Geometry optimization and energy parameter calculations using density-functional theory method and molecular docking of anticonvulsant therapeutic metal complexes of gabapentin

This work aims to give computational studies of Mn(II), Co(II), Ni(II) and Cu(II) complexes of gabapentin (Gpn), formulized as [M(Gpn)(H2O)3(Cl)].nH2O complexes (where n = 2-6), using DFT method. They were previously synthesized and characterized. DFT calculations are in good agreement with practical studies. Bond lengths of metal complexes reduced or increased rather than that of ligand due to complexation. Bond angles of complexes predict the octahedral environment around the central metal ions predicting sp3d2 or d2sp3hybridization. The calculated energy parameters are negative indicating stability of metal complexes. The small energy band gap of compounds predicts the higher biological activity and high tendency of electron transfer. The comparable frequencies of theoretical and experimental IR may be attributed to different phases of measurement. The induced fit docking SP G-score of the molecular interactions of drug (Gpn) and its metal(II) complexes show that all investigated compounds have a good interaction towards sertonine receptor 5-HT2C and D2 dopamine receptor proteins. Co(II)-Gpn interacts with active site residues of sertonine receptor 5-HT2C with an excellent dock score of -7.370 kcal/mol and RMSD = 1.581 Å. On the other hand, Ni(II)-Gpn has the best dock score of -6.638 kcal/mol and RMSD = 1.995 Å with D2 dopamine receptor. KEY WORDS: Gabapentin, Transition metals, DFT-method, molecular docking Bull. Chem. Soc. Ethiop. 2024, 38(2), 511-526.                                                                DOI: https://dx.doi.org/10.4314/bcse.v38i2.18