Initiators: ............................................................................................ 4

Synthesis of 3-hydroxypropyl 2-bromo-2-methylpropanoate 3:. ...................................... 4

Synthesis of polymers using ATRP ................................................................................... 4Synthesis of PSTY-Br4:. ................................................................................................... 4Synthesis of PMA-Br5: ................................................................................................... 5Synthesis of PtBA-Br6: ................................................................................................... 5Synthesis of HO-PSTY-Br7: ........................................................................................... 6

Synthesis of polymers with azide functionality ................................................................ 6Synthesis of PSTY-N3 8: .................................................................................................... 6

Synthesis of 2nd

Generation Homo and Miktoarm functional dendrons ....................... 7Synthesis of functional arm HO-PSTY-(-)2 12 ................................................................ 7Synthesis of functional arm star G2[G1PSTY-OH, G2PSTY2] 13.................................... 8Synthesis of functional arm star G2[G1PSTY-Br, G2PSTY2] 16 .................................... 9Synthesis of functional arm star G2[G1PSTY-N3, G2PSTY2] 19 ................................... 10Synthesis of functional arm star G2[G1PSTY-(3)2, G2PSTY2] 22................................. 10

Synthesis of 2nd

Generation Homo and Miktoarm functional dendrimers ................. 11Synthesis of 3-arm dendrimer G2[G1PSTY3,G2PSTY6] 23............................................ 11Synthesis of G2[G1PSTY3,G2PSTY2-PAA4] 26: .......................................................... 13

Degradation of 3-arm dendrimer G2[G1PSTY3,G2PSTY6] 23:. .................................... 13Degradation of mikto-arm dendrimerG2[G1PSTY3, G2PSTY2-P

tBA4] 25:................... 13Analytical Methodologies ..................................................................................................... 13

1H and13C Nuclear Magnetic Resonance (NMR): ............................................................. 14Attenuated Total Reflectance Fourier Transform Spectroscopy (ATR-FTIR):................... 14Size Exclusion Chromatography (SEC): ............................................................................. 14Atomic Absorption Spectroscopy (AAS): .......................................................................... 15

Scheme 1: Synthetic route to azido functional and alkyne functional linear polymers. ........ 16Scheme 2: Synthetic route to azido functional homo and mikto-arm stars and alkynefunctional PSTY stars. ............................................................................................................ 17Scheme 3: Synthetic route to homo and mikto-arm dendrimers. .......................................... 18Table 1: Size exclusion chromatographic data for the synthesis of 3-mikto-arm stars.......... 19Figure 1: Size exclusion chromatograms using refractive index detection of G2[G1PSTY-OH, G2PSTY2] 13 and G2[G1PSTY3,G2PSTY6] 23.. ........................................................... 19Figure 2: Size exclusion chromatograms using refractive index detection ofG2[G1PSTY-OH, G2PSTY2] 13 and G2[G1PSTY3,G2PSTY2-PMA4] 24.

f..............................................20

Figure 3: Size exclusion chromatograms using refractive index detection of G2[G1PSTY-OH, G2PSTY2] 13 and G2[G1PSTY3,G2PSTY2-PtBA4] 25.

f...............................................21Figure 4: Size exclusion chromatogramsusing refractive index detection ofG2[G1PSTY3,G2PSTY6] 23 and after degradation reaction with NaOCH3........................... 21Figure 5: Attenuated Total Reflectance Fourier Transform Infrared Spectra (ATR-FTIR) of(a) HO-PSTY-Br7 (b) HO-PSTY-N3 11 (c) HO-PSTY-(C)2 12 and (d) G2[G1PSTY-OH,G2PSTY2] 13. ......................................................................................................................... 22Figure 6: 1H NMR spectra of (a) HO-PSTY-Br7 (b) HO-PSTY-N3 11 and (c) HO-PSTY-()2 13. .................................................................................................................................... 23Figure 7: 1H NMR spectra of (a) G2[G1PSTY3,G2PSTY2-P

tBA4] 25 full spectrum (b)expanded section showing tert-butyl groups and (c) G2[G1PSTY3,G2PSTY2-PAA4] 26

expanded to show loss of tert-butyl groups and addition of trifluoroester. ............................ 24


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EXPERIMENTALMaterials: The following monomers were deinhibited before use by passing through a

basic alumina column; methyl acrylate (MA: Aldrich, .99%), styrene (STY: Aldrich, >99 %)

and tert-butyl acrylate (tBA: Aldrich, >99 %).

The following chemicals were used as received; alumina, activated basic alumina (Aldrich:

Brockmann I, standard grade, ~ 150 mesh, 58 ), anhydrous magnesium sulfate (MgSO4:

Scharlau, extra pure), sodium chloride (NaCl: Univar, 99.9 %), sodium methoxide (NaOCH3:

Aldrich, 95%), triethylamine (TEA: Fluka, 98 %), 2-bromoisobutyryl bromide (BIB: Aldrich,

98 %), 1,3-Propanediol (Fluka, >99 %), bromoacetyl bromide (BAB: Fluka, 98 %), sodium

azide (NaN3: Aldrich, I 99.5 %) and tripropargylamine (TPA: Aldrich, 98 %).

