High Throughput Preparation of UV-Protective Polymers from Essential Oils Extracts via the Biginelli Reaction

Transcription

1 Supporting Information High Throughput Preparation of UV-Protective Polymers from Essential Oils Extracts via the Biginelli Reaction Tengfei Mao a,b, Guoqiang Liu a, Haibo Wu a, Yen Wei a, Yanzi Gou b, Jun Wang b, Lei Tao* a a The Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing , P. R. China. b Science and Technology on Advanced Ceramic Fibers and Composites Laboratory, National University of Defense Technology, Changsha, , P. R. China. EXPERIMENTAL SECTION 1. Materials All chemicals and solvents were purchased from commercial sources and used without further purification. 2-(Acetoacetoxy)ethyl methacrylate (AEMA, Aladdin, 95%), benzaldehyde (Aladdin, > 99.5%), urea ( Sinopharm Chemical Reagent Co., Ltd, AR), methylurea (TCI, 98%), ethylurea (J&K, AR), thiourea (Sinopharm Chemical Reagent Co., Ltd, AR), methylthiourea (Heowns, 98%), MgCl 2 (Sinopharm Chemical Reagent Co., Ltd, AR, 99%), 3, 4-dimethoxybenzaldehhyde (Sinopharm Chemical Reagent Co., Ltd, AR), p-methoxybenzaldehyde (J&K, 98%), 4-oxy-3-methoxybenzaldehyde (Heowns, 98%), p-isopropylbenzaldehyde (Heowns, 98%), poly (ethylene glycol) methyl ether methacrylate (PEGMA-950, M n ~ 950 S1

2 g mol -1, Sigma-Aldrich), 2,2'-azobisisoheptonitrile (ABVN, Energy Chemical Reagent Co., Ltd, AR), 1,1-diphenyl-2-picrylhydrazyl (DPPH, Alfa Aesar, 97%), Roswell Park Memorial Institute-1640 (RPMI-1640) culture medium (Corning-Cellgro), phosphate buffered saline (PBS, ph~ , 0.01 M, Solarbio), fetal bovine serum (FBS, Gibco), penicillin-streptomycin solution (Gibco), trypsin-edta (Gibco, 0.25%), fluorescein diacetate (FDA, Sigma), propidium iodide (PI, 94%, Sigma), superoxide dismutase (SOD, from bovine erythrocytes, 3000 u/mg, Sigma), Phospho-Histone H2A.X (Ser139) Rabbit Monoclonal Antibody (Bytotime), Alexa Fluor 555-Labeled Donkey Anti-Rabbit IgG (Bytotime), paraformaldehyde (4%, Bytotime), cell sealing solution (Bytotime) and immunostaining permeabilization buffer with Triton X-100 (Bytotime) were used as purchased. 2. Instruments Gel permeation chromatography (GPC) analyses of polymers were performed using N, N-dimethyl formamide (DMF) containing 50 mm LiBr as the eluent. The GPC system was a Shimadzu LC-20AD pump system consisting of an auto injector, a MZ-Gel SDplus 10.0 µm guard column ( mm, 10 2 Å) followed by two PLgel 5 µm MIXED-D columns ( mm), a Shimadzu RID-10A refractive index detector. The system was calibrated with narrow molecular weight distribution polystyrene standards ranging from 200 to 10 6 g mol H NMR and 13 C NMR spectra were obtained using a JEOL JNM-ECA400 (400 MHz) spectrometer for all samples. The ESI-MS data were collected using a Micro TOF-QII Bruker. The FT-IR spectra S2

3 were recorded in a transmission mode on a Perkin-Elmer Spectrum 100 spectrometer (Waltham, MA, USA). Differential scanning calorimetry (DSC) was performed using TA instruments Q2000 operated at a scanning rate of 10 C/min. Thermal gravimetric analysis (TGA) was conducted on a TA instrument Q50 with a heating rate of 20 C/min. UV-Visible absorption spectra were recorded on a UV/Vis/NIR Perkin-Elmer lambda750 spectrometer (Waltham, MA, USA) using quartz cuvettes of 1 cm path length. The flow cytometry analyses were performed on a BD FACS Aria III flow cytometer. 3. Methods (Methacryloyloxy) ethyl 6-methyl-4-phenyl-dihydropyrimidin-2(1H)-one-5-carboxylate (M(1)(1)) The monomers (M(X)(Y)) were prepared simultaneously in an isothermal shaker via the HTP Biginelli reaction by different combinations of aromatic aldehydes and urea/thiourea derivatives. Typically, benzaldehyde (212 mg, 2.0 mmol), acetoacetoxy ethyl methacrylate (AEMA) (428 mg, 2.0 mmol), and urea (180 mg, 3.0 mmol) were put in a 3 ml centrifuge tube. Then, acetic acid (1.0 ml) and magnesium chloride (38 mg, 0.40 mmol) were added. The tube was sealed and put in a shaker (100 o C) for 2 h. At the end of reaction, reaction mixture (~ µl) was taken and used immediately for 1 H NMR analysis to calculate the conversion of the Biginelli reaction. The remaining crude was decanted into cold water, then washed three times by water and S3

4 then diethyl ether to get the final functional monomer M(1)(1) as a white powder (572 mg, yield: 83.2%). 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 9.26 (s, 1H, NHCCH 3 ), 7.77 (d, J = 3.4 Hz, 1H, NHCH), (m, 5H, Ph), 5.96 (s, 1H, CH 2 =C), 5.66 (s, 1H, CH 2 =C), 5.13 (d, J = 3.4 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 2.24 (s, 3H, NHCCH 3 ), 1.83(s, 3H, CH 3 C=CH 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , 98.92, 62.60, 61.27, 53.87, 17.97, IR (ν/cm 1 ): 3229, 3108, 2937, 1706, 1644, 1423, 1277, 1227, 1156, 1089, 1045, 1031, 950, 801, 726, 683. ESI-MS: observed (expected): ( ) [M + Na + ]. All other monomers were prepared through the same procedure (Methacryloyloxy) ethyl 4-(4-hydroxy-3-methoxyphenyl)-6-methyl-dihydropyrimidin-2(1H)-one -5-carboxylate (M(2)(1)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 9.26 (s, 1H, NHCCH 3 ), 8.98 (s, 1H, PhOH), 7.66 (d, J = 2.9 Hz, 1H, NHCH), 6.78 (s, 1H, Ph), 6.66 (d, J = 8.1 Hz, 1H, Ph), 6.58 (d, J = 8.1 Hz, 1H, Ph), 5.94 (s, 1H, CH 2 =C), 5.65 (s, 1H, CH 2 =C), 5.03 (d, J = 2.9 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.70 (s, 3H, PhOCH 3 ), 2.24 (s, 3H, S4

