Supporting Information
Journal of Polymer Science Part A:
Polymer Chemistry
Multi-Functional Initiator and Poly(carboxybetaine
methacrylamides) for building biocompatible surfaces using
‘Nitroxide Mediated Free Radical Polymerization’ strategies
Sinoj Abraham and Larry D. Unsworth*
Chemical and Materials Engineering Department, University of Alberta;
National Research Council (Canada) - National Institute for Nanotechnology; Edmonton, Alberta,
Canada.
E-mail: larry.unsworth@ualberta.ca
Synthesis of -Phosphonylated Nitroxide radical.
The synthesis of -phosphonylated radical, ‘‘N-tertbutyl-N-[1-diethylphosphono-1-ethyl] nitroxide’’,
includes two consecutive steps. Initially -aminophosphonate was synthesized by reacting tertbutylamine, acetaldehyde, and diethylphosphate. The mixture of tert-butylamine (100 mmol) and
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acetaldehyde (100 mmol) was stirred at 50 OC for 2 h under nitrogen atmosphere. After addition of
diethyl phosphite (150 mmol) at room temperature, the solution was stirred at 50 OC for 24h. The
reaction mixture was then diluted with diethyl ether (200 mL) and washed with HCl solution (5% v/v)
until pH 3. The aqueous phase was extracted with diethyl ether and sodium hydrogen carbonate was
added to this mixture until pH turns 8, which was then extracted with diethyl ether (2 × 60 mL). The
organic phase was separated and dried over anhydrous sodium sulphite. It was then filtered and
concentrated by solvent evaporation under reduced pressure yielding aminophosphonate (1) as colorless
oil with 68% yield. 1H NMR (500 MHz, CDCl3, 293 , ): 1.04 (9H), 1.32 (6H), 1.73 (3H), 2.71 (1H),
4.07 (2H), 4.11 (2H) ppm.
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C NMR (75 MHz, CDCl3, 293 K, ): 16.17, 16.36, 30.17, 49.89, 55.18,
61.8 ppm.
The above obtained -aminophosphonate (50 mmol) was dissolved in 100 mL dichloromethane in a
Schlenk flask and was immersed in an ice-water bath (0 OC). A solution of m-chloroperbenzoic acid
(100 mmol) in dichloromethane (200 mL) was added drop wise to this flask using a pressure equalizing
dropping funnel and stirred at room temperature for 10 h. It was then cooled in an ice-water bath and
saturated solution of sodium bicarbonate was added until the solution became neutral. The organic
phase was further washed with saturated sodium bicarbonate solution, and sodium chloride solution
consecutively, and dried over anhydrous sodiumsulphite. The product was isolated by solvent
evaporation and purified using silica gel chromatography (hexane/ethyl acetate 7:3). The pure phosphonylated nitroxide (2) was obtained as pale yellow-orange oil (71% yield).
Synthesis of carboxybetaine methacrylamide monomers (CBMA). Generally, the carboxybetaine
esters were synthesized by the quaternization reaction between N-[3-(dimethylamino)propyl]
methacrylamide with bromocarboxylate ester, viz, methylbromoacetate, ethyl 4-bromobutyrate and ethyl
6-bromohexanoate yielding CBMA-1, CBMA-3 and CBMA-5 respectively.
For the synthesis of CBMA-1 ester1, N-(3-dimethylaminopropyl)acrylamide (50 mmol), methyl
2
bromoacetate (75 mmol), and acetonitrile (50 mL) were reacted for 3 days at 45
O
C under N2
atmosphere. The product was filtered and then purified by dissolving in methanol and reprecipitated in
diethyl ether. 1H NMR (500 MHz, D2O, 298 K, ): 6.52 (1H, NH), 5.73 (1H, CH=C, trans), 5.34 (1H,
CH=C, cis), 4.04 (2H N+-CH2-CO), 3.89 (3H, O-CH3), 3.43 (2H, N-CH2), 3.41 ( 6H, 6H, N+CH3), 3.24
(2H, CH2-N+), 1.95 (3H, C=CH3), 1.92 (2H, N-C-CH2-C-N)ppm.
