Three Water Molecules Mediate Ring Opening of d -Glucose in Aqueous Solutions

High Resolution Image Download MS PowerPoint Slide The mechanism of d -glucose ring opening has long been debated, particularly with regard to whether proton transfer occurs through a concerted or stepwise pathway and how many water molecules participate in the process. Here, we employ ab initio molecular dynamics combined with metadynamics to investigate both possibilities. Our results identify a lower-energy concerted pathway in which proton transfer is mediated by a three-water hydrogen-bond network. Indeed, the transition state features a cyclic hydrogen-bonded water bridge linking OH 1 and O 5 . This bridge promotes proton transfer from OH 1 to O 5, thereby initiating ring opening via an asynchronous yet concerted mechanism. This study provides the first direct dynamical evidence for the involvement of a three-water cyclic network in d -glucose ring opening, in support of earlier mechanistic proposals. The computed activation barrier of 15–18 kcal mol –1 agrees closely with experimental estimates.