5 NHCCH 3 ), 1.83 (s, 3H, CH 3 C=CH 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , , 99.13, 62.57, 55.59, 53.52, 17.93, IR (ν/cm 1 ): 3250, 3120, 2942, 1706, 1644, 1522, 1450, 1371, 1284, 1226, 1155, 1093, 1032, 943, 861, 779. ESI-MS: observed (expected): ( ) [M + H + ] (Methacryloyloxy) ethyl 4-(3, 4-dimethoxyphenyl)-6-methyl-dihydropyrimidin-2(1H)-one -5-carboxylate (M(3)(1)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 9.21 (s, 1H, NHCCH 3 ), 7.70 (d, J = 3.2 Hz, 1H, NHCH), 6.84 (s, 1H, Ph), 6.82 (d, J = 2.0 Hz, 1H, Ph), 6.69 (d, J = 2.0 Hz, 1H, Ph), 5.92 (s, 1H, CH 2 =C), 5.64 (s, 1H, CH 2 =C) 5.07 (d, J = 3.2 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.82 (s, 3H, Ph-p-OCH 3 ), 3.78 (s, 3H, Ph-m-OCH 3 ), 2.24 (s, 3H, NHCCH 3 ), 1.81 (s, 3H, CH 3 C=CH 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , 98.73, 62.40, 61.07, 55.42, 55.28, 53.30, 17.74, IR (ν/cm 1 ): 3236, 3107, 2950, 1701, 1647, 1509, 1449, 1224, 1148, 1080, 1025, 950, S5

6 862, 800, 752. ESI-MS: observed (expected): ( ) [M + H + ] (Methacryloyloxy) ethyl 4-(4-methoxyphenyl)-6-methyl-dihydropyrimidin-2(1H)-one -5-carboxylate (M(4)(1)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 9.26 (s, 1H, NHCCH 3 ), 7.77 (d, J = 3.3 Hz, 1H, NHCH), 7.13 (d, J = 8.7 Hz, 2H, Ph), 6.83 (d, J = 8.7 Hz, 2H, Ph), 5.95 (s, 1H, CH 2 =C), 5.66 (s, 1H, CH 2 =C), 5.08 (d, J = 3.3 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.71 (s, 3H, PhOCH 3 ), 2.24 (s, 3H, NHCCH 3 ), 1.83 (s, 3H, CH 3 C=CH 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , 99.18, 62.60, 61.20, 55.08, 53.27, 17.93, IR (ν/cm 1 ): 3236, 3108, 2956, 1708, 1647, 1510, 1455, 1223, 1169, 1087, 1027, 950, 889, 821, 746. ESI-MS: observed (expected): ( ) [M + H + ] (Methacryloyloxy) ethyl 4-(4-isopropylphenyl)-6-methyldihydropyrimidin-2(1H)-one -5-carboxylate (M(5)(1)) S6

7 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 9.24 (s, 1H, NHCCH 3 ), 7.72 (d, J = 3.3 Hz, 1H, NHCH), (m, 4H, Ph), 5.95 (s, 1H, CH 2 =C), 5.67 (s, 1H, CH 2 =C), 5.09 (d, J = 3.3 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 2.82 (m, 1H, PhCH(CH 3 ) 2 ), 2.24 (s, 3H, NHCCH 3 ), 1.83 (s, 3H, CH 3 C=CH 2 ), 1.15 (d, J = 6.8 Hz, 6H, PhCH(CH 3 ) 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , 99.08, 62.63, 61.26, 53.54, 33.14, 23.92, 23.89, 17.97, IR (ν/cm 1 ): 3216, 3114, 2964, 1701, 1640, 1449, 1285, 1224, 1162, 1094, 1046, 950, 813, 691. ESI-MS: observed (expected): ( ) [M + H + ] (Methacryloyloxy) ethyl 6-methyl-4-phenyl-dihydropyrimidin-2(1H)-thione-5-carboxylate (M(1)(2)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): (s, 1H, NHCCH 3 ), 9.70 (d, J = 3.7 Hz, 1H, NHCH), (m, 5H, Ph), 5.95 (s, 1H, CH 2 =C), 5.66 (s, 1H, CH 2 =C), 5.16 (d, J = 3.7 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 2.28 (s, 3H, NHCCH 3 ), S7

8 1.83 (s, 3H, CH 3 C=CH 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , 62.50, 61.60, 53.96, 17.95, IR (ν/cm 1 ): 3305, 3175, 2971, 1701, 1633, 1558, 1449, 1374, 1312, 1169, 1094, 943, 875, 821, 766, 698. ESI-MS: observed (expected): ( ) [M + H + ] (Methacryloyloxy) ethyl 4-(4-hydroxy-3-methoxyphenyl)-6-methyl-dihydropyrimidin-2(1H)-thione -5-carboxylate (M(2)(2)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): (s, 1H, NHCCH 3 ), 9.71 (d, J = 4.8 Hz, 1H, NHCH), 8.98 (s, 1H, PhOH), 6.72 (s, 1H, Ph), 6.64 (d, J = 8.1 Hz, 1H, Ph), 6.53 (d, J = 8.1 Hz, 1H, Ph), 5.95 (s, 1H, CH 2 =C), 5.66 (s, 1H, CH 2 =C), 5.07 (d, J = 4.8 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.70 (s, 3H, PhOCH 3 ), 2.24 (s, 3H, NHCCH 3 ), 1.83 (s, 3H, CH 3 C=CH 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , , 99.03, 62.90, 55.68, 53.50, 17.29, IR (ν/cm 1 ): 3302, 3189, 2959, 1706, 1644, 1608, 1565, 1512, 1452, 1375, 1271, 1173, 1096, 1029, 944, 852, 779, 730. S8

