A Theoretical and Experimental Investigation of the Spectroscopic Properties of a DNA‐Intercalator Salphen‐Type Zn^II Complex

Abstract

The photophysical and DNA-binding properties of the cationic zinc(II) complex of 5-triethylammonium methyl salicylidene ortho-phenylenediiminato (ZnL(2+)) were investigated by a combination of experimental and theoretical methods. DFT calculations were performed on both the ground and the first excited states of ZnL(2+) and on its possible mono- and dioxidation products, both in vacuo and in selected solvents mimicked by the polarizable continuum model. Comparison of the calculated absorption and fluorescence transitions with the corresponding experimental data led to the conclusion that visible light induces a two-electron photooxidation process located on the phenylenediiminato ligand. Kinetic measurements, performed by monitoring absorbance changes over time in several solvents, are in agreement with a slow unimolecular photooxidation process, which is faster in water and slower in less polar solvents. Moreover, structural details of ZnL-DNA binding were obtained by DFT calculations on the intercalation complexes between ZnL and the d(ApT)2 and d(GpC)2 dinucleoside monophosphate duplexes. Two main complementary binding interactions are proposed: 1) intercalation of the central phenyl ring of the ligand between the stacked DNA base pairs; 2) external electrostatic attraction between the negatively charged phosphate groups and the two cationic triethylammonium groups of the Schiff-base ligand. Such suggestions are supported by fluorescence titrations performed on the ZnL/DNA system at different ionic strengths and temperatures. In particular, the values of the DNA-binding constants obtained at different temperatures provided the enthalpic and entropic contributions to the binding and confirmed that two competitive mechanisms, namely, intercalation and external interaction, are involved. The two mechanisms are coexistent at room temperature under physiological conditions.

Fluorescent dyes in the context of DNA‐binding: The case of Thioflavin T

“…All geometry optimizations were performed using the (TD)CAM‐B3LYP functional, with empirical dispersion corrections and the 6‐311 + G(d,p) basis set. In the case of the DNA bound dye, the geometry of the DNA pockets was kept frozen and described using the smaller 6‐31G basis set . To validate this choice for the description of the binding pocket, we have recalculated the transitions energies of the bound dye by using the 6‐31G(d) basis set: the results (not reported) show no differences compared to the 6‐31G ones as a result of the local character of the ThT excitation.…”

Human DNA Telomeres in Presence of Oxidative Lesions: The Crucial Role of Electrostatic Interactions on the Stability of Guanine Quadruplexes

“…In addition, the formation and stabilization of G4s induces the inhibition of the telomerase activity and hence may regulate the cells’ senescence. As such, some therapeutic strategies involving the stabilization of G4s by selective drugs have been proposed and actively studied as an alternative to conventional cancer chemotherapy [43,44,45,46] and more recently have been envisioned as antiviral agents—in particular against the Zika virus [47].…”

Sintesis dan Pencirian Kompleks Nikel(II) Salfen dengan Rantai Sisi Piperidina dan Kajian Interaksi dengan DNA Denggi

“…Lauria et al (2014) juga melaporkan penggunaan nikel(II), kuprum(II) dan zink(II) sebagai interkalator dengan DNA heliks ganda dua. Biancardi et al (2014) Kajian antara kompleks nikel(II) salfen dengan rantai sisi piperidina dan DNA denggi dijalankan bagi melihat interaksi yang berlaku antara kompleks dan DNA. Kajian terdahulu menunjukkan kompleks nikel(II) salfen berinteraksi dengan CT-DNA (DNA dupleks) dan DNA G-kuadrupleks dengan kekuatan ikatan berbeza (Georgiades et al 2010).…”