UV-Responsive Degradable Polymers Derived from 1-(4-Aminophenyl)ethane-1, 2-diol

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1 Supportin Inormtion UV-Rsponsiv Drdl Polymrs Drivd rom 1-(4-Aminophnyl)thn-1, 2-diol Lin M 1, Ryn Bumrtnr 2, Ynn Zhn 1, Ziyun Son 1, Kimin Ci 1 nd Jinjun Chn 1, 2 1 Dprtmnt o Mtrils Scinc nd Eninrin, Univrsity o Illinois t Urn Chmpin, Urn, Illinois, 61801, USA 2 Dprtmnt o Chmistry, Univrsity o Illinois t Urn Chmpin, Urn, Illinois, 61801, USA Corrspondnc to: Jinjun Chn (E-mil: jinjunc@illinois.du) Tl o contnts: Schm S1 - Synthsis o polyboc control polymr S2 Schm S2 - Synthsis o compound 3 S4 Schm S3 Synthsis o compound 4 S6 Fiur S1 - Drdtion o poly (1/2) chrctrizd y 1 H NMR S7 Fiur S2 - Stility o polyboc undr UV liht irrdition nd stility o poly (1/2) undr drk S8 Fiur S3 Pk ssinmnts o 3 tr UV-irrdition S9 Fiur S4 - Drdtion o 3 undr UV liht nd drk S10 Clcultion o Nitronzyl Clv nd F5 rls S11 Fiur S5 Stility o 3 tr on month S12 Fiur S6. HPLC monitorin drdtion o 3 tr UV irrdition S13 Fiur S7. Fluorscnc spctr chn o Nil Rd Lodd Poly(1/2) wtr suspnsion with incrs o UV liht irrdition tim. S14 Fiur S8 - Stility o Nil Rd lodd poly (1/2) nnoprticls S15 1 H NMR nd 13 C NMR spctr o synthsizd compounds ( Fi. S6-S20) S16 S1

2 Schm S1. Synthsis o polyboc Synthsis o 1-(4-minophnyl)thn-1,2-diol (5). 4-Vinylnilin (1, 8.4 mmol) nd K 2 OSO m, mmol) ws dissolvd in 120 ml o Acton/H 2 O (v/v = 3: 1), thn 2.08 ml o NMO solution (10 mmol) ws ddd. Th rction ws llowd or ovrniht nd tn 50 ml o sturtd quous solution o N 2 S 2 O 3 ws ddd. Atr stirrd or ovrniht, th rsultin solution ws xtrctd y EtOAc. Th product ws puriid y silic l column tr th rmovl o solvnt to iv whit solid 5. (Hxn: Ethyl Actt = 0: 1). (0.51, Yild: 40 %). 1 H NMR (DMSO-d 6, 500 MHz): δ 6.93 (d, 2H, ArH), 6.48 (d, 2H, ArH), 4.88 (s, 2H, -Ph- NH 2 ), 4.47 (s, 1H, -Ph-CH-OH), 4.45 (m, 1H, -Ph-CH-CH 2 ), 4.32 (m, 1H, -Ph-CH-CH 2 -OH), 3.30 (m, 2H, Ph-CH-CH 2 -OH). 13 C NMR (DMSO-d 6, 500 MHz): δ , , , , 74.48, ESI-MS (low rsolution, positiv mod): clcultd or C 8 H 11 NO 2, m/z, [M + H] + ; ound [M + H] +. Synthsis o trt-utyl (4-(1,2-dihydroxythyl)phnyl)crmt (6). Undr N 2, compound 5 (0.3, 2 mmol) nd Boc 2 O (0.915, 4.2 mmol) ws ddd into th 10 ml EtOH, nd th rction ws llowd to rct undr rluxin or 36 hours. Th solvnt ws rmovd y vcuum nd solid ws puriid y silic l chromtorphy to iv whit solid 6(thyl ctt: hxn = 1: 2 to 1: 1). (0.35, Yild: 80%). 1 H NMR (DMSO-d 6, 500 MHz): δ 9.25 (s, 1H, -Ph-NH - ), 7.36 (d, 2H, ArH), 7.16 (d, 2H, ArH), 5.10 (s, 1H, -Ph-CH-OH), 4.65 (m, 1H, -Ph-CH-CH 2 ), 4.41 (m, 1H, -Ph-CH-CH 2 -OH), 3.31 (m, 2H, Ph-CH-CH 2 -OH). 13 C NMR (DMSO-d 6, 500 MHz): δ , S2

