Syntheses, Structures and Biological Activity of Some Schiff Base Metal Complexes

: Four new binuclear Schiff base metal complexes [(MCl 2 ) 2 L] {M = Fe 1, Co 2, Cu 3, Sn 4, L = N,N’-1,4-Phenylenebis (methanylylidene) bis (ethane-1,2-diamine)} have been synthesized using direct reaction between proligand (L) and the corresponding metal chloride (FeCl 2 , CoCl 2 , CuCl 2 and SnCl 2 ). The structures of the complexes have been conclusively determined by a set of spectroscopic techniques (FT-IR, 1 H-NMR, and mass spectra). Finally, the biological properties of the complexes have been investigated with a comparative approach against different species of bacteria ( E. coli G - , Pseudomonas G - , Bacillus G +, Staphylococcus G + , and Streptococcus G + ).


Introduction:
Over decades Schiff base continue attracts antibiotic designer's attention because of distinctive chelating features 1 . Antibacterial activity of such ligand containing donor atoms can be enhanced significantly by coordination to a metal ion 2,3,4 . Moreover, some natural molecules such as chlorophyll, hemoglobin, carbonic anhydrase, vitamin B12, xanthine oxides, and hemocyanin clearly indicate the important linkage between organic ligand and metal elements 5 . Scientists have been employed Schiff base in a wide range of medical applications such as antibacterial 6,7 , antifungal 8 , antitumor 9 , antiviral 10 , anti-HIV 11 , herbicidal 12 , and anti-influenza virus 13 .
In light of these medical facts, we present herein the synthesis, spectroscopic characterization and biological activity of a series of Schiff base metal complexes 1-4. Chemical analysis evidence allows proposing a binuclear aggregation mode for these M II complexes of tetradentate Schiff-bases. The main objective of the present work was to find the antibacterial activity of these Schiff base metal complexes toward six different pathogens (E. coli G-, Pseudomonas G-, Bacillus G+, Staphylococcus G+, and Streptococcus G+).

Material and Methods: Chemical Materials
Terephthalaldehyde, 1,2-ethane-diamine, and metals chloride were purchased from commercial source Sigma-Aldrich and used as received. FT-IR spectra were recorded on a Bruker spectrometer. 1  705 base (Yield = 0.20 g, 80%. mp. = 265-267 o C) was used for complexation without any further purification.

Schiff Base Metal Complexes Synthesis
Complexes 1-4 were synthesised by the direct addition of the Schiff base proligand (L) to metal chloride in 1:2 molar ratio (Eqn. 2). The mixture was dissolved in hot ethanol and the obtained solution was boiled for 4 h with reflux and continuous stirring led to form colored products [15][16][17] .

Physical and Spectral Data [(FeCl 2 ) 2 L] 1
An excellent yield of complex 1 (0.18 g, 85 %, m. p. 140-142 o C) was obtained from a typical metathesis reaction between FeCl 2 and L (equation     4 and NH 4 Cl) fragments. These peaks (Fig. 11) mentioned above prove the proposed structure for complex 2.

Results and Discussion:
L proligand has been prepared according to previous reported procedure 14

Equation 1
A similar synthesis strategy was adopted (Eqn. 2) to synthesise complexes 1-4. It is a simple one pot reaction involved 1:2 molar ratio between the proligand (L) and (FeCl 2 , CoCl 2 , CuCl 2 , SnCl 2 ) in ethanol that led to synthesise very stable complexes 1-4 toward air and moisture. DMSO is the only effective solvent toward these complexes. Solubility difficulties of complexes 1-4 blocked our path to obtain suitable single crystals for crystallography structures analysis in this study. Thus, complexes structures were confirmed through different spectroscopic analyses.

FT-IR Spectra
FT-IR spectra of compounds 1-4 are in agreement with free ligand spectrum Figs. (1)(2)(3)(4). Azomethine (C=N) group of the complexes 1-4 is noticed between 1615-1620 cm −1 confirming ligand synthesis successfully 18 . The ṽ (C=N) moiety exhibit upward shift in 1697 (s) cm -1 after coordination to metal centre which is in agreement with the azomethine function that coordinated to metal ion of previous reported complexes 19 . The shift toward higher or lower frequencies is due to the interaction between the azomethine moiety and metal ions. Also, there are several factors that can affect the frequencies such as the metal ion nature and the coordination atoms. Moreover, medium bands that appear at 3535-2030 cm -1 of ligands may be assigned to ṽ NH group 20 . Appearance of a strong bands at the range 695-270 cm -1 for all compounds is assignable to the ṽ (M-N) vibrations because of dimeric nuclear of the complex confirming the metal azomethine coordination 21,22 . The spectrum also gave an idea about the successful of ligand synthesis through the vanishing of the carbonyl (C=O) of aldehyde. The (C-H) aromatic vibrations is another evidence that is usually used to characterize Schiff bases depending on the bundles that appeared at the region (3155-3030).

