Synthesis, Characterization and Biological Activity of Sodium Barbitone-Group-VIII Metals (viz. Ni(II), Pd(II) and Pt(II)) Complexes

This work aims to characterize, synthesize and evaluate the biological activity of sodium barbitone and their metal chelates Ni(II), Pd(II) and Pt(II). The new synthesized metal chelates are investigated by elemental analysis, IR, mass spectra, thermal analysis and biological activity. Square planer structure of the prepared complexes obtained from the result of analysis. The antibacterial and antifungal of sodium barbitone ligand and its conforming metal chelates were screened against bacterial species Gram positive (Staphylococ-cus aureus), Gram negative bacteria (Escherichia coli) and fungi Aspergillus flavus and Candida albicans fungi. Ampicillin and amphotericin were used as references for antibacterial and antifungal studies. The activity data show that the platinum group metals chelates have activity data show that some of the platinum group metals (viz. Pt(II) and Pd(II)) chelates have a promising biological activity comparing to sodium barbitone parent free ligand against bacterial and fungal species.


Introduction
Sodium barbitone 5,5-diethyl barbiturate derived from barbituric acid belongs to the family of 2,4-pyrimidione, is prepared by the neutralization of an aqueous solution of lactam with sodium hydroxide and then precipitating the salt by the addition of alcohol (Scheme 1). Sodium barbitone plays an important role in pharmaceutical applications it is a category of drugs that have varied applica-tions such as sedatives, hypnotics and anticonvulsants under an assortment of conditions and is also employed for anesthesia [1] [2].
Sodium barbital solutions have also been used as pH buffers for biological research, e.g., in immunoelectrophoresis or in fixative solutions [3] [4]. As barbital is a controlled substance, barbital-based buffers have largely been replaced by other substances [5].
The coordination chemistry of organotransition-metal complexes which have biologically active ligands has attracted tremendous interest over the years. The study of this complexes enable us understanding the role of these ligands in biological systems, in many biological systems compounds which containing pyrimidine ring play an important role, where they exist in nucleic acids, several vitamins, coenzymes and antibiotics [6] [7]. The nucleic acid is related to antimetabolites used in anticarcinogenic chemotherapy [8]. In recent years, the metal complexes of pyrimidine widely taught owing to their great variety of biological activity ranging from antimalarial, antibacterial, antitumoral, antiviral activities etc. [9]- [15].
The manufacture of plastics and pharmaceuticals products used barbituric acid.
Phenobarbital (5-ethyl-5-phenylbarbituric acid) is the drug used most commonly for convulsive disorders and is the drug of choice for infants and young children [16].
Barbiturates have a wide range of medicinal applications and have ability to coordinate with transition metals through one or both deprotonated nitrogen and carbonyl oxygen atoms, synthesis of their metal complexes has attracted our attention to synthesize and characterize barbitone complexes with nickel and some of the platinum group metals [Pd(II) and Pt(II)].

Reagents and Materials
In this study, the chemicals used are of highest purity available, it included sodium barbitone,

Biological Activity
Modified Kirby-Bauer disc diffusion method [17], has been used to determine the antimicrobial activity of the tested samples. Disc diffusion method for yeast developed by National Committee for VlinicalLaboratory Standards using approved standard method (M44-P). Plates inoculated with filamentous fungi as asprgillus flavus at 25˚C for 48 hours; Gram (+) bacteria as Staphylococcus aureus; Gram (-) bacteria a Escherichia coli, they were incubated at 35˚C -37˚C for 24 -28 hours and yeast as Candida albicans incubated at 30˚C for 24 -28 hours, then the diameters of the inhibition zones were measured in millimeters withslipping calipers of the National Committee for Vlinical Laboratory Standards.

Physical Properties and Elemental Analysis
The elemental analyses data of the given group VIII metals metal chelates considerable with the theoretical values within the limit of experimental mistake; as shown in Table 1.

FT-IR Spectroscopy
The FT-IR data of the free ligand and its corresponding metal chelates are examined and the results are presented in Table 2.   The IR data of metal chelates complexes are given in Table 2. The IR display various sharp bands in the mid infrared region, clearly indicating the presence of barbital [18]. The strong and broad absorptions bands at 34,583,545 and 3427 in complexes 1, 2 and 3 respectively are due to of lattice water [19].

Mass Spectra of Sodium Barbitone Metal Chelates
The electron impact mass spectra (EI-MS) of the newly prepared complexes are recorded at 70 ev and investigated.

Thermal Analyses
The TGA thermal analysis data of the synthesized metal chelates are tabulated in

Biological Activity
The comparison of the biological activity of the sodium barbitone and its corresponding metal chelates with the standards (ampicillin and amphotericin for antimicrobial and antifungal respectively) towards different organisms was described. The data are recorded in Table 5 and shown in Figure 3. The free ligand and its metal chelates were screened against C.albicans and A.flavas (fungi), S.aureus (G + ) and E.coli (G − ) to assess their potential antimicrobial agent.

Sodium Barbitone and Its Complexes
The metal complexes biological activities (Table 5, Figure 3) are higher than the free ligand towards the gram positive, gram negative bacteria and fungi species. In case of bacteria gram positive, gram negative the Ni(II) complex show highest bacterial activity than Pd(II) and Pt(II) complexes. The antimicrobial activities of the complexes in case of Candida albicans, Ni(II) shows the highest fungal activity than Pd(II), but Pt(II) has no innate activity against Candida albicans. In case of Aspergillus flavus the three metals Ni(II), Pd(II) and Pt(II) complexes have no activity towards it.
The experimental data presented in Table 5 suggest that the metal complexes of Ni(II), Pd(II) and Pt(II) are more toxic in comparison to their parent free ligand (sodium barbitone) itself in inhibiting the growth of microorganisms. This inhibiting because of the change in structure of the ligand on coordination to the metals and metal complexes when chelating act as more powerful bacteriostatic agents, so that the growth of microorganisms inhibiting. moreover, the polarity of the metal ion reduces by coordination because of the partial sharing of its positive charge with the donor groups within the chelate ring system formed during the coordination. This would suggest that the chelation could help the ability of the complex to cross a cell membrane and can be explained by Tweedy's chelation theory [25]. The Ni(II), Pd(II) and Pt(II) complexes show greater antibacterial activity towards bacteria. The variation in the activity of metal complexes against different organisms depends on the impermeability of the microorganism cells or on differences of ribosome of microbial cells [25] [26]. The increase in the antifungal activity of the metal complexes inhibits multiplication process of the microbes by blocking their activity sites. Such increased activity on metal chelation can be explained on the basis of Tweedy's chelation theory. While chelation is not the only factor for antimicrobial activity, it is an intricate blend of several aspects such as nature of the metal ion and the ligand, the geometry of the metal complexes, the lipophilicity, steric and pharmacokinetic factors [27].

Conclusion
In the present study, the free ligand sodium barbitone and it corresponding group VIII metals complexes Ni(II), Pd(II) and Pt(II) were prepared and structurally identified. The structures of free ligands and its metal chelates are proved by elemental analyses and applying spectroscopic measurements (FT-IR and mass spectra) and confirmed by thermal analyses. On the basis of their analytical data, we propose square planer geometry for metal complexes. The synthesized free ligand are found to be biologically active and their metal complexes showed significantly enhanced antibacterial and antifungal activities against microbial strains in comparison to the free ligand.