Synthesis, Characterization, Theoretical Crystal Structure, and Antibacterial Activities of Some Transition Metal Complexes of the Thiosemicarbazone (Z)-2-(pyrrolidin-2-ylidene)hydrazinecarbothioamide

Problem Statement. In Iraq like most third world countries, attempts discovered new antibiotic drugs derived from thiosemicarbazide and its metal complexes and developed the branch of applied in organic chemistry. Approach. New (Z)-2-(pyrrolidin-2-ylidene)hydrazinecarbothioamide (L) was synthesized in a good yield by the reaction of pyrrolidone with thiosemicarbazide. Co(II), Ni(II), and Cu(II) complexes of (L) were prepared and characterized by FT-IR, UV/visible spectra, 1HNMR, and CHN analyses. Moreover, charge, bond length, bond angle, twist angle, heat of formation, and steric energy were calculated by using of the ChemOffice program, and the DFT calculations for the complexes were done. The free ligand and its metal complexes were tested in vitro against several microorganisms (Staphylococcus aurous, E. coli, Proteus vulgaris, Pseudomonas, and Klebsiella pneumoniae) to assess their antimicrobial properties. Results. The study shows that these complexes have octahedral geometry; in addition, it has high activity against tested bacteria. Conclusion/Recommendations. Based on the reported results, it may be concluded that ligand acts as bidentate, neutral ligand, coordinating through one of the nitrogen and sulfur atoms.


are reported
o possess a wide variety of biological activities against bacteria, fungi, and certain type of tumors, and they are also a useful model for bioinorganic processes [4][5][6].The activity of these compounds is strongly dependent on the nature of the heteroatomic ring and the position of attachment to the ring as well as the form of thiosemicarbazone moiety [7].These are studied extensively due to their flexibility, selectivity, and sensitivity towards the central metal atom, and structural similarities with natural biological substances, and due to the presence of imine group (−N=CH−) which imparts the biological activity [8][9][10][11][12].There is no report on the complexes of (Z)-2-(pyrrolidin-2-ylidene)hydrazinecarbothioamide (L).We now present details of the complexes of (L) with cobalt(II), nickel(II), and copper(II) ion.


Materials and Methods

2.1.General.All chemicals used were of reagent grade (supplied by either Merck or Fluka) and used as supplied.The FTIR spectra in the range (4000-200) cm −1 were recorded as cesium iodide disc on FTIR 8300 Shimadzu Spectrophotomete

Proton NMR spectra wer
recorded on Bruker-DPX 300 MHz spectrometer with TMS as internal


Synthesis of the Complexes.

Metal salts (5 mmol) in hot ethanol (20 mL) were mixed with hot ethanolic solution of the ligand (10 mmol) and refluxed for 4 hours on a water bath; on cooling the contents, the colored complexes separated out in each case.The product was fi

um over P 4 O 10 .Purity of
he complexes was checked by thin layer chromatography (TLC).


Study of Complex Formation in Solution.

The complexes of the ligand with metal ions were studied in DMF, in order to determine the M : L ratio in the complex following the molar ratio method.A series of solutions were prepared having a constant concentration (10 −3 M) of the metal ion and (L).The M : L ratio was determined

rom the relationship between the absorpt
on of light and the molar ratio of M : L. The results of complexes formation in solution were listed in Table 1.


The Biological Activity for the Ligand and Its Complexes.

All tests with the microorganisms were obtained from the Biotechnology Division, Depart

nt of Applied Science, University of Technology, which wer
as follows: Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, and Staphylococcus aureus.Antibacterial activities of the ligand and the soluble complexes were evaluated by the disc diffusion technique [13].Filter paper (Whatman no.4) discs (6 mm diameter) were soaked in a solution of the test compounds of 10 −2 × 5 mg mL −1 concentration in DMF and placed on nutrient agar plates after drying to remove the solvent.The inhibition zones were measured after 24 h.DMF was used as control.The results are shown in Figure 2.


Results

General.The complexes were synthesized by reacting ligand with the metal ions in 1 : 2 molar ratio in ethanolic medium.


Infrared Spectroscopy.