The following solvents were used as received; Acetone (ChemSupply, AR), anisole

(Fluka, 98 %), chloroform (CHCl3: Univar, AR grade), dichloromethane (DCM: Labscan, AR

grade), diethyl ether (Univar, AR grade), methanol, anhydrous (MeOH: Mallinckrodt, 99.9 %,

HPLC grade), Milli-Q water (Biolab, 18.2 Mm), N,N-dimethylformamide (DMF: Labscan,

AR grade) and tetrahydrofuran (THF: Labscan, HPLC grade).

The following initiators, ligands and metals for the various polymerizations are given

below and used as received unless otherwise stated. N,N,N,N,N-

pentamethyldiethylenetriamine (PMDETA: Aldrich, 99 %), copper (I) bromide (CuBr:

Aldrich, 99.999 %), copper (II) bromide (CuBr2: Aldrich, 99 %), ethyl-2-bromoisobutyrate (1,

EBiB: Aldrich, 98 %) and methyl-2-bromopropionate (2, MBP: Aldrich, 98 %).


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Synthesis of ATRP Initiators:

Synthesis of 3-hydroxypropyl 2-bromo-2-methylpropanoate 3: 1,3-Propanediol (33.20 g,

0.44 mol) and triethylamine (2.21 g, 0.02 mol) were stirred in THF (60 ml) and cooled in an

ice bath. 2-bromoisobutyrylbromide (5.00 g, 0.02 mol) in THF (40 mL) was added dropwise

under nitrogen and the reaction mixture was stirred overnight at room temperature. The

mixture was filtered and the solvent evaporated on a rotary evaporator. The resultant clear oil

was taken up in diethyl ether (200 mL) and the organics washed with 10% (v/v) HCl (1*200

mL), brine (1*200 mL) and water (1*200 mL). The organic layer was dried with magnesium

sulphate and the solvent removed on a rotary evaporator. The product was purified by column

chromatography (with 40/60 ethyl ether/hexane as eluting solvent), resulting in a clear oil. 1H

NMR (CDCl3) 4.60 4.49 (s, br, 1H, OH); 4.17 (t,1J = 7.96 Hz, 2H, CH2); 3.48 (t,

1J = 6.32

Hz, 2H, CH2); 1.87 (s, 6H, CH3); 1.75 (q,1J = 6.32 Hz, 2H, CH2).

Synthesis of polymers using ATRP

Synthesis of PSTY-Br4: Freshly purified styrene (15.06 g, 0.145 mol), PMDETA (0.190

mL, 9.09 x 10-4 mol), EBiB (1, 0.145 g, 7.44 x 10-4 mol) and CuBr2 (0.0346 g, 1.55 x 10-4 mol)

were added to a 50 mL Schlenk flask equipped with a magnetic stirrer then purged with N 2 for

20 min. After stirring for 1 h CuBr (0.109 g, 7.60 x 10 -4 mol) was carefully added under

positive N2 flow and the reaction mixture purged with N2 for a further 5 min. The flask was

placed in a temperature controlled oil bath at 80 oC for 205 min. The reaction was terminated

by quenching in liquid nitrogen and then exposure to air. The polymerization mixture was

diluted with THF then the copper salts removed by passage through an activated basic alumina

column. The solution was concentrated by airflow and the polymer recovered by precipitation

into methanol, then filtered and dried for 48 h under high vacuum at 25 oC. The polymer was

characterized by SEC (Mn = 5120, PDI = 1.09).


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Synthesis of PMA-Br 5: Freshly purified methyl acrylate (25.1261 g, 0.292 mol),PMDETA (0.262 g, 1.51 x 10-3 mol), EBiB (1, 0.285 g, 1.46 x 10-3 mol) and anisole (10 mL)

were added to a 50 mL Schlenk flask equipped with a magnetic stirrer then purged with N 2 for

15 min. CuBr (0.099 g, 6.90 x 10-4 mol) and CuBr2 (0.160 g, 7.16 x 10-4 mol) were then

carefully added under positive N2 flow and the mixture purged with N2 for a further 10 min.

The flask was placed in a temperature controlled oil bath at 60oC and the polymerisation

allowed to proceed for 23 h. The reaction was terminated by quenching in liquid nitrogen and

then exposure to air. The polymerization mixture was diluted with chloroform and the copper

salts removed by passage through an activated basic alumina column. The polymer solution

was washed 3 times with water and the organic layer dried over anhydrous MgSO4. The

polymer was then recovered by removal of the chloroform under vacuum. The polymer was

dried for 24 h under vacuum at 25 oC, and analysed by SEC (Mn = 4200, PDI = 1.06).