9 ESI-MS: observed (expected): ( ) [M + Na + ] (Methacryloyloxy) ethyl 4-(3, 4-dimethoxyphenyl)-6-methyl-dihydropyrimidin-2(1H)-thione -5-carboxylate (M(3)(2)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): (s, 1H, NHCCH 3 ), 9.62 (d, J = 3.5 Hz, 1H, NHCH), 6.85(s, 1H, Ph), 6.80 (d, J = 2.0 Hz, 1H, Ph), 6.67 (d, J = 2.0 Hz, 1H, Ph), 5.90 (s, 1H, CH 2 =C), 5.63 (s, 1H, CH 2 =C), 5.09 (d, J = 3.5 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.72 (s, 3H, Ph-p-OCH 3 ), 3.70 (s, 3H, Ph-m-OCH 3 ), 2.28 (s, 3H, NHCCH 3 ), 1.82 (s, 3H, CH 3 C=CH 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , 62.30, 61.40, 55.51, 55.26, 52.66, 17.74, IR (ν/cm 1 ): 3306, 3169, 2955, 1716, 1693, 1639, 1570, 1512, 1453, 1385, 1320, 1298, 1260, 1231, 1180, 1154, 1023, 943, 854, 811, 767, 732. ESI-MS: observed (expected): ( ) [M + H + ] (Methacryloyloxy) ethyl 4-(4-methoxyphenyl)-6-methyl-dihydropyrimidin-2(1H)-thione -5-carboxylate (M(4)(2)) S9

10 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): (s, 1H, NHCCH 3 ), 9.62 (d, J = 3.7 Hz, 1H, NHCH), 7.09 (d, J = 8.7 Hz, 2H, Ph), 6.84 (d, J = 8.7 Hz, 2H, Ph), 5.93 (s, 1H, CH 2 =C), 5.66 (s, 1H, CH 2 =C), 5.09 (d, J = 3.7 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.70 (s, 3H, PhOCH 3 ), 2.27 (s, 3H, NHCCH 3 ), 1.81 (s, 3H, CH 3 C=CH 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , 62.50, 61.53, 55.17, 53.25, 17.29, IR (ν/cm 1 ): 3294, 3177, 2955, 1712, 1643, 1608, 1564, 1510, 1455, 1380, 1310, 1245, 1167, 1092, 1029, 947, 886, 832, 789, 755. ESI-MS: observed (expected): ( ) [M + H + ] (Methacryloyloxy) ethyl 4-(4-isopropylphenyl)-6-methyldihydropyrimidin-2(1H)-thione -5-carboxylate (M(5)(2)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): (s, 1H, NHCCH 3 ), 9.70 (d, J = 3.6 Hz, 1H, NHCH), (m, 4H, Ph), 5.95 (s, 1H, CH 2 =C), 5.66 (s, 1H, CH 2 =C), 5.13 S10

11 (d, J = 3.6 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 2.84 (m, 1H, PhCH(CH 3 ) 2 ), 2.24 (s, 3H, NHCCH 3 ), 1.83 (s, 3H, CH 3 C=CH 2 ), 1.17 (d, J = 6.9 Hz, 6H, PhCH(CH 3 ) 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , 62.53, 61.59, 53.63, 33.12, 23.28, 23.39, 17.79, IR (ν/cm 1 ): 3299, 3173, 2959, 1703, 1647, 1655, 1512, 1471, 1437, 1376, 1302, 1272, 1245, 1171, 1126, 1088, 1025, 936, 880, 856, 813, 771, 711. ESI-MS: observed (expected): ( ) [M + H + ] (Methacryloyloxy) ethyl 1, 6-dimethyl-4-phenyl-dihydropyrimidin-2(1H)-thione-5-carboxylate (M(1)(3)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 7.99 (d, J = 3.9 Hz, 1H, NHCH), (m, 5H, Ph), 5.95 (1H, CH 2 =C), 5.66 (s, 1H, CH 2 =C), 5.15 (d, J = 3.9 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.10 (s, 3H, NCH 3 ), 2.24 (s, 3H, NCCH 3 ), 1.83 (s, 3H, CH 3 C=CH 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , 62.97, 61.99, 52.69, 30.24, 18.36, IR (ν/cm 1 ): 3213, 3101, 2932, 1700, 1607, 1450, 1384, 1348, 1322, 1280, 1247, S11

12 1171, 1139, 1077, 962, 765, 706. ESI-MS: observed (expected): ( ) [M + H + ] (Methacryloyloxy) ethyl 4-(4-hydroxy-3-methoxyphenyl)-1, 6-dimethyl-dihydropyrimidin-2(1H)-one -5-carboxylate (M(2)(3)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 8.89 (s, 1H, PhOH), 7.88 (d, J = 3.8 Hz, 1H, NHCH), 6.75 (s, 1H, Ph), 6.65 (d, J = 8.0 Hz, 1H, Ph), 6.56 (d, J = 8.0 Hz, 1H, Ph), 5.95 (s, 1H, CH 2 =C), 5.66 (s, 1H, CH 2 =C), 5.05 (d, J = 3.8 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.70 (s, 3H, PhOCH 3 ), 3.10 (s, 3H, NCH 3 ), 2.24 (s, 3H, NCCH 3 ), 1.83 (s, 3H, CH 3 C=CH 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , , 99.50, 63.29, 55.09, 52.34, 30.44, 18.56, IR (ν/cm 1 ): 3342, 3088, 2955, 1719, 1701, 1675, 1625, 1512, 1463, 1429, 1377, 1345, 1319, 1275, 1195, 1141, 1089, 1032, 979, 865, 763, 733, 674. ESI-MS: observed (expected): ( ) [M + H + ] (Methacryloyloxy) ethyl 4-(3, 4-dimethoxyphenyl)-1, 6-dimethyl-dihydropyrimidin-2(1H)-one -5-carboxylate (M(3)(3)) S12

