Supplementary Material for Synthesis of Compact Multidentate Ligands to Prepare Stable Hydrophilic Quantum Dot Fluorophores 5-[1,2]-Dithiolan-3-yl-pentanoic acid 2-[2-(2-{2-[2-(2-hydroxy-ethoxy)-ethoxy]-ethoxy}- ethoxy)-ethoxy]-ethyl ester [TA-HEG]: Compound (2). Compound 2 was prepared from thioctic acid and hexaethylene glycol following the procedure used for compound 1. Yield: 53% as a yellow oil. TLC (EtAc/MeH 95:5) R f 0.35; 1 H-NMR (400 MHz, CDCl 3 ): δ(ppm) 4.19 (t, J = 4.8 Hz, 2H), 3.69 3.51 (m, 22H), 3.13 (m, 2H), 2.76 (s, 1H), 2.43 (s, 1H), 2.32 (t J = 7.5 Hz, 2H), 1.88 (m, 1H), 1.62 (m, 4H), 1.43 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ(ppm) 172.76, 72.10, 69.99, 69.92, 69.68, 68.53, 62.87, 60.95, 55.73, 39.65, 37.92, 34.00, 33.33, 28.11, 24.03. [TA-PEG 400]: Compound (3). Compound 3 was prepared from thioctic acid and poly(ethylene glycol) 400 MW following the procedure used for compound 1. Yield: 75% as a yellow oil. TLC (CHCl 3 /MeH/acetone 90:5:5) R f 0.3; 1 H-NMR (400 MHz, CDCl 3 ): δ(ppm) 4.09 (t, J = 4.8 Hz, 2H), 3.52 (m, 36H), 3.02 (m, 2H), 2.52 (s, 1H), 2.33 (m, 1H), 2.22 (t, J = 7.4 Hz, 2H), 1.79 (m, 1H), 1.54 (m, 4H), 1.34 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ(ppm) 173.06, 72.26, 70.16, 69.89, 68.74, 63.08, 61.21, 55.93, 49.94, 39.83, 38.10, 34.19, 33.53, 28.31, 24.22. [TA-PEG 600]: Compound (4). Compound 4 was prepared from thioctic acid and poly(ethylene glycol) 600 MW following the procedure used for compound 1. Yield: 75% as a yellow oil. TLC (CHCl 3 /MeH/acetone 90:5:5) R f 0.3; 1 H-NMR (400 MHz, CDCl 3 ): δ(ppm) 4.18 (t, J = 4.8 Hz, 2H), 3.7 3.5 (m, ~ 50H), 3.11 (m, 2H), 2.58 (br s, 1H), 2.43 (m, 1H), 2.31 (t, J = 7.4 Hz, 2H), 1.87 (m, 1H), 1.7 1.55 (m, 4H), 1.5 1.35 (m, 2H) 13 C NMR (100 MHz, Supporting Information 1 of 26
CDCl 3 ): δ(ppm) 172.83, 72.10, 70.08, 69.87, 68.64, 62.96, 61.12, 55.81, 39.73, 38.00, 34.10, 33.43, 28.21, 24.13. [TA-PEG-1000]: Compound (5). Compound 5 was prepared from thioctic acid and poly(ethylene glycol) 1000 MW following the procedure used for compound 1. The reaction provides a yellow waxy solid with a yield of ~ 52%. TLC (CHCl 3 /MeH 9:1) R f 0.4; 1 H-NMR (400 MHz, CDCl 3 ): δ(ppm) 4.15 (t, J = 4.7 Hz, 2H), 3.7 3.5 (m, ~ 90H), 3.14 (m, 2H), 2.50 (br s, 1H), 2.44 (m, 1H), 2.33 (t, J = 7.4 Hz, 2H), 1.85 (m, 1H), 1.75 1.5 (m, 4H), 1.4 1.3 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ(ppm) 173.08, 72.30, 70.20, 69.93, 68.79, 63.11, 61.25, 55.96, 50.01, 39.87, 38.13, 34.23, 33.58, 28.35, 24.26. 