Unveiling n → π* interactions: convergence of quantum crystallography and computational insights

Abstract

We report the identification and characterization of a n → π* interaction between halide anions and a cationic purine nucleobase. Through a combined quantum crystallographic and computational approach, we demonstrate that perpendicular anion⋯(sp²)carbon contacts occur consistently at the C2 position of the purine nucleobase, with geometries and energies comparable to hydrogen bonds. High-resolution X-ray charge density analysis of 2[Br]·H₂O confirms the existence of a bond path and an electron density depletion on C2, supporting a charge-transfer interaction. Complementary theoretical studies reveal a lone pair-to-π* orbital delocalization mechanism, with second-order NBO energies up to 6 kcal mol⁻¹. The interaction persists with various anions, hydration levels, and C2 substitutions, highlighting its robustness and potential relevance in supramolecular chemistry. This study provides the experimental validation of an n → π* contact, supported by topological and electrostatic descriptors.