title: Evaluation of the regioselective delactonization of tri-sialic acid lactone by in-solution molecular dynamics simulation.
abstract: An approximate model for the delactonization of tri-sialic acid lactone is presented with two water-layers that led to neutral hydrolysis of δ-lactone. The hydrolytic reactivity was studied with a 10-ns in-solution molecular dynamics simulation. The initial step of this hydrolysis involves a reactant water nucleophile complex via a proton transfer with another water molecule. Therefore, the probability of water molecules localized at the hydrolytic center correlates to the hydrolysis of δ-lactone. The stepwise delactonization of α2,8-(NeuAc)(3) lactone results/resulted from water concentration discrepancy near the carbonyl carbon of lactones in two water oxygen···carbonyl carbon shells, and the distances of OC···O(water) layers were 2.8 Å and 5.1 Å. Based on in-solution molecular dynamics study, the motion of water molecules over the re-face of the carbonyl groups was used for the quantitative description of the residence probability, p, whose value is 0.11 for lactone I and 0.33 for lactone II. The geometric criteria used to determine the residence statistics are (1) the distance of water-oxygen···carbonyl carbon in less than 5.1 Å and (2) the cone angle, θ, of carbonyl OC···O(water) in the range of 85-115°. As expected, a higher residence probability at lactone II led to its faster hydrolysis. Both the radial g(r) and angular p(θ) pair distribution functions of water oxygen and carbonyl groups of lactones ensure a better surrounding hydration encounter for lactone II. In contrast, water molecules around lactone I are deduced due to a steric hindrance by the turn structure of α2,8-(NeuAc)(3) lactone.
authors.affiliation: Department of Chemistry, National Taiwan University, Taipei 106, Taiwan. jasonhemlot@gmail.com
authors.forename: Chien-Sheng
authors.initials: CS
authors.lastname: Chen
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Yu
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Hsu
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.forename: Jim-Min
authors.initials: JM
authors.lastname: Fang
authors.forename: Shih-Hsiung
authors.initials: SH
authors.lastname: Wu
mesh_terms: D002236:Carbohydrate Conformation; D006868:Hydrolysis; D007783:Lactones / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D012794:Sialic Acids / Q000737:chemistry*; D012996:Solutions; D013237:Stereoisomerism
chemical_list: D007783:Lactones; D012794:Sialic Acids; D012996:Solutions