Ferrocene-Conjugated Oxidovanadium(IV) Complexes as Potent Near-IR Light Photocytotoxic Agents

Abstract

Ferrocene-conjugated oxidovanadium(IV) complexes [VO(Fc-tpy)(B)](ClO₄)₂ (1–4) and [VO(Ph-tpy)(dppz)](ClO₄)₂ (5) as a control [Fc = (η⁵-C₅H₄)Fe^II(η⁵-C₅H₅), Fc-tpy = 4′-ferrocenyl-2,2′:6′,2″-terpyridine, Ph-tpy = 4′-phenyl-2,2′:6′,2″-terpyridine, B = heterocyclic base: 2,2′-bipyridine (bpy in 1), 1,10-phenanthroline (phen in 2), dipyridoquinoxaline (dpq in 3), dipyridophenazine (dppz in 4)] were prepared and their DNA binding, DNA photocleavage activity and photocytotoxicity studied. The crystal structure of [VO(Fc-tpy)(bpy)](PF₆)₂·3Me₂CO shows a vanadyl group in six-coordinate V^IVON₅ coordination geometry, in which Fc-tpy and bpy display tridentate meridional and bidentate N-donor axial–equatorial binding modes, respectively. The one-electron paramagnetic complexes exhibit a charge-transfer band near 590 nm in DMF. The V^IV/V^III redox couple in 1–4 appears near –0.7 V, whereas the Fc moiety shows a response near 0.6 V vs. SCE in DMF/0.1 M TBAP. The complexes are good binders to calf thymus DNA with K_b values of 10⁴–10⁶M^–1. DNA melting and viscometric data suggest groove and/or partial intercalative DNA binding of the complexes. Complexes 3–5 display DNA photocleavage activity in near-IR light of 785 nm. Complex 4 shows significant photocytotoxicity in visible light (400–700 nm) in HeLa cells with low dark toxicity.