Cellular uptake and remarkable photocytotoxicity of pyrenylter pyridine oxovanadium(IV) complexes of dipyridophenazine bases

Abstract

Pyrenylterpyridine (pytpy) oxovanadium(IV) complexes [VO(pytpy)(L)]Cl2 (1–6) of the dipyridophenazine bases (L), viz., dipyrido-6,7,8,9-tetrahydrophenazine (dpqC in 1), dipyrido[3,2-a:2′,3′-c]phenazine-2-carboxylic acid (dppzc in 2), dipyrido[3,2-a:2′,3′-c]phenazine-11-sulfonic acid (dppzs in 3), 7-aminodipyrido[3,2-a:2′,3′-c]phenazine (dppza in 4), benzo-[i]dipyrido[3,2-a:2′,3′-c]phenazine (dppn in 5) and dipyrido[3,2-a:2′,3′-c]phenazine (dppz in 6) were prepared, characterized and their DNA binding, photocleavage activity and photocytotoxicity studied. The complexes which showed a d–d band near 750 nm in DMF are efficient binders to calf thymus DNA (Kb: 3.2 × 105–2.9 × 106 M−1). The complexes showed significant pUC19 DNA cleavage in near-IR light of 785 nm forming radical dotOH radicals and photocytotoxicity in HeLa cells in visible light with the benzo-[i]dipyrido[3,2-a:2′,3′-c]phenazine complex 5 showing a remarkably low IC50 value of 0.036 μM. Flow-cytometric analysis shows a high sub-G1 phase cell cycle arrest in HeLa cells by the complexes on photo-irradiation. The photocytotoxicity correlates well with the hydrophobicity, photosensitizing ability and DNA binding propensity of the complexes.