Rational modulation of N and O binding in Fe(III) complex formation derived from hydroxychloroquine: Synthesis, spectroscopic, computational, and docking simulation with human thrombin plasma

• Published in: Journal of molecular structure 2022-04, Vol.1254, p.132268, Article 132268
• Main Authors: El-Sayed, Doaa S., Elbadawy, Hemmat A., Khalil, Tarek E.
• Format: Article
• Language: English
• Subjects: Computational; Docking; Fe(III) complex; Hydroxychloroquine; Spectral study
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.132268

•[Fe-HCQ] complex was synthesized, characterized with different spectroscopic tools.•Computational studies predicted the electronic behavior of Fe(III) complex.•Topological analysis interpreted bonding behavior around Fe(III) center.•Molecular docking investigated the binding of Fe-HCQ towards human thrombin plasma. Hydroxychloroquine (HCQ) can bind with Fe(III) by both N and O atoms to form either [Fe-HCQ] or [Fe-(HCQ)2] complex. The characterization of the product developed as a result of the reaction between HCQ and Fe(III) salt suggested the formation of [Fe-HCQ] complex. Rational studies characterized the synthesized complex with several types of spectroscopic analysis such FT-IR, UV-Visible and mass spectra and XRD evaluation. The computational analysis involved in this study view an investigation about the electronic behavior around the central metal atom coordinated to the donor ligand atoms. The postulation discussed the formation of [Fe-HCQ] complex rather than [Fe-(HCQ)2] complex. Quantum reactivity parameters (Physiochemical properties) and FMOs analysis were studied. Important topological parameters such as electronic localization function (ElF), average local ionization energy (ALIE), and molecular electrostatic potential (MEP) analyses were studied; also, non-covalent interaction- reduced density gradient (NCI-RDG) analysis illustrated the type of interactions in HCQ and [Fe-HCQ]. Molecular docking of the ligand and its synthesized complex was performed on the protein crystal structure (5TO3) of human thrombin plasma, and a good predicted result was obtained in inhibiting thrombosis acceleration with the synthesized Fe-complex. Molecular dynamic simulation analysis was applied to predict the stability of the studied compounds based on energetic variables and RMSD values. [Display omitted]