Synthesis, characterization, antibacterial and antitumoral activities of mononuclear zinc complexes containing tridentate amine based ligands with N3 or N2O donor groups

• Structures for the complexes were determined by X-ray diffraction and NMR.
• Complex (4) shows the highest cytotoxic activity promoting cell death by apoptosis.
• Morphological analysis of leukemia cells by TEM confirms cell death by apoptosis.
• Complex (2) reaches almost 100% of inhibition against three strains of S. aureus.
• Morphological investigation by TEM suggests effect on bacteria cell division.

The synthesis and characterization of the four zinc(II) complexes [Zn(HL1)Cl2] (1), [Zn(H2L2)Cl2](2), [Zn(H2L3)Cl2] (3) and[Zn(H2L4)Cl2] (4), where HL1 = (bis-2-pyridylmethyl)amine, H2L2 = (2-hydroxybenzyl-2-pyridylmethyl)amine, H2L3 = N-2[(pyridine-2-ylmethyl)amino)ethanol, H2L4 = 1-[(pyridine-2-ylmethyl)-amino]-propan-2-ol are reported; (3) and (4) are new while (2) was reported previously but its structure had not been determined. The complexes were characterized by elemental analysis, IR, UV–Vis and NMR spectroscopic, electrospray ionization mass spectrometry (ESI(+)-MS) and tandem mass spectrometry ESI(+)-MS/MS). X-ray diffraction studies were performed for complexes (1)–(3) revealing the presence of mononuclear structures in the solid state. The X-ray analyses of (1) and (3) demonstrate that HL1 and HL2 act as tridentate ligands, while the ligand H2L2 in (2) is bidentate. The cytotoxic properties of the ligands and of all the complexes were examined using human leukemia THP-1, U937 and Molt-4 cells. Complex (4) exhibited the highest cytotoxicity in this series with an IC50 value of 75 ± 1 μmol L−1 against U937 cells. Transmission electron microscopy (TEM) reveals ultrastructural changes typical of apoptotic cells. The induction of apoptosis was confirmed by the annexin V assay. The antimicrobial activity of complexes (1)–(4) was also investigated in vitro against four Gram-positive bacteria (ATCC10832, ATCC25923, COL) and the clinical Staphylococcus aureus isolate LSA88 (SEC/SEF/TSST-1+). Complex (2) showed the most potent inhibitory activity, reaching almost 100% of inhibition against all strains tested. Morphological investigations using TEM indicate that the antibacterial activity of complex (2) may be associated with the inhibition of cell wall and therefore cell division.

Herein we present the spectroscopic and structural characterization of four new zinc complexes and biological results concerning the cytotoxic activity on human leukemia cells lines (THP-1, U937 and Molt-4) and antimicrobial activity in vitro against four Gram-positive bacteria (ATCC10832, ATCC25923, COL) and one animal strain Staphylococcus aureus LSA88 (SEC/SEF/TSST-1+).Figure optionsDownload as PowerPoint slide