Evaluation of nucleotide C–Br⋯O–P contacts from ONIOM calculations: Theoretical insight into halogen bonding in nucleic acids

Halogen bonding can direct the local stereochemical properties of nucleic acids by unique geometric preferences but has been inaccessible to most theoretical studies. Using a two-layer ONIOM method, halogen bonds buried in nucleic acid environments were studied by modeling the nucleotide C–Br⋯O–P contacts in 1P54 and 1RLG (PDB code). Several unconventional methods, associated with the electron density distributions of the interacting atoms, showed the formation of halogen bonds through visualization of such non-covalent interactions in real space. The contributions of halogen bonds to the local conformation of the backbones were also demonstrated through comparison with parallel binding of non-brominated nucleotides.