Coordination Modes of a Schiff Base Derived from Substituted 2-Aminothiazole with Chromium(III), Manganese(II), Iron(II), Cobalt(II), Nickel(II) and Copper(II) Metal Ions: Synthesis, Spectroscopic and Antimicrobial Studies

Transition metal complexes of Cr(III), Mn(II), Fe(II), Co(II), Ni(II) and Cu(II) metal ions with general stoichiometry [ML2.2H2O] and [ML3], where M= Mn(II), Cr(III), Fe(II), Co(II), Ni(II) and Cu(II), L= Schiff base derived from the condensation of 2-amino-4(4’-phenyl/methylphenyl)-5methyl-thiazole with 4-acetyl-1(3-chloro phenyl)-3-methyl-2-pyrazoline-5ones, have been synthesized and structurally characterized by elemental analysis, molar conductance measurements, magnetic susceptibility measurements and spectral techniques like IR, UV, H NMR, C NMR and Mass Spectra. All the complexes were found to be octahedral geometry. The ligand and its complexes have been screened for their antifungal and antibacterial activities against three fungi, i.e. Alternaria brassicae, Aspergillus niger and Fesarium oxysporum and two bacteria, i.e. Xanthomonas compestris and Pseudomonas aeruginosa.


Introduction
The thiazole ring is important in nature.It occurs, for example, in thiamine, a coenzyme required for the oxidative decarboxylation of α-keto acids.A tetrahydrothiazole also appears in the skeleton of penicillin which is one of the first and still most important of the broadspectrum antibiotics.Thiazolamine are key intermediates for synthesizing many pharmaceuticals 1 .Some thiazolidone are valuable medicines 2 .It is obvious that compounds with the thiazole ring have potential biological activity.It is also known that some Schiff bases are effective antitumor drugs and antibacterials.Aminothiazoles are known to be ligands of the estrogen receptor and as a novel class of adenosine receptor antagonists 3 .We were interested in examining the biological activities of NO-donnor schiff's bases and their transition metal complexes, thus, in this article, we report the anti fungal and antibacterial activities of the Schiff base ligands 1-(3-chlorophenyl)-3methyl-4-(1-((5-methyl-4-phenylthiazol-2-yl)imino)ethyl)-1H-pyrazol-5-ol (L), 1-(3chlorophenyl)-3-methyl-4-(1-((5-methyl-4-(p-tolyl)thiazol-2-yl)imino)ethyl)-1H-pyrazol-5-ol (L 1 ) and Its complexes with Cr(III), Mn(II), Fe(II), Co(II), Ni(II) and Cu(II) metal ions.The ligand and its complexes were characterized by physiochemical and spectral studies.

Experimental
All the chemicals used in the present study were of A.R. grade.1,4-Dioxane and methanol (SD's fine chemical Ltd., Mumbai and Merck chemicals., Mumbai) were used without further purification.Absolute ethanol from alembic chemical works Co. Ltd., Baroda was used after distillation.Cr(III), Mn(II), Co(II), Ni(II), Cu(II) metal acetate and Fe(II) sulphate (SD's fine chemical Ltd, Qualigens-Glaxo, Mumbai and Merck chemicals., Mumbai) were used.
Melting points were taken in one side open capillaries on a melting point apparatus having model number VMP-D of a make VEEGO.The Mass spectra of all ligands were recorded on the instrument named LCMS-2010A of make Shimadzu.Carbon, Hydrogen and Nitrogen were estimated on a Thermo fisher (Thermo electron corporation Limited), Flash Elemental Analyzer-1112.The 1 H NMR and 13 C NMR spectra of all the ligands [in Deuterated Chloroform(CDCl 3 )] were recorded on a AVANCE-II 400 of make BRUKER spectro-photometer using TMS [(CH 3 ) 4 Si] as internal standard.The Infrared spectra of the ligands studied in the present work were recorded on the model FT-IR-8300 of Shimadzu in KBr (Zydus Research Center, Ahmedabad, India).

Synthesis of the metal complexes
To hot solution of Schiff base ligands (1 mmol) in dioxane (15 mL), a hot solution of corresponding metal salt like nitrate, chloride, acetate or sulphate (1 mmol) in dioxane (10 mL) was added slowly with constant stirring.The resulting mixture was refluxed for 8 to 10 h at 85 to 90 ˚C.On cooling the mixture overnight at 0 ˚C, the colored product which separated out was filtered, washed with dioxane and dried under vacuum oven at 60 ˚C.

Results and Discussion
The synthesized novel Schiff base ligands, 1-

Mass spectra
Mass spectra provide a vital clue for elucidation of compounds.The ESI mass spectrum of ligand L and L 1 are given below.The spectrum in Figure 1 shows the molecular ion peak at m/z = 423.14 and the isotopic peak at m/z = 424.99due to 35 Cl and 37 Cl isotopes of ligand L. The spectrum in Figure 2 shows the molecular ion peak at m/z = 437.13and the isotopic peak at m/z = 439.18due to 35 Cl and 37 Cl isotopes.In both the spectra the molecular ion peak is base peak and the intensity of these peaks reflects the stability and abundance of the ions 5 .