13 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 7.93(d, J = 3.8 Hz, 1H, NHCH), 6.82 (s, 1H, Ph), 6.78 (d, J = 2.1 Hz, 1H, Ph), 6.67 (d, J = 2.1 Hz, 1H, Ph), 5.95 (s, 1H, CH 2 =C), 5.66 (s, 1H, CH 2 =C), 5.09 (d, J = 3.8 Hz, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.70 (s, 3H, Ph-p-OCH 3 ), 3.69 (s, 3H, Ph-m-OCH 3 ), 3.10 (s, 3H, NCH 3 ), 2.24 (s, 3H, NCCH 3 ), 1.83 (s, 3H, CH 3 C=CH 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , 62.77, 61.79, 55.45, 55.22, 53.13, 30.45, 18.86, IR (ν/cm 1 ): 3224, 3103, 2936, 1711, 1679, 1633, 1514, 1440, 1387, 1348, 1303, 1262, 1233, 1180, 1137, 1080, 1063, 1028, 979, 936, 859, 803, 757, 669. ESI-MS: observed (expected): ( ) [M + Na + ] (Methacryloyloxy) ethyl 4-(4-methoxyphenyl)-1, 6-dimethyl-dihydropyrimidin-2(1H)-one -5-carboxylate (M(4)(3)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 7.92 (d, J = 3.8 Hz, 1H, NHCH), 7.10 (d, J = 8.7 Hz, 2H, Ph), 6.81 (d, J = 8.7 Hz, 2H, Ph), 5.95 (1H, CH 2 =C), 5.66 (1H, CH 2 =C), S13

14 5.08 (d, J = 3.8 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.70 (s, 3H, PhOCH 3 ), 3.10 (s, 3H, NCH 3 ), 2.24 (s, 3H, NCCH 3 ), 1.83 (s, 3H, CH 3 C=CH 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , 62.97, 61.92, 55.20, 53.40, 30.54, 18.26, IR (ν/cm 1 ): 3225, 3097, 2956, 1710, 1681, 1612, 1506, 1450, 1418, 1381, 1325, 1298, 1280, 1243, 1171, 1150, 1083, 1030, 974, 939, 844, 814, 780, 750. ESI-MS: observed (expected): ( ) [M + Na + ] (Methacryloyloxy) ethyl 4-(4-isopropylphenyl)-1, 6-dimethyl-dihydropyrimidin-2(1H)-one -5-carboxylate (M(5)(3)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 7.97 (d, J = 3.8 Hz, 1H, NHCH), (m, 4H, Ph), 5.95 (s, 1H, CH 2 =C), 5.66 (s, 1H, CH 2 =C), 5.13 (d, J = 3.8 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.10 (s, 3H, NCH 3 ), 2.82 (m, 1H, PhCH(CH 3 ) 2 ), 2.24 (s, 3H, NCCH 3 ), 1.83 (s, 3H, CH 3 C=CH 2 ), 1.15 (d, J = 6.0 Hz, 6H, PhCH(CH 3 ) 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , 63.00, 61.98, 52.36, 34.24, 30.74, 24.01, 23.89, 18.87, IR (ν/cm 1 ): 3231, 3097, 2662, 1726, 1706, 1676, 1625, 1423, 1383, 1351, 1296, 1274, S14

15 1242, 1187, 1139, 1083, 1064, 1041, 970, 953, 895, 880, 862, 845, 819, 765. ESI-MS: observed (expected): ( ) [M + Na + ] (Methacryloyloxy) ethyl 1, 6-dimethyl-4-phenyl-dihydropyrimidin-2(1H)-thione-5-carboxylate (M(1)(4)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 9.89 (d, J = 4.7 Hz, 1H, NHCH), (m, 5H, Ph), 5.95 (s, 1H, CH 2 =C), 5.66 (s, 1H, CH 2 =C), 5.13 (d, J = 4.7 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.48 (s, 3H, NCH 3 ), 2.24 (s, 3H, NCCH 3 ), 1.83 (s, 3H, CH 3 C=CH 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , 62.45, 62.08, 52.00, 36.28, 17.94, IR (ν/cm 1 ): 3325, 3189, 2943, 1708, 1626, 1518, 1449, 1380, 1353, 1285, 1244, 1148, 1066, 943, 884, 827, 752, 698. ESI-MS: observed (expected): ( ) [M + Na + ] (Methacryloyloxy) ethyl 4-(4-hydroxy-3-methoxyphenyl)-1, 6-dimethyl-dihydropyrimidin-2(1H)-thione -5-carboxylate (M(2)(4)) S15

16 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 9.79 (d, J = 4.6 Hz, 1H, NHCH), 8.97 (s, 1H, PhOH), 6.73 (s, 1H, Ph), 6.66 (d, J = 8.1 Hz, 1H, Ph), 6.55 (d, J = 8.1 Hz, 1H, Ph), 5.95 (s, 1H, CH 2 =C), 5.66 (s, 1H, CH 2 =C), 5.09 (d, J = 4.6 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.70 (s, 3H, PhOCH 3 ), 3.48 (s, 3H, NCH 3 ), 2.24 (s, 3H, NCCH 3 ), 1.82 (s, 3H, CH 3 C=CH 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , 98.98, 63.38, 62.08, 54.40, 58.38, 30.02, 18.35, IR (ν/cm 1 ): 3334, 3202, 2959, 1709, 1629, 1512, 1451, 1429, 1380, 1350, 1320, 1271, 1151, 1076, 1029, 945, 860, 815, 775, 733. ESI-MS: observed (expected): ( ) [M + H + ] (Methacryloyloxy) ethyl 4-(3, 4-dimethoxyphenyl)-1, 6-dimethyl-dihydropyrimidin-2(1H)-thione -5-carboxylate (M(3)(4)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 9.82 (d, J = 4.6 Hz, 1H, NHCH), 6.83 (s, 1H, Ph), 6.78 (d, J = 2.1 Hz, 1H, Ph), 6.66 (d, J = 2.1 Hz, 1H, Ph), 5.91 (s, 1H, CH 2 =C), 5.63 (s, 1H, CH 2 =C), 5.12 (d, J = 4.6 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.83 (s, 3H, Ph-p-OCH 3 ), 3.75 (s, 3H, Ph-m-OCH 3 ), 3.48 (s, 3H, NCH 3 ), 2.20 (s, 3H, NCCH 3 ), 1.80 (s, 3H, CH 3 C=CH 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , S16

