A combined quantum-mechanical and classical molecular
dynamics
study of a recent Ru(II) complex with potential dual anticancer action
is reported here. The main basis for the multiple action relies on
the merocyanine ligand, whose electronic structure allows the drug
to be able to absorb within the therapeutic window and in turn efficiently
generate1O2for photodynamic therapy application
and to intercalate within two nucleobases couples establishing reversible
electrostatic interactions with DNA. TDDFT outcomes, which include
the absorption spectrum, triplet states energy, and spin–orbit
matrix elements, evidence that the photosensitizing activity is ensured
by an MLCT state at around 660 nm, involving the merocyanine-based
ligand, and by an efficient ISC from such state to triplet states
with different characters. On the other hand, the MD exploration of
all the possible intercalation sites within the dodecamer B-DNA evidences
the ability of the complex to establish several electrostatic interactions
with the nucleobases, thus potentially inducing DNA damage, though
the simulation of the absorption spectra for models extracted by each
MD trajectory shows that the photosensitizing properties of the complex
remain unaltered. The computational results support that the anti-tumor
effect may be related to multiple mechanisms of action.