Weak H-bonds. Comparisons of CH⋯O to NH⋯O in proteins and PH⋯N to direct P⋯N interactions

Abstract

Whereas CH···O H-bonds are usually weaker than interpeptide NH···O H-bonds, this is not necessarily the case within proteins. The nominally weaker CH···O are surprisingly strong, comparable to, and in some cases stronger than, the NH···O H-bonds in the context of the forces that hold together the adjacent strands in protein β-sheets. The peptide NH is greatly weakened as proton donor in certain conformations of the protein backbone, particularly extended structures, and forms correspondingly weaker H-bonds. The PH group is a weak proton donor, but will form PH···N H-bonds. However, there is a stronger interaction in which P can engage, in which the P atom, not the H, directly approaches the N electron donor to establish a direct P···N interaction. This approach is stabilized by the same sort of electron transfer from the N lone pair to the P-H σ* antibond that characterizes the PH···N H-bond.

Analysis of Hydrogen Bonds in Crystals

“…They were computed to be´4.74 kcal/mol for NH¨¨¨O and´2.06 kcal/mol for CH¨¨¨O, a little less than half the NH¨¨¨O value. These values correspond nicely with other calculations designed to compute these HB energies in other systems [60,68,81,[94][95][96]. The substantial interaction energy for NH···O comes even at the expense of a H-bond that suffers certain distortions from the intermolecular orientation it would adopt in the absence of intramolecular constraints associated with the full molecule I.…”

Dissection of the Factors Affecting Formation of a CH∙∙∙O H-Bond. A Case Study

“…They were computed to be −4.74 kcal/mol for NH···O and −2.06 kcal/mol for CH···O, a little less than half the NH···O value. These values correspond nicely with other calculations designed to compute these HB energies in other systems [60,68,81,[94][95][96]. The substantial interaction energy for NH···O comes even at the expense of a H-bond that suffers certain distortions from the intermolecular orientation it would adopt in the absence of intramolecular constraints associated with the full molecule I.…”

Carbon-Oxygen Hydrogen Bonding in Biological Structure and Function

“…Much of the insight gained thus far on the relevance of these interactions derives from computational studies of the relative strengths of CH⅐⅐⅐O bonds in protein structures. For details on these studies, we suggest previous reviews on com- putational studies of biological CH⅐⅐⅐O bonds (3,47). These studies have generally shown CH⅐⅐⅐O bonds to be weak interactions, typically exhibiting half the bond energy of a conventional hydrogen bond in gas-phase calculations.…”

“…However, several studies have illustrated that even aliphatic carbon atoms are capable of forming weak hydrogen bonds, which are denoted as CH⅐⅐⅐O hydrogen bonds (1,2). In contrast, with increased polarization due to adjacent atoms, carbon atoms can theoretically participate in hydrogen bonds as strong as those formed by conventional donors, specifically oxygen or nitrogen (3,4).…”