17 135.37, , , , , , 62.25, 61.88, 54.76, 61.26, 52.71, 30.24, 18.86, IR (ν/cm 1 ): 3330, 3197, 2955, 1709, 1627, 1511, 1452, 1417, 1380, 1349, 1295, 1256, 1141, 1078, 1022, 946, 861, 812, 765, 702. ESI-MS: observed (expected): ( ) [M + Na + ] (Methacryloyloxy) ethyl 4-(4-methoxyphenyl)-1, 6-dimethyl-dihydropyrimidin-2(1H)-thione -5-carboxylate (M(4)(4)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 9.82 (d, J = 4.6 Hz, 1H, NHCH), 7.09 (d, J = 8.7 Hz, 2H, Ph), 6.83 (d, J = 8.7 Hz, 2H, Ph), 5.95 (s, 1H, CH 2 =C), 5.66 (s, 1H, CH 2 =C), 5.12 (d, J = 4.6 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.71 (s, 3H, PhOCH 3 ), 3.48 (s, 3H, NCH 3 ), 2.20 (s, 3H, NCCH 3 ), 1.81 (s, 3H, CH 3 C=CH 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , 62.45, 62.01, 54.51, 59.44, 30.12, 18.05, IR (ν/cm 1 ): 3326, 3197, 2955, 1707, 1627, 1509, 1442, 1382, 1347, 1295, 1247, 1149, 1076, 1029, 943, 885, 814, 779, 754, 702. ESI-MS: observed (expected): ( ) [M + H + ] (Methacryloyloxy) ethyl 4-(4-isopropylphenyl)-1, 6-dimethyl-dihydropyrimidin-2(1H)-thione -5-carboxylate (M(5)(4)) S17

18 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 9.83 (d, J = 4.6 Hz, 1H, NHCH), (m, 4H, Ph), 5.95 (s, 1H, CH 2 =C), 5.66 (s, 1H, CH 2 =C), 5.15 (d, J = 4.6 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.48 (s, 3H, NCH 3 ), 2.82 (m, 1H, PhCH(CH 3 ) 2 ), 2.24 (s, 3H, NCCH 3 ), 1.83 (s, 3H, CH 3 C=CH 2 ), 1.15 (d, J = 6.9 Hz, 6H, PhCH(CH 3 ) 2 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , 62.48, 62.07, 51.67, 40.28, 30.32, 23.80, 23.95, 18.95, IR (ν/cm 1 ): 3330, 3177, 2959, 1707, 1633, 1548, 1510, 1443, 1422, 1385, 1356, 1342, 1318, 1293, 1243, 1166, 1144, 1076, 954, 876, 856, 818, 779, 744. ESI-MS: observed (expected): ( ) [M + Na + ] (Methacryloyloxy) ethyl 1-ethyl-6-methy-4-phenyl-dihydropyrimidin-2(1H)-thione-5-carboxylate (M(1)(5)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 7.93 (d, J = 3.6 Hz, 1H, NHCH), (m, 5H, Ph), 5.95 (s, 1H, CH 2 =C), 5.67 (s, 1H, CH 2 =C), 5.13 (d, J = 3.6 Hz, 1H, S18

19 NHCH), (m, 4H, COOCH 2 CH 2 ), 3.80 (dd, J 1 =14.4 Hz, J 2 = 7.0 Hz, 2H, NCH 2 CH 3 ), 2.24 (s, 3H, NCCH 3 ), 1.83 (s, 3H, CH 3 C=CH 2 ), 1.07 (t, J = 7.0 Hz, 3H, NCH 2 CH 3 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , 62.56, 61.62, 52.48, 37.05, 17.97, 15.59, IR (ν/cm 1 ): 3218, 3107, 2950, 1698, 1606, 1450, 1391, 1322, 1267, 1230, 1171, 1142, 1087, 997, 950, 889, 853, 791, 765, 706. ESI-MS: observed (expected): ( ) [M + Na + ] (Methacryloyloxy) ethyl 4-(4-hydroxy-3-methoxyphenyl)-1-ethyl-6-methy-dihydropyrimidin-2(1H)-one -5-carboxylate (M(2)(5)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 8.89 (s, 1H, PhOH), 7.80 (d, J = 3.5 Hz, 1H, NHCH), 6.73 (s, 1H, Ph), 6.64 (d, J = 8.0 Hz, 1H, Ph), 6.55 (d, J = 8.0 Hz, 1H, Ph), 5.95 (s, 1H, CH 2 =C), 5.66 (s, 1H, CH 2 =C), 5.10 (d, J = 3.5 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.80 (dd, J 1 = 9.6 Hz, J 2 = 7.1 Hz, 2H, NCH 2 CH 3 ), 3.79 (s, 3H, PhOCH 3 ), 2.24 (s, 3H, NCCH 3 ), 1.83 (s, 3H, CH 3 C=CH 2 ), 1.07 (t, J = 7.1 Hz, 3H, NCH 2 CH 3 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , S19

