# Synthesis, Characterization, HSA/DNA Binding, and Cytotoxic Activity of [RuCl2(η6-p-cymene)(bph-κN)] Complex

## TL;DR

A new ruthenium complex was created and tested for its ability to bind to proteins and DNA, showing potential as an anticancer drug.

## Contribution

The study introduces a novel ruthenium complex with demonstrated DNA binding and selective cytotoxicity against cancer cells.

## Key findings

- The complex binds to HSA and DNA via hydrophobic interactions and intercalation.
- It shows selective cytotoxicity against pancreatic and colorectal cancer cells.
- Antioxidant activity was observed with effective radical scavenging.

## Abstract

A novel ruthenium(II) complex, [RuCl2(η6-p-cymene)(bph-κN)] (1), was synthesized and structurally characterized using FTIR and NMR spectroscopy. Density functional theory (DFT) calculations supported the proposed geometry and allowed for comparative analysis of experimental and theoretical spectroscopic data. The interaction of complex 1 with human serum albumin (HSA) and calf thymus DNA was investigated through fluorescence quenching experiments, revealing spontaneous binding driven primarily by hydrophobic interactions. The thermodynamic parameters indicated mixed quenching mechanisms in both protein and DNA systems. Ethidium bromide displacement assays and molecular docking simulations confirmed DNA intercalation as the dominant binding mode, with a Gibbs free binding energy of −34.1 kJ mol−1. Antioxidant activity, assessed by EPR spectroscopy, demonstrated effective scavenging of hydroxyl and ascorbyl radicals. In vitro cytotoxicity assays against A375, MDA-MB-231, MIA PaCa-2, and SW480 cancer cell lines revealed selective activity, with pancreatic and colorectal cells showing the highest sensitivity. QTAIM analysis provided insight into metal–ligand bonding characteristics and intramolecular stabilization. These findings highlight the potential of 1 as a promising candidate for further development as an anticancer agent, particularly against multidrug-resistant tumors.