6,8-Dimercapto-octanoic acid 2-[2-(2-{2-[2-(2-hydroxy-ethoxy)-ethoxy]-ethoxy}-ethoxy)- ethoxy]-ethyl ester [DHLA-HEG]: Compound (8). Compound 8 was prepared according to the above general procedure described for compound 7. It yields a colorless oil with ~ 85% efficiency. TLC (EtAc/MeH 9:1) R f 0.4; 1 H-NMR (400 MHz, CDCl 3 ): δ(ppm) 4.19 (t, J = 4.8 Hz, 2H), 3.65 (m,20h), 3.57 (t, J = 4.5 Hz, 2H), 2.88 (m, 1H), 2.67 (m, 3H), 2.32 (t, J = 7.3 Hz, 2H), 1.87 (m, 1H), 1.75 1.38 (m, 7H), 1.32 (t, J = 8.0 Hz, 1H), 1.27 (d, J = 7.7 Hz, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ(ppm) 173.11, 72.29, 70.22, 70.16, 69.90, 68.79, 63.11, 61.23, 42.40, 38.95, 38.34, 33.63, 26.13, 24.17, 21.93. [DHLA-PEG 400]: Compound (9). Compound 9 was also prepared according to the above general procedure for 7. The procedure has a yield of ~ 75% and provides a colorless oil. TLC (CHCl 3 /MeH 95:5) R f 0.25; 1 H-NMR (400 MHz, CDCl 3 ): δ(ppm) Supporting Information 2 of 26
[DHLA-PEG 600]: Compound (10). Compound 10 was also prepared according to the above general procedure for 7. The procedure has a yield of ~ 93% and provides a colorless oil. TLC (CHCl 3 /MeH/acetone 90:5:5) R f 0.25; 1 H-NMR (400 MHz, CDCl 3 ): δ(ppm) 4.18 (t, J = 4.8 Hz, 2H), 3.62 (m, ~50H), 2.88 (m, 1H), 2.66 (m, 3H), 2.31 (t, J = 7.3 Hz, 2H), 1.85 (m, 1H), 1.75 1.35 (m, 7H), 1.31 (t, J = 8.0 Hz, 1H), 1.26 (d, J = 7.6 Hz, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ(ppm) 173.20, 72.37, 70.31, 70.05, 68.91, 63.21, 61.38, 42.51, 39.04, 38.47, 33.74, 26.24, 24.27, 22.02. [DHLA-PEG-1000]: Compound (11). The general procedure described above for compound 6 was employed to prepare compound 7. The final product was a colorless waxy solid with 83% yield. TLC (CHCl 3 /MeH 9:1) R f 0.4; 1 H-NMR (400 MHz, CDCl 3 ): δ(ppm) 4.05 (t, J = 4.8 Hz, 2H), 3.47 (m, ~ 90H), 2.90 (s, 1H), 2.75 (m, 1H), 2.52 (m, 2H), 2.19 (t, J = 7.4 Hz, 2H), 1.75 (m, 1H), 1.62 1.24 (m, 7H), 1.22 (t, J = 8.0 Hz, 1H), 1.70 (d, J = 7.6 Hz, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ(ppm) 172.84, 72.07, 70.05, 69.84, 68.63, 62.92, 61.07, 42.24, 38.75, 38.19, 33.46, 25.96, 24.00, 21.74. Supporting Information 3 of 26
Table S1. Chart of solubility and representative solvents for dispersion of QDs coated with the following ligands. Capping Ligand: TP/TP DHLA DHLA-PEG Solubility Non-polar Polar Amphiphilic Representative Hexane, Basic buffers Both acidic and basic Solvents chloroform, toluene methanol, ethanol, buffers, methanol, ethanol, dimethylformamide, dimethylformamide, dimethylsulfoxide dimethylsulfoxide, chloroform References: (1) Gunsalus, I. C.; Barton, L. S.; Gruber, W. J. Am. Chem. Soc. 1956, 78, 1763-1766. (2) Wagner, A. F.; Walton, E.; Boxer, G. E.; Pruss, M. P.; Holly, F. W.; Folkers, K. J. Am. Chem. Soc. 1956, 78, 5079-5081. Supporting Information 4 of 26