A study
nd comparison of infrared spectra of free ligand and its metal complexes (Table 2) infers that the ligand behaves as neut

l bidentate and its met
ls are coordinated through N and S of the thioketo group (Figure 1).

Strong bands in the 3396 and 3275 cm −1 regions were observed and attributed to N-H vibrations in the ligand.The negligible effect on these frequencies after complexation precludes the possibility of complexation at this group.The absorption at 1600 cm −1 in free ligand can be attributed to (C=N) stretching vibration of imine nitrogen, which is in a good agreement with previous observations.On complexation, this frequency was observed to be shifted to a lower wave number (Table 2).These observations suggest the involvement of unsaturated nitrogen atoms of the azomethine groups in bonding with the metal ions.Coordination of sulfur with the metal ion would result in the displacement of electrons towards the latter, thus resulting in the weakening of the (C=S) bond.Hence, on complexation (C=S) stretching vibrations should decrease and those of (C-N) should increase.The IR spectral bands in the ligand are practically unchanged in the complexes but show some new bands with medium to weak intensity in the 520-440 cm −1 region tentatively assigned to (M-N) and (M-S).(M-Cl) is tentatively assigned in the 360-350 cm −1 region [14,15].


Magnetic Susceptibility.

At room temperature, all the complexes under study show the magnetic moment in the range of 2.1-4.7 B.M. corresponding with the unpaired electrons.The magnetic moment of Co(II) complex is 4.1 BM showing that the Co(II) complex is typically a high sp

dral structure [16].Fo
Ni(II) complex, the observed magnetic moment value is 3.0 BM which is well within the expected range for Ni(II) complex with octahedral stereochemistry (2.83-4.0BM).The magnetic moment for Cu(II) complex is 2.0 BM.The reported values for the Cu(II

complex have no majo
spin orbital interactions (1.75-2.20 BM) [16,17].Thus the present Cu(II) complex is without any spin orbital interaction with octahedral geometry.In octahedral Cu(II) complex, the ground state is 2Eg, and large spin

T 1g(P) .This shows
that these complexes have octahedral geometry.


UV-Visible Spectroscopy


Nickel(II) Complexes.

The electronic spectra of the Ni(II) complex show absorption bands at 9000, 13000, and 24000 cm −1 and may be assigned to the transitions 3 A 2 g → 3 T 2 g, 3 A 2 g → 3 T 1g(F) , and 3 A 2g(F) → 3 T 1g(P) corresponding with an octahedral geometry.


Copper(II)

Complex.The Cu(II) complex under study displays absorption bands 13400 and 16000 cm −1 .These bands were assigned to the following transitions from a distorted octahedral geometry [18]: 2 B 1 g
→ 2 A 1 g, 2 B 1 g → 2 B 2 g.

Stereo Suggest

Structures of C
mplexes.

According to the above-mentioned data (spectra, molar conductance, molar ratio, and magnetic properties), the proposed structures of completes were shown as in Figure 1.


Biological Activity

It is known that chelation tends to make the ligand act as more powerful

d potent ba
tericidal agents, thus killing more of the bacteria than the ligand.It is observed that, in a complex, the positive charge of the metal is partially shared with the donor atoms present in the ligands, and there may be π-electron delocalization over the whole chelate [19].This increases the lipophilic character of the metal chelate and favours its permeation through the lipoid layer of the bacterial membranes.The increased lipophilic character of these complexes seems to be the reason of their enhanced


Stability Study

These data show that the atomic charge was affected by the presence of substituent of rings as shown in Tables 3, 4, and 5.As a reference compound, the unsubstituted ligand (Figure 3), the data for minimized geometry, and the 3dgeome

ical struct
re are shown in (Figure 3).


Discussion

All the solid complexes are stable in air.The metal complexes are soluble in DMF and DMSO.Table 1 shows the colors, elemental analyses, and molar conductivities of the cobalt(II), nickel(II), and copper(II) complexes.Thiosemicarbazones can coordinate with metal ions as neutral ligand.The C, H, and N data indicate that the complexes of neutral ligand are coordinated to the metal ion, and the other coordination positions were occupied by chlorine, as confirmed by the IR spectra of the complexes.The antibacterial screening (Figure 2) indicates that the complexes inhibit the growth of Staphylococcus aurous and Klebsiella, whereas