Computational Assessment of a Dual-Action Ru(II)-Based Complex: Photosensitizer in Photodynamic Therapy and Intercalating Agent for Inducing DNA Damage

A combined quantum-mechanical and classicalmolecular dynamicsstudy of a recent Ru-(II) complex with potential dual anticancer actionis reported here. Inspection of photophysical properties and structuralfeatures evidences the possibility of the complex to act as both singletoxygen generator and intercalating agent. A combined quantum-mechanical and classical moleculardynamicsstudy of a recent Ru-(II) complex with potential dual anticancer actionis reported here. The main basis for the multiple action relies onthe merocyanine ligand, whose electronic structure allows the drugto be able to absorb within the therapeutic window and in turn efficientlygenerate O-1(2) for photodynamic therapy applicationand to intercalate within two nucleobases couples establishing reversibleelectrostatic interactions with DNA. TDDFT outcomes, which includethe absorption spectrum, triplet states energy, and spin-orbitmatrix elements, evidence that the photosensitizing activity is ensuredby an MLCT state at around 660 nm, involving the merocyanine-basedligand, and by an efficient ISC from such state to triplet stateswith different characters. On the other hand, the MD exploration ofall the possible intercalation sites within the dodecamer B-DNA evidencesthe ability of the complex to establish several electrostatic interactionswith the nucleobases, thus potentially inducing DNA damage, thoughthe simulation of the absorption spectra for models extracted by eachMD trajectory shows that the photosensitizing properties of the complexremain unaltered. The computational results support that the anti-tumoreffect may be related to multiple mechanisms of action.