7.0 6.0 2.0 5.0 1.0 0.0 1.432 2.411 2.328 2.310 2.291 1.873 1.630 2.14 4.18 1.17 2.54 2.48 3.100 4.0 3.0 Supporting Information 5 of 26 7.260 3.623 4.201 4.189 4.177 2.05 3.14 12.47 2.07 S S TA-TEG in d-chloroform H
175 150 125 Supporting 100 Information 6 of 26 75 50 25 0 172.938 77.320 77.000 76.680 72.166 70.164 70.051 69.851 68.682 62.971 61.141 55.876 39.775 38.053 34.127 33.458 28.240 24.156 S S TA-TEG in d-chloroform H
7.0 6.0 2.0 5.0 1.0 0.0 2.439 2.354 2.335 2.317 1.899 1.669 1.656 1.458 1.453 2.08 4.10 1.00 2.02 1.00 2.784 1.17 3.111 4.221 4.209 4.197 1.99 23.52 2.00 Supporting 4.0 Information 3.0 7 of 26 7.260 S S TA-HEG in d-chloroform n = 5 H n
175 150 125 100 Supporting Information 8 of 26 75 50 25 0 172.761 77.321 77.000 76.680 72.101 69.987 69.916 68.528 62.871 60.948 55.730 39.644 37.922 33.999 33.328 28.104 24.032 S S TA-HEG in d-chloroform n=5 n H
7.0 2.0 4.0 3.0 Supporting Information 9 of 26 6.0 5.0 1.0 0.0 1.344 7.260 2.326 2.240 2.222 2.203 1.787 1.542 2.532 2.15 4.18 1.00 2.05 1.01 1.25 3.518 3.513 3.290 3.279 2.994 4.102 4.090 4.078 2.21 4.71 38.68 2.00 S S TA-PEG400 in d-chloroform n ~ 8 H n
175 150 125 Supporting 100 Information 10 of 26 75 50 25 0 173.081 77.319 77.000 76.681 72.298 70.201 69.933 68.791 63.114 61.250 55.957 50.010 39.867 38.128 34.235 33.577 28.353 24.259 TA-PEG400 in d-chloroform S S n ~ 8 n H
7.0 6.0 2.0 5.0 1.0 0.0 2.456 2.439 2.354 2.335 2.317 1.899 1.658 1.460 1.456 2.08 4.13 1.04 2.01 1.10 3.112 3.0 Supporting 4.0 Information 11 of 26 7.260 3.627 4.221 4.209 4.197 H 2.02 52.18 2.00 TA-PEG600 in d-chloroform S S n n ~ 12
150 Supporting 100 Information 12 of 26 50 0 172.830 77.320 77.000 76.680 72.096 70.076 69.867 68.644 62.960 61.116 55.806 39.727 37.998 34.100 33.430 28.206 24.126 TA-PEG600 in d-chloroform H S S n n ~ 12
7.0 2.0 3.0 6.0 1.0 2.500 2.400 2.331 2.312 2.294 1.871 1.658 1.541 1.368 1.97 3.10 1.02 0.93 2.04 1.00 8.46 3.504 4.118 4.104 4.092 Supporting Information 4.0 13 of 26 5.0 99.63 4.27 0.92
175 TA-PEG1000 in d-chloroform 150 125 Supporting 100 Information 14 of 26 75 50 25 0 173.082 77.319 77.000 76.681 72.297 70.201 69.932 68.791 63.114 61.250 55.956 50.009 39.866 38.127 34.234 33.576 28.352 24.257 H S S n n ~ 20
