Synthesis and Antimicrobial Activities of Novel Palladium (II) Complexes of Active Schiff’s Base Ligand Derived from 5-Bromo Isatin

. This paper presents the synthesis and antimicrobial studies of Palladium (II) complexes of ThioSemicarbazone Pd(L 1 H) 2 Cl 2 and Semicarbazone Pd(L 2 H) 2 Cl 2 derived from 5-Bromo Isatin. All complexes reported here had been characterised by 1 H NMR and IR spectral studies .the complexes are diamagnetic in nature and showing square planner geometry. The IR spectral data reveals that both the Schiff’s bases behave as bidentate ligands and are co-ordinated to Pd (II) metal through the sulfur and hydrogenic nitrogen atom . All the new synthesized compounds were screened for antibacterial activity against four of the test organisms like Bacillus pumilus, Micrococcus Lutes, E.coli, Salmonella abony.


INTRODUCTION
Several studies [1-2] have shown a growing interest in transition metal complexes of Schiff base ligands in past few decades. The introduction of metal ion and metal compound to the biological system for therapeutic purpose occupies an important part. Research has shown that various co-ordination compounds have found their application in the treatment of various diseases. Interest in medicinal chemistry has been stimulated by improved methods of biological test procedures and clinical diagnosis. It attempts to establish relationship between chemical structure and biological activity and links biodynamic behaviour to the chemical reactivity and physical properties of therapeutic agents. Medicinal chemistry involves the isolation, characterization, elucidation of structure and synthesis of compounds [3][4][5][6][7][8][9][10][11][12] which can be used as medicine for the prevention of disease. Co-ordination compounds are compounds containing one or more coordinate bonds, which is a link between a pair of electrons in which both electrons are donated by one of the atoms. The metal complexes of semicarbzones and thiosemicarbazone [13][14][15][16][17] have aroused considerable interest in view of their industrial and biological importance. Many of these compounds possess a wide spectrum of medicinal properties.Thiosemicarbazides and thiosemicrbazones react as chelating agents with transition metals ions by bonding through the sulfur and hydrogenic nitrogen atom. In the present investigation we have synthesized and characterize some new biologically active Schiff's base complexes of palladium metals in order to evaluate their antibacterial activity.

EXPERIMENTAL 2.1 Preparation of Chalcones
In the three necked round bottom flask a mixture of 0.1M 5-Bromo Istain and 50mL ethanol were taken and stirred for 1 h [18 -20]. Meanwhile the 25mL solution of 20% caustic soda mixed with 0.1mol aromatic ketone was prepared. Above solution was added slowly to ethanolic solution of bromoisatin maintaining temperature of 15-20 o C. Then the reaction mass was refluxed on water bath for 2-3 h. The progress of reaction was monitored by Thin Layer Chromatography (TLC) method. After completion of the reaction, the mixture was cooled on ice salt bath. It was filtered and washed with water and the resulting chalcone re-crystallized with ethyl acetate.

Preparation of Preparation of Ligands
The ligands of hydrazinecarbothiamide (L 1 H) of 5-Bromo Isatinand hydrazine-carboxamide (L 2 H) of 5-Bromo Isatin are prepared as follows:

Preparation of hydrazinecarbothiamide (L 1 H) of 5-bromoindolinedione:
The 0.01 mol of chalcone [21-28] was added to 25 mL of THF and 0.012 mol thiosemicarbazide was added along with 5 g of sodium acetate. The reaction mixture was then refluxed on water bath for 2-3 h. The progress of reaction was monitored by TLC method. After completion of the reaction, the mixture was cooled on ice-salt mixture; it was then filtered and re-crystallized with alcohol.

Preparation of hydrazine-carboxamide (L 2 H) of 5-bromoindolinedione:
The mixture of 0.01 mol chalcone and 0.012 mol semicarbazide hydrochloride was added to 50 mL of THF. To that 5g of sodium acetate was added. The reaction mixture was refluxed on water bath for 2-3 h. The progress of reaction was monitored by TLC method. After completion of the reaction, the reaction mixture was cooled, filtered and the product obtained was re-crystallized by alcohol. The crystalized powder was further subjected to Silica gel column chromatograpphy (2% EtoAc-Hexane) to get purified product.

RESULT AND DISCUSSION
The ligand (L 1 H): In the IR spectrum [33] of ligand (L 1 H) bands corresponding to -NH 2 and -NH groups appeared at 3463 and 3263 cm -1 respectively.thebands corresponding to ᵥ(C = S) and ᵥ(C=N) groups appeared at 818 and1587 cm -1 . In the ligand (L 2 H): the band corresponding v (C=O) appeared at 1711 cm -1 . On complexation the bands corresponding to ᵥ(C=N) and ᵥ(C = S) (in case of thiosemicarbazone) are shifted towards lower side (ca.20-30 cm -1 ). This suggest that the ligand acts as a bidentate chelating agent coordinating through nitrogen of ᵥ(C=N) group and sulphur of ᵥ(C = S) group. In case of semicarbazone the bands corresponding to ᵥ(C=N) [34] and ᵥ(C = O) are shifted towards lower side (ca.20-30 cm -1 ) suggest that the ligand acts as a bidentate chelating agent coordinating through nitrogen of ᵥ(C=N) group and oxygen of ᵥ(C = O) group. In the 1 H NMR spectrum of ligands & complexes the most common NMR multiplets for Aromatic rings protons are found to be resonating around δ7.5-δ8.4 whereas the broad singlet for >NH &-NH 2 group protons appeared around δ3.3-δ3.6. A sharp singlet peak for olefinic protons (>C=C-H) group in ligands as well as in the complexes are observed in the range of δ7.1-δ7.4. The distinguishing singlet peak around δ9.0 in ligands are due to (>C=N-group) azomethine protons but in the complexes this singlet was shifted to downfield & appears at δ9.3 due to co-ordination thorough >C=N-group.

Plate Diffusion Method
The compound was weighed (25 mg) and dissolved in methanol/DMF and phosphate buffer (2:8).
The compounds were taken at 1000 mcg/mL per hole of petridish containing M.agar medium or antibiotic assay medium No.11. The hole in the medium should be more than 2.5 mm and 7.8 mm diameter. These holes in the petridish were then filled with antibacterial solution. The plates were then placed in refrigerator for 10 o C, at 15 o C for diffusion of the compounds and then incubated for 24 h at 37 o C. After the incubation period was over the zone of inhibitions were measured in mm as distance from source and are reported. Bacterial activity of the ligand and their metal complexes are recorded Table 1