Electronic Supplementary Information for
Synthesis of click-reactive HPMA copolymers using RAFT polymerization for drug delivery
applications
Ebbesen MF, Schaffert D, Crowley ML, Oupický D and Howard KA*
3-azidopropan-1-amine
Fig. S1 1H NMR spectrum for 3-azidopropan-1-amine in CDCl3. 1H-NMR (400 MHz, CDCl3): δH
(ppm) = 1.16 (s, 2H, CH2NH2), 1.72 (quintet, 2H, CH2CH2CH2), 2.79 (t, 2H, CH2NH2), 3.37 (t, 2H,
CH2N3).
N-(3-azidopropyl)methacrylamide
Fig. S2 13C NMR spectrum for N-(3-azidopropyl)methacrylamide in CDCl3. 13C NMR (100 MHz,
CDCl3): δC (ppm) = 18.6 (CH3), 28.7 (CH2CH2CH2), 37.4 (CH2NH), 49.6 (CH2N3), 119.6 (C=CH2),
139.9 (C=CH2), 168.6 (C=O).
Fig. S3 1H NMR spectrum for N-(3-azidopropyl)methacrylamide in CDCl3. 1H-NMR (400 MHz,
CDCl3): δH (ppm) = 1.85 (quintet, 2H, CH2CH2CH2), 1.97 (dt, 3H, CH3), 3.45-3.37 (m, 4H,
CH2CH2CH2), 5.34 (m, 1H, CH(E)-C-CH3), 5.69 (m, 1H, CH(Z)-C-CH3), 6.13 (s, 1H, NH).
N-(2-hydroxypropyl)methacrylamide
Fig. S4 1H NMR spectrum for N-(2-hydroxypropyl)methacrylamide in CDCl3. 1H-NMR (400 MHz,
CDCl3): δH (ppm) = 1.21 (dd, 3H, CH(OH)-CH3), 1.97 (s, 3H, C(CH2)CH3)), 2.77 (bs, 1H,
C(OH)H), 3.18 (ddd, 1H, NH-CH2), 3.50 (ddd, 1H, NH-CH2), 3.96 (m, 1H, OH), 5.35 (dq, 1H,
CCH2), 5.73 (dq, 1H, CCH2), 6.32 (br s, 1H, NH).
p(HPMA0.95-co-AzMA0.05) copolymer
Fig. S5 1H NMR spectrum for p(HPMA0.95-co-AzMA0.05). 1H-NMR (400 MHz, D2O): δH (ppm) =
1.0 – 1.6 (m, 6H, CH(OH)-CH3 (HPMA) and backbone CH3), 1.6 – 2.2 (m, 2H, backbone CH2 and
CH2CH2CH2 (AzMA)), 3.10 (m, 1H, C(OH)H (HPMA)), 3.20 (m, 2H, NH-CH2), 3.41 (m, 0.105H,
N3-CH2 (AzMA)), 3.93 (m, 1H, OH (HPMA)), 7.5 - 7.9 (m, 1H, NH).
Prop-2-yn-phosphocholine (PPhCh)
Fig. S6 1H NMR spectrum for PPhCh. 1H-NMR (400 MHz, D2O): δH (ppm) = 2.98 (t, 1H, C≡CH),
3.24 (bs, 9H, N(CH3)3), 3.70 (dt, 2H, (CH3)3N-CH2), 4.36 (m, 2H, CH2-CH2-O), 4.57 (dd, 2H, CCH2).
p(HPMA-co-AzMA)-graft-PhCh with X = 1 eq. PPhCh.
Fig. S7 1H NMR spectrum for p(HPMA0.95-co-AzMA0.05)-graft-PhCh, X = 1 eq. PPhCh. 1H-NMR
(400 MHz, D2O): δH (ppm) = 1.0 – 1.6 (m, CH(OH)-CH3 (HPMA) and backbone CH3), 1.6 – 2.2
(m, backbone CH2 and AzMA CH2CH2CH2), 3.10 (m, C(OH)H (HPMA)), 3.21 (m, NH-CH2), 3.23
(m, N(CH3)3), 3.66 (m, (CH3)3N-CH2), 3.93 (m, OH (HPMA)), 4.28 (m, CH2-CH2-O), 4.50 (m,
CH2-CH2-triazole), 5.05 (m, O-CH2-triazole), 7.5 - 7.9 (m, NH), 8.13 (bs, triazole-H).
1 eq.
3000
2500
0.3 eq.
2000
cm-1
0 eq.
1500
1000
Fig. S8 ATR-FTIR spectrum for p(HPMA0.95-co-AzMA0.05)-graft-PhCh, X = 0, 0.3 and 1 eq.
PPhCh. νmax(ATR-FTIR): 2100 cm−1(N3). The azide related peak gradually diappears with higher
PPhCh amounts.
p(HPMA-co-AzMA)-graft-PEG, X = 0.9 eq. PPEG
Fig. S9 1H NMR spectrum for p(HPMA0.98-co-AzMA0.02) -graft-PEG, X = 0.9 eq. PPEG. 1H-NMR
(400 MHz, D2O): δH (ppm) = 1.0 – 1.6 (m, CH(OH)-CH3 (HPMA) and backbone CH3), 1.6 – 2.2
(m, backbone CH2 and AzMA CH2CH2CH2), 2.46 (m, PEG triazole-CH2), 3.10 (m, C(OH)H
(HPMA)), 3.21 (m, NH-CH2), 3.40 (s, OCH3), 3.72 (m, OCH2 (PEG)), 3.93 (m, OH (HPMA)), 4.43
(m, CH2-CH2-triazole), 7.5 - 7.9 (m, NH), 8.09 (bs, triazole-H).
3.0 eq.
3000
2500
0.9 eq.
2000
cm-1
0.5 eq.
1500
0 eq.
1000
Fig. S10 ATR-FTIR spectrum for p(HPMA0.98-co-AzMA0.02)-graft-PEG, X = 0, 0.5, 0.9 and 3.0 eq.
PPEG. νmax(ATR-FTIR): 2100 cm−1. The azide related peak gradually diappears with higher PPEG
amounts.