Supporting Information. Stable Dioxetane Precursors as Highly Selective. for Singlet Oxygen

Transcription

1 Supporting Information Stable Dioxetane Precursors as Highly Selective Trap-and-Trigger Chemiluminescent Probes for Singlet Oxygen Laura A. MacManus-Spencer, Douglas E. Latch, Kim M. Kroncke, and Kristopher McNeill* University of Minnesota, Department of Chemistry, 207 Pleasant St. SE, Minneapolis, Minnesota This supporting information file describes the syntheses of probes 1a, 1b (and their precursors) 2a, and 3-(1,4-epidoxy-4-methyl-1,4-dihydro-1-naphthyl)-propionate (MNPO 2 ), as well as experimental details for the laser flash photolysis (LFP) experiments to measure rate constants for the total quenching of singlet oxygen by 1a, 1b, and diethylenetriaminepentaacetic acid (DTPA). S-1

2 General methods: All reagents for the syntheses of 1a, 1b, 2a, and their precursors were purchased from commercial suppliers. Significantly higher yields were obtained using titanium(iii) chloride (TiCl 3 ) from Aldrich. Tetrahydrofuran (THF) was distilled from Na/benzophenone ketyl under nitrogen, methylene chloride and triethylamine (Et 3 N) were distilled from calcium hydride under nitrogen. N,Ndimethylformamide (DMF) was vacuum distilled from calcium hydride and stored over activated 3 Å molecular sieves. Perinaphthenone, diethylenetriaminepentaacetic acid (DTPA), deuterium oxide (D 2 O), and sodium deuteroxide (NaOD, 40 wt.% solution in D 2 O, 99+% D) were purchased from commercial suppliers. Synthesis of 3-(tert-butyldimethylsiloxy)benzoic acid methyl ester: 3-Hydroxybenzoic acid methyl ester was protected according to the procedure of Kendall, et al., 1 in which 3-hydroxybenzoic acid methyl ester (2.44 g, 16.1 mmol, 1 eq.) was combined with tert-butyldimethylsilyl chloride (4.85 g, 32.2 mmol, 2 eq.), imidazole (3.29 g, 48.3 mmol, 3 eq.), and 4-dimethylaminopyridine (0.196 g, 1.61 mmol, 0.1 eq.) in dry, distilled 0.1 M DMF in dry, distilled CH 2 Cl 2 (200 ml total) and stirred at room temperature overnight. Saturated NH 4 Cl solution (50 ml) was added to the reaction mixture. The aqueous phase was extracted with EtOAc (3 100 ml), and the organic phase was washed with brine (2 100 ml) and dried with Na 2 SO 4. The product was concentrated in vacuo. Following chromatography on silica (5:1 Hex:EtOAc), the product was isolated as a colorless oil (4.05 g, 15.2 mmol, 94% yield). 1 H NMR (CDCl 3, 300 MHz): δ 7.65 (d, t, J = 1.2, 8.1 Hz, 1 H), 7.50 (d, d, J = 1.5, 2.4 Hz, 1 H), 7.30 (t, J = 7.8 Hz, 1 H), 7.04 (d, d, d, J = 1.2, 2.7, 8.4 Hz, 1 H), 3.91 (s, 3 H), 1.00 (s, 9 H), 0.22 (s, 6 H). Synthesis of 3-(tert-butyldimethylsiloxy)-3,6,9,12-tetraoxa-1-tridecyl-13-(tert-butyldimethylsiloxy)benzoate: 3-(tert-butyldimethylsiloxy)benzoic acid (1.01 g, 4.0 mmol), 1,3- dicyclohexylcarbodiimide, (1.06 g, 5.16 mmol), 4-dimethylaminopyridine (0.097 g, 0.79 mmol), and mono-silylated tetraethylene glycol (1.54 g, 6.1 mmol) were stirred at room temperature in dry CH 2 Cl 2 until TLC analysis indicated complete conversion. Flash chromatography on silica (5:1 Hex:EtOAc) S-2

