Design of New Schiff-Base Copper(II) Complexes: Synthesis, Crystal Structures, DFT Study, and Binding Potency toward Cytochrome P450 3A4

Tunde L Yusuf; Segun D Oladipo; Sizwe Zamisa; Hezekiel M Kumalo; Isiaka A Lawal; Monsurat M Lawal; Nonhlangabezo Mabuba

doi:10.1021/acsomega.1c00906

Design of New Schiff-Base Copper(II) Complexes: Synthesis, Crystal Structures, DFT Study, and Binding Potency toward Cytochrome P450 3A4

ACS Omega. 2021 May 19;6(21):13704-13718. doi: 10.1021/acsomega.1c00906. eCollection 2021 Jun 1.

Authors

Tunde L Yusuf¹, Segun D Oladipo², Sizwe Zamisa³, Hezekiel M Kumalo⁴, Isiaka A Lawal⁵, Monsurat M Lawal⁴, Nonhlangabezo Mabuba¹

Affiliations

¹ Department of Chemical Sciences, University of Johannesburg, Doornfontein, P.O. Box 17011, Johannesburg 2028, South Africa.
² Department of Chemical Sciences, Olabisi Onabanjo University, P. M. B., 2002 Ago-Iwoye, Nigeria.
³ School of Chemistry and Physics, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
⁴ Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
⁵ Chemistry Department, Faculty of Applied and Computer Science, Vaal University of Technology, Vanderbijlpark Campus, Boulevard, 1900 Vanderbijlpark, South Africa.

Abstract

We report the synthesis and crystal structures of three new copper(II) Schiff-base complexes. The complexes have been characterized by elemental analysis and Fourier transform infrared (FT-IR) and UV-visible spectroscopies. The X-ray diffraction (XRD) analysis reveals that complexes 1 and 3 crystallize in a monoclinic space group C2/c and 2 in a triclinic space group P1̅, each adopting a square planar geometry around the metal center. We use a density functional theory method to explore the quantum chemical properties of these complexes. The calculation proceeds with the three-dimensional (3D) crystal structure characterization of the complexes in which the calculated IR and UV-vis values are comparable to the experimental results. Charge distribution and molecular orbital analyses enabled quantum chemical property prediction of these complexes. We study the drug-likeness properties and binding potentials of the synthesized complexes. The in silico outcome showed that they could serve as permeability-glycoprotein (P-gp) and different cytochrome P450 substrates. Our calculations showed that the complexes significantly bind to cytochrome P450 3A4.