Synthesis , Characterization , and Biological Activity of Mn ( II ) , Fe ( II ) , Co ( II ) , Ni ( II ) , Cu ( II ) , Zn ( II ) , and Cd ( II ) Complexes of N-Thiophenoyl-N ′-Phenylthiocarbohydrazide

Mn(II), Fe(II), Co(II), Ni(II), Cu(II), Zn(II), andCd(II) complex ofN-thiophenoyl -N-phenylthiocarbohydrazide (H2 TPTH) have been synthesized and characterized by elemental analysis, magnetic susceptibility measurements, infrared, NMR, electronic, and ESR spectral studies.e complexes were found to have compositions [Mn(HTPTH)2], [Co(TPTH) (H2O)2], [Ni(TPTH) (H2O)2], [Cu(TPTH)], [Zn(H TPTH)], [Cd(H TPTH)2], and [Fe(H TPTH)2(EtOH)]. e magnetic and electronic spectral studies suggest square planar geometry for [Cu(TPTH)], tetrahedral geometry for [Zn(TPTH)] and [Cd(H TPTH)2], and octahedral geometry for rest of the complexes.e infrared spectral studies of the 1 : 1 deprotonated complexes suggest bonding through enolic oxygen, thiolato sulfur, and both the hydrazinic nitrogens. us, H2TPTH acts as a binegative tetradentate ligand. H2 TPTH and its metal complexes have been screened against several bacteria and fungi.


Introduction
e expansion of research in the coordination chemistry of nitrogen-sulphur donor ligands such as substituted thiosemicarbazides [1], thiosemicarbazones [2][3][4], and dithiocarbazates [5], during the recent years has been due to their remarkable antineoplastic activity against a variety of tumors [6] in addition to their applicable antifungal [7] and antibacterial [8] activities.Sulphur and nitrogen containing ligands and their transition metal complexes are also used as corrosion inhibitors [9,10] and extreme pressure lubricant additives [11].Keeping in view the above biological activity of the ligands, we planned to undertake the synthesis, characterization, antibacterial, and antifungal activity of the 3d-metal complexes of N-thiophenoyl-N ′ -phenylthiocarbohydrazide (H 2 TPTH) (Figure 1), having oxygen and sulphur as donors.is legand is expected to form addition complexes without loss of protons and deprotonated complexes by loss of one or both the hydrazinic protons.

Starting Materials.
All the chemicals used were of analytical grade.Ammonium polysulphide [12] and carboxymethyldithiobenzoate [13] were prepared by literature methods.

Preparation of N-iophenoyl-N
′ -Phenylthiocarbohydrazide (H 2 TPTH).N-thiophenoyl-N ′ -phenylthiocarbohydrazide (H 2 TPTH) was prepared by mixing solutions of 2-thiophene carboxylic acid hydrazide (20 mmol) and carboxymethyldithiobenzoate (20 mmol) each dissolved separately in 50 mL of 0.5 N NaOH and allowing the mixture to stand at room temperature for 2 hrs.e product precipitated by adding dilute AcOH dropwise to the above ice-cold mixture, was �ltered off, washed with H 2 O, dried, and recrystallized from EtOH.

