{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T13:07:21Z","timestamp":1793279241665,"version":"4.5.0"},"reference-count":41,"publisher":"AIP Publishing","issue":"16","funder":[{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/X033139\/1"],"award-info":[{"award-number":["EP\/X033139\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pubs.aip.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,10,28]]},"abstract":"<jats:p>Understanding how solvent molecules participate in chemical reaction mechanisms remains a central challenge in molecular simulations. Here, we investigate the mechanism and kinetics of glucose mutarotation in aqueous solution using a combined well-tempered metadynamics and mean force integration approach, within the framework of canonical transition state theory. We compute free energy landscapes and kinetic rate coefficients for the \u03b1 \u2192 \u03b2 mutarotation in pure water, as well as in systems representative of water\/methanol and water\/acetone mixtures. Our simulations indicate that ring opening and closure occur via concerted, solvent-assisted pathways, with ring opening identified as the rate-determining step. The temperature dependence of the predicted kinetic constant is quantitatively consistent with experimental data, while the reactivity modulation by organic co-solvents is captured qualitatively. Overall, the results provide molecular-level insight into solvent-mediated carbohydrate chemistry, demonstrating that the solvent participates in all key reactive steps and highlighting how enhanced sampling techniques can yield mechanistic and kinetic information in explicitly solvated reactive systems.<\/jats:p>","DOI":"10.1063\/5.0288357","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T10:37:56Z","timestamp":1761215876000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Solvent-mediated mechanism and kinetics of glucose mutarotation from enhanced sampling simulations"],"prefix":"10.1063","volume":"163","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4250-631X","authenticated-orcid":false,"given":"Francesco","family":"Serse","sequence":"first","affiliation":[{"name":"Department of Chemistry, Materials and Chemical Engineering 1 , Politecnico di Milano, Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio","family":"Trespi","sequence":"additional","affiliation":[{"name":"Institute of Energy and Process Engineering, ETH Zurich 2 , 8092 Zurich,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4841-9321","authenticated-orcid":false,"given":"Matteo","family":"Paloni","sequence":"additional","affiliation":[{"name":"Thomas Young Centre and Department of Chemical Engineering, University College London 3 , London WC1E 7JE,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3371-2090","authenticated-orcid":false,"given":"Matteo","family":"Salvalaglio","sequence":"additional","affiliation":[{"name":"Thomas Young Centre and Department of Chemical Engineering, University College London 3 , London WC1E 7JE,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Mazzotti","sequence":"additional","affiliation":[{"name":"Institute of Energy and Process Engineering, ETH Zurich 2 , 8092 Zurich,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"317","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"issue":"1","key":"2025102306375351300_c1","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1002\/aic.690050107","article-title":"Simplified calculation of chemical equilibria in hydrocarbon systems containing isomers","volume":"5","year":"1959","journal-title":"AIChE J."},{"issue":"3","key":"2025102306375351300_c2","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1021\/i100011a009","article-title":"Chemical thermodynamic properties of isomer groups","volume":"22","year":"1983","journal-title":"Ind. 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