20 145.89, , , , , , , 99.09, 62.92, 61.50, 55.08, 53.52, 37.05, 17.92, 15.70, IR (ν/cm 1 ): 3221, 3096, 2959, 1717, 1669, 1511, 1451, 1379, 1320, 1271, 1227, 1147, 1080, 1033, 949, 864, 811, 757, 719. ESI-MS: observed (expected): ( ) [M + Na + ] (Methacryloyloxy) ethyl 4-(3, 4-dimethoxyphenyl)-1-ethyl-6-methy-dihydropyrimidin-2(1H)-one -5-carboxylate (M(3)(5)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 7.85 (d, J = 3.5 Hz, 1H, NHCH), 6.82 (s, 1H, Ph), 6.78 (d, J = 2.0 Hz, 1H, Ph), 6.68 (d, J = 2.0 Hz, 1H, Ph), 5.95 (s, 1H, CH 2 =C), 5.66 (s, 1H, CH 2 =C), 5.06 (d, J = 3.5 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.80 (dd, J 1 = 15.2 Hz, J 2 = 7.0 Hz, 2H, NCH 2 CH 3 ), 3.70 (s, 3H, Ph-p-OCH 3 ), 3.68 (s, 3H, Ph-m-OCH 3 ), 2.24 (s, 3H, NCCH 3 ), 1.83(s, 3H, CH 3 C=CH 2 ), 1.07 (t, J = 7.0 Hz, 3H, NCH 2 CH 3 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , 62.36, 61.42, 54.91, 54.23, 53.21, 36.95, 17.86, 15.62, IR (ν/cm 1 ): 3229, 3100, 2955, 1713, 1680, 1512, 1449, 1387, 1315, 1255, 1225, 1138, 1082, 1026, 974, 858, 812, 759, 719. S20

21 ESI-MS: observed (expected): ( ) [M + Na + ] (Methacryloyloxy) ethyl 4-(4-methoxyphenyl)-1-ethyl-6-methy-dihydropyrimidin-2(1H)-one -5-carboxylate (M(4)(5)) 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 7.85 (d, J = 3.6 Hz, 1H, NHCH), 7.10 (d, J = 8.8 Hz, 2H, Ph), 6.82 (d, J = 8.8 Hz, 2H, Ph), 5.95 (s, 1H, CH 2 =C), 5.66 (s, 1H, CH 2 =C), 5.06 (d, J = 3.6 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.80 (m, 2H, NCH 2 CH 3 ), 3.70 (s, 3H, PhOCH 3 ), 2.24 (s, 3H, NCCH 3 ), 1.82 (s, 3H, CH 3 C=CH 2 ), 1.07 (t, J = 7.0 Hz, 3H, NCH 2 CH 3 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , 62.56, 61.55, 54.57, 53.07, 37.02, 17.98, 15.82, IR (ν/cm 1 ): 3228, 3107, 2983, 1709, 1679, 1604, 1512, 1454, 1423, 1391, 1319, 1253, 1227, 1141, 1082, 1034, 994, 949, 817, 778, 756. ESI-MS: observed (expected): ( ) [M + Na + ] (Methacryloyloxy) ethyl 4-(4-isopropylphenyl)-1-ethyl-6-methy-dihydropyrimidin-2(1H)-one -5-carboxylate (M(5)(5)) S21

22 1 H NMR (400 MHz, DMSO-d 6, δ/ppm): 7.85 (d, J = 3.6 Hz, 1H, NHCH), (m, 4H, Ph), 5.95 (s, 1H, CH 2 =C), 5.66(s, 1H, CH 2 =C), 5.08 (d, J = 3.6 Hz, 1H, NHCH), (m, 4H, COOCH 2 CH 2 ), 3.80 (dd, J 1 = 14.4 Hz, J 2 = 7.1 Hz, 2H, NCH 2 CH 3 ), 2.82 (m, 1H, PhCH(CH 3 ) 2 ), 2.24 (s, 3H, NCCH 3 ), 1.83 (s, 3H, CH 3 C=CH 2 ), 1.15 (d, J = 6.9 Hz, 6H, PhCH(CH 3 ) 2 ), 1.02 (t, J = 7.1 Hz, 3H, NCH 2 CH 3 ). 13 C-NMR (100 MHz, DMSO-d 6, δ/ppm): , , , , , , , , , , , 62.59, 61.61, 53.22, 37.62, 34.04, 24.05, 23.98, 17.95, 15.63, IR (ν/cm 1 ): 3228, 3101, 2963, 1715, 1673, 1617, 1515, 1453, 1391, 1322, 1279, 1230, 1171, 1141, 1081, 993, 948, 837, 814, 762, 715. ESI-MS: observed (expected): ( ) [M + Na + ] HTP preparation of polymers (P(X)(Y)) The polymers (P(X)(Y)) were prepared through HTP radical polymerization of M(X)(Y). Typically, M(1)(1) (0.69 g, 2.0 mmol), ABVN (0.01 g, 0.04 mmol) were charged into a 15 ml centrifuge tube along with DMF (2.0 ml). The tube was sealed with a rubber septum and purged by nitrogen flow for 15 min and then put into an isothermal shaker (70 C) for 14 h. The polymerization was quenched by putting the test tube into an ice-water bath. Sample (~ µl) was taken for 1 H NMR and GPC S22

23 analyses. The polymer was purified by precipitation in diethyl ether for three times and then dried under vacuum as a white powder (P(1)(1)) (0.62 g, ~ 90%). The other polymers were simultaneously prepared through the same procedure Copolymerization of M(1)(2) and PEGMA. M(1)(2) (0.36 g, 1.0 mmol), PEGMA-950 (0.95g, 1.0 mmol), ABVN (0.01 g, 0.04 mmol) were charged into a dry Schlenk tube along with DMF (2.0 ml). The Schlenk tube was sealed with a rubber septum and purged by nitrogen flow for 15 min, then put into a 70 o C oil bath for 12 h. At the end of the polymerization, the mixture was precipitated in diethyl ether 3 times, and then dried under vacuum to obtain a viscous yellowish copolymer P(1)(2)-co-P(PEGMA) for further characterization and use (1.12 g, ~ 85%). Copolymers P(1)(4)-co-P(PEGMA), P(2)(4)-co-P(PEGMA), P(4)(2)-co-P(PEGMA), and P(4)(4)-co-P(PEGMA) were similarly prepared HTP analysis of the radical scavenging ability of polymers Polymer solutions (200 µl, 5 mg/ml in DMSO) were added in a 96-well plate, DMSO (200 µl) was used as the control. Then, the solution of radical (DPPH radical as a model) (20 µl, 5 mg/ml in DMSO) was added to each polymer solution and the control. The 96-well plate was kept at 25 C with gentle shaking and taken photos every 5 min. S23

