Avibactam–Cyclodextrin Inclusion Complexes: Computational and Thermodynamic Insights for Drug Delivery, Detection, and Environmental Scavenging

Alcázar, Jackson; Campodónico, Paola; López, René

Publication:
Avibactam–Cyclodextrin Inclusion Complexes: Computational and Thermodynamic Insights for Drug Delivery, Detection, and Environmental Scavenging

dc.contributor.author	Alcázar, Jackson
dc.contributor.author	Campodónico, Paola
dc.contributor.author	López, René
dc.date.accessioned	2025-10-07T14:40:02Z
dc.date.available	2025-10-07T14:40:02Z
dc.date.issued	2025
dc.description.abstract	The escalating crisis of multidrug resistance, together with the persistence of antibiotic residues in clinical and environmental matrices, demands integrated strategies that couple sensitive detection, efficient decontamination, and controlled delivery. However, current techniques for quantifying avibactam (AVI)—a broad-spectrum β-lactamase inhibitor— such as HPLC-UV lack the sensitivity and specificity required for both therapeutic drug monitoring and environmental surveillance. Encapsulation of AVI within cyclodextrins (CDs) may simultaneously enhance its stability, bioavailability, and detectability, while the high binding affinities of CDs position them as molecular traps capable of scavenging residual AVI. In this study, the inclusion complexation of AVI with various CDs was examined through molecular dynamics (MD) simulations, experimental isothermal titration calorimetry (ITC), and non-covalent interaction (NCI) analysis. Stable 1:1 inclusion complexes were observed between AVI and β-cyclodextrin (β-CD), 2,6-dimethyl-β-cyclodextrin (DM-βCD), and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), with standard Gibbs free energies of binding (∆G◦) of –3.64, –3.24, and –3.11 kcal/mol, respectively. In contrast, γ-cyclodextrin (γ-CD) exhibited significantly weaker binding (∆G◦ = –2.25 kcal/mol). DFT-based NCI analysis revealed that cooperative interaction topology and cavity complementarity, rather than the sheer number of localized contacts, govern complex stability. Combined computational and experimental data establish β-CD derivatives as effective supramolecular hosts for AVI, despite an entropic penalty in the DM-β-CD/AVI complex. These CD–AVI affinities support the development of improved analytical methodologies and pharmaceutical formulations, and they also open avenues for decontamination strategies based on molecular trapping of AVI.
dc.description.version	Versión Publicada
dc.identifier.citation	Alcázar, J.J.; Campodónico, P.R.; López, R. Avibactam– Cyclodextrin Inclusion Complexes: Computational and Thermodynamic Insights for Drug Delivery, Detection, and Environmental Scavenging. Molecules 2025, 30, 3401. https:// doi.org/10.3390/molecules30163401
dc.identifier.doi	https://doi.org/10.3390/molecules30163401
dc.identifier.uri	https://hdl.handle.net/11447/10324
dc.language.iso	en
dc.subject	Avibactam
dc.subject	β-Lactamase inhibitor
dc.subject	Supramolecular derivatization
dc.subject	Cyclodextrin inclusion complex
dc.subject	Molecular dynamics simulation
dc.subject	Isothermal titration calorimetry
dc.title	Avibactam–Cyclodextrin Inclusion Complexes: Computational and Thermodynamic Insights for Drug Delivery, Detection, and Environmental Scavenging
dc.type	Article
dcterms.accessRights	Acceso Abierto
dcterms.source	Molecules
dspace.entity.type	Publication