H-NMR Spectra
The 1 H-NMR spectra of the complexes 1-4 were recorded in DMSO-d 6 at room temperature (Figs. [5][6][7][8]. After complexation signals have shifted down or up field which can help to have better understand the behaviour of these complexes in solution. Because of the deshielding of protons, it is well known that the electron density reduces after bonding 23,24 . Moreover, the presence bimetallic species can increase the NMR spectra complexity due to the inequivalent in symmetry consequent of the dinuclear species. Iron Schiff base complex [(FeCl 2 ) 2 L] is further confirmed by NMR spectra. The 1 H-NMR spectrum given in Fig. (5) exhibited singlet beam in the aromatic region (8.51 ppm) assigned to the phenyl aromatic protons and the integrations calculation of those protons found to the correspond compound. The spectrum also shows one triplet bands notice at (3.90 ppm) to the methylene groups. Chemical integrations show the singlet that appeared at (2.50. ppm) related to azomethine. Noticeable overlap in signals due to the paramagnetic of Iron and dinuclear species that formed in solution which lead to increasing the 1 H-NMR spectra complexity 25 . Cobalt Schiff base complex [(CoCl 2 ) 2 L] was studied using 1 H-NMR spectroscopy that confirm the formation of fully condensed Schiff base complex. The triplet signal appearing in (3.26 ppm) of the 1 H-NMR spectra of cobalt complex are attributed to the methylene groups. In addition, independent signal is observed at 8.49 ppm related to aromatic protons of the phenyl group. The azomethine (HC=N) is observed at 2.50 ppm for [(CoCl 2 ) 2 L]. The bonding between the nitrogen atom of azomethine and metal centre is proved by the downfield chemical shift observations. The aromatic signal is downfield shifted in the spectra of [(CuCl 2 ) 2 L] complex due to the paramagnetic. Methylene group shows one signal at 2.50 ppm. Azomethine protons are affected and shifted down field in comparison between NMR spectra of complex with free ligand. The 1 H-NMR spectra of [(SnCl 2 ) 2 L] complex exhibit a peak at 8.28 ppm, which is due to aromatic protons. The sharp singlet at 5.7 ppm and 6.047 ppm respectively assigned to for the (CH=N-) proton which clearly prove the magnetic effect that leads to up field shift in such protons 26 . The azomethine signal is noticed at 2.50 ppm for [(SnCl 2 ) 2 L]. The chemical shift belongs to the NH 2 protons in the proligand was not observed in any of the complexes 1-4. It is well known that such NH 2 protons did not detect so these peaks disappeared from spectrum.

Mass Spectra
Seventy V cone voltage are employed to complexes 1, 2, 3 and 4 to record mass spectra. Such voltage can minimise dissociation on ligand axials. Some peaks belong to a range of fragments that exhibited different values more or less than the calculated values. This behaviour is commonly known in mass spectra analysis due to the differences in isotopic abundance that occurred naturally for chemical elements. While, the voltage amount and the size of the substitution groups relatively can affect peak intensity.

Biological Activity
The collected antibacterial results are presented in Table 1 according to the minimum inhibitory concentration and the inhibition zone. Anti-bacterial behavior of complexes 1, 2, 3, and 4 were screened in vitro toward a set of pathogens according to standards guidelines 18 using disc diffusion method and broth culture method. The minimum effective concentrations of compounds were also investigated. Complexes at low dose showed good to excellent inhibition toward tested bacteria (E. coli G-, Pseudomonas G-, Bacillus G+, Staphylococcus G+, and Streptococcus G+). [(FeCl 2 ) 2 L] metal complex showed a small inhibition zone (3 mm) on E. coli G-growth and did not exhibit any destruction action against Pseudomonas G-(0 mm). While in comparison with complex 1 complexes 2-4 exhibited significant inhibition activity toward E. coli G-and Pseudomonas G-Table 1 ( Fig. 13 and 14). Complex 1 also was found to have very limited destruction activity (4 mm

Conclusions:
Schiff base metal complexes [(MCl 2 ) 2 L] were synthesized as mentioned before [21][22][23] . Complexes exhibit an excellent stability toward air and mixture. These complexes 1-4 were synthesised and characterized by different techniques. The melting points, Mass spectra, IR, and 1 H-NMR, confirmed the formation of the binuclear complexes. A distorted square planar geometry was proposed for the metal centers of complexes (1-4) based on structure analysis. Complexes revealed promising antibacterial activities toward different pathogenic strains of bacteria (E. coli G-, Pseudomonas G-, Bacillus G+, Staphylococcus G+, and Streptococcus G+).