Instrumentation.
Complexes were analysed for their metal content, following a standard procedure [14] by decomposing the complexes with a mixture of HNO 3 and HCl followed by H 2 SO 4 .Sulphur and chloride were determined as BaSO 4 and AgCl, respectively.Carbon, hydrogen, and nitrogen were estimated on a EA 1108 CHN Elemental Analyser.Magnetic susceptibility measurements were made at room temperature on a Cahn-Faraday balance using Hg[Co(NCS) 4 ] as calibrant.Electronic spectra were recorded on a CARY-2390 UV-Visible Spectrophotometer as Nujol mulls [15].IR Spectra were recorded in the 4000-400 cm −1 region (KBr disc) on a JA SCO FT/FR-5300 spectrophotometer.e 1 H and 13 C NMR spectra were obtained in DMSO-D 6 on a JEOL FX-300 Q FT/NMR spectrometer using TMS as internal reference.ESR spectra were recorded on a Xband spectrometer model EPR-112 using DPPH as a ⟨g⟩ marker.e electrical conductivity of the pressed pellets of the complexes was obtained by a conventional two-probe method in the 303-383 K range with contact made on the pellet surfaces using graphite paint.A Keith ley 236 SMU was used to measure the resistance.
2.5.Bactericidal Screening.e antibacterial activity of the ligand and the complexes was evaluated using the disc diffusion technique [16].A stock solution of 2000 g cm −3 was made by dissolving 2 mg cm −3 of each compound in DMSO and it was serially doubled diluted upto �ve dilutions, giving the concentrations of 1000, 250, 125, and 62.5 g cm −3 .Filter paper (Whattman No. 42) discs (6 mm dia) were soaked in these solutions of different concentrations and placed on nutrient agar plates.e plates were then incubated for 24 hrs at 37 ∘ C. e inhibition zones around the discs were measured aer 24 hrs.Cotrimoxazole was used as a standard drug in the form of disc, containing trimethoprim-1.25 g and sulfamethoxazole = 23.75 g per disc.e zones of inhibition were found to be 20, 32, and 18 mm against Staph aureus, Escherichia coli, and Pseudomonas aeruginosa, respectively, in agreement with the sensitive zone reported in the literature.
2.6.Fungicidal Screening.e antifungal activity was evaluated by a drug dilution technique.e solution of the test compounds was prepared as described earlier to which Sabouraud's dextrose broth and slightly turbid suspension of fungus in normal saline (10 L) were added and placed in an incubator for 48-72 hrs.A turbidity in the solution indicated the growth of fungus, which is represented as − sign, however, a clear solution showed that there was no growth of fungus and is represented as + sign.e cases where compounds showed antifungal activity, no growth was observed in the solution.Amphotericin B was used as a standard drug.

Results and Discussion
All the complexes are insoluble in water, methanol, and ethanol but are soluble in polar organic solvents such as DMSO and DMF.[Mn(H TPTH) 2 ] and [Co(TPTH)(H 2 O) 2 ] are more soluble in DMSO than other complexes.e complexes having 1 : 1 metal-ligand stoichiometry (Table 1) are formed by loss of two protons from the legend, generating a conjugated system.Because of steric considerations, all the four potential sites cannot be attached to a single metal and, therefore, the ligand binds in a polymeric fashion.Accordingly, the 1 : 1 complexes show high-melting points.e following equations represent the formation of the ligand and the complexes: (5) 3.1.Magnetic Moments and Electronic Spectra.e magnetic moments and electronic spectral data of the complexes are given in Tables 1 and 2  show the absence of both the (NH), (C=O), and (C=S) bands and in place of these two new bands appear at 1580 and 745 cm − , due to (N=C) of NCO and (C-S) modes, respectively, suggesting that both -NH-NH protons are lost via enolisation and thioenolisation and bonding of the resulting enolic oxygen and thiolato sulfur takes place with the metal ion.Further, the thioamide I, II, and (N-N) bands at 1460, 1325, and 1000 in the free ligand undergo a positive shi of 33, 65, and 70 cm − , respectively, in the spectra of the complexes [19] suggesting the involvement of these groups as bonding sites.ese observations show the involvement of thiolato sulfur and both the hydrazinic nitrogens, in addition to the enolic oxygen in bonding.us, H 2 TPTH acts as a binegative tetradentate ligand in the 1 : 1 complexes.4) in DMSO-d 6 shows a signal at  9.86 and 9.72 ppm due to the presence of -NH-NH-protons which are lost on D 2 O exchange.e protons due to the thiophene ring appear at  7.12 (s, 1H), 7.32 (d, 1H), and 7.56 (s, 1H) ppm and the benzene ring protons appear as a multiplet at at  6.64 −6.92(m, 5H) ppm [20].
e  H NMR spectrum of [Mn(H TPTH) 2 ] shows separate signals for the thiophene ring protons at  7.04 (s, 1H), 7.30 (d, 1H), and 7.51 (s, 1H) ppm and for benzene ring protons at  6.62-6.90(m, 5H) ppm.e two signals appearing at  9.66 and 4.16 ppm are due to the presence of -NH-C(O) and -N=C(SH) protons, respectively.e latter is formed due to the thioenolization of the ligand.All the thiophene and benzene ring protons are observed nearly at the same position in the complex as compared to those of the H 2 TPTH, suggesting noninvolvement of the ring sulphur in bonding.
e 3 C NMR spectrum of (H 2 TPTH) ( T 3: Important IR spectral bands (cm −1 ) and their assignments.On the basis of physicochemical studies and the foregoing discussion, the proposed structures of the complexes are shown in Figure 2.

