Cl–π Interactions in Protein–Ligand Complexes

Abstract A geometry analysis of Cl–π interactions in protein–ligand complex crystal structures, showed two distinct geometries: “edge‐on” approach of a Cl atom to a ring atom or CC bond and “face‐on” approach towards the ring centroid, with an average interatomic distance of 3.6 Å. The interaction energies were estimated as a sum of the CCSD(T) correlation contribution and the Hartree–Fock energy at the complete basis set limit, for the geometries of the benzene–chlorohydrocarbon model structures at the energy minimum obtained by potential energy surface scans using RMP2(FC)/cc‐pVTZ. The calculated Cl–π interaction energy was −2.01 kcal/mol, and the dispersion force was found to be the major source of attraction. We also discuss the geometry flexibility in Cl–π interactions.