DFT Simulation of Structural and Optical Properties of 9‑Aminoacridine Half-Sandwich Ru(II), Rh(III), and Ir(III) Antitumoral Complexes and Their Interaction with DNA

In this work, we
use DFT-based methods to simulate the chemical
structures, optical properties, and interaction with DNA of a recently
synthesized chelated C^N 9-aminoacridine arene Ru­(II) anticancer agent
and two new closely related Rh­(III) and Ir­(III) complexes using DFT-based
methods. Four chemical models and a number of theoretical approaches,
which representatively include the PBE0, B97D, ωB97X, ωB97X-D,
M06, and M06-L density functionals and the LANL2DZ, def2-SVP, and
def2-TZVP basis sets, are tested. The best overall accuracy/cost performance
for the optimization process is reached at the ωB97X-D/def2-SVP
and M06/def2-SVP levels of theory. Inclusion of explicit solvent molecules
(CHCl3) further refines the geometry, while taking into
account the crystal network gives no significant improvements of the
computed bond distances and angles. The analysis of the excited states
reveals that the M06 level matches better the experimental absorption
spectra, compared to ωB97X-D. The use of the M06/def2-SVP approach
is therefore a well-balanced method to study theoretically the bioactivity
of this type of antitumoral complexes, so we couple this TD-DFT approach
to molecular dynamics simulations in order to assess their reactivity
with DNA. The reported results demonstrate that these drugs could
be used to inject electrons into DNA, which might broaden their applications
in photoactivated chemotherapy and as new materials for DNA-based
electrochemical nanodevices.