Synthesis of PtBA-Br 6: Freshly purified tert-butyl acrylate (15.03 g, 0.117 mol),

PMDETA (0.516 mL, 2.47 x 10-3 mol), MBP (2, 0.392 g, 2.35 x 10-3 mol), CuBr2 (0.029 g,

1.30 x 10-4 mol) and acetone (4.2 mL) were added to a 50 mL Schlenk flask, equipped with a

magnetic stirrer, and purged with N2 for 20 min. After stirring for 1 h, CuBr (0.338 g, 2.36 x

10-3 mol) was added carefully under positive N2 flow and the mixture purged with N2 for a

further 5 min. The flask was placed in a temperature controlled oil bath at 60oC and the

polymerisation allowed to proceed for 4 h. The reaction was terminated by quenching with

liquid nitrogen and exposure to air. The polymerization mixture was diluted with THF then the

copper salts removed by passage through an activated basic alumina column. The solution was

concentrated by airflow, and the polymer recovered by precipitation into cold 50 % v/v

MeOH/water. The filtrate was dried for 48 h under high vacuum at 25 oC. The polymer was

characterized by SEC (Mn = 6180, PDI = 1.10).


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Synthesis of HO-PSTY-Br7: Freshly purified styrene (3.0 g, 2.88 x 10-2 mol), PMDETA

(0.026 g, 1.5 x 10-4 mol), pre-formed CuBr2/PMDETA complex (0.00595 g, 1.5 x 10-5 mol),

and 3 (0.031 g, 1.38 x 10-4 mol) were added to a 10 mL Schlenk flask equipped with a

magnetic stirrer and purged with N2 for 15 min. CuBr (0.0215 g, 1.5 x 10-4 mol) was then

carefully added under positive N2 flow and then purged with N2 for a further 10 min. The flask

was placed in a temperature controlled oil bath at 80oC for 2 h. The reaction was terminated by

quenching in liquid nitrogen and then exposure to air. The polymerization mixture was diluted

with THF then the copper salts removed by passage through an activated basic alumina

column. The solution was concentrated by airflow and the polymer recovered by precipitation

into methanol, then filtered and dried for 48 h under high vacuum at 25 oC. The polymer was

characterized by SEC (Mn = 6258 and PDI = 1.10).

Synthesis of polymers with azide functionality

Synthesis of PSTY-N3 8: A typical azidation procedure was as follows: NaN3 (0.278 g, 4.3

mmol) was added to a stirred solution of PSTY-Br (4, 2.0 g, 0.39mmol) in 20 mL of DMF .

The reaction mixture was stirred for 24 h at 50 oC in a temperature controlled oil bath. The

polymer was precipitated in MeOH, recovered by vacuum filtration and washed exhaustively

with water and MeOH. The polymer was dried under high vacuum for 48 h at 25 oC.

Similarly, HO-PSTY-N3 (11) was prepared from HO-PSTY-Br (7).

PMA-Br (5) and PtBA-Br (6) were azidated using the same procedure as above but purified

by precipitation into cold 50 % v/v MeOH/water, filtered and dried under vacuum to give

azidated polymers PMA-N3 (9) and PtBA-N3 (10).


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Synthesis of 2nd

Generation Homo and Miktoarm functional dendrons

Synthesis of functional arm HO-PSTY-(-)2 12

Method A: 10 eq. CuBr/PMDETA: HO-PSTY-N3 (11, 1.120 g, 1.78 x 10-4 mol),

PMDETA (0.284 g, 1.64 x 10-3 mol), TPA (0.431 g, 3.29 x 10-3 mol) and 10 mL of DMF was

added to a 10 mL Schlenk flask equipped with a magnetic stirrer. The reaction mixture was

purged with N2 for 10 min after which CuBr (0.233 g, 1.63 x 10-3 mol) was added under a N2

blanket . The mixture was then purged with N2 for a further 5 min. The reaction mixture was

stirred for 2 h at 80 oC in a temperature controlled oil bath. The solution was then diluted with

THF, and passed through a basic alumina column. The solution was concentrated under N2

flow and the polymer recovered by precipitation into cold MeOH and then filtered. The

polymer was redissolved in DMF (5 mL) and re-precipitated into cold MeOH, filtered and

dried under vacuum.

Method B: 0.5 eq. CuBr/PMDETA: HO-PSTY-N3 (11, 0.4385 g, 7.01 x 10-5 mol),

PMDETA (0.0061 g, 3.49 x 10

-5

mol),TPA (0.184 g, 1.40 x 10

-3

mol) and 4.4 mL of DMFwere added to a 10 mL Schlenk flask equipped with a magnetic stirrer. The reaction mixture

was then purged with N2 for 10 min after which CuBr (0.0051 g, 3.55 x 10-5 mol) was acrefully

added under a positive flow of N2. The mixture was then purged with N2 for a further 5 min.

The reaction mixture was stirred for 2 h at 80 oC in a temperature controlled oil bath. The

polymer was recovered by precipitation into MeOH and then filtered. The polymer was

redissolved in DMF (4 mL) and re-precipitated into MeOH, filtered and dried under vacuum.

