Elucidation of inclusion compounds between beta-cyclodextrin/local anaesthetics structure: a theoretical and experimental study using differential scanning calorimetry and molecular mechanics

Pinto, LMA; de Jesus, MB; de Paula, E; Lino, ACS; Alderete, JB; Duarte, HA; Takahata, Y

Abstract

Two local anaesthetics, Bupivacaine (BVC) and Lidocaine (LDC), were studied by experimental as well as theoretical methods. These compounds were associated with a drug delivery system of cyclodextrins (CDs). We used Differential Scanning Calorimetry (DSC) for experimental measurements. We calculated enthalpy change for the process of association between drug and CD. Calculations were performed using Molecular Mechanics (MM) with MM+ and OPLS Forced Fields. Both 1:1 and 1:2 stoichiometries were studied. DSC result indicates formation of stable inclusion compounds for all cases. A difference between physical mixture and inclusion compound was observed. The OPLS GB/SA (OPLSw) results show that the difference of enthalpy change between 1:1 and 1:2 stoichiometries is ca. ±1kcalmol-1 for BVC. For LDC, the corresponding difference is ca. 10kcalmol-1. This indicates that ring out type of docking is stable for the 1:1 stoichiometry. Head-to-head alignment was predicted to be stable in 1:2 stoichiometries. 1:1 and 1:2 associations coexist and establish a dynamic equilibrium. © 2004 Elsevier B.V. All rights reserved.

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Título según WOS: Elucidation of inclusion compounds between beta-cyclodextrin/local anaesthetics structure: a theoretical and experimental study using differential scanning calorimetry and molecular mechanics
Título según SCOPUS: Elucidation of inclusion compounds between ?-cyclodextrin/local anaesthetics structure: A theoretical and experimental study using differential scanning calorimetry and molecular mechanics
Título de la Revista: JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM
Volumen: 678
Número: 01-mar
Editorial: ELSEVIER SCIENCE BV
Fecha de publicación: 2004
Página de inicio: 63
Página final: 66
Idioma: English
URL: http://linkinghub.elsevier.com/retrieve/pii/S0166128004001502
DOI:

10.1016/j.theochem.2004.02.036

Notas: ISI, SCOPUS