New insights into the visible-light-induced DNA cleavage activity of dipyridoquinoxaline complexes of bivalent 3d-metal ions

Abstract

Dipyridoquinoxaline (dpq) complexes of bivalent 3d-metal ions, viz., [Fe^II(dpq)₃](PF₆)₂ (1), [Co^II(dpq)₃](ClO₄)₂ (2), [Ni^II(dpq)₃](ClO₄)₂ (3), [Cu^II(dpq)₂(H₂O)](ClO₄)₂ (4), [Zn^II(dpq)₃](ClO₄)₂ (5), and [Zn^II(dpq)₂(DMF)₂](ClO₄)₂ (5a) (DMF = N,N-dimethylformamide), are prepared and their photoinduced DNA cleavage activity studied. Structural characterization for the complexes 1 and 5a is done by single-crystal X-ray crystallography. All the complexes show efficient binding propensity to calf thymus DNA with a binding constant (K) value of ~10⁵ M^-1. Complexes 1, 2, and 4 show metal-based cyclic voltammetric responses at 1.2, 0.4, and 0.09 V (vs SCE) in DMF 0.1 M [Buⁿ₄N](ClO₄) assignable to the respective Fe^III/Fe^II, Co^III/Co^II, and Cu^II/Cu^I couples. The Ni^II and Zn^II complexes do not show any metal-based redox process. The dpq-based reductions are observed in the potential range of -1.0 to -1.7 V vs SCE. DNA melting and viscosity data indicate the groove-binding nature of the complexes. Control experiments using distamycin-A suggest a minor groove-binding propensity of the complexes. The complexes exhibit photoinduced cleavage of supercoiled pUC19 DNA in UV light of 365 nm. The diamagnetic d⁶-Fe^II and d¹⁰-Zn^II complexes are cleavage-inactive on irradiation with visible light. The paramagnetic d⁷-Co^II and d⁹-Cu^II complexes exhibit efficient DNA cleavage activity on photoirradiation at their respective d-d band. The paramagnetic d⁸-Ni^II complex displays only minor DNA cleavage activity on irradiation at its d-d band. The DNA cleavage reactions at visible light under aerobic conditions involve the formation of hydroxyl radical. The CoII complex shows photocleavage of DNA under an argon atmosphere. Theoretical calculations on the complexes suggest a photoredox pathway in preference to a type-2 process forming singlet oxygen for the visible-light-induced DNA cleavage activity of the 3d-metal complexes. The theoretical data also predict that the photoredox pathway is favorable for the 3d⁷-Co^II and 3d⁹-Cu^II complexes to exhibit DNA cleavage activity, while the analogous 3d⁶-Fe^II and 3d⁸-Ni^II complexes are energetically unfavorable for the exhibition of such activity under visible light. The Co^II and Cu^II complexes are better suited for designing and developing new metal-based PDT agents than their cleavage-inactive Fe^II, Ni^II, and Zn^II analogues.