RCH3· · ·O interactions in biological systems: Are they trifurcated H-bonds or noncovalent carbon bonds?

Abstract

In this manuscript, we combine high-level ab initio calculations on some model systems (XCH3 σ-hole/H-bond donors) and a Protein Data Bank (PDB) survey to distinguish between trifurcated H-bonds and noncovalent carbon bonds in XCH3· · ·O complexes (X = any atom or group). Recently, it has been demonstrated both experimentally and theoretically the importance of noncovalent carbon bonds in the solid state. When an electron-rich atom interacts with a methyl group, the role of the methyl group is commonly viewed as a weak H-bond donor. However, if the electron-rich atom is located equidistant from the three H atoms, the directionality of each individual H-bond in the trifurcated binding mode is poor. Therefore, the XCH3· · ·O interaction could be also defined as a tetrel bond (C· · ·O interaction). In this manuscript, we shed light into this matter and demonstrate the importance of XCH3· · ·O noncovalent carbon bonding interactions in two relevant protein-substrate complexes retrieved from the PDB.