Dinuclear platinum(II) complexes as the pattern for phosphate backbone binding: a new perspective for recognition of binding modes to DNA

J Biol Inorg Chem. 2022 Feb;27(1):65-79. doi: 10.1007/s00775-021-01911-6. Epub 2021 Oct 29.

Abstract

The mechanism of action of most approved drugs in use today is based on their binding to specific proteins or DNA. One of the achievements of this research is a new perspective for recognition of binding modes to DNA by monitoring of changes in measured and stoichiometric values of absorbance at 260 nm. UV-Vis and IR spectroscopy, gel electrophoresis and docking study were used for investigation of binding properties of three dinuclear platinum(II) complexes containing different pyridine-based bridging ligands, [{Pt(en)Cl}2(μ-4,4'-bipy)]Cl2·2H2O (Pt1), [{Pt(en)Cl}2(μ-bpa)]Cl2·4H2O (Pt2) and [{Pt(en)Cl}2(μ-bpe)]Cl2·4H2O (Pt3) to DNA (4,4'-bipy, bpa and bpe are 4,4'-bipyridine, 1,2-bis(4-pyridyl)ethane and 1,2-bis(4-pyridyl)ethene, respectively). In contrast to the system with well-known intercalated ligand (EtBr), covalently bound ligand (cis-Pt) and with minor groove binder (Hoechst 33258), which do not have significant differences in measured and stoichiometric values, the most pronounced deviations are recorded for two dinuclear platinum(II) complexes (Pt1 and Pt2), as a consequence of complex binding to the phosphate backbone and bending of DNA helix. The hydrolysis of complexes and changes in DNA conformation were also analysed as phenomena that may have an impact on the changes in absorbance.

Keywords: DNA binding modes; Dinuclear Pt(II) complex; Pyridine-based bridging ligands; Quantum–mechanical calculations; UV–vis spectroscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / chemistry
  • DNA / chemistry
  • Ligands
  • Phosphates
  • Platinum* / chemistry

Substances

  • Antineoplastic Agents
  • Ligands
  • Phosphates
  • Platinum
  • DNA