Binary and ternary complexes involving ethambutol and bio-relevant ligands such as amino acids, peptides and DNA constituents: speciation studies and theoretical approach

Abstract

The interaction of Cu(II) with ethambutol (EMB) was investigated. The complexes formed are the 1:1 complex, Cu(EMB) and the deprotonated forms, Cu(EMB)H_-1 and Cu(EMB)H_-2. The pK_a values of the induced ionization of the hydroxyl group of EMB upon coordination are 6.76 and 7.93. The formation equilibria of the ternary complexes Cu(EMB)L, involving the secondary ligand such as amino acids, peptides or DNA constituents (L), were investigated. Ternary complexes with amino acids showed Cu(EMB)L and the protonated form Cu(EMB)LH. The pK_a value of the protonated complexes are 5.75–9.09. Peptides form Cu(EMB)L and the deprotonated form Cu(EMB)LH_-1. DNA constituents form Cu(EMB)L and Cu(EMB)L₂. The thymine complex is more stable than that of uridine. Uridine-5’-monophosphate forms a stronger complex than uridine; inosine-5^’-monophosphate (IMP) forms in addition the protonated form of the 1:1 complex. It forms a more stable complex with Cu(EMB)²⁺ than inosine. The speciation diagrams were evaluated. Density functional theory (DFT) calculations were performed. The calculations included investigation of molecular electrostatic potential surfaces. A molecular docking analysis of ethambutol and its complex with mycobacterium tuberculosis (PDB ID: 5UHG) is investigated.

Keywords:

• Ethambutol complexes
• binary and ternary complexes
• speciation
• effect of solvent
• DFT
• molecular docking

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.