24 To quantitatively analyze the kinetics of scavenging reaction between DPPH radical and the polymers, the polymer and DPPH solutions were mixed as abovementioned, then the mixtures (20 µl) were diluted with DMSO (100 µl), and the absorbance values of the mixtures, which are proportional to the concentrations of DPPH radical, were recorded on a UV/Vis/NIR Perkin-Elmer lambda750 spectrometer at 520 nm every 2 min. Each sample was tested three times in parallel, and the absorbance data were present as Mean ± SD Cell Culture L929 cells are a fibroblast cell line from mice. They were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin and streptomycin. Cells were incubated at 37 C, 5% CO 2. Culture medium was changed every two days to maintain the exponential growth of the cells Cytotoxicity and UV-resistant evaluation The cytotoxicity and the UV-resistant capability of different polymers to L929 cells were evaluated by a cell count kit-8 (CCK-8) assay. Briefly, cells (~ cells/ml) were seeded in two 96-well plates (plate A and plate B) in culture medium (100 µl, 10% FBS and 1% penicillin and streptomycin). After attachment, cells were washed with PBS and added culture medium containing different concentrated polymers. Cells in plate A were cultured for 24 h, washed with PBS three times, then incubated in 100 µl of culture medium containing 10% CCK-8 solution at 37 o C for 2 h. The plate was put into a microplate reader (VICTORTM X3 PerkinElmer 2030 S24

25 Multilabel Plate Reader) to record the absorbance (450 nm). The absorbance values of cells in pure culture medium were defined as 100% viability, and culture medium without cells were defined as 0%. The data were present as Mean ± SD (n = 5) to indicate the cytotoxicity of different polymers to L929 cells. Statistical analyses (SPSS 15.0) of results were performed by Student s t-test for independent samples. Values of P < 0.05 were considered significant. Cells in plate B were put under a UV sterilamp (~ 254 nm, 40 W) for 15 min (300 ± 20 µw/cm 2 ), then cultured for 24 h. The viability of cells was analyzed through a CCK-8 assay as abovementioned. The data were present as Mean ± SD (n = 5) to reflect the UV-resistant capability of different polymers. The viability of cells in pure culture medium without UV irradiation was defined as 100%. Statistical analyses (SPSS 15.0) of results were performed by Student s t-test for independent samples. Values of P < 0.05 were considered significant Cell-protection ability of selected copolymer in comparison with superoxide dismutase (SOD) L929 cells (~ cells/ml) were added copolymer P(1)(4)-co-P(PEGMA) (10 mg/ml in 100 µl of culture medium) and exposed to a UV sterilamp for 15 min (300 ± 20 µw/cm 2 ). Then, the cells were cultured for 24 h and added the PBS-FDA-PI mixed solution (FDA: 3 µg/ml; PI: 3 µg/ml, 100 µl) to simultaneously observe the live and dead cells through nm and nm band-pass excitation filters (I3 and N2.1). CCK-8 assay was also performed to quantitatively evaluate the cell viability. Cells cultured with SOD (10 mg/ml) were used as the control. Cells in S25

26 culture medium only without UV irradiation were used as the blank. Different UV irradiation time (30 min, 45 min, 300 ± 20 µw/cm 2 ) to cells cultured with P(1)(4)-co-P(PEGMA) (10 mg/ml in 100 µl of culture medium) was also performed, and the cells were analyzed through the same procedure Staining of the damaged DNA The red fluorescent antibody (Alexa Fluor 555) was used to detect damaged DNA (phosphorylation of H2AX) in cells before/after UV irradiation. L929 cells (~ cells/ml) were added copolymer P(1)(4)-co-P(PEGMA) (10 mg/ml in 100 µl of culture medium), then exposed to a UV sterilamp for 15 min (300 ± 20 µw/cm 2 ). The cells were cultured for another 24 h, then immobilized with 4% paraformaldehyde solution for 15 min. After washing three times by PBS, cells were sealed by a sealing solution for 1 h, then kept in the primary antibody solution (Phospho-Histone H2A.X (Ser139) Rabbit Monoclonal Antibody; 1/500 dilution) for 1 h. The cells were washed three times by PBS, then incubated with the Alexa Fluor 555 labeled secondary antibody (Alexa Fluor 555-Labeled Donkey Anti-Rabbit IgG; 1/500 dilution) for 1 h. The cells were washed by PBS three times, then imaged by a fluorescence microscope (Leica Germany; nm band-pass excitation filters). L929 cells in culture medium were treated by same process as the control. The damaged DNA in cells before UV irradiation was stained through the same assay Flow cytometry analyses of the damaged DNA L929 cells (~ cells/ml) were added copolymer P(1)(4)-co-P(PEGMA) (10 mg/ml in 100 µl of culture medium), exposed to a UV sterilamp for 15 min (300 ± S26

27 20 µw/cm 2 ) prior to 24 h culture, then collected by trypsin digestion and centrifugation (1000 r/min, 5 min). The collected cells were kept in immunostaining permeabilization buffer (with Triton X-100, 1 ml) for 15 min (25 o C), centrifuged (1000 r/min, 5 min) and washed twice by PBS. Then, the cells were kept in the primary antibody solution (Phospho-Histone H2A.X (Ser139) Rabbit Monoclonal Antibody; 1/250 dilution) for 0.5 h (37 o C), washed twice by PBS, and kept in the Alexa Fluor 555 labeled secondary antibody solution (Alexa Fluor 555-Labeled Donkey Anti-Rabbit IgG; 1/250 dilution) for 0.5 h (37 o C). The treated cells were centrifuged (1000 r/min, 5 min) and suspended in PBS (1 ml) for the flow cytometry analyses (BD FACS Aria III flow cytometer, DsRed channel: excitation wavelength 561 nm). Cells in culture medium without copolymer were used as the control, and cells in culture medium without UV irradiation were used as the blank. S27