Method C: Cu (wire): HO-PSTY-N3 (11, 0.6427 g, 1.17 x 10-4 mol), PMDETA (0.0101

g, 5.84 x 10-5 mol),TPA (0.306 g, 2.33 x 10-3 mol) , Cu (wire, 0.30 g) and 6.4 mL of DMF

was added to a 10 mL Schlenk flask equipped with a magnetic stirrer. The reaction mixture

was stirred for 4 h at 80 oC in a temperature controlled oil bath. The polymer was recovered by


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precipitation into MeOH and then filtered. The polymer was redissolved in DMF (6 mL) and

re-precipitated into MeOH, filtered and dried under vacuum.

Synthesis of functional arm star G2[G1PSTY-OH, G2PSTY2] 13

Method A: 10 eq. CuBr/PMDETA: 12 (prepared by Method A, 0.300 g, 4.79 x 10-5mol),

PSTY-N3 (8, 0.528 g, 1.03 x 10-4 mol),PMDETA (0.163 g, 9.40 x 10-4 mol) and 8 mL of

DMF were added to a 10 mL Schlenk flask equipped with a magnetic stirrer. The reaction

mixture was purged with N2 for 10 min after which CuBr (0.133 g, 9.27 x 10-4 mol) was

carefully added under a positive flow of N2. The reaction mixture was purged with N2 for a

further 5 min. The reaction mixture was stirred for 2 h at 80 oC in a temperature controlled oil

bath. The solution was diluted with THF and passed through a basic alumina column. The

solution was concentrated under N2 flow, and the polymer precipitated into cold methanol,

filtered and dried under vacuum.

The above procedure was repeated for the synthesis of the functional mikto-arm stars

G2[G1PSTY-OH, G2PMA2] (14) and G2[G1PSTY-OH, G2PtBA2] (15) using PMA-N3 (9) and

PtBA-N3 (10) respectively.

Method B: 0.5 eq. CuBr/PMDETA: 12 (prepared by Method B, 0.22 g, 3.55 x 10-5 mol),

PSTY-N3 (8, 0.40 g, 7.73 x 10-5 mol),PMDETA (0.0066 g, 3.83 x 10-5 mol) and 6 mL of

DMF were added to a 10 mL Schlenk flask equipped with a magnetic stirrer. The reaction

mixture was purged with N2 for 10 min after which CuBr (0.0055 g, 3.83 x 10-5 mol) was

carefully added under a positive flow of N2. The mixture was then purged with N2 for a further

5 min. The reaction mixture was stirred for 3 h at 80 oC in a temperature controlled oil bath..

The polymer was precipitated into cold methanol, filtered and dried under vacuum.


G2[G1PSTY-OH, G2PMA2] (14) and G2[G1PSTY-OH, G2Pt

BA2] (15) using PMA-N3 (9) and


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PtBA-N3 (10) respectively. These polymers were purified by precipitation into water, then


Method C: Cu (wire): 12 (prepared by Method C, 0.198 g, 3.60 x 10-5 mol), PSTY-N3 (8,

0.4234 g, 7.56 x 10-5 mol), Cu (wire, 1.0 g) and 6 mL of DMF were added to a 10 mL Schlenk

flask equipped with a magnetic stirrer. The reaction mixture was stirred for 4 h at 80 oC in a

temperature controlled oil bath. The polymer was precipitated into cold methanol, filtered and

dried under vacuum.


G2[G1PSTY-OH, G2PMA2] (14) and G2[G1PSTY-OH, G2PtBA2] (15) using PMA-N3 (9) and

PtBA-N3 (10) respectively. These polymers were purified by precipitation into water, then


Synthesis of functional arm star G2[G1PSTY-Br, G2PSTY2] 16

13 (0.50 g, 2.94 x 10-5 mol), TEA (4.5 L, 3.2 x 10-5 mol) and 1.5 mL of dry DCM

were added to a 10 mL Schlenk flask equipped with stirrer bar while purged with N2. BAB

(12.7 L, 1.47 x 10-4 mol) in 0.5mL of dry DCM was added dropwise under N2 to the stirred

mixture over a period of 20 min. at room temperature. After complete addition the mixture

was allowed to stir for a further 16 h at room temperature. The polymer was precipitated in

MeOH, then filtered and washed 3 times with MeOH (20 mL). The recovered polymer was

dried for 24 h under vacuum.

The above procedure was used for the synthesis of the functional mikto-arm stars

G2[G1PSTY-Br, G2PMA2] (17) and G2[G1PSTY-Br, G2PtBA2] (18) using G2[G1PSTY-OH,

G2PMA2] (14) and G2[G1PSTY-OH, G2PtBA2] (15) respectively.


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Synthesis of functional arm star G2[G1PSTY-N3, G2PSTY2] 19

NaN3 (0.0166 g, 2.67 x 10-4 mol) was added to a stirred solution of16 (0.450 g, 2.67 x 10-5

mol) in 2 mL DMF. The reaction mixture was stirred for 24 h at 50 oC in a temperature

controlled oil bath. The polymer was precipitated in water with vigorous stirring, filtered and

dried under high vacuum.