12.0 1.0 2.0 3.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 Supporting Information 15 of 26 4.0 0.0 1.370 1.350 1.330 1.305 1.286 2.918 2.691 2.394 2.376 2.358 1.889 1.94 7.25 1.05 1.99 2.03 1.00 7.260 DHLA in d-chloroform S S H
230 220 210 200 190 180 ppm (f1) 170 160 150 140 130 120 110 100 90 Supporting Information 16 of 26 80 70 60 50 40 30 20 10 0-10 179.897 77.318 77.000 76.681 42.544 39.100 38.466 33.745 26.248 24.086 22.110 DHLA in d-chloroform S S H
7.0 1.0 6.0 5.0 0.0 1.277 1.257 1.237 1.220 1.201 2.233 2.215 2.196 1.752 2.27 7.27 1.03 2.04 2.0 2.545 2.778 1.98 Supporting 4.0 Information 3.0 17 of 26 7.260 1.07 3.516 4.099 4.087 4.075 14.17 2.00 SH SH DHLA-TEG in d-chloroform H
175 150 125 100 Supporting Information 18 of 26 75 50 25 0 173.025 77.319 77.000 76.680 72.182 70.207 70.104 69.899 68.735 63.003 61.180 42.339 38.887 38.269 33.558 26.060 24.101 21.871 SH SH DHLA-TEG in d-chloroform H
7.0 6.0 1.0 2.0 Supporting 4.0 Information 3.0 19 of 26 5.0 0.0 1.288 1.268 1.248 1.229 1.210 8.04 2.254 2.236 2.218 1.774 1.13 2.16 2.569 7.260 2.800 2.23 1.13 3.532 4.117 4.106 4.093 2.27 25.82 2.00 SH SH DHLA-HEG in d-chloroform H
175 150 125 Supporting 100 Information 20 of 26 75 50 25 0 173.112 77.320 77.000 76.680 72.291 70.220 70.155 69.903 68.787 63.107 61.226 42.400 38.946 38.341 33.632 26.128 24.165 21.928 SH SH DHLA-HEG in d-chloroform H
2.0 1.0 Supporting Information 4.0 3.0 21 of 26 7.0 6.0 5.0 0.0 7.260 1.327 1.308 1.288 1.265 1.246 2.314 2.296 2.278 1.833 1.822 1.567 2.632 2.859 3.591 4.179 4.167 4.155 2.06 7.36 1.01 2.04 2.00 2.94 37.66 2.00
150 Supporting 100 Information 50 22 of 26 0 173.323 77.319 77.000 76.682 72.417 70.400 70.352 70.075 68.962 63.280 61.463 42.552 39.114 38.539 33.796 26.313 22.116
7.0 6.0 1.0 2.0 Supporting 4.0 Information 3.0 23 of 26 5.0 0.0 1.352 1.332 1.312 1.290 1.270 2.43 1.601 9.30 2.347 2.329 2.310 1.866 7.260 1.33 2.39 2.667 2.892 3.617 4.213 4.201 4.189 2.24 1.25 69.34 2.00 DHLA-PEG600 in d-chloroform SH SH n ~ 12 H n
175 150 125 Supporting 100 Information 24 of 26 75 50 25 0 173.201 77.319 77.000 76.681 72.308 70.265 70.012 68.868 63.182 61.355 42.461 39.014 38.444 33.701 26.215 24.226 22.019
7.0 1.0 6.0 5.0 0.0 1.241 1.222 1.202 1.179 1.160 1.91 6.85 2.204 2.186 2.168 1.722 0.93 1.94 2.0 2.517 Supporting 4.0 Information 3.0 25 of 26 7.260 1.85 2.896 2.750 3.472 4.066 4.054 4.042 0.96 1.12 85.84 2.00 DHLA-PEG1000 in d-chloroform SH SH n ~ 20 H n
150 100 Supporting Information 26 of 26 50 0 172.836 77.320 77.000 76.680 72.076 70.050 69.840 68.626 62.920 61.074 42.242 38.748 38.188 33.456 25.959 24.003 21.739 DHLA-PEG1000 in d-chloroform H SH SH n n ~ 20