Synthesis, Spectroscopic, and Antimicrobial Studies of Binuclear Metallocene (M = Ti, Zr, or Hf) Derivatives of Bis(mercaptoazoles)

The reactions of (η 5 − C5H5)2MCl2 (M = Ti, Zr, or Hf) with mercaptoazoles (LH2), namely, bis(mercaptotriazoles), bis(mercap- tooxadiazoles), and bis(mercaptothiadiazoles) in 2 : 1 molar ratio, respectively, have been studied in dry tetrahydrofuran in the presence of n-butylamine and the binuclear complexes of the type [{(η − C5H5)2 M}2(L)] (M = Ti/Zr/Hf) are obtained. Tentative structural conclusions are drawn for the reaction products based upon elemental analysis, electrical conductance, magnetic moment, and spectral data (UV-Vis, IR, 1H NMR, and 13C NMR). FAB-mass spectra of few complexes of each series were also carried out to confirm the binuclear structures. Studies were conducted to assess the growth-inhibiting potential of the complexes synthesized, and the ligands against various fungal and bacterial strains.


INTRODUCTION
The chemistry of transition metal complexes containing heterocyclic thione donors continues to be of interest on account of their interesting structural features and also because of their biological importance [1][2][3][4][5][6]. The combination of the exocyclic thione/thiol group and the heterocyclic molecule, which may contain nitrogen, oxygen, or sulphur or a combination thereof, generates a group of molecules with considerable coordination potential [1][2][3]. The coordination behavior of such molecule depends upon reaction conditions, nature of metal ion, and pH of the medium. The stimulus for much of the research into the coordination chemistry of heterocyclic thione/thiol donors status from their wide ranging applications [7][8][9], viz., in analytical chemistry, in metal finishing, and electroplating industries uses as polyolefin stabilizers and as vulcanization accelerators. Fungicidal, insecticidal, and acaricidal activities have also been reported. Other biological applications include thyrotoxic activity; centred nervous system depressant and a platinum pyridine thione complex have been patented for clinical use in cancer treatment [1][2][3]. However, so far no report is available on the coordination behavior of bis(mercaptoazoles).
In this paper, we describe the synthesis, characterization, antifungal, and antibacterial studies on titanium(IV)/zir- (Gram-positive Bacillus subtilis and Gram-negative Escherichia coli). The plates were incubated for 24 hours at 30 ± 1 • C and the inhibition around each disc was measured in mm.

Preparation of complexes
To a solution of bis(cyclopentadienyl)titanium(IV)/zirconium(IV)/hafnium(IV), chloride (20 mmol) in dry tetrahydrofuran (∼40 cm 3 ) was added appropriate bis(mercaptotriazole/oxadiazole/thiadiazole) (10 mmol). To the resulting solution, dry n-butylamine (20 mmol) was added and the mixture was stirred for several hours at room temperature. nbutylamine hydrochloride remains soluble in tetrahydrofuran. The colored precipitate, thus obtained, was thoroughly washed with tetrahydrofuran and dried in vacuo.
For the sake of brevity, the details of all reactions along with physical characteristics and analytical data of the products are given in Table 1.

Electronic spectra
The electronic spectra of complexes, recorded in dimethylformamide, show a single band in the region 22 800-24 000 cm −1 which can be assigned [13] to the chargetransfer bond. In addition, the ligand and the complexes show band around 32 000 cm −1 , which is assigned to π → π * transition of the azomethine linkage.

