Low-barrier hydrogen bonds LBHBs

More recently, Cassidy et aid conducted additional H NMR experiments to evaluate the basicities of the dyad H57-D102 in the tetrahedral complexes of chymotrypsin with the peptidyl trifluoromethyl ketones (TFKs) N-acetyl-L-Leu-DL-Phe-CFs and A-acetyl-oL-Phe-CFs. The proton bridging His-57 and Asp-102 is part of a low-barrier hydrogen bond (LBHBs). In H NMR spectra at pH 7.0, these protons appear at 8 18.9 and 18.6 ppm. 

Scheme 4.2 Bond energy as a function of hydrogen position (black solid line), assuming identical pff, values for the donor and acceptor, relative to the lowest vibrational energy level of the hydrogen atom (highlighted by a dotted line), (a) A standard, symmetric hydrogen bond (b) the corresponding low-barrier hydrogen bond (LBHB). The red line represents the probability density function [27, 28].

The topic of low-barrier hydrogen bonds (LBHBs) and the question of how they are involved in enzyme function has been discussed heavily in the literature recently. Hydrogen bonds between two bases of nearly matched proton affinity often exhibit strongly perturbed bond lengths and spectroscopic parameters it remains somewhat unclear exactly how the spectroscopic parameters reflect total energy or reactivity. In this study, we report H NMR chemical shift data and surveys of structural preferences for the well-studied 0-H---0 systems, and also for less studied, but biologically important N-H-0 systems, in particular the imidazole and imidazolium functionality. The H shifts also show interesting trends in comparison with O-H-O motifs, which will require further scrutiny. 

Hydrogen bonds appear to be essential in all enzyme-catalyzed reactions, although why they are essential and how they promote function is an open question. In recent years a specific hypothesis for their involvement in catalysis has emerged so-called low-barrier hydrogen bonds (LBHB) have been proposed to lower the transition state energy for many enzymatic reactions, including those of serine protease, citrate... 

After the experimental demonstration of TSS by HBs, it has been proposed by several workers that HBs stabilize TSs in a special nonelectrostatic way, which was termed low-barrier hydrogen bond (LBHB).107 109 The LBHB proposal has suggested that catalytic HBs involve a flat minimum rather than a double minimum. Unfortunately, this suggestion (which is sometimes true) does not allow one to distinguish the LBHB proposal from the previous proposal of ionic HBs (and thus, does not provide a testable definition). 

Schutz, C.N. and Warshel, A. (2004). The low-barrier hydrogen bond (LBHB) proposal revisited the case of the Asp...His pair in serine proteases. Proteins 55 (3), 711-723... 

Low-barrier hydrogen bonds (LBHB). Some enzymes have been proposed to catalyze their reactions by forming a so-called low-barrier, partially covalent (delocalized) hydrogen... 

Recently much attention has been devoted to the detailed mechanism by which the class of enzymes called serine proteases work. These enzymes catalyze the ubiquitous and paramount cleavage of peptide bonds and all have the so-called catalytic triad (His-Asp-Ser) in common. A number of studies have suggested that a low barrier hydrogen bond (LBHB) is involved in the reaction mechanism as a partial proton transfer between His and Asp (N-H---0). In... 

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