Schiff base oxovanadium(IV) complexes of phenanthroline bases showing DNA photocleavage activity at near-IR light and photocytotoxicity

Abstract

Oxovanadium(IV) complexes [VO(L)(B)](ClO₄) (1-3) of N-2-pyridylmethylidine-2-hydroxyphenylamine (HL) Schiff base and phenanthroline bases (B), viz. 1,10-phenanthroline (phen in 1), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq in 2) or dipyrido[3,2-a:2',3'-c]phenazine (dppz in 3), were prepared, characterized and their DNA binding property, photo-induced DNA cleavage activity and photocytotoxicity in HeLa cells studied. The crystal structure of 1 shows the presence of a VO²⁺ moiety in VO₂N₄ coordination geometry. The complexes show a d-d band at 1830 nm in DMF. The complexes display an oxidative V(V)-V(IV) response near 0.5 V versus SCE and a reductive V(IV)/V(III) response near -0.65 V in DMF-0.1 M TBAP. The complexes that are avid binders to CT DNA giving K_b values within 7.1×10⁴ to 3.2×10⁵ M^-1, do not show any significant chemical nuclease activity in presence of 3-mercaptopropionic acid or glutathione. The dpq and dppz complexes are photocleavers of pUC19 DNA in UV-A light of 365 nm forming both ¹O₂ and ^⋅OH radicals and in near-IR light of 785 nm forming ^·OH radicals. The dppz complex exhibits photocytotoxicity in visible light in HeLa cells (IC₅₀=6.8μM). Flow-cytometric study on this complex shows a high sub-G1 phase in light compared to dark indicating PDT effect.