Supplementary Data on T16 and 3H-T16 Syntheses

Supplemental data on T16 and 3H-T16 structure and syntheses

Figure. Chemical structure of bis-thiazolium salts. (A) T16. (B) [3H]T16.

T16 (1, 12-dodecanemethylene bis[4-methyl-5-ethylthiazolium] diiodide) was prepared according to the synthesis shown in scheme 1.

a. 5-Ethyl-4-methylthiazole. 4-Methyl-5-vinylthiazole (5g, 40mmol) in methanol (200mL) was hydrogenated over palladium (5.14g, 10% on charcoal, 1 mass equivalent) using a Parr apparatus (pressure 800mbar) at room temperature for 4 hours. The solution was filtered twice through celite and over a 0.45m filter (Millipore Millex-HV) to remove the metal catalyst. The solvent was removed in vacuo to give the product as a colourless oil with sufficient purity to be used in the next procedure. (ESI-MS: [m/z]+ = 127 ; 1H NMR (250 MHz, DMSO-D6) : δ 1.2 (t, 3H, CH3−CH2), 2.3 (s, 3H, CH3−C=C), 2.75 (q, 2H, −CH2−CH3), 8.8 (s, 1H, S−CH=N+))

b. 1, 12-Diiodododecane. 1, 12-Dibromododecane (25g, 76mmol) and sodium iodide (34.32g, 229mmol) were stirred for 15 minutes at room temperature in acetone (500mL). The mixture was then heated under reflux for 3 hours, after which the solvent was removed and water (400mL) was added. The product was extracted from the aqueous solution with ether (3 x 200mL) and the combined organic phases were dried (MgSO4) and evaporated in vacuo. The resulting solid was recrystallized from methanol to give the product as white crystals (yield = 95%). (mp 42 - 43 °C ; 1H NMR (250 MHz, CDCl3) : δ 1,25 (s, 16H, −(CH2)8−), 1,8 (m, 4H, −CH2−CH2−I), 3,15 (t, 4H, −CH2−I); 95 % yield).

c. T16 (1, 12-dodecanemethylene bis[4-methyl-5-ethylthiazolium diiodide). 5-Ethyl-4-methylthiazole (4.71g, 3.7mmol) and 1, 12-diiodododecane (5.22g, 12.3mmol) in acetonitrile (250mL) were heated under reflux for 14 days. The solvent was removed, water (400mL) was added, and the product was extracted with ether (3 x 200mL). The solvent was removed and the solid was recrystallized from isopropanol to give the product as brown crystals (yield = 98%). (ESI-MS : [m/z]2+ = 211; 1H NMR (250 MHz, DMSO-D6) : δ 1,05 (dd, 6H, CH3−CH2), 1,35 (m, 16H, −(CH2)8−), 1,9 (m, 4H, −CH2−CH2−N+), 2,6 (s, 6H, CH3−C=C), 3,0 (q, 4H, −CH2−CH3), 4,5 (t, 4H, −CH2−N+), 10,1 (s, 2H, S−CH=N+); 98 % yield).

3H-T16 (3H-1, 12-dodecanemethylene bis[4-methyl-5-ethylthiazolium] diiodide) (scheme 2)

d. 1, 12-dodecanemethylene bis(4-methyl-5-vinylthiazolium) diiodide. 4-methyl-5-vinylthiazole (2.03g, 16mmol) and diiodododecane (2.4g, 5mmol) were stirred at reflux in DMF (150mL) for 4 hours. After this time, the solvent was removed in vacuo to give a mixture that contains the unsaturated product. The product was purified by preparative HPLC to give a yellow oil. (HPLC gradient AcCN:H2O:TFA 25:74.9:0.1 to 60:39.9:0.1, retention time 18 minutes); ESI-MS : [m/z]2+ = 209; 1H NMR (250 MHz, DMSO-D6) : δ 1,35 (m, 16H, −(CH2)8−), 1,9 (m, −CH2−CH2−N+), 2,6 (s, 6H, CH3−C=C), 4,5 (t, 4H, −CH2−N+), 5,85 (dd, 4H, CH2=CH), 7,1 (dd, 2H, −CH=CH2), 10,1 (s, 2H, S−CH=N+).

e. 3H-T16 (3H-1, 12-dodecanemethylene bis[4-methyl-5-ethylthiazolium] diiodide).1, 12-dodecanemethylene bis(4-methyl-5-vinylthiazolium) diiodide (10mg) and palladium (20.14mg, 10% on charcoal) in methanol (1mL) was treated with tritium (500mbar) at room temperature for 1 hour. The catalyst was removed by centrifugation (5000rpm, 10min) and filtration through a 0.45m Millipore filter. The solution was cryodistilled three times from methanol (2mL) for 12 hours under reduced pressure (5 milliTorr) for removing labile tritium atoms. The enriched product was weighed (5.9mg) and dissolved in ethanol (1mL) to give a solution of the product with a specific activity of 69Ci/mmol.