Structure and stability of an eventual inclusion complex formed by Lidocaine and two cyclodextrins (α- and β-CD) were investigated using molecular mechanics and quantum-chemical methods in the gas phase and in water. The molecular docking and quantum chemical calculations results show that no inclusion complex is formed between α-CD and Lidocaine molecule, while the conformational research allowed observing two minimum-energy structures between this molecule and β-CD. From a potential energy scan, a partial inclusion of the two ends of Lidocaine by the secondary face of the cavity of β-CD is observed with a better stability for the complex including the ((-N(C2H5)2) group in it. The minimum energy conformers, obtained by semi empirical method (PM3), have been exposed to fully geometry optimization employing ONIOM2 calculations by combining PM3 method with B3LYP, M06-HF and WB97XD functionals at 6-311G (d,p) basis set. The results show that complexation reactions are thermodynamically favored (G° ˂ 0) and the inclusion complexes are energetically stables and well structured (S° ˂ 0). According to the analysis of natural bond orbitals, the Van der Waals interactions are the sole driving forces that ensure the stability of the formed complexes.

Nourredine Meddah-Araibi, Teffaha Fergoug, Mansour Azayez, Cherifa Zelmat, Jendara Ali Cherif and Youcef Bouhadda