Molecular encapsulation of hydroxychloroquine by cucurbit[n]urils: A combined molecular dynamics simulation and quantum chemical study
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Issued Date
2026-07-01
Resource Type
ISSN
10933263
eISSN
18734243
Scopus ID
2-s2.0-105034727412
Journal Title
Journal of Molecular Graphics and Modelling
Volume
146
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Molecular Graphics and Modelling Vol.146 (2026)
Suggested Citation
Nunthaboot N., Wongngam P., Rajchakom C., Wanno B., Boonma T., Nutho B. Molecular encapsulation of hydroxychloroquine by cucurbit[n]urils: A combined molecular dynamics simulation and quantum chemical study. Journal of Molecular Graphics and Modelling Vol.146 (2026). doi:10.1016/j.jmgm.2026.109395 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/116128
Title
Molecular encapsulation of hydroxychloroquine by cucurbit[n]urils: A combined molecular dynamics simulation and quantum chemical study
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Corresponding Author(s)
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Abstract
The inclusion complexation of hydroxychloroquine (HCQ), a biologically active pharmaceutical compound, with three cucurbit[n]urils, CB[6], CB[7], and CB[8], was investigated using a combination of molecular dynamics simulations and quantum chemical calculations. The results indicate that HCQ can be accommodated within the cavity of CB[6], preferentially inserting its aliphatic side chain into the host interior. For CB[7], two distinct binding modes were observed, in which either the aliphatic chain or the aromatic quinoline ring enters the cavity, reflecting greater conformational flexibility in the host-guest association. In contrast, the larger and more adaptable cavity of CB[8] enables deeper penetration of HCQ, leading to a single, well-defined, and highly stabilized binding configuration. Among the hosts examined, CB[8] establishes the most extensive stabilizing interactions with either neutral or di-protonated forms of HCQ, particularly through contacts at its carbonyl-lined portals. In agreement with these structural features, MM/PBSA binding free-energy calculations reveal enhanced host-guest complementarity and the strongest binding affinity for the CB[8] complex. Taken together, these results identify CB[8] as the most promising cucurbituril host for applications involving HCQ encapsulation and potential drug-delivery strategies.