3 afforded the product as a colorless oil in 68.9% yield (2.28 g, 3.46 mmol). 1 H NMR (CDCl 3, 300 MHz): δ 7.66 (d, t, J = 1.2, 7.5 Hz, 1 H), 7.51 (d, d, J = 1.8, 2.4 Hz, 1 H), 7.29 (t, J = 8.1 Hz, 1 H), 7.03 (d, d, d, J = 0.9, 2.4, 8.1 Hz, 1 H), 4.47 (t, J = 4.8 Hz, 2 H), 3.84 (t, J = 8.1 Hz, 2 H), (t, J = 5.1 Hz, 2 H), (m, 8 H), 3.55 (t, J = 5.4 Hz, 2 H), 1.00 (s, 9 H), 0.89 (s, 9 H), 0.22 (s, 6 H), 0.06 (s, 6 H); 13 C NMR (CDCl 3, 75 MHz): δ 166.5, 155.8, 131.6, 129.5, 125.0, 122.8, 121.3, 72.8, 70.9, 70.8, 69.4, 64.4, 62.9, 26.1, 25.8, 18.5, 18.3, -4.3, -5.1; IR (neat, cm -1 ): 2955, 2858, 1724, 1601, 1585, 1439, 1487, 1472, 1288, 1254, 1225, 1102, 1004; HRMS calculated for C 27 H 50 O 7 Si 2 Na [(M+Na) + ]: , found Synthesis of 2-[1-(3-tert-butyldimethylsiloxy)phenyl)-1-methoxymethylene]tricyclo[ ]decane (1a): The synthesis followed the preparation of Sabelle, et al. 2 All glassware was dried in an oven overnight. A 250-mL three-necked flask was fitted with a reflux condenser, an addition funnel, and a septum in a glove box under inert atmosphere. A mixture of adamantanone (0.366 g, 2.4 mmol, 1 eq.) and 3-(tert-butyldimethylsiloxy)benzoic acid methyl ester (0.519 g, 2.4 mmol, 1 eq.) in 5 ml dry THF was added to the addition funnel. TiCl 3 (3.00 g, 19.5 mmol, 8 eq.) in a suspension of 25 ml dry THF was added to the reaction flask. The reaction was removed from the glove box, kept under inert atmosphere, and cooled in an ice bath. LiAlH 4 (1 M solution in Et 2 O, 9.74 ml, 9.74 mmol, 4 eq.) was added slowly with constant stirring. After 10 minutes at 0 ºC, Et 3 N (1.19 g, 11.7 mmol, 1.65 ml, 5 eq.) was added, and the suspension was heated to reflux for 1 hour. After this period, the mixture of 3-tertbutyldimethylsiloxybenzoic acid methyl ester and adamantanone in the addition funnel was added dropwise to the refluxing reaction over 2 hours, and heating was continued overnight. The reaction was cooled to room temperature and quenched with CH 3 OH (25 ml). The reaction mixture was added to water (300 ml), and the aqueous phase was extracted with Et 2 O (3 100 ml). The organic phase was dried with Na 2 SO 4 and concentrated in vacuo. Following chromatography on silica (97:3:0.1 Hex:EtOAc:Et 3 N) and preparative TLC purification, 1a was isolated as a colorless oil (0.441 g, 1.15 mmol, 48% yield). 1 H NMR (CDCl 3, 300 MHz): δ 7.21 (t, J = 7.5 Hz, 1 H), 6.92 (d, J = 7.5 Hz, 1 H), S-3

4 (m, 2 H), 3.30 (s, 3 H), 3.25 (s, 1 H), 2.64 (s, 1 H), (m, 12 H), 0.99 (s, 9H), 0.20 (s, 6 H). Synthesis of 2-[1-(3-tert-butyldimethylsilyloxy)phenyl)-3,6,9,12-tetraoxa-1-tridecyl-13-hydroxymethylene]tricyclo-[ ]decane (1b): The same procedure was followed as for the synthesis of 1a with the exception that 3-(tert-butyldimethylsiloxy)-3,6,9,12-tetraoxa-1-tridecyl-13-(tertbutyldimethylsiloxy)benzoate (1.59 g, 2.9 mmol) was used in place of 3-(tertbutyldimethylsiloxy)benzoic acid methyl ester. Following chromatography on silica (20:1:0.1 to 5:1:0.1 Hex:EtOAc:Et 3 N), the silyl-protected product was isolated as a pale yellow oil in a 54.3% yield (1.05 g, 1.6 mmol). The silyl-protected product (50.1 mg, mmol) was then selectively deprotected with p-toluenesulfonic acid (1.5 mg, mmol) in 3:1 CH 2 Cl 2 :MeOH at 0 o C. The reaction was monitored by TLC. Decomposition occurred when the reaction was run longer than 90 min. The reaction was quenched by the addition of excess Et 3 N, and the solvent was concentrated under reduced pressure. Following silica chromatography (1:1:0.1 Hex:EtOAc:Et 3 N), 1b was isolated as a colorless oil in a 90% yield (37.3 mg, mmol). 1 H NMR (CDCl 3, 300 MHz): δ 7.19 (t, J = 7.5 Hz, 1 H), 6.92 (d, J = 7.5 Hz, 1 H), (m, 2 H), (m, 16 H), 3.30 (s, 1 H), 2.66 (s, 1 H), 2.47 (t, J = 6.3 Hz, 1 H), (m, 12 H), 0.98 (s, 1 H), 0.20 (s, 1 H); 13 C NMR (CDCl 3, 75 MHz): δ 155.5, 141.8, 137.0, 132.4, 129.1, 122.7, 121.2, 119.5, 72.7, 70.9, 70.7, 70.7, 70.5, 70.3, 68.4, 61.9, 39.4, 39.1, 37.3, 32.5, 30.3, 28.5, 25.8, 18.4, -4.3; IR (neat, cm -1 ): 3462, 2902, 2849, 1654, 1597, 1577, 1480, 1306, 1284, 1251, 1097, 1081; HRMS calculated for C 31 H 50 O 6 SiNa [(M+Na) + ]: , found Preparation of 4-methoxy-4-(3-tert-butyldimethylsiloxyphenyl)spiro[1,2-dioxetane-3,2'-tricyclo- [ ]decane] (2a): The dioxetane of 1a was prepared according to the preparation of Sabelle, et al. 3 Ozone was bubbled through a cooled ( 78 ºC) suspension of triphenyl phosphite (82.3 mg, mmol, 1.5 eq.) in dry CH 2 Cl 2 (8 ml) until the solution turned light blue. The reaction solution was purged with oxygen until the light blue color disappeared. 1a (0.068 g, mmol, 1 eq.) in dry CH 2 Cl 2 (2 ml) was added at 78 ºC, and the reaction solution was stirred and warmed to room temperature. The solvent was S-4

