Synthesis, cytotoxicity, and biomacromolecule binding: Three isomers of nitrosylruthenium complexes with bidentate bioactive molecules as co-ligands

Abstract

Three isomeric nitrosylruthenium complexes [RuNO(Qn)(PZA)Cl] (P1, P2, and P3) with bioactive small molecules 8-hydroxyquinoline (Qn) and pyrazinamide (PZA) as co-ligands were synthesized, and their crystal structures were determined using X-ray diffraction technique. The cellular toxicity of the isomeric complexes was compared to understand the effects of the geometries on the biological activity of the complexes. Both the complexes and the human serum albumin (HSA) complex adducts affected the extent of proliferation of HeLa cells (IC₅₀: 0.77-1.45 μM). P2 showed prominent activity-induced cell apoptosis and arrested cell cycles at the G1 phase. The binding constants (K_b) of the complex with calf thymus DNA (CT-DNA) and HSA were quantitatively evaluated using fluorescence spectroscopy in the range of 0.17-1.56 × 10⁴ M^-1 and 0.88-3.21 × 10⁵ M^-1, respectively. The average binding site (n) number was close to 1. Moreover, the structure of HSA and the P2 complex adduct solved at the resolution of 2.48 Å revealed that one PZA-coordinated nitrosylruthenium complex bound at the subdomain I of HSA via a noncoordinative bond. HSA could serve as a potential nano-delivery system. This study provides a framework for the rational design of metal-based drugs.

Keywords: Biomacromolecules; Cytotoxicity; Isomers; Nitrosylruthenium complex; Photodynamic.