C NMR (75 MHz, D2O 298 K, 
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169.17, 167.46, 139.70, 118.676, 62.24, 61.44, 55.02, 54.48, 36.43, 22.37, 18.47 ppm.
For the synthesis of CBMA-3 ester2, N-(3-dimethylaminopropyl)acrylamide (50 mmol), ethyl 4bromobutyrate (60 mmol), and acetonitrile (30 mL) were reacted for 4 days at 60 OC under nitrogen
atmosphere. The compound was formed as a semi solid was dissolved in methanol and precipitated in
diethyl ether. 1H NMR (500 MHz, D2O, 298 K, ): 6.32 (1H, NH), 5.74 (1H, CH=C, trans), 5.37 (1H,
CH=C, cis), 4.05 (2H O-CH2), 3.43 (2H, N-CH2), 3.26 ( 6H, 6H, N+CH3), 3.17-3.14 (4H, CH2-N+ and
N+-CH2), 2.16 (2H, N-C-CH2-C-CO), 2.03 (2H, CH2-CO), 1.96 (3H, C=CH3), 1.92 (2H, N-C-CH2-CN), 1.19 (3H, CH3) ppm.
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C NMR (75 MHz, D2O 298 K,  173.14, 166.97, 139.70, 118.64, 66.26,
62.17, 60.08, 50.98, 36.44, 30.84, 26.50, 21.87, 19.27, 18.45, 14.09 ppm.
For the synthesis of CBMA-5-ester3, N-(3-dimethylaminopropyl) acrylamide (50 mmol), ethyl 6bromohexanoate (55 mmol), and acetonitrile (30 mL) were reacted for five days at 45 OC under nitrogen
atmosphere. The resulting viscous oil was then dissolved in acetone and precipitated in diethyl ether. 1H
NMR (500 MHz, D2O, 298 K, ): 6.24 (1H, NH), 5.74 (1H, CH=C, trans), 5.37 (1H, CH=C, cis), 4.07
(2H O-CH2), 3.41 (2H, N-CH2), 3.26 ( 6H, 6H, N+CH3), 3.14-3.08 (4H, CH2-N+ and N+-CH2), 2.32 (2H,
CH2-CO), 2.07 (2H, N-C-CH2-C-C-C), 1.95 (3H, C=CH3), 1.92 (2H, N-C-CH2-C-N), 1.60 (2H, CH2-CCO), 1.34 (2H, C-C-CH2-C-C), 1.21 (3H, CH3) ppm.
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C NMR (75 MHz, D2O 298 K,  177.54,
161.07, 139.72, 118.66, 64.48, 63.14, 62.21, 51.16, 36.43, 34.53, 26.50, 26,35, 25.03, 21.64, 18.43,
14.24 ppm.
These products were then hydrolyzed by passing their solution in water through a column of
Amberlite IRA-400 (hydroxide form) ion-exchange resin. Water was removed under reduced pressure at
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50 OC and product was then washed with anhydrous acetone and anhydrous ether. The solvent was then
removed under reduced pressure and monomers were dried and stored at 0 OC.
Figure- S1
Figure S1. Thermo gravimetric analysis of initiator and polymer (PolyCBMA-5) bonded silicon wafer
surface. The grafting density was calculated on the basis of TGA weight loss.
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Figure –S2
Figure S2. 1HNMR spectra of [poly(carboxybetaine methacrylamide)] free molecules resulted from
solution polymerization
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Figure –S3
Figure S3. GPC profiles of [poly(carboxybetaine methacrylamide)]. PolyCBMA-5 was formed with the
highest molecular weight.
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References
1.
Kathmann, E. E.; White, L. A.; McCormick, C. L. Polymer 1997, 38, 879.
2.
Kathmann, E. E.; White, L. A.; McCormick, C. L. Polymer 1997, 38, 871.
3.
Kathmann, E. E.; McCormick, C. L. J. Polym. Sci. Part A: Polym. Chem. 1997, 35, 243.
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