The induction of cell death by phosphine silver(I) thiocyanate complexes in SNO-esophageal cancer cells.

Zelinda Humana, Apollinaire Munyanezab, Bernard Omondib, Natasha M Sanabriaa,b, ReinoutMeijboomb,Marianne J. Cronjéa

aDepartment of Biochemistry, University of Johannesburg, PO Box 524, Auckland Park, Johannesburg 2006, South Africa.

bResearch Centre for Synthesis and Catalysis, Department of Chemistry, University of Johannesburg, PO Box 524, Auckland Park, Johannesburg 2006, South Africa.

Supplementary information

Experimental

Synthesis of [AgSCN(PPh3)2]2(1);

In a 100 cm3round bottomed flask, solid AgSCN (0.1032 g, 0.62 mmol) was added to the solution of triphenylphosphine (PPh3) (0.3161 g, 1.20 mmol) in ethanol (30 cm3) and DMSO (30 cm3).The reaction mixture was heated under reflux for 5.5 hours. The solution was filtered hot and the ethanol was evaporated. The solution was left to crystallize from which small white crystals were isolated. Yield: 0.3181 g (74%). m.p.: 218-220; Anal. Reqd. for C74H60Ag2N2S2P4: C, 64.36; H, 4.38; N, 2.02; S, 4.64%. Found: C, 64.42; H, 4.71; N, 2.05; S, 4.69%. IR (ν in cm-1): 3046 (ν(aromatic, =C-H),w); 2090 (ν(SCN), s); 1539 (w)1478, 1433 (ν(C=C aromatic), m); 1327, 1306 (w); 1183, 1157 (w); 1094, 1070 (asymm, m); 1025 (w); 996 (w); 743 (ν(aromatic, δ C-H), s); 692 (ν(aromatic, δ C-H, meta), s; 1H NMR (400 MHz, CDCl3): δ (ppm) 7.32(m, 30H, H-aromatic); 13C{H} NMR (100 MHz, CDCl3): δ (ppm) 128.94 (d, δ1= 128.89, δ2= 128.98, 1J(P-C)=6.8 Hz, meta C); 130.20 (para C); 132.16 (d, δ1= 132.03, δ2= 132.28, 1J(P-C)=18.8 Hz, ipso C); 133.82 (d, δ1= 133.73, δ2= 133.90, 1J(P-C)=12.8 Hz, ortho C); 31P{H} NMR (161 MHz, CDCl3): δ (ppm) 8.29.

Synthesis of [AgSCN{P(4-MeC6H4)3}2]2(2);

In a 100 cm3 round bottomed flask, 0.100 g of AgSCN (0.603 mmol) and 0.367 g (1.206 mmol) of [P(4-MeC6H4)3] were dissolved in 30 cm3 of pyridine. The reaction mixture was stirred under refluxovernight. After filtration, the pyridine solution was allowed to stand at room temperature and a solid crashed out. The latter was collected and re-crystallized in acetonitrile. Yield: 0.314 g (58%). m.p.:181; Anal. Calcd.forC86H84Ag2N2S2P4: C, 66.67; H, 5.46; N, 1.81. Found: C, 66.62; H, 5.24; N, 1.65%. IR (ν in cm-1):3014 (ν(=C-H),w); 2918, 2863 (ν(alkane, C-H, stretch), asymm, w)2130-2069 (ν(SCN), m); 1642, 1597 (ν(C=C aromatic), m); 1497, 1445(ν(C=C aromatic), m); 1396 (ν(CH3bend), m); 839-802 (ν(aromatic, C-H bend, meta), s); 708 (ν(aromatic, C-H bend, ortho), m). 1H NMR (CDCl3, δ, 300 MHz): 2.47 (s, 3H); 7.22 (d, 2H); 7.35 (d, 2H); 13C{H} NMR(CDCl3, δ, 75.5 MHz): 21.76; 129.00; 129.39; 134.22; 140.69; 31P{H} NMR (CDCl3, δ, 121.4 MHz): 7.48.

Synthesis of[AgSCN{P(4-FC6H4)3}2]2 (3);

This complex was synthesized by heating one equivalent of P(4-FC6H4)3 (0.335 g, 1.06 mmol) with AgSCN (0.176 g, 1.06 mmol) in acetonitrile (10.0 cm3) under reflux. Recrystallization from acetonitrile produced colourless crystals suitable for X-ray diffraction. Yield: 0.410 g (97.1%); m.p.:210-215; Anal. Calcd.forC74H48Ag2N2S2P4F12: C, 55.66; H, 3.03; N, 1.75. Found: C, 55.67; H, 3.26; N, 1.72%; IR (ν in cm-1): 3029 (ν(=C-H), w); 2360 (ν(C-H), w); 2081 (ν(SCN), m); 1586, 1558, 1541 (ν(C=C aromatic), asymm, s); 1492 (asymm, s) 1394 (ν(C=C aromatic), m); 1299, 1273, 1224, 1158; 1093 (s), 1043 (m) 1012 (s); 824 (ν(aromatic),asymm, s); 707 (ν(aromatic),asymm, s); 1H NMR(400 MHz, CDCl3): δ (ppm) 6.940 (t); 7.280 (t); 13C{H} NMR(100 MHz, CDCl3):δ(ppm)116.36 (q); 128.22 (q); 135.73 (q); 169.05 (d); 31P{H} NMR(161 MHz, CDCl3): δ (ppm) 2.82.

Synthesis of [AgSCN{P(4-ClC6H4)3}2]2(4);

In a 100 ml round bottomed flask, 0.100 g ofAgSCN (0.603 mmol) and 0.440 g (1.206 mmol) of [P(p-ClC6H4)3] were dissolved in 30 cm3 of pyridine. The reaction mixture was stirred under refluxovernight. After filtration, the pyridine solution was allowed to stand at room temperature for the product to crystallize. A suitable crystal was collected for the crystal structure determination. The crystallized product was also used for other characterizations.Yield: 0.467 g (76%). m.p.:207; Anal. Calcd.forC74H48Ag2N2S2P4Cl12: C, 49.53; H, 2.70; N, 1.56; S, 3.57%. Found: C, 49.38; H, 2.81; N, 1.62; S, 3.21%; IR ( v in cm-1):3056 (ν(=C-H),wk); 2076 (ν(SCN), asymm, s); 1575, 1560, 1477 (ν(C=C aromatic), m); 1386 (m); 1298 (w); 1182 (w); 1099, 1080 (s); 1102 (s); 813 (s); 744 (ν(aromatic), s); 703 (ν(C-Cl), m); 1H NMR(CDCl3, δ, 300 MHz):7.31 (d, 2H), 7.45 (d, 2H); 13C{H} NMR(CDCl3, δ, 75.5 MHz): 129.66; 130.95; 135.36; 137.47; 31P{H} NMR (CDCl3, δ, 121.4 MHz): 3.27.