Carbon-Centered Hydrogen Bonds in Proteins.

Abstract

Hydrogen bonding (H-bonding) without lone pair(s) of electrons and π-electrons is a concept developed 2-3 years ago. H-bonds involving less electronegative tetrahedral carbon are beyond the classical concept of H-bonds. Herein, we present the first report on H-bonds with tetravalent carbons in proteins. A special bonding arrangement is needed to increase the negative charge density around the sp3-hybridized carbon atom. Therefore, less electronegative elements such as As and Mg, when bonded to sp3-C, enable the C-atoms as H-bond acceptors. Careful protein structure analysis aided by several quantum chemical calculations suggests that these H-bonds are weak to moderate in strength. We developed an empirical equation to estimate the C-H···C H-bond energy in proteins from the distances between the C- and H-atoms. In proteins, the binding energies range from -5.4 to -14.0 kJ/mol. The C-H···C H-bonds assist the substrate binding in proteins. We also explored the potential role of these carbon-centered H-bonds in C-H bond activation through σ-bond metathesis. To our surprise, contribution from these H-bonds is almost of similar magnitude as that from C-H···π H-bonds for C-H bond activation.