(Pyrazolylmethyl)pyridine platinum(II) and gold(III) complexes: Synthesis, structures and evaluation as anticancer agents

Reactions of 2-(3,5-dimethylpyrazol-1-ylmethyl)pyridine (L1), 2-(3,5-diphenylpyrazol-1-ylmethyl)pyridine (L2), 2-(3,5-di-tert-butylpyrazol-1-ylmethyl)pyridine (L3) and 2-(3-p-tolylpyrazol-1-ylmethyl)pyridine (L4) with K-2[PtCl4] in a mixture of ethanol and water formed the dichloro platinum complexes [PtCl2(L1)] (1), [PtCl2(L2)] (2), [PtCl2(L3)] (3) and [PtCl2(L4)] (4). Complex 1, [PtCl2(L1)], could also be prepared in a mixture of acetone and water. Performing the reactions of L2 and L3 in a mixture of acetone and water, however, led to C-H activation of acetone under mild conditions to form the neutral acetonyl complexes [Pt(CH2COCH3) Cl(L2)] (2a) and [Pt(CH2COCH3) Cl(L3)] (3a). The same ligands reacted with HAuCl4 center dot 4H(2)O in a mixture of ethanol and water to form the gold salts [AuCl2(L1)][AuCl4] (5) [AuCl2(L2)][Cl] (6) [AuCl2(L3)][Cl] (7) and [AuCl2(L4)][AuCl4] (8); however, with the pyrazolyl unit in the para position of the pyridinyl ring in 4-(3,5-dimethylpyrazol-1-ylmethyl)pyridine (L5), 4-(3,5-diphenylpyrazol-1-ylmethyl)pyridine (L6) neutral gold complexes [AuCl3(L5)] (9) and [AuCl2(L6)] (10) were formed; signifying the role the position of the pyrazolyl group plays in product formation in the gold reactions. X-ray crystallographic structural determination of L6, 2, 3 3a, 8 and 10 were very important in confirming the structures of these compounds; particularly for 3a and 8 where the presence of the acetonyl group confirmed C-H activation and for 8 where the counter ion is AuCl4-. Cytotoxicity studies of L2, L4 and complexes 1-10 against HeLa cells showed the Au complexes were much less active than the Pt complexes. (C) 2009 Elsevier B. V. All rights reserved.