Influence of diimine bidentate ligand in the nitrosyl and nitro terpyridine ruthenium complex on the HSA/DNA interaction and antiviral activity

Abstract

Nitric oxide (NO) acts in different physiological processes, such as blood pressure control, antiparasitic activities, neurotransmission, and antitumor action. Among the exogenous NO donors, ruthenium nitrosyl/nitro complexes are potential candidates for prodrugs, due to their physicochemical properties, such as thermal and physiological pH stability. In this work, we proposed the synthesis and physical characterization of the new nitro terpyridine ruthenium (II) complexes of the type [Ru^II(L)(NO₂)(tpy)]PF₆ where tpy = 2,2':6′,2″-terpyridine; L = 3,4-diaminobenzoic acid (bdq) or o-phenylenediamine (bd) and evaluation of influence of diimine bidentate ligand NH.NHq-R (R = H or COOH) in the HSA/DNA interaction as well as antiviral activity. The interactions between HSA and new nitro complexes [Ru^II(L)(NO₂)(tpy)]⁺ were evaluated. The K_a values for the HSA–[Ru^II(bdq)(NO₂)(tpy)]⁺ is 10 times bigger than HSA–[Ru^II(bd)(NO₂)(tpy)]⁺. The sites of interaction between HSA and the complexes via synchronous fluorescence suppression indicate that the [Ru^II(bdq)(NO₂)(tpy)]⁺ is found close to the Trp-241 residue, while the [Ru^II(bd)(NO₂)(tpy)]⁺ complex is close to Tyr residues. The interaction with fish sperm fs-DNA using direct spectrophotometric titration (K_b) and ethidium bromide replacement (K_SV and K_app) showed weak interaction in the system fs-DNA-[Ru^II(bdq)(NO)(tpy)]⁺. Furthermore, fs-DNA–[Ru^II(bd)(NO₂)(tpy)]⁺ and fs-DNA–[Ru^II(bd)(NO)(tpy)]³⁺ system showed higher intercalation constant. Circular dichroism spectra for fs-DNA–[Ru^II(bd)(NO₂)(tpy)]⁺ and fs-DNA–[Ru^II(bd)(NO)(tpy)]³⁺, suggest semi-intercalative accompanied by major groove binding interaction modes. The [Ru^II(bd)(NO₂)(tpy)]⁺ and [Ru^II(bd)(NO)(tpy)]³⁺ inhibit replication of Zika and Chikungunya viruses based in the nitric oxide release under S-nitrosylation reaction with cysteine viral.