Stacking Effects on Anthraquinone/DNA Charge-Transfer Electronically Excited States

Abstract

The design of more efficient photosensitizers is a matter of great importance in the field of cancer treatment by means of photodynamic therapy. One of the main processes involved in the activation of apoptosis in cancer cells is the oxidative stress on DNA once a photosensitizer is excited by light. As a consequence, it is very relevant to investigate in detail the binding modes of the chromophore with DNA, and the nature of the electronically excited states that participate in the induction of DNA damage, for example, charge-transfer states. In this work, we investigate the electronic structure of the anthraquinone photosensitizer intercalated into a double-stranded poly(dG-dC) decamer model of DNA. First, the different geometric configurations are analyzed by means of classical molecular dynamics simulations. Then, the excited states for the most relevant poses of anthraquinone inside the binding pocket are computed by an electrostatic-embedding quantum mechanics/molecular mechanics approach, where anthraquinone and one of the nearby guanine residues are described quantum mechanically to take into account intermolecular charge-transfer states. The excited states are characterized as monomer, exciton, excimer, and charge-transfer states based on the analysis of the transition density matrix, and each of these contributions to the total density of states and absorption spectrum is discussed in terms of the stacking interactions. These results are relevant as they represent the footing for future studies on the reactivity of anthraquinone derivatives with DNA and give insights on possible geometrical configurations that potentially favor the oxidative stress of DNA.

Exciton Dynamics in J- and H-Aggregates of a Tricarbocyanine Near-Infrared Dye

“…Based on the fact that the dye-1859 J-aggregates are excited selectively, the formation of the 1400 nm maximum is due to its coexistence with H-aggregates. The nature of this state is discussable: it can correspond to either the CT exciton state, which is often dark because the transition dipole moment from the ground state to charge-transfer states is small in the case of a relatively large separation between the donor, i.e., the Jaggregate, and the acceptor (H-aggregate), 48 or it can correspond to the dark singlet exciton in which antiparallel monomer dipoles of the H-dimer cancel each other. In the latter case, both an electron and a hole are transferred, and one should speak of energy transfer.…”

Theoretical Investigation of the 4,5-Dibromorodamine Methyl Ester (TH9402) Photosensitizer Used in Photodynamic Therapy: Photophysics, Reactions in the Excited State, and Interactions with DNA

“…Figure schematically shows the reduced model used for the geometry optimization of the complexes. Six Li + ions were added to the reduced structure to neutralize the phosphate negative charges and were initially located near the phosphate groups, at distances between 7 and 12 Å from the center of the complex in accordance with the counter-ion distribution function obtained from the molecular dynamics study of Cárdenas and Nogueira on anthraquinone/DNA complex . The position of these six Li + ions was also optimized along the geometry optimization of the complexes.…”

“…Six Li + ions were added to the reduced structure to neutralize the phosphate negative charges and were initially located near the phosphate groups, at distances between 7 and 12 Å from the center of the complex in accordance with the counter-ion distribution function obtained from the molecular dynamics study of Caŕdenas and Nogueira on anthraquinone/DNA complex. 78 The position of these six Li + ions was also optimized along the geometry optimization of the complexes. The electrostatic effects of the solvent during the geometry optimizations were treated by means of the C-PCM continuum model.…”

Photodynamic Therapy—An Up-to-Date Review

“…Type I mechanism supposes the transition of PS molecules from the ground state to the singlet excited state and to the triplet excited state [8]. Then, through electron transfer, these excited PS molecules interact with the substrate to form free radicals [29][30][31]. In contrast, in the photodynamic reaction of type II, excited PS molecules transfer energy to molecular oxygen to produce highly active singlet oxygen that further interacts with lipids, proteins, and nucleic acids, causing cell death by necrosis or apoptosis [8,22,29].…”