(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 K2[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 · 4H2O 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, 33a, 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.

Graphical abstractA series of (pyrazolylmethyl)pyridine compounds react with either platinum(II) chloride or gold(III) chloride starting materials to form bidentate chelated platinum or gold complexes when the pyrazolyl unit is ortho to the pyridine nitrogen. Such reactions produce neutral, mononuclear platinum complexes, but with gold form monocationic complexes. If the reaction is performed in a mixture of water and acetone, some of the (pyrazolylmethyl)pyridine platinum dichloride complexes readily activate a C–H bond in acetone to form acetonyl platinum complexes.Figure optionsDownload full-size imageDownload as PowerPoint slide