Photocytotoxic Oxidovanadium(IV) Complexes of Polypyridyl Ligands Showing DNA‐Cleavage Activity in Near‐IR Light

Abstract

Listen

Translate article

AbstractOxidovanadium(IV) complexes [VO(pyphen)(L)]Cl2 (1, 2) and [VO(pydppz)(L)]Cl2 (3, 4), where L is 1,10‐phenanthroline (phen in 1 and 3) and dipyrido[3,2‐a:2′,3′‐c]phenazine (dppz in 2 and 4) are prepared and characterized. The crystal structure of [VO(pyphen)(phen)](ClO4)2 (1a) shows a six‐coordinate VN5O geometry with a VO2+ moiety in which the polypyridyl ligand binds in a meridional fashion and the phen ligand displays a chelating binding mode with an N‐donor site trans to the oxidovanadyl group. The complexes show a d–d band within 720–750 nm in DMF. The one‐electron paramagnetic complexes are 1:2 electrolytes in DMF. The complexes exhibit an irreversible VIV/VIII redox response near –0.85 V vs. SCE in DMF/0.1 M TBAP. The complexes bind to calf thymus (ct) DNA giving Kb values within 7.5 × 104 to 1.1 × 106 M–1. The complexes show poor chemical nuclease activity in the dark and exhibit significant DNA‐photocleaving activity in near‐IR light of 705 and 785 nm forming ·OH radicals. Complexes 2–4 show remarkable photocytotoxicity in HeLa cancer cells. FACS analysis of the HeLa cells treated with complex 4 shows cell death as highlighted by the sub G1 peak. Propidium iodide staining data indicate apoptosis as the primary mode of cell death.