Biological Important Ni ( II ) Ternary Complexes Derived from 2-Substituted Benzothiazoles and Amino Acids

Biological important ternary complexes of the type [NiCl(L-L) (A-A)(H2O)] and [Ni(L-L ́)(A-A)(H2O)2], where A-A = Glycine (Gly), Alanine (Ala), L-L = 2-(2 ́-aminophenyl)benzothiazole (APBT) and L-L ́ = 2-(2 ́hydroxyphenyl)benzothiazole (HPBT), 2-(2 ́-mercaptophenyl)benzothiazole (MPBT) have been synthesized. These complexes have been characterized by elemental analysis, molecular weight determination, conductivity, magnetic measurements, infrared, electronic spectral and TGA studies. On the basis of above described studies an octahedral geometry has been suggested for these complexes. All these complexes are coloured, thermally stable, monomeric and non-electrolytic in nature. The ligands and their metal complexes were tested against pathogenic fungi Aspergillus niger and Fusarium oxysporum to assess their fungicidal properties, the antifungal activity data reveals that these metal complexes are found more fungitoxic than the parent ligands.


Introduction
Compounds with a benzothiazole moiety have received considerable attention because of their widespread occurrence in biologically active molecules such as antitumor, antimaleria, fungicide, anti-HIV, antiviral and analgesic agents 1.3 .Recently, radiolabeling of benzothiazole derivatives have been developed for PET imaging in the detection of alzheimer diseases 4 .These compounds also have many industrial applications; for example some 2-substitued benzothiazole are utilized as fluorescence agents in textile dyeing, antioxidants and valcanization accelerators of rubber.
A large number of benzimidazole derivative have been synthesized and patented as fungicide 5.6 .The formation and structural aspects of some transition metal complexes of 2-substituted benzimidazole derivatives have been reported by Seth et al. 7 and various other workers 8,9 .We describe here the synthesis, characterization and biological activity of Ni(II) ternary complexes derived from 2-substituted benzothiazole viz.2-(2´-aminophenyl)benzothiazole (APBT), 2-(2´-hydroxyphenyl)benzothiazole (HPBT), 2-(2´-mercaptophenyl)benzothiazole (MPBT) and amino acids viz.glycine (Gly) and alanine (Ala) ligands.As the biological activity is often augmented when a ligand form complexes.The resulting mixed ligand complexes may be of potential biological importance.The structure of ligands used to synthesize the Ni(II) ternary complexes are shown in Figure 1 and 2.

Experimental
All the solvents were distilled prior to use, o-aminothiophenol, anthranilic acid, salicylic acid, thiosalicylic acid, NiCl 2 .6H 2 O were purchased from Merck and used as such.

Physical measurements
Microanalysis was carried out at the CDRI Lucknow, India.Melting points were determined on a capillary melting point apparatus and are uncorrected, IR spectra were recorded (with KBr pellets) on a SHIMADZU 8400 SPIR spectrophotometer.Electronic spectra were recorded on a Varian-Cary UV-visible spectrometer.Magnetic moments were measured on a Gouy balance.Molar conductance were measured in 10 -3 M DMF on a Systronics conductivity bridge model 305.Molecular weights were determined by the Rast camphor method.Nitrogen was determined by the Kjeldahl's method and sulfur was estimated by the Messenger's method.Chloride was determined by the Volhard's method.nickel was estimated gravimetrically 19 .

Reflux
Where L-L = APBT, L-L´ = HPBT, MPBT and A-A = Gly, Ala These reactions are processed easily and lead to the formation of coloured solids, which are stable to air and moisture.The resulting Ni(II) ternary complexes are soluble in DMSO and DMF.The molar conductance values of 10 -3 M solutions of these complexes lay in the range 10-20 Ω -1 cm 2 mol -1 in dry DMF, indicating their non-electrolytic behaviour 10 .The monomeric nature of these complexes has been confirmed by the molecular weight determination.The analytical data and physical properties of the ligands and their Ni(II) ternary complexes are given in Table 1.The compounds were characterized on the basis of following studies.

Infrared spectra
The important IR spectral bands and their tentative assignments are presented in Table 2.The ligands APBT, HPBT, MPBT, Gly and Ala act as bidentate ligands in these Ni(II) ternary complexes using nitrogen, oxygen and sulfur as donor atoms.The IR spectra of APBT, Gly/Ala shows two strong bands in the region 3400-3370 cm -1 and 3310-3250 cm -1 due to v as (N-H) and v s (N-H) vibrations of NH 2 of these ligands, respectively.These bands are shifted to lower frequency by 35-80 cm -1 in the respective Ni(II) ternary complexes, suggesting the coordination through nitrogen lone pair of the NH 2 group to the Ni atom without any deprotanation 11 .It is further supported by appearance of the new bands in the region 436-432 cm -1 due to v(Ni←N) vibration.The appearance of absorption bands in the region 448-445 cm -1 may be assigned to v(Ni-O) vibration.The occurrence of non-ligand absorption band in the region 320-315 cm -1 may be attributed to v(Ni-Cl) vibration 12 .
Table 2. IR spectral data (cm -1 ) of ligands (APBT, HPBT, MPBT) and Ni(II The broad band at 3330 cm -1 due to v(O-H) phenolic mode of HPBT, disappears in the Ni(II) ternary complexes, indicating the deprotonation of the OH group and coordination of phenolic oxygen to the Ni atom with the formation of Ni-O bond.This gets further support by the appearance of bond in the region 455-452 cm -1 due to v(Ni-O) vibrations 13 .The IR spectrum of MPBT shows a band at 2560 cm -1 due to v(S-H) (thiophenolic) vibration, which disappears in the Ni(II) ternary complexes, suggesting the deprotonation of -SH group and coordination through thiophenolic sulfur with the Ni atom.It is further supported by the appearance of new band in the region 335-332 cm -1

TGA studies of Ni(II) ternary complexes
The existence of coordinated water molecule in these Ni(II) ternary complexes is confirmed by TGA studies.The coordinated water molecules are lost in the temperature range 100 to 310 °C.The ultimate product of the thermal decomposition in these complex is nickel oxide.Thus, on the basis of analytical data and above describe studies, an octahedral geometry may be assigned for these Ni(II) ternary complexes.The toxicity increased as the concentration was increased.The antifungal activity data also reveals that Ni(II) ternary complexes of MPBT and Gly/Ala are more fungitoxic than the complexes of APBT and HPBT 18 ligands, respectively.

Biological activity
The antifungal activity of ligands (APBT, HPBT and MPBT) and their Ni(II) ternary complexes were carried out against pathogenic fungi, namely Aspergillus niger and Fusarium oxysporum by radial growth methods.The solution of the test compound were prepared (50, 100 and 200 ppm) in dimethylformamide.The linear growth of the fungus was recorded by measuring the diameter of the fungus colony after 72 h and the percentage inhibition was calculated as 100 (C-T)/C, where T are the diameter of the fungus colony in the control and text plates respectively.The results of antifungal activity of the ligands and Ni(II) ternary complexes have been compared with the conventional fungicide Bavistin taken as standards (Table 4).

Table 1 .
The analytical data and physical properties of the ligands and their Ni(II) ternary complexes