28 Supporting Data Figure S1. a) AEMA: A(X): B(1): MgCl 2 = 1:1:1.5:0.2. b) 1 H NMR spectra (DMSO-d 6, 400M) of M(X)(1) monomers. S28

29 Figure S2. a) AEMA: A(X): B(2): MgCl 2 = 1:1:1.5:0.2. b) 1 H NMR spectra (DMSO-d 6, 400M) of M(X)(2) monomers. S29

30 Figure S3. a) AEMA: A(X): B(3): MgCl 2 = 1:1:1.5:0.2. b) 1 H NMR spectra (DMSO-d 6, 400M) of M(X)(3) monomers. S30

31 Figure S4. a) AEMA: A(X): B(5): MgCl 2 = 1:1:1.5:0.2. b) 1 H NMR spectra (DMSO-d 6, 400M) of M(X)(5) monomers. Figure S5. Experimental setup for the HTP synthesis of polymers. S31

32 Figure S6. Crude 1 H NMR spectra (DMSO-d 6, 400M) of M(X)(4) after HTP polymerization for conversion calculation. Figure S7. GPC traces of P(X)(4). S32

33 Figure S8. HTP analysis of monomers: monomer solutions (200 µl, 5 mg/ml in DMSO), DMSO as the control. a) Samples after adding the DPPH radical solution (20 µl, 5 mg/ml in DMSO), 0 min; b) 5 min; c) 10 min; d) 20 min. Figure S9. GPC traces of P(1)(2)-co-P(PEGMA), P(2)(4)-co-P(PEGMA), and P(1)(4)-co-P(PEGMA). S33

34 Figure S10. a) 1 H NMR spectra (DMSO-d 6, 400M) and b) GPC traces of P(4)(2)-co-P(PEGMA), P(4)(4)-co-P(PEGMA). S34

35 Figure S11. a) A DPPH assay to test the radical scavenging ability of P(1)(2)-co-P(PEGMA), P(1)(4)-co-P(PEGMA), P(2)(4)-co-P(PEGMA), P(4)(2)-co-P(PEGMA), and P(4)(4)-co-P(PEGMA). Polymer solutions: 200 µl, 5 mg/ml in DMSO; the DPPH radical solution: 20 µl, 5 mg/ml in DMSO. b) Absorbance of DPPH radical vs time in the presence of different polymers. These mixtures (20 µl) were diluted in DMSO (100 µl) and tested by a microplate reader (VICTORTM X3 PerkinElmer 2030 Multilabel Plate Reader, 520 nm). The data are presented as means ± SD, n = 5. S35

36 Figure S12. 1 H NMR spectrum (DMSO-d 6, 400M) of P(PEGMA). Cell Viability (%) (mg/ml) Figure S13. Cytotoxicity of superoxide dismutase (SOD) to L929 cells. 24 h culture, cell viability in culture medium only as the 100%. The data are presented as means ± SD, n = 5. S36

37 Figure S14. FDA/PI double staining of L929 cells with UV irradiation in the presence of P(1)(4)-co-P(PEGMA) (10 mg/ml), a) 30 min; b) 45 min, bar = 100 µm; c) cell viability (with copolymer) after 15 min, 30 min, 45 min UV irradiation, respectively. SOD was used as the control and the viability of cells in medium only without UV irradiation was defined as 100%. The data are presented as means ± SD, n = 5. S37

38 Figure S15. Staining of the damaged DNA in L929 cells, a) with/without UV irradiation; b) with/without UV irradiation in the presence of P(1)(4)-co-P(PEGMA). Green light: nm band-pass excitation filters, bar = 100 µm. S38

39 Table S1. The Biginelli-type monomers (M(X)(Y)). Product M. P. ( o C) a Conversion (%) b Yield (%) c M(1)(1) M(2)(1) M(3)(1) M(4)(1) M(5)(1) M(1)(2) M(2)(2) M(3)(2) M(4)(2) M(5)(2) M(1)(3) M(2)(3) M(3)(3) M(4)(3) M(5)(3) M(1)(4) M(2)(4) M(3)(4) M(4)(4) M(5)(4) M(1)(5) M(2)(5) M(3)(5) M(4)(5) M(5)(5) a. Measured by differential scanning calorimeter (DSC) at a scanning rate of 10ºC/min. b. Calculated by the 1 H NMR (DMSO-d 6, 400 MHz). c. Isolated yields. S39

40 Table S2. The Biginelli-type homopolymers (P(X)(Y)). Polymer Conversion (%) a M n (GPC) b PDI b T c g ( o C) T d d ( o C) P(1)(1) P(2)(1) P(3)(1) P(4)(1) P(5)(1) P(1)(2) P(2)(2) P(3)(2) P(4)(2) P(5)(2) P(1)(3) P(2)(3) P(3)(3) P(4)(3) P(5)(3) P(1)(4) P(2)(4) P(3)(4) P(4)(4) P(5)(4) P(1)(5) P(2)(5) P(3)(5) P(4)(5) P(5)(5) a. Polymerization conversion, calculated by the 1 H NMR (DMSO-d 6, 400 MHz). b. Measured by GPC using DMF as eluent (1 ml/min). c. Measured by DSC at a scanning rate of 10ºC/min. d. Temperature at weight-loss ratio of 10%, measured by TGA with a heating rate of 20 C/min. S40

41 Table S3. Summary properties of synthetic copolymers. Copolymer P(1)(2)-co-P(PE GMA) P(1)(4)-co-P(PE GMA) P(2)(4)-co-P(PE GMA) Feeding ratio Ratio of DHPM: PEG a M n (GPC) b PDI b Water solubility c 1:1 0.90: > 150 mg 1:1 0.93: > 150 mg 1:1 0.91: > 150 mg a. Calculated by the 1 H NMR (DMSO-d 6, 400 MHz). b. Measured by GPC using DMF as eluent (1 ml/min). c. Measured in 1.0 ml of water. S41