The above procedure was used for the synthesis of the functional mikto-arm stars

G2[G1PSTY-N3, G2PMA2] (20) andG2[G1PSTY-N3, G2PtBA2] (21) using G2[G1PSTY-Br,

G2PMA2] (17) and G2[G1PSTY-Br, G2PtBA2] (18) respectively.

Synthesis of functional arm star G2[G1PSTY-(3)2, G2PSTY2] 22

Method A: 10 eq. CuBr/PMDETA: 19 (prepared by Method A, 0.200 g, 1.18 x 10-5

mol), PMDETA (25 L, 1.20 x 10-4 mol),TPA (34 L, 2.35 x 10-4 mol) and 2mL of DMF

was added to a 10 mL Schlenk flask equipped with magnetic stirrer. The reaction mixture was

purged with N2 for 20 min after which CuBr (0.0168 g, 1.17 x 10

-4

mol) was carefully added

under a positive flow of N2. The mixture was then purged with N2 for a further 5 min. The

reaction mixture was stirred for 2 h at 80 oC in a temperature controlled oil bath. The solution

was then diluted with THF and passed through a basic alumina column. The solution was

concentrated under N2 flow, and the polymer precipitated into cold methanol then filtered. The

polymer was redissolved in DMF (5 mL) and re-precipitated in cold MeOH, filtered and dried

under vacuum.

Method B: 0.5 eq. CuBr/PMDETA: 19 (prepared by Method B, 0.1498 g, 9.25 x 10-6

mol),TPA (26 L, 1.84 x 10-4 mol) and 1 mL of DMF were added to a 10 mL Schlenk flask

equipped with magnetic stirrer. The solution was then purged with N2 for 20 min. To the

reaction mixture was carefully added a 100 L aliquot of a deoxygenated solution containing,

PMDETA (49 L, 2.34 x 10-4 mol) and CuBr (0.033 g, 2.30 x 10-4 mol) in 5 mL DMF, under


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positive N2 flow and the reaction mixture was then purged with N2 for a further 5 min. The

reaction mixture was stirred for 3 h at 80 oC in a temperature controlled oil bath. The polymer

was precipitated into cold methanol then filtered. The polymer was redissolved in DMF (2 mL)

and re-precipitated in cold MeOH, filtered and dried under vacuum.

Method C: Cu (wire): 19 (prepared by Method C, 0.2366 g, 1.34 x 10-5 mol), TPA (38

L, 2.69 x 10-4 mol), Cu (wire, 0.355 g) and 2.5 mL of DMF were added to a 10 mL Schlenk

flask equipped with magnetic stirrer. The reaction mixture was stirred for 4 h at 80 oC in a

temperature controlled oil bath. The polymer was precipitated into cold methanol then filtered.

The polymer was redissolved in DMF (2.5 mL) and re-precipitated in cold MeOH, filtered and

dried under vacuum.

Synthesis of 2nd

Generation Homo and Miktoarm functional dendrimers

Synthesis of 3-arm dendrimer G2[G1PSTY3,G2PSTY6] 23

Method A: 10 eq. CuBr/PMDETA: 22 (prepared by Method A, 5.3 mg, 3.12 x 10

-7

mol),19 (prepared by Method A, 11.2 mg, 6.59 x 10-7 mol), PMDETA (1.4 L, 6.47 x 10-6 mol) and

0.5 mL of DMF was added to a 10 mL Schlenk flask equipped with a magnetic stirrer. The

solution was purged with N2 for 10 min after which CuBr (1.3 mg, 9.1 x 10-6 mol) was

carefully added under a positive flow of N2. and the reaction mixture was then purged with N2

for a further 5 min. The flask was placed in a temperature controlled oil bath and stirred at 80

oC for 2 h, at which a sample removed for SEC analysis. The star dendrimer was then purified

from the bulk reaction by fractionation using SEC. The fractionated polymer23f was then

analysed by SEC.

The above procedure was used for the synthesis of the mikto-arm dendrimers

G2[G1PSTY3,G2PSTY2-PMA4] (24 and 24f) and G2[G1PSTY3,G2PSTY2-P

tBA4] (25 and

25f) using G2[G1PSTY-N3, G2PMA2] (20) and G2[G1PSTY-N3, G2PtBA2] (21) respectively.


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Method B: 0.5 eq. CuBr/PMDETA: 22 (prepared by Method B, 4.9 mg, 3.03 x 10 -7 mol)

and 19 (prepared by Method B, 10.8 mg, 6.67 x 10-7 mol) in 0.5 mL of DMF was added to a 10

mL Schlenk flask equipped with a magnetic stirrer bar. The solution was purged with N2 for 10

min after which a 100 L aliquot of a deoxygenated solution containing PMDETA (7 L, 3.35

x 10-5 mol) and CuBr (4.8mg, 3.35 x 10-5 mol) in 10 mL DMF was dispensed into the reaction

under a positive N2 flow. The reaction solution was then purged with N2 for a further 5 min.

The reaction mixture was stirred for 4 h at 80 oC in a temperature controlled oil bath after

which a sample was removed for SEC analysis.