3 138.86, , , , 79.51, 74.16, 68.18, ESI-MS (low rsolution, positiv mod): clcultd or C 8 H 11 NO 2, m/z, [M + N] + ; ound [M + N] +. Synthsis o polyboc. To th solution o compound 6 (150 m, 0.59 mmol) nd zlic cid dichlorid (133.4 m, 0.59 mmol) in DCM (5 ml), nhydrous pyridin (190 ul, 6 mmol) ws ddd dropwis ovr 10 min undr nitron. Th solution ws stirrd or 22 h t room tmprtur. Th rction mixtur ws concntrtd to 0.5 ml undr vcuum, nd prcipittd into cold mthnol (10 ml). Th prcipitt ws collctd y cntriution t 4000 r.p.m. nd drid undr vcuum. PolyBoc ws otind s whit solid (100 m, yild 40%) M n = 8.0 kd; M w /M n = δ (m, 4H, ArH), 6.76 (s, 1H, Ar-NH-CO-O-), 5.95 (s, 1H, Ph-CH-O- CO), 4.28 (s, 2H, -CH-CH 2 O-CO-), (m, 4H, -CO-CH 2 -CH 2 -), (m, 10H, - OCO-CH 2 -(CH 2 ) 5 -CH 2 -), 124 (-Ph-NH-CO-O-C(CH 3 ) 3 ). S3

4 Schm S2. Synthsis o compound 3 Synthsis o 1-(4-((((2-nitronzyl)oxy)cronyl)mino)phnyl)-2-((4-(pyrn-1-yl)utnoyl) oxy) thyl 4-(pyrn-4-yl) utnot (3). To th solution o 1-pyrnutyric cid (PBA) (228 m, mmol) in nhydrous DCM (7 ml), SOCl 2 (1.5 ml, 20 mmol) ws ddd. Th rsultin solution ws htd to rlux or 3 h nd th solvnt ws rmovd undr vcuum. Th rsultin liquid rsidu ws usd dirctly without puriiction. Th ov rsidu ws dissolvd in nhydrous DCM (5 ml) ollowd y ddition o th solution o compound 1 (100 m, 0.3 mmol) in DCM/THF (1: 3, v/v, 16 ml) t 0 o C. Trithylmin (210 µl, 1.5 mmol) ws thn ddd. Th rction solution ws llowd to rdully wrm up to room tmprtur nd stirrd ovrniht. Th rsultin solution ws iltrd nd th iltrt ws wshd with rin (3 50 ml). Th ornic lyr ws drid with nhydrous N 2 SO 4 nd crud product ws otind tr rmovl o solvnt. Th inl product ws otind y silic l column chromtorphy usin rdint lution (thyl ctt: hxn = 1:4 to 1:2, v/v). Th product ws thn urthr puriid usin silic l column to iv compound 3 s whit solid (60 m, yild 23%). 1 H NMR (CDCl 3, 500 MHz): δ (m, 16H, PyH), (m, 2H, ArH), (m, 2H, ArH), (m, 4H, ArH), 6.78 (s, 1H, -O-CO-NH-Ph), 6.07 (d, 1H, Ph-CH-), 5.54 (d, 2H, O 2 N-Ph-CH 2 -), (m, 2H, -CH-CH 2 -O-CO-), 3.25 (m, 4H, -O-CO-CH 2 -CH 2 -CH 2 -), S4

