title: Bare histidine-serine models: implication and impact of hydrogen bonding on nucleophilicity.
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.
authors.affiliation: Centrale Marseille, Aix Marseille Université, CNRS iSm2 UMR 7313, 13397, Marseille, France. julien.leclaire@centrale-marseille.fr
authors.forename: Julien
authors.initials: J
authors.lastname: Leclaire
authors.forename: Messaoud
authors.initials: M
authors.lastname: Mazari
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Colin
authors.initials: C
authors.lastname: Bonduelle
authors.forename: Olivier
authors.initials: O
authors.lastname: Thillaye du Boullay
authors.forename: Blanca
authors.initials: B
authors.lastname: Martin-Vaca
authors.forename: Didier
authors.initials: D
authors.lastname: Bourissou
authors.forename: Innocenzo
authors.initials: I
authors.lastname: De Riggi
authors.forename: Rémy
authors.initials: R
authors.lastname: Fortrie
authors.forename: Frédéric
authors.initials: F
authors.lastname: Fotiadu
authors.forename: Gérard
authors.initials: G
authors.lastname: Buono
mesh_terms: D000215:Acylation; D006639:Histidine / Q000737:chemistry*; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry; D011522:Protons; D012694:Serine / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D007093:Imidazoles; D011522:Protons; D012694:Serine; D006639:Histidine
keywords: NMR spectroscopy; amino acids; density functional calculations; hydrogen bonding; nucleophilicity