G2[G1PSTY3,G2PSTY2-PMA4] (24) and G2[G1PSTY3,G2PSTY2-PtBA4] (25) using

G2[G1PSTY-N3, G2PMA2] (20) and G2[G1PSTY-N3, G2PtBA2] (21) respectively.

The reactions were maintained at 80 oC for 19 h.

Method C: Cu (wire): 22 (prepared by Method C, 5.0 mg, 2.82 x 10 -7 mol), 19 (prepared

by Method C, 10.5 mg, 5.93 x 10

-7

mol),Cu (wire, 50.0 mg) and 0.5 mL of DMF was added toa 10 mL Schlenk flask equipped with magnetic stirrer. The reaction mixture was stirred for 4h

at 80 oC in a temperature controlled oil bath and then a sample was removed for SEC analysis.

The star dendrimer was then purified from the bulk reaction by fractionation using SEC. The

fractionated polymer23fwas then analysed by SEC.


G2[G1PSTY3,G2PSTY2-PMA4] (24 and 24f) and G2[G1PSTY3,G2PSTY2-P

tBA4] (25 and

25f) using G2[G1PSTY-N3, G2PMA2] (20) and G2[G1PSTY-N3, G2P

tBA2] (21) respectively.

Method D: Cu (wire): 22 (prepared by Method B, 5.0 mg, 3.08 x 10 -7 mol) and 19

(prepared by Method B, 11.0 mg, 6.79 x 10 -7 mol), Cu (wire, 50.0 mg) and 0.5 mL of DMF

was added to a 10 mL Schlenk flask equipped with magnetic stirrer. The reaction mixture was


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stirred for 4h at 80 oC in a temperature controlled oil bath and then a sample was removed for

SEC analysis.


G2[G1PSTY3,G2PSTY2-PMA4] (24) and G2[G1PSTY3,G2PSTY2-PtBA4] (25) using

G2[G1PSTY-N3, G2PMA2] (20) and G2[G1PSTY-N3, G2PtBA2] (21) respectively.

Synthesis of G2[G1PSTY3,G2PSTY2-PAA4] 26: G2[G1PSTY3,G2PSTY2-PtBA4] (25, 10

mg, 3.43 10-5 mol. tBA groups) was dissolved in 0.5 mL of DCM. TFA (20 mg, 1.72 10-4

mol) was added and the solution was stirred overnight at 25 oC after which the solution was

dried with a nitrogen stream. The material was then further dried for 48 h at 25oC in a high

vacuum oven. Hydrolysis of the tBA groups was confirmed by the loss of the tert-butyl groups

in the 1H spectrum situated at 1.35ppm.

Degradation of 3-arm dendrimer G2[G1PSTY3,G2PSTY6] 23: To a 250 L aliquot of the

reaction mixture from the synthesis of G2[G1PSTY3,G2PSTY6] 23 was added THF (1 mL) and

NaOCH3 (10 mg, 1.85 x 10-4 mol). The mixture was stirred at room temperature for 16 h, then

diluted with THF and analysed by SEC.

Degradation of mikto-arm dendrimerG2[G1PSTY3, G2PSTY2-PtBA4] 25: G2[G1PSTY3,

G2PSTY2-PtBA4] (25, 2 mg) was dissolved in 1 mL of THF. NaOCH3 (0.1 mg, 1.85 x 10

-6

mol) was added and the solution stirred for 16 h at room temperature. The mixture was then

analysed by SEC.

Analytical Methodologies


14/24

14

1H and 13C Nuclear Magnetic Resonance (NMR): All NMR spectra were recorded on a

Bruker DRX 500 MHz spectrometer using an external lock (CDCl3) and utilizing a standard

internal reference (solvent reference). 13C NMR spectra were recorded by decoupling the

protons and all chemical shifts are given as positive downfield relative to these internal

references.

Attenuated Total Reflectance Fourier Transform Spectroscopy (ATR-FTIR): ATR-FTIR

spectra were recorded between 4000 and 550 cm-1 in a Perkin Elmer FT-2000 FTIR

spectrometer equipped with a single reflection diamond window. Each spectrum had a 32 scan

accumulation using a spectral resolution of 8 cm-1.

Size Exclusion Chromatography (SEC): The molecular weight distributions of

nanoparticles were measured by SEC. All polymer samples were dried prior to analysis in a

vacuum oven for two days at 40 oC. The dried polymer was dissolved in tetrahydrofuran (THF)

(Labscan, 99%) to a concentration of 1 mg/mL. This solution was then filtered through a 0.45

m PTFE syringe filter. Analysis of the molecular weight distributions of the polymer

nanoparticles was accomplished by using a Waters 2695 Separations Module, fitted with two

Ultrastyragel linear columns (7.8 x 300 mm) kept in series. These columns were held at a

constant temperature of 35oC for all analyses. The columns used separate polymers in the

molecular weight range of 500 2 million g/mol with high resolution. THF was the eluent used

at a flow rate of 1.0 mL/min. Calibration was carried out using narrow molecular weight PSTY

standards (PDI ~ 1.1) ranging from 500 2 million g/mol. Data acquisition was performed

using Waters Millenium software (ver. 3.05.01) and molecular weights were calculated by

using a 5th order polynomial calibration curve.