5 (d, 4H, -O-CO-CH 2 -CH 2 -CH 2 -), (m, 4H, -O-CO-CH 2 -CH 2 -CH 2 -). 13 C NMR (CDCl 3, 500 MHz): δ 173.2, 172.7, 152.7, 138.0, 135.6, 133.9, 132.5, 131.9, 131.5, 131.0, 130.1, 129.1, 128.9, 127.9, 127.7, 127.1, 126.0, 126.3, 125.2, 124.9, 123.8, 118.7, 77.2, 73.0, 66.0, 63.8, 34.1, 33.9, 32.7, ESI-MS (low rsolution, positiv mod): clcultd or C 56 H 44 N 2 O 8 N, m/z, [M + N] + ; ound [M + N] +. S5

6 Schm S3. Synthsis o 2-hydroxy-2-phnylthyl octnot (4) Synthsis o 2-hydroxy-2-phnylthyl octnot (4). Trithylmin (0.242, 2.4 mmol) ws ddd dropwis into th solution o 1-Phnyl-1,2-thndiol (0.256, 2 mmol) nd octnoyl chlorid (0.325, 2 mmol) in DCM (20 ml) undr nitron t 0 o C. Th rction solution ws llowd to rdully wrm up to room tmprtur nd stirrd ovrniht nd iltrd. Th iltrt ws drid nd crud solid ws otind. Th product ws puriid y silic l column chromtorphy (hxn: thyl ctt = 15: 1, v/v) to iv compound 4 s colorlss oil (158 m, yild 30%). 1 H NMR (CDCl 3, 500 MHz): δ (m, 5H, ArH), 4.96 (d, 1H, -CH-CH 2 - O), (m, 1H, -CH-CH 2 -O), (m, 1H, -CH-CH 2 -O), 2.55 (s, 1H, Ph-CH-OH), (m, 2H,-O-CO-CH 2 -CH 2 -), (m, 2H,-O-CO-CH 2 -CH 2 - ), (m, 8H, - O-CO-CH 2 -CH 2 -(CH 2 ) 4 -CH 3 ), (m, 3H, -CH 3 ). 13 C NMR (CDCl 3, 500 MHz): δ 173.4, 142.7, 128.7, 127.9, 126.9, 70.9, 69.0, 34.1, 31.7, 29.0, 25.0, 25.1, 22.7, ESI-MS (low rsolution, positiv mod): clcultd or C 16 H 24 O 3 N, m/z, [M + N] + ; ound [M + N] +. S6

7 ) ) c) Fiur S1. () Proposd mchnism o drdtion o poly (1/2) tr th rmovl o protctin roup; 1 H NMR spctr o poly (1/2) in DMSO-d 6 : D 2 O (10: 1, v/v) or () nd tr (c) UV irrdition (365 nm, 50 mw/cm 2, 40 min) with incution or 72 h t 37 o C. S7

8 Fiur S2. () GPC curvs o polyboc or UV irrdition nd tr UV liht irrdition or 2 h in DMF/H 2 O (v/v, 95: 5) ollowd y 96 h incution t 37 C; () GPC curvs o poly (1/2) or nd tr incution undr drk t 37 o C or 7 dys in DMF/H 2 O (95: 5, v/v). Not: Dirnt siz xclusion column ws usd to chrctriz polyboc nd poly (1/2). S8

9 ) ) c) Fiur S3. 1 H NMR spctr in DMSO-d 6 : D 2 O (5: 1, v/v) o () 3 tr UV irrdition (365 nm, 50 mw cm -2 ) or 80 min nd incution undr drk or 80 h; () 2-hydroxy-2-phnylthyl octnot (4); (c) F5. Astrisks rprsnt pks du to solvnts. S9

10 ) ) c) d) Fiur S4. 1 H NMR spctr o 3 in DMSO-d 6 : D 2 O (5: 1, v/v) () or UV irrdition; () nd tr UV irrdition (365 nm, 50 mw/cm 2 ) or 80 min without incution; nd (c) incution undr drk t 37 o C or 80 h; (d) 1 H NMR spctrum o F5 in DMSO-d 6 : D 2 O (5: 1, v/v). Astrisks rprsnt pks du to solvnts. S10