Infrared spectra
The important infrared spectra of the ligands, mercapto azoles, and their corresponding titanium(IV)/zirconium(IV)/hafnium(IV) derivatives are given in Table 2. The  Compound ion. All these bonds are similar to those reported [19] for bis(cyclopentadienyl)titanium(IV)/zirconium(IV)/hafnium (IV) chloride. The appearance of these bands for cyclopentadienyl ring indicates that (η 5 -C 5 H 5 ) group remains in the complexes. The infrared spectra of bis(mercaptotriazoles), bis(mercaptooxadiazoles), and bis(mercaptothiadiazoles) show one weak band at 2480-2550 cm −1 due to the −SH group vibration. However, in the spectra of complexes, this band disappears indicating the coordination through sulphur after deprotonation. This is further supported [11] by the appearance of band at ca. 340-380 cm −1 , assignable to ν(M−S). A strong band in the region of 1585-1560 cm −1 in the ligands is characteristics [18] of ν(C=N) ring group. However, in the complexes the ν(C=N) band is found to split in two; where one band is located almost at the original position, that is, at ca. 1580 cm −1 due to uncoordinated ν(C=N) and other is shifted to lower frequency (∼20-25 cm Thus, the infrared spectra reflect that all bis(mercaptoazoles), that is, bis(mercaptotriazoles), bis(mercaptooxadiazoles), and bis(mercaptothiadiazoles) act as dibasic, tetradentate chelating agents coordinating through two thiol sulphur atoms and two ring azomethine nitrogen atoms. 1

H NMR spectra
The proton magnetic resonance spectra of ligands and their corresponding bis(cyclopentadienyl)titanium(IV)/zirconium(IV)/hafnium(IV) derivatives were recorded (Table 3) in DMSO-d 6 . The intensities of all the resonance lines were determined by planimetric integration. The following conclusions can be derived by comparing the spectra of ligands and their corresponding derivatives. The appearance of single, sharp signal for cyclopentadienyl ring indicates that there is rapid rotation of the cyclopentadienyl ring around the metal ring axis. 13

C NMR spectra
The 13 C NMR spectra of ligands and the corresponding complexes were recorded in DMSO. The 13 C resonance signals are assigned according to chemical shift theory. The C 5 H 5 rings give rise to one resonance at ca. δ 115.0. The considerable shift in the position of carbons (attached with mercapto group in the ligands; δ 150-160) indicates the coordination through mercapto group. Thus, on the basis of elemental analysis, electrical conductance and spectral data, the following structures (IV) are tentatively proposed for titanium(IV)/zirconium(IV)/ hafnium(IV) complexes. Proposed binuclear structure has also been confirmed by FAB mass spectra of few complexes of each series.
Attempts are being made to grow single crystal of the complexes suitable for X-ray studies but so far no success has been achieved.

Antifungal activity
The fungicidal activity of the ligands and their corresponding complexes were evaluated in DMF against Aspergillus niger, Aspergillus fumigate, and Helminothosporim oryzae by the agar plate technique at 1000, 100, and 10 ppm concentration with triplicate determination in each case. The average percentage inhibition was calculated using the expression: (%) = 100(C−T)/C where C and T are the diameters of the fungus colony in control and test plates, respectively. The recorded results (Table 4)  The variation in the effectiveness of different biocidal agents against different organisms [21] depends upon the permeability of the cells or differences in ribosomes of antimicrobial agent.

Antibacterial activity
The antibacterial activity of the complexes together with the parent ligands has been screened against Gram-positive Bascillus subtilis and Gram-negative Eschericlia coli at 1000 pm concentration. The results (Table 5) show that activity increases on chelation. The activity of the ligands is affected by the nature of substituents; this in relation to the lipophilicity of the ligands and their membrane permeability, a key factor in determining the entry inside the cell. The results lead to the following conclusions.
(a) The complexes are slightly more toxic than the parent ligands. (b) The titanium complexes show better activity than zirconium and hafnium complexes. (c) The ligands bis(mercaptothiadiazoles) and their complexes show slightly better activity than bis(mercaptotriazoles) and their derivatives which in turn show slightly better activity than bis(mercaptooxadiazoles) and their derivatives. (d) The presence of phenyl ring at R increases the antibacterial activity.  Table 5: Antibacterial activity of titanium(IV)/zirconium(IV)/hafnium(V) complexes with bis(mercaptoazoles).