Bare Histidine–Serine Models: Implication and Impact of Hydrogen Bonding on Nucleophilicity |
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Authors: | Dr. Julien Leclaire Dr. Messaoud Mazari Yuan Zhang Dr. Colin Bonduelle Dr. Olivier Thillaye du Boullay Prof. Blanca Martin‐Vaca Dr. Didier Bourissou Dr. Innocenzo De Riggi Dr. Rémy Fortrie Prof. Frédéric Fotiadu Prof. Gérard Buono |
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Affiliation: | 1. Centrale Marseille, Aix Marseille Université, CNRS iSm2 UMR 7313, 13397, Marseille (France);2. University of Toulouse, UPS, LHFA, 118 Route de Narbonne, 31062 Toulouse CEDEX 09 (France) and CNRS, LHFA UMR 5069, 31062 Toulouse (France) |
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Abstract: | A new family of 2‐hydroxyalk(en/yn)ylimidazoles has been evaluated as serine–histidine bare dyad models for the ring‐opening reaction of L ‐lacOCA, a cyclic O‐carboxyanhydride. These models were selected to unravel the implication of intramolecular hydrogen bonding and to substantiate its influence on the nucleophilicity of the alcohol moiety, as it is suspected to occur in enzyme active sites. Although designed to exclusively facilitate the preliminary step of proton transfer during the studied ring‐opening reaction, these minimalistic models depicted a measureable increase in reactivity relative to the isolated fragments. A couple of reliable experimental and theoretical methods have been developed to readily monitor the strength of the intramolecular hydrogen bond in dilute solution. Results show that the folded conformers are the most nucleophilic species because of the intramolecular hydrogen bond. |
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Keywords: | amino acids density functional calculations hydrogen bonding NMR spectroscopy nucleophilicity |
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