Selective Copper(II) Complexes against Mycobacterium tuberculosis

The present paper describes the synthesis, characterization, and biological activity of five quinoline derivatives, DCQ; ACQ12; ACQ13; ACQ14; ACQophen, and their respective copper-(II) complexes. The class of organic compounds is composed of 4,7-dichloroquinoline (DCQ) and its derivatives containing aliphatic diamines, 1,2-ethanediamine (ACQ12); 1,3-propanediamine (ACQ13); 1,4-butanediamine (ACQ14); and an aromatic diamine, o-phenylenediamine (ACQophen), as a side chain at the 4-position of the quinoline ring. Single-crystal X-ray diffraction was used to determine the structure of the Cu-DCQ complex (1:2 M:L ratio), while the structure of the Cu-ACQ12 complex (1:1 M:L ratio) was obtained from powder X-ray diffraction (PXRD) data. Spectroscopic (IR, Raman, UV-vis) and analytical data supported coordination through the quinoline nitrogen atom in all complexes. DFT (M06-2X/6-31G) calculations complemented the experimental results, revealing distinct coordination geometries and molar ratios: Cu-ACQ13 and Cu-ACQ14 exhibit a 1:1 (M:L) stoichiometry with distorted square-planar Cu-(II) centers, while Cu-ACQophen crystallizes in a 1:2 (M:L) ratio featuring a slightly elongated square-pyramidal geometry, consistent with nonelectrolytic behavior in DMSO. Theoretical vibrational frequencies showed good agreement with experimental spectra, validating the proposed models. The organic and inorganic compounds described here showed potent activity against Mycobacterium tuberculosis (Mtb) and selectivity indexes. The Cu-ACQophen complex exhibited relevant antitubercular activity with a low MIC₉₀ value, about 1.68 μmol L ^-1, and a high selectivity index, SI = 48. Complexes Cu-DQC and Cu-ACQ12 also demonstrated SI values >10.