Interstitial water and the formation of low barrier hydrogen bonds: A computational model study

Abstract

The B3LYP/D95þ(d,p) analysis of the uncharged low barrier hydrogen bond (LBHB) between 4-methyl-1H-imidazole (Mim) and acetic acid (HAc) shows that uncharged LBHBs can be formed either by adding three water molecules around the cluster or by placing the Mim-HAc pair in a dielectric environment created by a polarizable continuum model with a permittivity larger than 20.7. The permittivity of environment around uncharged LBHB can be lowered significantly by including water molecules into the system. A Mim-HAc LBHB stabilized with one water molecule observed in diethyl ether (e ¼ 4.34), with two water molecules in toluene (e ¼ 2.38), and with three water molecules in vacuo (e ¼ 1). Solvation models with different numbers of water molecules predict average differences in the proton affinities of the hydrogen bonded bases (DPA) for stable uncharged LBHB systems in vacuo to be 91.5 kcal/mol being different from the DPA values close to zero in charge-assisted LBHB systems. The results clearly indicate that small amounts of interstitial water molecules at the active site of enzymes do not preclude the existence of LBHBs in biological catalysis. Our results also show that interstitial water molecules provide a useful clue in the search for uncharged LBHBs in an enzymatic environment and the number of water molecules can be used as a relative measure for the polarity around the direct environment of LBHBs.

Direct evidence of a low barrier hydrogen bond in the catalytic triad of a Serine protease

“…The primary focus of most of the studies has been on the NMR chemical shielding effects of the catalytic His aromatic nuclei; 1 H, 15 N and 13 C. Unusual large low- field shift of the N δ1 H protons, for single-well H-bonds (20–22 ppm) and for LBHB (17–19 ppm) has been proposed as one of the main criteria for the formation of a short, strong hydrogen bond under protonation of the catalytic His in complex with Asp in the intermediate induced complexes of serine type proteases with inhibitors 5 . This has been confronted in many theoretical 4 , 13 and experimental studies 3 , 14 . It was argued that the large down field shifts that is seen for the proton between His….Asp 4 is equally consistent with both the LBHB and the SIHB 15 .…”

In Situ Measurement of Surface Functional Groups on Silica Nanoparticles Using Solvent Relaxation Nuclear Magnetic Resonance

“…The decrease of the water absorbance indicates the blockage of the micropores due to the grafting of the functional groups. The coordination number of the adsorbed water molecules varies for different surface functional group. − One NH 2 group can coordinate with two H 2 O molecules, while one COOH and OH molecule can coordinate with three and two H 2 O molecules, respectively, as shown in Figure S8.…”