The photocytotoxicity of a series of anticancer trans-dihydroxido [Pt(N(3))(2)(
OH)(2)(NH(3))(X)] (X = alkyl or aryl
amine)
platinum(IV) diazido complexes has been examined, and the influence of cis-trans isomerism has been investigated. A series of photoactivatable Pt(IV)-azido complexes has been synthesized: The synthesis, characterization, and photocytotoxicity of six mixed-
ligand ammine/
amine Pt(IV) diazido complexes, cis,trans,cis-[Pt(N(3))(2)(
OH)(2)(NH(3))(X)] where X = propylamine (4c), butylamine (5c), or pentylamine (6c) and aromatic complexes where X =
pyridine (7c),
2-methylpyridine (8c), or
3-methylpyridine (9c) are reported. Six all-trans isomers have also been studied where X =
methylamine (2t),
ethylamine (3t),
2-methylpyridine (8t),
4-methylpyridine (10t),
3-methylpyridine (9t), and 2-bromo-3-methylpyridine (11t). All of the complexes exhibit intense
azide-to-Pt(IV) LMCT bands (ca. 290 nm for trans and ca. 260 nm for cis). When irradiated with UVA light (365 nm), the Pt(IV) complexes undergo photoreduction to Pt(II) species, as monitored by UV-vis spectroscopy. The trans isomers of complexes containing aliphatic or aromatic
amines were more photocytotoxic than their cis isomers. One of the cis complexes (9c) was nonphotocytotoxic despite undergoing photoreduction. Substitution of NH(3)
ligands by MeNH(2) or EtNH(2) results in more potent photocytotoxicity for the all-trans complexes. The complexes were all nontoxic toward human keratinocytes (HaCaT) and A2780 human
ovarian cancer cells in the dark, apart from the
3-methylpyridine (9t), 2-bromo-3-methylpyridine (11t), and
4-methylpyridine (10t) derivatives.