SYNTHESIS, CHARACTERISATION AND BIOLOGICAL PROPERTIES OF SOME METAL(II) COMPLEXES OF VARIOUS PYRIMIDINE SCHIFF BASES AND THEIR ANALOGUES

Abstract

Metal complexes are important precursors of antimalarial, antimicrobial and anticancer agents. Although pyrimidinyl ligands are known to exhibit biological acivity, studies on metal(II) complexes of some pyrimidines have focused on the non-amino substituted derivatives with no information on ligands of 2-aminopyrimidine derivatives with 2-hydroxy-1-naphthaldehyde and 2-hydroxy-1,4-naphthoquinone. Therefore, the aim of this study was to synthesise and characterise metal(II) complexes of aminopyrimidinyl ligands of 2-hydroxy-1-napthaldehyde/2-hydroxy-1,4-naphthoquinone and evaluate their biological properties. The pyrimidinyl ligands were synthesised from 2-amino-pyrimidine derivatives with 2-hydroxyl-1-napthaldehyde or 2-hydroxy-1,4-naphthoquinone in methanol under reflux at 55-60oC. The ligands were separately reacted with Mn(CH3CO2)2.4H2O, FeSO4.7H2O, Co(CH3CO2)2.4H2O, Ni(CH3CO2)2.4H2O, Cu(CH3CO2)2.H2O and Zn(CH3CO2)2.2H2O, after which the products were further reacted with 2,2’-bipyridine. The compounds were characterised using nuclear magnetic resonance (NMR), infrared (IR) and electronic (UV/Vis) spectroscopy, elemental analysis (CHN), mass spectrometry (EIMS), conductivity and magnetic susceptibility measurements. Antimicrobial activities were evaluated at 10 mg/mL (and inocula suspension of 106 CFU/mL), using agar diffusion methods against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC-25922), Pseudomonas aeruginosa (ATCC-27853), Proteus mirabilis (ATCC-12459), Bacillus cereus (ATCC-8035), Klebsilla oxytoca (ATCC-70603), Aspergillus niger, Aspergillus flevus and Rhizopus Stolonifer. Antioxidant properties were assessed at 50, 100, 200 µg/mL using 2,2’-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging and ferrous ion chelating assays and compared with standard ascorbic acid. The synthesised ligands were 3-{[-(pyrimidin-2-yl)imino]methyl}napthalen-2-ol, 3-{[(4,6-dihydroxypyrimidin-2-yl)imino]methyl}napthalen-2-ol, 3-{[(4,6-dimethylpyrimidin-2-yl)imino]methyl}napthalen-2-ol, 2-(pyrimidin-2-ylamino)naphthalene-1,4-dione, 2-(4,6-dihydroxypyrimidin-2-ylamino)naphthalene-1,4-dione and 2-(4,6-dimethylpyrimidin-2-ylamino)naphthalene-1,4-dione. The ligands and complexes were obtained in 59-86 and 46-96% yields, respectively. The 1HNMR spectra displayed HC=N and N-H signals at 8.22-9.55 and 3.38-4.95 ppm, respectively, while 13CNMR spectra showed C=N signal at 163.98-168.7 ppm. These corroborate the formation of ligands. Infrared spectra confirmed ligands’ bidentate nature and coordination with metal(II) ions through imine/deprotonated amide nitrogen and through the deprotonated naptho/ketonic oxygen atoms. Intra-ligand (𝜋∗←n, 𝜋∗←𝜋) bands observed at 22182-29019 and 30030-39361 cm-1 shifted to lower wave numbers in the complexes confirming coordination of the ligands with metal ions. The d-d transitions of the complexes were consistent with tetrahedral/square planar and octahedral geometries. The CHN data suggest 2:1 (L:M) and 1:1:1 (Ligand:Metal:Bipyridine) stoichiometry for the symmetrical and heteroleptic complexes. The complexes were non-electrolytes with conductivity values of 4.72-16.09 Ohm-1mol-1cm2 in dimethylsulphoxide. Manganese(II) and iron(II) complexes exhibited magnetic moments of 5.54-6.02 and 4.97-5.25 B.M indicative of high spin geometries. [Mn(L1)2].H2O, however, gave 4.39 B.M suggesting tetrahedral geometry. Cobalt(II) and nickel(II) complexes displayed moments of 4.65-5.14 and 2.77-3.59 B.M (symmetrical complexes), 4.29-4.53 and 3.49-3.80 B.M (heteroleptic complexes), respectively, corroborating octahedral and tetrahedral geometries. Copper(II) and zinc(II) complexes had moments of 1.75-2.21 and 0.09-0.43 B.M, indicating square planar, tetrahedral and octahedral geometries for the complexes. The ligands and complexes had antimicrobial activities against tested organisms, with inhibitory zones of 5.5-20.0 and 6.5-34.0 mm, respectively. The antioxidant potentials with ferrous ion chelating assay showed 89.74-92.10% (IC50 of 92–154 µg/mL), while DPPH radical scavenging ability of 69.74-85.10% (IC50 of 79-118 µg/mL) were obtained. Spectral and magnetic data of the metal(II) pyrimidinyl derivatives indicated tetrahedral, square planar and octahedral geometries and the complexes showed potentials for biological application.