NMR spectra
NMR data of ligand L are given in Table 2. Its 1 H NMR spectrum (Figure 3) displays three singlets at ca. δ 2.43 -2.86 ppm (s, 9H, 3H 3 C-C) due to the nine protons of three methyl groups, at ca. δ 7.12-8.08ppm (m, 9H, aromatic) due to the protons of two phenyl rings and a singlet at ca. δ 13.75 ppm (s, 1H, -OH) due to the alcohol and NMR data of ligand L 1 are given in Table 3.Its 1 H NMR spectrum (Figure 4) displays four singlets at ca. δ 2.36 -2.86 ppm (s, 12H, 4H 3 C-C) due to the twelve protons of four methyl groups, at ca. δ 7.12-8.08ppm (m, 9H, aromatic) due to the protons of two phenyl rings and a singlet at ca. δ 13.73 ppm (s, 1H, -OH) due to the alcohol 6 .In the same manner 13 C-NMR spectrum of ligand L 1 (Figure 6) describe in Table 3.

IR spectra
Selected IR bands of the ligand and its complexes are listed in Table 4.The infrared spectra of the both ligands L and L 1 show υ O-H (weakly H-bonded) at 3345 cm -1 and 3320 cm -1 respectively 7 .The absence of this band in all the metal complexes indicates the removal of proton of hydroxyl group of pyrazolin ring during the chelation.This is further supported by the shift of C-O frequency from ~1315 cm -1 (in ligand) to the higher frequency 1330-1400 cm -1 (in complexes) 8 .The sharp intense band at 1626 cm -1 and 1627 cm -1 respectively in the ligands can be assigned to υ C=N (azomethine).A downward shift (∆υ = 15-35 cm -1 ) in υ C=N (azomethine) is observed upon coordination indicating that the nitrogen of azomethine group is involved in coordination.All the complexes show broad band in the region 3250 cm -1 to 3500 cm -1 which may be assigned to υ O-H of coordinated water 9 .To account for the octahedral stereochemistry of the metal complexes, the coordination of two water molecules is expected.The bands in the range between 450 cm -1 to 590 cm -1 may be due to metal-nitrogen stretching vibration 10 of Cr(III), Mn(II), Fe(II), Co(II), Ni(II) and Cu(II) complexes.The bands in the range between 600 cm -1 to 690 cm -1 may be due to metal-oxygen stretching vibration 11 of Cr(III), Mn(II), Fe(II), Co(II), Ni(II) and Cu(II) complexes.A less intense band between 1610 cm -1 -1560 cm -1 in the spectrum of ligand may be assigned to υ C=N (pyrazolin ring) 12 .All the metal complexes do not show shifting in υ C=N compared to its respective ligands.This suggests that the nitrogen atom of the ring has not participated in the chelation.However, in water containing chelates, this band is observed as a broad.This may be due to coupling of the bending mode of coordinated water molecules with υ C=N 13 .

Electronic spectra
The electronic spectra of the complexes were recorded in DMSO solution.Both the ligands show two absorption bands (Figure 7) at 37313 cm -1 , 26385 cm -1 and (Figure 8) 37453 cm -1 , 26246 cm -1 respectively.No absorption was observed in the visible region for any of the ligands.In the absence of Quantum mechanical calculation, it is not possible to assign the absorption bands to definite electronic transitions with complete certainty.However, it appears reasonable to assign the bands to π→ π * transitions.The electronic spectra of chromium(III) complexes display the d-d transition bands in the region 23,000-15,900 cm -1 and 29,100-24,500 cm -1 .This transitions may be assigned to the 4 A 2g → 4 T 2g (υ 1 ) and 4 A 2g → 4 T 1g (F) (υ 2 ) and respectively.The transitions correspond to the typical octahedral geometry of the complexes.
The electronic spectra of iron(II) complexes display the d-d transition broad bands in the region 14,700-12,300 cm -1 and 27,300-25,100 cm -1 .The latter high energy band might be charge transfer in nature and low energy band may be assigned to the spin-allow transition 5 T 2g → 5 E g which correspond to the typical octahedral geometry of the complexes.
The electronic spectra of cobalt(II) complexes display the d-d transition bands in the region 9,350-8,400 cm -1 , 20,000-18,600 cm -1 and 28,100-26,500 cm -1 .The first two bands may be correspond to 4 T 1g (F) → 4 T 2g (F) υ 1 and 4 T 1g (F) → 4 T 1g (P) υ 3 transitions respectively.These bands are the characteristics of high spin octahedral Co(II) complexes.However υ 2 band is not observed because of its proximity to strong υ 3 transitions.
For the Cu(II) complexes with D 4 h symmetry, three spin allowed transitions 2 B 1g → 2 A 1g (υ 1 ), 2 B 1g → 2 B 2g (υ 2 ) and 2 B 1g → 2 E g (υ 3 ) are possible but the electronic spectra of Cu(II) complexes display two bands at 14,367 cm -1 , 21,448 cm -1 and 14,198 cm -1 , 21,290 cm -1 respectively.There should be third transition but we could not observe the same which may be due to very close energy values of different states.Absence of any spectral band below 10000 cm -1 rule out the possibility for tetrahedral structure of the present complexes are also suggestive for distorted octahedral geometry of the complexes.

