CHinteractions

CHinteractions is a term used to describe a class of weak non-covalent interactions that involve carbon-hydrogen groups participating in attractive contacts. These interactions include C–H...Y hydrogen bonds, where Y is an electronegative atom such as O, N, S, or a halogen; CH…π contacts with aromatic or other π-systems; and CH…metal interactions observed in some organometallic contexts. Individually weaker than most classical hydrogen bonds, CHinteractions can collectively influence molecular recognition, conformational preferences, and crystal packing.

Geometrically, C–H donors in CHinteractions tend to align toward lone pairs or π-surfaces, with shorter contacts and more linear approaches generally indicating stronger interactions. Energetically, contributions are typically small on a per-contact basis and arise from a combination of electrostatics, polarization, and dispersion. The cumulative effect of multiple CHinteractions can be biologically and chemically meaningful, particularly in crowded environments such as protein binding pockets, DNA grooves, or densely packed crystal lattices.

CHinteractions are studied across disciplines, including chemistry, biochemistry, and materials science. Experimental evidence comes from X-ray crystallography, which can reveal close C–H…acceptor contacts, and from NMR and infrared spectroscopy that suggest changes in electronic environments. Computational approaches, such as dispersion-corrected density functional theory and energy decomposition analyses, help quantify their contributions and elucidate their role in binding affinity and structure.

Applications of recognizing CHinteractions include rational ligand design, crystal engineering, and the interpretation of conformational landscapes in biomolecules. They are generally considered supplementary to stronger interactions but can be decisive in determining preferred geometries and assemblies under specific conditions.