Structural Determination of Cephalexin/β-Cyclodextrin Inclusion Complex and its Validation using Molecular Simulation Methods

Abstract

In this work, molecular simulation methods combining molecular docking and the structure elucidation of inclusion complex of cephalexin/β-cyclodextrin (β-CD) was determined using 1H NMR. Molecular docking studies showed that the complex formation process between β-CD and cephalexin was favourable and spontaneous because of negative values of binding energies. Molecular docking studies also confirmed the entry of aromatic ring into the cavity. Molecular mechanics studies were performed for aromatic ring of cephalexin, in different orientations and from both cavity ends, to measure the parameters of inclusion depth and mode of entry. The resultant structure was studied for HOMO-LUMO gap to validiate the method. The final structure was established using 1H NMR, molecular mechanics, HOMO-LUMO gap and molecular docking.

Investigation of the Affinity of Ceftobiprole for Selected Cyclodextrins Using Molecular Dynamics Simulations and HPLC

“…Standard enthalpies (∆Hs) of complex formation were determined based on the heats of formation of each ingredient. Other studies of cephalosporin/CD complexes generally involve the manual or docking-assisted building of the complex structure, followed by energy minimisation using a selected force field, and then calculating the binding energy or ∆H of formation [16][17][18][19]; however, MD studies are then omitted, and the obtained energy does not take into account solvation nor the change in the entropy of the system. Interestingly, it has also been proposed to calculate ∆G using the Generalised Born Surface Area (GBSA) equation applied directly to the structures predicted in the docking study, without performing MD simulations [20].…”

Cyclodextrin Inclusion Complexes with Antibiotics and Antibacterial Agents as Drug-Delivery Systems—A Pharmaceutical Perspective

“…To understand the basic aspects of the cefalexin (the first generation of cephalosporins) binding mechanism to the β-CD cavity, structural characterisation was performed by NMR, molecular mechanics, quantum mechanical calculations, and molecular docking [64]. * Abbreviations used in the tables are expanded in the section "List of abbreviations", and additional explanations are provided below Table 1.…”

“…To understand the basic aspects of the cefalexin (the first generation of cephalosporins) binding mechanism to the β-CD cavity, structural characterisation was performed by NMR, molecular mechanics, quantum mechanical calculations, and molecular docking [ 64 ].…”