Photosensitizer in a molecular bowl and its effect on the DNA-binding and -cleavage activity of 3d-metal scorpionates

Abstract

Ternary 3d-metal complexes [M(Tp^Ph)(B)](ClO₄) (1-8), where M is Co(II), Ni(II), Cu(II) and Zn(II), Tp^Ph is anionic tris(3-phenylpyrazolyl)borate, and B is N,N-donor heterocyclic base, namely, 1,10-phenanthroline (phen, 1-4) and dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 5-8), were prepared from a reaction of the perchlorate salt of the metal with KTp^Ph and B in CH2Cl2. The complexes were characterized by various physicochemical methods. 4-6 and 8 were structurally characterized by single-crystal X-ray crystallography. The crystal structures of the complexes show the presence of discrete cationic complexes having a square-pyramidal (4 + 1) coordination geometry in which two nitrogen atoms of the phenanthroline base (B) and two nitrogen atoms of the Tp^Ph ligand occupy the basal plane and one nitrogen of the Tp^Ph ligand binds at the axial site. The phenyl groups of the Tp^Ph form a bowl-shaped structure that essentially encloses the {M(phen/dpq)} moiety. DNA-binding studies were carried out using various spectral techniques and from viscosity measurements. The complexes show moderate binding propensity to calf thymus DNA at the minor groove, giving binding constant values (K_b) of ~10⁴ M^-1. The complexes exhibit poor DNA-cleavage activity in the dark in the presence of 3-mercaptopropionic acid (MPA) or hydrogen peroxide (H₂O₂). The photoinduced DNA-cleavage activity of the complexes was investigated using UV-A radiation of 365 nm and visible light of two different wavelengths with a tunable multicolor Ar-Kr mixed gas ion laser source. The dpq complexes show efficient photoinduced DNA-cleavage activity via a metal-assisted photoexcitation process involving the formation of singlet oxygen as the cleavage active species in a type-II pathway. The paramagnetic d⁷-Co(II)-dpq and d⁹-Cu(II)-dpq complexes exhibit efficient DNA-cleavage activity in visible light. The paramagnetic d⁸-Ni(II)-dpq complex displays only minor DNA-cleavage activity in visible light. Diamagnetic d¹⁰-Zn(II)-dpq complex shows only UV-A light-induced DNA cleavage but no apparent DNA-cleavage activity in visible light. Steric protection of the photoactive quinoxaline moiety of the dpq ligand inside the hydrophobic {M(Tp^Ph)} molecular bowl has a positive effect on the photoinduced DNA-cleavage activity.