in
(C=S), suggesting an additional bonding through thione sulfur.Furthermore, the spectra of these complexes show a positive shi of 20 cm − in (N-N) indicating that one hydrazinic nitrogen is also involved in bonding.e presence of (NH) at 3180 cm − and (C=O) at 1625 cm − in [Cd(H TPTH) 2 ] indicates loss of NH proton via thioenolisation.Further, the band at 1460, 1325, and 1000 cm − due to thioamide I, II and (N-N) undergo positive shis of 25, 15, and 20 cm − , respectively, showing the involvement of thiolato sulfur[18] and one hydrazinic nitrogen in bonding.e IR spectra of [M(TPTH)(H 2 O) 2 ] (M = Co(II), Ni(II)) and [M(TPTH)] (M = Cu(II) and Zn(II)) Candida kefri; b: Candida albicans.Control: amphotericin B. Growth and no growth of fungi are represented by -and + sign, respectively.
e magnetic and electronic spectral studies suggest square planar geometry for [Cu(TPTH)], tetrahedral geometry for [Zn(TPTH)] and [Cd(H TPTH) 2 ], and octahedral geometry for the rest of the complexes.e infrared spectral studies of the 1 : 1 deprotonated complexes suggest bonding through enolic oxygen, thiolato sulfur, and both the hydrazinic nitrogens.e ESR spectrum of [Cu(TPTH)] shows that the unpaired electron is present in the   2 − 2 orbital of Cu(II).e ligand H 2 TPTH shows antibacterial activity against S. aureus, E. coli and P. aeruginosa and antifungal activity against C. kefri and C. albicans.e complexes Mn(H TPTH) 2 ], [Cu(TPTH)] and [Zn(TPTH)] also show antibacterial activity against the bacteria S. aureus, E. coli, and P. aeruginosa and antifungal activity against the C. kefri and C. albicans.

2 F 2 :
Proposed structure of the complexes.
[17]spectively.[Mn(HTPTH) 2 ] shows a magnetic moment, 5.76 B.M. and exhibits a band at 16140 cm − assigned to the 6 A g →  T g transition for the octahedral geometry[17].emagneticmoment5.31 B.M. and presence of bands at 11770 and 20840 cm − owing to the 5 T 2 → 5 B  and charge-transfer transitions, respectively, suggests a high-spin square pyramidal geometry for [Fe(H TPTH)2 (EtOH)]⋅[Co(TPTH)(H 2 O) 2 ]shows a magnetic moment of 4.92 B.M. and exhibits a d-d band at 16675 cm − , assigned to the  T g (F) →  T g (P) ( 3 ) transition for a distorted octahedral geometry.Ni(TPTH)(H 2 O) 2 ] exhibits a magnetic moment of 3.06 B.M. and shows a band at 16140 cm − attributed to the 3 A 2g (F) → 3 T g (F) ( 2 ) transition for a distorted octahedral geometry around Ni(II).[Cu(TPTH)] shows a magnetic moment of 1.98 B.M. indicating the presence of one unpaired electron.e complex shows a d-d band at 15635 cm − due to the envelope of the 2 2 (EtOH)] show only one peak at 3125 cm − due to (NH), suggesting loss of one hydrazinic proton via enolisation/thioenolisation.A strong band at 1640 cm − in the ligand due to (C=O) is found to be absent in these complexes, and in place of this a new band due to (N=C) of NCO appears, suggesting that enolic oxygen is involved in bonding.[Mn(H TPTH) 2 ] shows a negative shi of 15 cm −

Table 5 )
shows eleven signals, of which two signals at  181 and 163 ppm are due to the C=S and C=O carbons, respectively.e chemical shis for the benzene and thiophene ring carbons in H 2 C.T.: charge-transfer; L: intraligand transition.
6: Antibacterial activity of H 2 TPTH and its complexes.Pseudomonas aeruginosa.Control: cotrimoxazole.+ and − , over the parentheses indicate the zone of inhibition and no zone of inhibition, respectively.T 7: Antifungal activity of H 2 TPTH and its complexes.