Cu(II) and Zn(II) Complexes of New 8-Hydroxyquinoline Schiff Bases: Investigating Their Structure, Solution Speciation, and Anticancer Potential

Abstract

We report the synthesis and characterization of three novel Schiff bases (L1−L3) derived from the condensation of 2-carbaldehyde-8-hydroxyquinoline with amines containing morpholine or piperidine moieties. These were reacted with CuCl 2 and ZnCl 2 yielding six new coordination compounds, with the general formula ML 2 , where M = Cu(II) or Zn(II) and L = L1−L3, which were all characterized by analytical, spectroscopic (Fourier transform infrared (FTIR), UV−visible absorption, nuclear magnetic resonance (NMR), or electron paramagnetic resonance (EPR)), and mass spectrometric techniques, as well as by singlecrystal X-ray diffraction. In the solid state, two Cu(II) complexes, with L1 and L2, are obtained as dinuclear compounds, with relatively short Cu−Cu distances (3.146 and 3.171 Å for Cu 2 (L1) 4 and Cu 2 (L2) 4 , respectively). The free ligands show moderate lipophilicity, while their complexes are more lipophilic. The pK a values of L1−L3 and formation constants of the complex (for ML and ML 2 ) species were determined by spectrophotometric titrations, with the Cu(II) complexes showing higher stability than the Zn(II) complexes. EPR indicated the presence of several species in solution as pH varied and binding modes were proposed. The binding of the complexes to bovine serum albumin (BSA) was evaluated by fluorescence and circular dichroism (CD) spectroscopies. All complexes bind BSA, and as demonstrated by CD, the process takes several hours to reach equilibrium. The antiproliferative activity was evaluated in malignant melanoma cells (A375) and in noncancerous keratinocytes (HaCaT). All complexes display significant cytotoxicity (IC 50 < 10 μM) but modest selectivity. The complexes show higher activity than the free ligands, the Cu(II) complexes being more active than the Zn(II) complexes, and approximately twice more cytotoxic than cisplatin. A Guava ViaCount assay corroborated the antiproliferative activity.

Synthesis of Zn(ii) coordination complexes, their molecular design and docking with SARS-CoV-2 RBD protein and Omicron spike protein

“…The Zn-O bond distances in the Zn(II) complex [Zn(L)] (2) were in the same range (2.1024(9)-2.1290(9) Å) found in other Zn(II) complexes described in the literature. [75][76][77] On the other hand, the two Zn-N imine bond distances were shorter and closely related to similar Zn(II) complexes reported in the literature. [75][76][77] The packing views of the Zn(II) complexes [Zn(L)(en)]ClO 4 (1) and [(Zn(L) 2 )] (2) (along a-c axis) are illustrated in Fig.…”

“…[75][76][77] On the other hand, the two Zn-N imine bond distances were shorter and closely related to similar Zn(II) complexes reported in the literature. [75][76][77] The packing views of the Zn(II) complexes [Zn(L)(en)]ClO 4 (1) and [(Zn(L) 2 )] (2) (along a-c axis) are illustrated in Fig. S18 and S19 (ESI †), respectively.…”