DNA Photosensitization by an "Insider": Photophysics and Triplet Energy Transfer of 5-Methyl-2-pyrimidone Deoxyribonucleoside

Chemistry. 2015 Aug 3;21(32):11509-16. doi: 10.1002/chem.201501212. Epub 2015 Jul 1.

Abstract

The main chromophore of (6-4) photoproducts, namely, 5-methyl-2-pyrimidone (Pyo), is an artificial noncanonical nucleobase. This chromophore has recently been reported as a potential photosensitizer that induces triplet damage in thymine DNA. In this study, we investigate the spectroscopic properties of the Pyo unit embedded in DNA by means of explicit solvent molecular-dynamics simulations coupled to time-dependent DFT and quantum-mechanics/molecular-mechanics techniques. Triplet-state transfer from the Pyo to the thymine unit was monitored in B-DNA by probing the propensity of this photoactive pyrimidine analogue to induce a Dexter-type triplet photosensitization and subsequent DNA damage.

Keywords: DNA; energy transfer; molecular dynamics; nucleobases; photophysics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry
  • DNA / drug effects*
  • DNA / radiation effects*
  • DNA Damage / drug effects*
  • Deoxyribonucleosides / chemistry*
  • Deoxyribonucleosides / pharmacology*
  • Energy Transfer
  • Molecular Structure
  • Photochemical Processes
  • Photosensitivity Disorders / chemically induced*
  • Photosensitizing Agents / chemistry*
  • Photosensitizing Agents / pharmacology*

Substances

  • 5-methyl-2-pyrimidone deoxyribonucleoside
  • Deoxyribonucleosides
  • Photosensitizing Agents
  • DNA