Investigation of the energetics of C-H⋯O hydrogen bonds in the DNA i-motif via the equilibrium between alternative intercalation topologies

Jean Louis Leroy, Karim Snoussi, Maurice Guéron

Research output: Contribution to journalArticlepeer-review

Abstract

The existence of C-H⋯O hydrogen bonds in organic and biological molecules is suggested by the observation in crystal structures of short hydrogen-to-oxygen distances (<0.27 nm) and of the approximate alignment of the C-H and H⋯O segments. However, the associated free energy is rarely known. Here, we determine the free energy of C-H⋯O bonds in the i-motif, a four-stranded intercalated structure of DNA strands carrying a stretch of at least two cytidines. It includes narrow grooves that bring the phosphate groups of two anti-parallel strands in close proximity, thus enhancing electrostatic repulsion. But the sugar moieties are also close, and may form pairs suitable for C-H1′⋯O4′ hydrogen bonds across the groove. It has been suggested that such bonds could explain the narrowness of the grooves and the stability of the i-motif. An opportunity for the evaluation of the free energy of such hydrogen bonds comes from the observation that the oligo-deoxynucleotides d(Cn) (n = 2 to 6) form two i-motif structures with different intercalation topologies. The most conspicuous difference between them is that one forms two more sugar pairs than the other. In high salt, where electrostatic effects of the phosphate charge distribution are reduced, the free energy difference between the two structures should come mostly from the corresponding C-H⋯O bonds, whose free energy could then be determined. The model can be tested by its prediction that the equilibrium constant between the two structures should be independent of n in high salt, and this is supported by NMR measurements, except for the quite short strand d(C2). The equilibrium constant corresponds to a free energy difference of -5.2 kJ mol-1. This is assigned to the difference (two) in the number of sugar pairs. The geometry derived from solution structures indicates a single C-H⋯O bond within each pair, for a free energy per bond of 2.6 kJ mol-1. This is much less than values commonly quoted for C-H⋯O bonds (e.g. 7.5 kJ mol-1), probably because the C-H⋯O bonds of sugar pairs are not formed anew in one structure, but replace C-H⋯O bonds to water in the other structure. Given the small value of the associated free energy, it seems difficult to single out C-H⋯O bonds as a structural determinant of the formation and stability of the i-motif.

Original languageEnglish (US)
Pages (from-to)S171-S176
JournalMagnetic Resonance in Chemistry
Volume39
Issue numberSPEC. ISS.
DOIs
StatePublished - Dec 2001

Keywords

  • DNA
  • H
  • H-bonded CH
  • Hydrogen bonds
  • NMR
  • Narrow groove
  • i-motif

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)

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