New mixed ligand zinc(II) complexes based on the antiepileptic drug sodium valproate and bioactive nitrogen-donor ligands. Synthesis, structure and biological properties.

Starting from the precursor [Zinc Valproate complex] (1), new mixed ligand zinc(II) complexes of valproic acid and nitrogen-based ligands, formulating as, [Zn(valp)22,9-dmphen] (2), [Zn2(valp)4(quin)2] (3), [Zn(valp)2(2-ampy)2] (4), and [Zn(valp)2(2-ampic)2] (5) (valp = valproate, 2,9-dmphen = 2,9-dimethyl-1,10-phenanthroline, quin = quinoline, 2-ampy = 2-aminopyridine, 2-ampic = 2-amino-6-picoline) were synthesized and characterized using IR, (1)H NMR, (13)C{(1)H} NMR and UV-Vis spectrometry. The crystal structures of complexes 2, 3 and 4 were determined using single-crystal X-ray diffraction. The complexes were also evaluated for their anti-bacterial activity using in-vitro agar diffusion method against three Gram-positive (Micrococcus luteus, Staphylococcus aureus, and Bacillus subtilis) and three Gram-negative (Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis) species. Complex 2 showed considerable activity against all tested microorganisms and the effect of complexation on the anti-bacterial activity of the parent ligand of 2 was also investigated. The anti-bacterial activity of 2,9-dmphen against Gram-negative bacteria was enhanced upon complexation with zinc valproate. On the other hand, complexes 1 and 3 showed weak inhibition activity against the tested species and complexes 4 and 5 didn't show any activity at all. Two methods were used for testing the inhibition of ferriprotoporphyrinIX bio-mineralization: a semi-quantitative micro-assay and a previously self-developed quantitative in-vitro method. Both were used to study the efficiency of these complexes in inhibiting the formation of the Malaria pigment which considered being the target of many known anti-malarial drugs such as Chloroquine and Amodiaquine. Results showed that the efficiency of complex 2 in preventing the formation of ß-Hematin was 80%. The efficiency of Amodiaquine as a standard drug was reported to give 91%.

Copper (II) complexes of the anti-inflammatory drug naproxen and 3-pyridylmethanol as auxiliary ligand. Characterization, superoxide dismutase and catecholase--mimetic activities.

The synthesis and spectral characterization of binary copper (II) complex of the non-steroidal anti-inflammatory drug naproxen (Nap) with formula [Cu(2)(Nap)(4)](n) (1) and its ternary complex with 3-pyridylmethanol (3-pym) of formula [Cu(Nap)(2)(3-pym)(2)](n) (2) were investigated. Complex 1 is polymeric consisting of units of the known paddle-wheel dicopper (II) tetracarboxylates of four naproxenate ions bridging the two copper atoms. The units are axially connected through the neighboring carboxylate oxygen atoms. The X-ray molecular structure measurements of complex 2 showed that it is polymeric consisting of mononuclear units having trans-CuN(2)O(2) + O(2) chromophores which are bridged by 3-pyridylmethanol ligands through their methanolic oxygen atoms. The measured superoxide dismutase (SOD) mimetic activities of the complexes indicated that complexes 1 and 2 are excellent SOD mimics with an IC(50) of 0.30 microM for complex 1 and 0.39 microM for complex 2. The catecholase activities of the complexes toward the aerobic oxidation of 3,5-di-tert-butylcatechol (DTBC) to 3,5-di-tert-butylquinone (DTBQ) showed that both complexes have moderate catalytic oxidase activities.