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

摘要

Reactions of 2-(3,5-dimethylpyrazol-1-ylmethyl)pyridine (L1), 2-(3,5-diphenylpyrazol-1-ylmethyl)pyri_dine (12), 2-(3,5-di-tert-butylpyrazol-1-ylmethyl)pyridine (L3) and 2-(3 -p-tolylpyrazol-1 -ylmethyl )pyri_dine (IA) with K_2[PtC1_4] in a mixture of ethanol and water formed the dichloro platinum complexes [PtC1_2(Ll)] (1), [PtC1_2(L2)] (2), [PtCl_2(L3)1(3) and [PtCl_2(L4)1(4). Complex 1, [PtCl_2(L1)], could also be pre_pared 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(CH_2C00H_3)CI(L2)] (2a) and [Pt(CH_20OCH_3)Cl(L3)] (3a). The same ligands reacted with HAuCI_4 4H_2O in a mixture of ethanol and water to form the gold salts [AuC1_2(Ll)][AuC1_4] (5) [AuC1_2(L2)][CI] (6) [AuC1_2(L3)][CI] (7) and [AuC1_2(L4)][AuC1_41 (8); however, with the pyrazolyl unit in the para position of the pyridinyl ring in 4-(3,5-dimethylpyrazol-1-ylmethyl)pyridine (LS), 4-(3,5-diph_enylpyrazol-1-ylmethyl)pyridine (L6) neutral gold complexes [AuCl_3(L5)] (9) and [AuCl_2(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 AuCI_4~-. Cytotoxicity studies of 12, L4 and complexes 1-10 against HeLa cells showed the Au complexes were much less active than the Pt complexes.