5 removed in vacuo. Following chromatography on silica (97:3:0.1 Hex:EtOAc:Et 3 N), 2a was isolated as a colorless oil (15.2 mg, mmol, 21% yield). 1 H NMR (CDCl 3, 300 MHz): δ (m, 4 H), 3.23 (s, 3 H), 3.02 (s, 1 H), (m, 13 H), 0.99 (s, 9 H), 0.20 (s, 6 H). Preparation of 3-(1,4-epidoxy-4-methyl-1,4-dihydro-1-naphthyl)-propionate (MNPO 2 ): The endoperoxide of 4-methyl-1-naphthalenepropionic acid (MNP, the synthesis of which is described elsewhere 4 ) was prepared using H 2 O 2 /MoO 2-4 as a chemical source of 1 O 2 according to the method of Aubry. 5 The MNPO 2 was stored as a frozen stock solution in ph mm phosphate buffer. Laser flash photolysis measurements: Rate constants for the total quenching of the time-resolved 1 O 2 phosphorescence signal, k tot, by 1a and 1b were determined by laser flash photolysis (LFP) using an apparatus and methods described previously. 6 LFP samples containing perinaphthenone (100 µm) and various concentrations of 1a or 1b in CH 2 Cl 2 were excited at 355 nm. The k tot value for DTPA was also determined by LFP. LFP samples containing perinaphthenone (100 µm) and various concentrations of DTPA in basic (pd 11) D 2 O were excited at 355 nm. The calculated k tot values are summarized in Table S1. References (1) Kendall, P. M.; Johnson, J. V.; Cook, C. E. J. Org. Chem. 1979, 44, (2) Sabelle, S.; Renard, P.-Y.; Pecorella, K.; de Suzzoni-Dezard, S.; Creminon, C.; Grassi, J.; Mioskowski, C. J. Am. Chem. Soc. 2002, 124, (3) Sabelle, S.; Hydrio, J.; Leclerc, E.; Mioskowski, C.; Renard, P.-Y. Tetrahedron Lett. 2002, 43, (4) Pierlot, C.; Hajjam, S.; Barthelemy, C.; Aubry, J. M. J. Photochem. Photobiol., B 1996, 36, (5) Aubry, J. M. J. Am. Chem. Soc. 1985, 107, (6) Latch, D. E.; Stender, B. L.; Packer, J. L.; Arnold, W. A.; McNeill, K. Environ. Sci. Technol. 2003, 37, S-5

6 Table S1. Rate constants for the total quenching of 1 O 2, k tot, for 1a, 1b, and DTPA. Compound 1a 1b DTPA k tot (M -1 s -1 ) a 4.5 (± 0.2) 10 5 b 8.7 (± 0.3) 10 5 b 1.0 (± 0.1) 10 7 c a Calculated from laser flash photolysis data. Values represent the average and one standard deviation from three replicate experiments. b Data obtained in CH 2 Cl 2. c Data obtained in basic D 2 O. S-6