Synthesis, Characterization and In-Vitro Antimicrobial Studies of M 2+ Complexes of p- Chlorophenyl-, p- Bromophenyl-Dithiocarbamates

This study reports the synthesis of metal complexes of mixed ligands p-Chlorophenyl-, p-Bromophenyl-dithiocarbamates. The spectral properties of the metal complexes [Zn(II), Cd(II), Hg(II), Cu(II), Co(II) and Ni(II)] were obtained using the FTIR and UV/Vis spectroscopic techniques. Their antibacterial studies revealed that these complexes as well as the ligands could serve as possible antibacterial agents against pathogens. Melting point and solubility measurements were also carried out. It was observed that these complexes were non-toxic, non-electrolytic and stable solids.


Introduction
Dithiocarbamate is a group of organic compound, an analogue of carbamates in which both oxygen atoms are replaced by sulphur atoms [1]. The transition metal complexes (TMCs) of dithiocarbamates have been reported and applied in different areas of material science [2] [3] [4]. This is due to their stability in different oxidation states [5]. Metal complexes of dithiocarbamates have been studied extensively due to their biological, agricultural, chemical, medicinal, pharmaceutical and industrial applications [3] [6]. The presence of the dithiocarbamate moiety in some biologically active molecules has generated interest in their potentials for medical application [7] [8] [9] [10] [11]. Development of metal based pharmaceuticals has received tremendous attention due to increased resistance to current generation of antibiotics by pathogens [12] [13] [14]. The TMCs of mixed ligands have been used in past and recent times for optimal applications especially in the area of medicine [5] [15]. This work was therefore designed to synthesize, characterize and evaluate the antimicrobial activities of mixed ligands p-Chlorophenyland p-Bromophenyl-dithiocarbamates metal complexes.
Thiocarbamate itself has been synthesized and characterized and reported for its potency against bacteria such as Escherchia coli, Staphylococcus aureus, Bactillus subtilis etc. and fungi such as Aspergillus niger, Monilia americana, Candida albicans etc. [5] [15] [16]. Also, a lot of metals have been reported for their medicinal and pharmaceutical applications. Bringing them together with ligands like the thiocarbamates creates synergistic effects for improved efficiency [5] [15] [16].

Materials and Methods
All chemicals and reagents used are analytical grade with no further purification needed. They include methanol, carbon disulphide, ammonium solution, toluene, ethanol, phosphorus pentaoxide, sodium carbonate, chloroacetic acid, p-chlorophenyl amine, p-bromophenyl amine. The Gallen Kamp melting point apparatus was used to determine the melting points of the synthesized metal complexes. The Uv-vis measurements of the metal complexes were recorded in DMSO using Perkin Elmer Lambda 25 spectrophotometer from 800 -200 cm −1 , while the FTIR data were obtained by using KBr discs on a Perkin Elmer 2000 FT-IR spectrophotometer in the range 4000 -370 cm −1 .

Synthesis of Ammonium p-Chlorophenyl Dithiocarbamate Ligand, L1
9.6 g of p-chloroaniline, 6 ml of carbon disulphide and 11ml of ammonium hydroxide were added into a 250 ml round bottom flask fitted to a reflux condenser, magnetic stirrer and thermometer. The mixture was stirred vigorously, the reaction was maintained at 30˚C -35˚C by external cooling, a heavy yellow precipitate of ammonium p-chlorophenyl dithiocarbamate was separated out. The mixture was filtered and residue washed off with 30 ml portion of a 3% aqueous solution of ammonium chloride and with two 15 ml portions of 96% ethanol, dried in a desiccator (sodium hydroxide and phosphorus pentoxide as desiccant) ( Figure 1).

Synthesis of Ammonium p-Bromophenyl Dithiocarbamate Ligand, L2
9.92 g of p-bromoaniline, 15 ml of carbon disulphide and 15 ml of ammonium hydroxide were added into a 250 ml round bottom flask fitted to a reflux condenser, magnetic stirrer and thermometer. The mixture was stirred vigorously, the reaction was maintained at 30˚C -35˚C by external cooling, initially, the mixture turned milky and suddenly, a deep red was obtained. At the end of the

Biological Activities Antibacterial Assay (In Vitro)
The ligands and their metal complexes were screened in vitro for their antibac-

Physical Parameters
Electro Thermal Digital melting point apparatus was used to obtain the melting points of the ligands and TMCs. The percentage yields values of the ligands and TMCs were relatively high (76% -92%). The melting points showed that the compounds are stable in solid states ( Table 1). The ligands were soluble in water, polar organic solvents and sparingly soluble in non-polar organic solvents.
The TMCs were insoluble in water, but soluble in most organic solvents ( Table   2). The solubility test suggests that the synthesized compounds are non-polar.    Partially  soluble  Insoluble  Partially  soluble  Insoluble  Insoluble   Ethyl acetate  Sparingly soluble  Soluble  Soluble  Insoluble  Insoluble  Partially  soluble  Soluble  Soluble   Acetone  Insoluble  Sparingly soluble  Soluble  Insoluble  Insoluble  Soluble  Sparingly  soluble   Sparingly  soluble   Propan-2-ol  Insoluble  Soluble  Soluble  Insoluble  Insoluble  Soluble  Insoluble  Insoluble   DMSO  Soluble  Soluble  Soluble  Soluble  Soluble  Sparingly  soluble  Soluble  Soluble   Water  Soluble  Soluble  Insoluble  Insoluble  Insoluble  Insoluble  Insoluble  Insoluble

Spectroscopic Studies
The results of the FTIR spectroscopy (Table 3)

Antimicrobial Assay
The antimicrobial activity of the ligands and TMCs were investigated in vitro against some selected bacteria such as Escherichia coli, Serratia mercescens and Staphylococcus aereus. From Table 4 and Table 5, they showed good activity against the bacterial infections, with Cd (II), Hg (II), Co (II) and Cu (II) showing better activities than the ligands and standard drug. The TMCs were poor against the fungal infections.

Conclusion
This study showed that some ligands and metal complexes synthesized could be used as potent drugs against the tested bacterial infections. Further studies however, are needed to ascertain their toxicity status and compatibility with human physiology.

Conflicts of Interest
The author declares no conflicts of interest regarding the publication of this paper.