Publications

Binding modes of a flexible ruthenium polypyridyl complex to DNA

Author(s)
Meritxell Malagarriga Pérez, Leticia González
Abstract

Ruthenium(II) polypyridyl complexes are attractive binders to DNA. Modifying the hydrophobicity, shape, or size of the ancillary ligands around the central ruthenium atom can induce changes in the binding mode to the DNA double helix. In this paper, we investigate the binding modes of [Ru(2,2'-bipyridine)2 (5-{4-[(pyren-1-yl)methyl]-1H-1,2,3-triazol-4-yl}-1,10-phenanthroline)]2+ (RuPy for short), a metal complex featuring a flexible pyrene moiety known for its intercalative properties. Classical molecular dynamics simulations are employed to gain insight into the non-covalent binding interactions of RuPy with two different 20 base pair DNA sequences, poly(dA)poly(dT) (AT) and poly(dC)poly(dG) (CG). In addition to examining the intercalation of the pyrene moiety from the major groove, the stability of RuPy-DNA adducts is investigated when the metal complex interacts externally with the DNA and with the major and minor groove pockets. The results indicate that external interaction and major groove binding are not stable, whereas intercalation consistently forms stable adducts. Minor groove binding showed less stability than intercalation and more variability, with some trajectories transitioning to intercalation, involving either the pyrene moiety or a bipyridine ligand. Pyrene intercalation, especially from the minor groove, was the most stable, while bipyridine intercalation was less favorable and associated with higher binding free energies.

Organisation(s)
Department of Theoretical Chemistry, Research Platform Accelerating Photoreaction Discovery
External organisation(s)
Vienna Doctoral School in Chemistry (DoSChem)
Journal
Physical Chemistry Chemical Physics
Volume
26
Pages
27116-27130
No. of pages
15
ISSN
1463-9076
DOI
https://doi.org/10.1039/d4cp02782e
Publication date
10-2024
Peer reviewed
Yes
Austrian Fields of Science 2012
104017 Physical chemistry, 103006 Chemical physics
Keywords
ASJC Scopus subject areas
Physics and Astronomy(all), Physical and Theoretical Chemistry
Portal url
https://ucrisportal.univie.ac.at/en/publications/binding-modes-of-a-flexible-ruthenium-polypyridyl-complex-to-dna(a349aad1-24d5-4110-9e1d-b1c6afa30b15).html