Binding kinetics calculations of the inclusion of some benzoic acid derivatives and paracetamol in β CD

Djamel Eddine Khatmi (1, 2) , Belgacem Bezzina (1) , Stéphane Humbel (2)

1 جامعة 8 مايو 45، قالمة [الجزائر] = Université du 8 mai 1945 Guelma [Algérie] = University 8 mai 1945 Guelma [Algeria]
2 ISM2 - Institut des Sciences Moléculaires de Marseille

This theoretical study is designed to identify the main driving forces of the inclusion of some benzoic acid (BA) derivatives as well as Paracetamol (ParCM) with β-cyclodextrin (β-CD) by computing the kinetics of binding. Unbiased molecular dynamics (MD) simulations were carried out. The guest molecules were used in ionized and non-ionized states. Based on the computed values of the dissociation rate constant koff, the hydrophobic interactions were discussed. The results show that the more hydrophobic molecule in the non-ionized state give most stable complexes; whereas in the ionized state, less hydrophobic molecules give most stable complexes, meaning a clear charge effect. The low percentage of time of observed H-bonds during the MD simulations is an indication that ones may play only a secondary role in the stability of the non-ionized inclusion complexes, and they don’t play any role in the stability of the ionized complexes. The comparison between the obtained results and those obtained experimentally gives a reasonably agreement.

Mots clés: Cyclodextrin; Inclusion complexes; Molecular dynamic simulation; Binding Kinetics; Benzoic acid derivatives; Paracetamol.

Domaines: Chimie théorique et/ou physique

Djamel Eddine Khatmi, Belgacem Bezzina, Stéphane Humbel. Binding kinetics calculations of the inclusion of some benzoic acid derivatives and paracetamol in β CD. Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2020, 96 (3-4), pp.373-379. ⟨10.1007/s10847-020-00976-1⟩. ⟨hal-02922032⟩