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15

Atomic Absorption Spectroscopy (AAS):

Prior to analysis, all polymer samples were digested in 3 mL of 70 % HNO3 and heated for

30 min until evolution of red NO2 fumes ceased. After cooling, these solutions were then

filtered through filter paper and transferred quantitatively into 25 mL volumetric flasks, and

filled up to the mark with Milli-Q water. Sample concentrations were diluted where

necessary so as to be calculated against Cu(NO3)2 standards (0.1-1 ppm). An Analyst 100

Perkin Elmer multi-elemental atomic absorption spectrometer (AAS) equipped with hollow

cathode lamps was used for the copper determination. The AAS instrument was adjusted for

the optimum conditions. The sample solutions obtained were directly aspirated in order to

determine copper concentrations.


16/24

16

Schemes, Tables & Figures

Scheme 1: Synthetic route to azido functional and alkyne functional linear polymers.

Br

O

O Br

O

OHOBr

O

O

O

OBrn

O

ON3n

O

OBrn

OO

O

ON3n

OO

O

ON3n

OO

O

OBrn

OO

HO O

O

N

NN

Nn

O

OBrnHO

O

ON3

nHO

O

O

O

O

NaN3

DMF, 50oC

NaN3DMF, 50oC

NaN3DMF, 50oC

NaN3DMF, 50oC

N

1 2 3

4 5 6 7

8 9 10 11

12


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17

Scheme 2: Synthetic route to azido functional homo and mikto-arm stars and alkyne

functional PSTY stars.

HO O

O

N

NN

Nn

HO O

O

N

NN

Nn

N

NN

NN

N

O

On

O

On

OO

O O

HO O

O

N

NN

N

n

N

NN

NN

N

O

On

O

On

HO O

O

N

NN

N

n

N

NN

NN

N

O

On

O

On

OO

O O

O O

O

N

NN

N

N

NN

NN

N

O

O

O

O

OO

O O

O

Br O O

O

N

NN

N

N

NN

NN

N

O

O

O

O

OO

O O

O

Br

O O

O

N

NN

N

N

NN

NN

N

O

O

O

O

O

Br

O O

O

N

NN

N

N

NN

NN

N

O

O

O

O

O

N3 O O

O

N

NN

N

N

NN

NN

N

O

O

O

O

OO

O O

O

N3

O O

O

N

NN

N

N

NN

NN

N

O

O

O

O

OO

O O

O

N3

O O

O

N

NN

Nn

N

NN

NN

N

O

On

O

On

O

N

NN

N

12

8 9 10

TEA, DCM

BrBr

TEA, DCM

Br

O

Br

TEA, DCM

Br

O

Br

NaN3

DMF, 50oC

NaN3

DMF, 50oC

NaN3DMF, 50oC

N

16 17

13 14 15

18

1920 21

22


18/24

18

Scheme 3: Synthetic route to homo and mikto-arm dendrimers.

O

O

O

N

N

N

N

n

NN

NN

N

N

O

O

n

O

O

n

O

NN

N

N

O

O

O N

NN N

n

NNN

N

NN

O

On

O

O

n

O

N

NN

N

O

O

O

N

NN

N

n

N N

N

NN

N

O

O

n

O

O

n

O

N NN

O

O

O

N

N

N

N

n

NN

N

NN

N

OO

n

OO

n

O

NN

N

O

O

O N

NN N

n

NNN

NN

NO

On

O

O

n

O

NNN

N

O

O

O

N

NN

N

n

N NN

NN

N

O

O

n

O

O

n

O

N NN

O

O

O

N

N

N

N

n

NN

N

NN

N

OO

n

OO

n

O

NN

N

O

O

O

O

O

O

O

O

O

O

O N

NN N

n

NNN

NN

NO

On

O

O

n

O

NNN

N

O

O

O

N

NN

N

n

N NN

NN

N

O

O

n

O

O

n

O

N NN

O

O

O

N

N

N

N

n

NN

NNN

N

OO

n

OO

n

O

NN

N

OO

O

O

O

O

O

O

O

O

O

N

NN

N

n

NN

N

NN

N

O

O

n

O

O

n

O

NN

N

N

O

O

ON

NN

N

n

NN

N

NN

N

O

On

O

O

n

O

NNN

O

O

O

N

N

N

N

n

NN

NNN

N

OO

n

O O

n

O

N

N

N

OOH

OH

O

O

OH

O

OH

TFA,DCM

TFA,DCM

22

19

20

21


19/24

19

Table 1: Size exclusion chromatographic data for the synthesis of 3-mikto-arm stars

G2 dendrons Method A Method B Method C

PDI Mp Mp,theory PDI Mp Mp,theory PDI Mp Mp,theory

13 1.17 18200 18170 1.17 16440 18170 1.27 16650 16800

14 1.22 19080 20310 1.27 17000 20310 1.31 18480 18940

15 1.15 14960 15730 1.19 12300 15730 1.27 12880 14360

0

20000

40000

60000

80000

3 3.5 4 4.5 5 5.5LogMw

d(Log(w(M)))