11 Clcultion o prcnt o clvd nitronzyl roup nd prcnt o rlsd F5. Prcnt o clvd nitronzyl roup (%) = Intrtion o pk d (or UV irrdition)-intrtion o pk d(tr UV irrdition) Intrtion o pk ' 100% +Intrtion o pk Prcnt o rlsd F5 (%) = Intrtion o pk ' (Intrtion o pk ' +Intrtion o pk )/2 100% Not: Durin clcultion, w st totl intrtion o pk nd intrtion o pk s 1 nd othr pk s intrtion rr to thm. S11

12 ) ) Fiur S5. 1 H NMR spctr o 3 in DMSO-d 6 : D 2 O (5: 1, v/v) or () nd tr () incution t 37 o C or on month. Astrisks rprsnt pks du to solvnts. S12

13 Fiur S6. HPLC trc monitorin drdtion o 3 tr UV irrdition in CH 3 CN/H 2 O (9: 1, v/v). (i) 3 or UV irrdition. (ii) 3 with lontion o incution tim tr UV irrdition (365 nm, 50 mw cm -2 ) or 1 h in CH 3 CN/H 2 O (9: 1, v/v). (iii) uthntic F5 whos rtntion tim is out 1.54 min. F2 lutd out t 5.04 min which ws conirmd y HR-ESI. S13

14 Fiur S7. Fluorscnc spctr chn o Nil Rd lodd Poly(1/2) nnoprticls wtr suspnsion with incrs o UV liht irrdition tim (365 nm, 50 mw cm -2 ). (λ Ex = 556 nm). S14

15 Fiur S8. Fluorscnt intnsity o Nil Rd lodd poly (1/2) nnoprticls incutd in DIwtr or svn dys. S15

16 H 2 O c d j h i j d h c i DMSO Chmicl Shit (ppm) Fiur S9. 1 H NMR spctrum o 2-nitronzyl (4-vinylphnyl)crmt in DMSO-d Chmicl Shit (ppm) Fiur S10. 13C NMR spctrum o 2-nitronzyl (4-vinylphnyl)crmt in DMSO-d 6 S16

17 H 2 O c d h l i j k h l kji d d THF DMSO THF Chmicl Shit (ppm) Fiur S11. 1 H NMR spctrum o 1 in DMSO-d Chmicl Shit (ppm) Fiur S C NMR spctrum o 1 in DMSO-d 6. S17

18 S18 Fiur S13. 1 H NMR spctrum o poly (1/2) in CDCl CHCl 3 Chmicl Shit (ppm) k l h c d i j m n k l h cd i j m n

19 Ar-H d c CHCl 3 c d DMF H 2 O Chmicl Shit (ppm) Fiur S14. 1 H NMR spctrum o compound 3 in CDCl 3 Ar-H Chmicl Shit (ppm) Fiur S C NMR spctrum o compound 3 in CDCl 3 S19

20 k-o c k o l n m d h i j d -i j CHCl 3 c c Chmicl Shit (ppm) Fiur S16. 1 H NMR spctrum o 4 in DMSO-d Chmicl Shit (ppm) Fiur S C NMR spctrum o 4 in DMSO-d 6. S20

21 Fiur S18. HMBC spctrum o 4 in CDCl 3. S21

22 c d d H 2 O c DMSO Chmicl Shit (ppm) Fiur S19. 1 H NMR spctrum o 5 in DMSO-d Chmicl Shit (ppm) Fiur S C NMR spctrum o 5 in DMSO-d 6. S22

23 h c d h d H 2 O DMSO Chmicl Shit (ppm) Fiur S21. 1 H NMR spctrum o 6 in DMSO-d Chmicl Shit (ppm) Fiur S C NMR spctrum o 6 in DMSO-d 6. S23

24 j i h c d i j CHCl 3 c d MOH h Chmicl Shit (ppm) Fiur S23. 1 H NMR spctrum o polyboc in CDCl 3. S24

Synthesis and properties of a dually cleavable graft copolymer comprising pendant acetal linkages

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