Thermogravimetric analysis of Mn(II), Fe(II), Co(II), Ni(II) and Cu(II) complexes
The thermograms of this group of metal complexes show three stages decomposition (Table 5).All the metal complexes do not show weight loss below 120 °C, it indicates the absence of lattice water in the metal complexes.The first stage decomposition is obtained in the temperature range 140-210 °C.The % weight loss in this range is corresponds the loss of two coordinated water molecules [15][16][17] .The second stage decomposition is obtained in the temperature range 210-400 °C.The % weight loss in this range is corresponds % weight loss of two Schiff base ligands.
The third stage decomposition range is obtained in the temperature range 400-900 °C.The % weight loss in this range is corresponds % weight loss of metal oxide residue.

Thermogravimetric analysis of Cr(III) complexes
The thermograms of all Cr(III) metal complexes show two stage decompositions are listed in Table 6.All the metal complexes do not show % weight loss below 205 °C suggest the absence of coordinated and/or lattice water molecule/molecules.The first and second stage decomposition in the thermogram curves shows the removal of three Schiff base ligands.
The decomposition temperatures (>250 °C) of the metal complexes indicate that they are thermally quite stable, suggesting strong metal-ligand bonding 18 .All the metal complexes show further weight loss beyond 250 °C, which may be due to the weight loss of organic matter (ligand), leaving metal(II) or metal(III) oxide as the final product of the thermal decomposition 19 .
The effect of the ligands and their metal complexes in the growth media were investigated by standard microbiological parameters.Concentration of the test compounds were kept constant (500 ppm) during all the experiments.The bacterial, fungal and yeast cultures were maintained on nutrient-agar, potato dextrose-agar and YEDP culture-tubes (slants) respectively and were sub cultured every fortnight and stored at 0-5 °C temperature.
The compounds were tested in vitro for the antibacterial activity against Bacterial [Escherichia coli, Bacillus subtilis and S. aureus] and fungal [A.niger] and yeast [S.cerevisiae] cultures with both ligands and their metal complexes using Agar cup assay method.

Conclusion
On the basis of these results obtained for elemental analysis, infrared spectra, electronic spectra, TGA analysis and magnetic susceptibility measurements the following structures are proposed for the complex compounds of both ligands.The synthesized metal complexes in comparison to the uncomplexed Schiff base ligand were screened for their antibacterial activity against pathogenic bacteria species (Escherichia coli, Bacillus subtilis, S. aureus, A. niger and S. cerevisiae).The activity of the Schiff base complexes became more pronounced when coordinated with metal ions.The biological activity of the complexes follow the order Co(II)=Ni(II)> Mn(II), Fe(III), Cu(II).

Figure 1 .Figure 2 .
Figure 1.Mass spectrum of the ligand L

The 13 C
NMR spectrum of ligand L (Figure 5) displays the signals corresponding to the different non-equivalent carbon atoms at different values of δ as follows: at ca. δ 12.72 ppm, δ 17.87 ppm and δ 18.31 ppm (H 3 C-C) corresponding to carbon atoms of methyl groups; at ca. δ 102.96 ppm (C=C) due to carbon atom of pyrazolone ring; at ca. δ 116.97-134.36ppm due to aromatic carbon atoms; at ca. δ 139.79 (C=C) due to carbon atom of thiazole ring; at ca. δ 148.48 (C=N) due to carbon atom of pyrazolone ring; at ca. δ 148.51 (C=C) due to carbon atom of thiazole ring; at ca. δ 154.94 (C-OH) due to carbon atom of pyrazolone ring; at ca. δ 161.49(C=N) due to carbon atom of azomethine and at ca. δ 165.51 (C=N) due to carbon atom of thiazole ring.

Figure 5 .Figure 6 .
Figure 5. 13 C NMR spectrum of the ligand L

Figure 7 .Figure 8 .
Figure 7. UV spectra of the ligand L

Table 1 .
Analytical data and physical properties of complexes * decomposition temperature

Table 2 .
The NMR data of Schiff base ligand L

Table 3 .
The NMR data of Schiff base ligand L 1

Table 4 .
Selected IR bands of Schiff base ligand L, ligand L 1 and its complexes

Table 5 .
Thermo analytical results of metal complexes of Schiff base ligand L and ligand L 1

Table 6 .
Thermo analytical results of Cr(III) complexes of Schiff base ligand L and ligand L 1

•
The Fe(II) metal complexes are moderately effective against E.coli, S. aureus S. cerevisiae & A. niger and mostly effective against B. subtilis.• The Co(II) metal complex is slightly effective against S. aureus when moderately effective against E. coli, B. subtilis & S. cerevisiae and mostly effective against A. niger.• The Ni(II) metal complexes are slightly effective against S. aureus & A. niger when moderately effective against E. coli and mostly effective against B. subtilis and S. cerevisiae.• The Cu(II) metal complexes are slightly effective against E.coli & S. cerevisiae when moderately effective against B. subtilis, S. aureus and A. niger.