0

20000

40000

60000

80000

3 3.5 4 4.5 5 5.5LogMw

d(Log(w(M)))

0

20000

40000

60000

80000

3 3.5 4 4.5 5 5.5LogMw

d(Log(w(M)))

0

20000

40000

60000

80000

100000

3 3.5 4 4.5 5 5.5LogMw

d(Log(w(M)))

Figure 1: Size exclusion chromatograms using refractive index detection of G2[G1PSTY-

OH, G2PSTY2] 13 and G2[G1PSTY3,G2PSTY6] 23.fAfter fractionation by SEC. (a) Method

A: 10 eq. CuBr/PMDETA (b) Method B: 0.5 eq. CuBr/PMDETA (c) Method C: Cu (wire)

(d) Method D: Cu (wire).

9

1323

f

23

(a) (b)

13 23

9

13 23

9

(c) (d)

23

9

13

23f


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20

0

20000

40000

60000

80000

3 3.5 4 4.5 5 5.5LogMw

d(Log(w(M)))

0

20000

40000

60000

80000

3 3.5 4 4.5 5 5.5LogMw

d(Log(w(M)))

0

20000

40000

60000

80000

3 3.5 4 4.5 5 5.5LogMw

d(Log(w(M)))

0

20000

40000

60000

80000

3 3.5 4 4.5 5 5.5LogMw

d(Log(w(M)))

Figure 2: Size exclusion chromatograms using refractive index detection ofG2[G1PSTY-

OH, G2PSTY2] 13 and G2[G1PSTY3,G2PSTY2-PMA4] 24.fAfter fractionation by SEC. (a)

Method A: 10 eq. CuBr/PMDETA (b) Method B: 0.5 eq. CuBr/PMDETA (c) Method C: Cu

(wire) (d) Method D: Cu (wire).

13

24f

24

(a)

13

24

24

(b)

13

(c)

9

9

9

(d)

9

13

24

24


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21

0

20000

40000

60000

80000

3 3.5 4 4.5 5 5.5LogMw

d(Log(w(M

)))

0

20000

40000

60000

80000

3 3.5 4 4.5 5 5.5LogMw

d(Log(w(M

)))

0

20000

40000

60000

80000

3 3.5 4 4.5 5 5.5LogMw

d(Log(w(M)))

0

20000

40000

60000

80000

3 3.5 4 4.5 5 5.5LogMw

d(Log(w(M)))

Figure 3: Size exclusion chromatograms using refractive index detection of G2[G1PSTY-

OH, G2PSTY2] 13 and G2[G1PSTY3,G2PSTY2-PtBA4] 25.

fAfter fractionation by SEC. (a)

Method A: 10 eq. CuBr/PMDETA (b) Method B: 0.5 eq. CuBr/PMDETA (c) Method C: Cu

(wire) (d) Method D: Cu (wire).

0

20000

40000

60000

80000

3 3.5 4 4.5 5 5.5

LogMw

d(Log(w(M)))

Figure 4: Size exclusion chromatogramsusing refractive index detection ofG2[G1PSTY3,G2PSTY6] 23 and after degradation reaction with NaOCH3.

25f

(a)

13

25

(b)

1325

(c)

9

9

9

1325

(d)

2513

9 25

23

After

Degradation


22/24

22

Figure 5: Attenuated Total Reflectance Fourier Transform InfraredSpectra (ATR-FTIR) of (a) HO-PSTY-Br7 (b) HO-PSTY-N3 11 (c) HO-PSTY-(C)2 12 and (d) G2[G1PSTY-OH, G2PSTY2] 13.

40

50

60

70

80

90

100

500 1000 1500 2000 2500 3000 3500

Wavenumbers (cm-1)

%Transmittance

O

Br

R

nHO

O

87

97

1700 2200 2700 3200

Wavenumbers (cm-1)

%

Transmittance

RN

N

NN

87

97

1700 2200 2700 3200

Wavenumbers (cm-1)

%Transmittance

b

87

97

1700 2200 2700 3200

Wavenumbers (cm-1)

%Transmittance

RN

N N

N

NN

N

N

NN

O

O

O

O

13

(a)

(b)

(c)

(d)

2 2 00 270 0 3 2 00

Wavenumbers ( cm - 1 )

aR

N3

N3

C:C-H


23/24

23

Figure 6: 1H NMR spectra of (a) HO-PSTY-Br7 (b) HO-PSTY-N3 11 and (c) HO-PSTY-()2 13.

(a)

(b)

(c)


24/24

Figure 7: 1H NMR spectra of (a) G2[G1PSTY3,G2PSTY2-PtBA4] 25 full

spectrum (b) expanded section showing tert-butyl groups and (c)G2[G1PSTY3,G2PSTY2-PAA4] 26 expanded to show loss of tert-butyl

groups and addition of trifluoroester.

(c)

(b)

(a)

click reaction prp

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