title: Lone-pair-π interactions: analysis of the physical origin and biological implications.
abstract: Lone-pair-π (lp-π) interactions have been suggested to stabilize DNA and protein structures, and to participate in the formation of DNA-protein complexes. To elucidate their physical origin, we have carried out a theoretical multi-approach analysis of two biologically relevant model systems, water-indole and water-uracil complexes, which we compared with the structurally similar chloride-tetracyanobenzene (TCB) complex previously shown to contain a strong charge-transfer (CT) binding component. We demonstrate that the CT component in lp-π interactions between water and indole/uracil is significantly smaller than that stabilizing the Cl(-)-TCB reference system. The strong lp(Cl(-))-π(TCB) orbital interaction is characterized by a small energy gap and an efficient lp-π* overlap. In contrast, in lp-π interactions between water and indole or uracil, the corresponding energy gap is larger and the overlap less efficient. As a result, water-uracil and water-indole interactions are weak forces composed by smaller contributions from all energy components: electrostatics, polarization, dispersion, and charge transfer. In addition, indole exhibits a negative electrostatic potential at its π-face, making lp-π interactions less favorable than O-Hπ hydrogen bonding. Consequently, some of the water-tryptophan contacts observed in X-ray structures of proteins and previously interpreted as lp-π interactions [Luisi, et al., Proteins, 2004, 57, 1-8], might in fact arise from O-Hπ hydrogen bonding.
authors.affiliation: CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 5/A4, CZ-625 00 Brno, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Novotný
authors.forename: Sophia
authors.initials: S
authors.lastname: Bazzi
authors.forename: Radek
authors.initials: R
authors.lastname: Marek
authors.forename: Jiří
authors.initials: J
authors.lastname: Kozelka
mesh_terms: D004247:DNA / Q000737:chemistry*; D004583:Electrons; D006860:Hydrogen Bonding; D007211:Indoles / Q000737:chemistry*; D055672:Static Electricity; D014364:Tryptophan / Q000737:chemistry*; D014498:Uracil / Q000737:chemistry*
chemical_list: D007211:Indoles; D014498:Uracil; C030374:indole; D014364:Tryptophan; D004247:DNA