Evaluation of the Solvent Competitive Binding in Halogen and Chalcogen Bonding: A Theoretical Theory Study for Supramolecular Applications

Abstract

Noncovalent interactions such as halogen bonding (HaB) and chalcogen bonding (ChB) are increasingly utilized in host-guest chemistry and supramolecular catalysis due to their high directionality and tunable strength. However, the choice of solvent remains a critical challenge, as solvent molecules can compete with the intended substrates for the electrophilic sigma-hole sites of the catalysts or receptors. In this work, we present a comprehensive DFT study (PBE0-D3/def2-TZVP) analyzing the competitive binding of seven common solvents (acetonitrile, ether, water, methanol, DMF, DMSO, and acetone) with four model electrophilic probes: CF3-I, CF3-Br, CF3-Se-CF3, and CF3-Te-CF3. By evaluating the interaction energies and Molecular Electrostatic Potential (MEP) surfaces, accounting for the dielectric constant of each medium, we establish a classification of solvent competitiveness. Our results provide an experimental guide for identifying the least competitive solvents, thereby optimizing the efficiency of HaB and ChB driven molecular recognition and catalytic processes in solution.