Synthesis, Spectral and Antibacterial Studies of Binuclear Titanium(IV) / Zirconium(IV) Complexes of Piperazine Dithiosemicarbazones

The reactions of mono(cyclopentadienyl)titanium(IV) trichloride and bis(cyclopentadienyl)titanium(IV)/ zirconium(IV) dichloride with a new class of dithiosemicarbazone, derived by condensing piperazine dithiosemicarbazide with benzaldehyde (L1H2), 2-chlorobenzaldehyde (L2H2), 4-nitrobenzaldehyde (L3H2) or salicylaldehyde (L4H4) have been studied and different types of binuclear products, viz. [{CpTiCl2}2L], [{Cp2MCl}2L], ((L=L1, L2 or L3), [{CpTiCI}2L4] and [{Cp2M}2L4] (M=Yi or Zr), have been isolated. Tentative structures are proposed for these complexes based upon elemental analyses, electrical conductance, magnetic moment and spectral (electronic, IR, 1H and 13C NMR) data. Attempts have been made to establish a correlation between antibacterial activity and the structures of the products.


INTRODUCTION
Thiosemicarbazones and their metal complexes are of considerable current interest because of their potentially beneficial pharmacological properties and a wide variation in their modes of bonding and stereochemistry /1-6/. Heterocyclic thiosemicarbazones exercise their beneficial therapeutic properties in mammalian cells by inhibiting ribonucleotide reductase, a key enzyme in the synthesis of DNA precursors /7/. Their ability to provide this inhibitory action is thought to be owing to coordination via their N N S tridentate ligating system. Recent developments in the structural nature of metal complexes of heterocyclic thiosemicarbazones are correlated with their biological activities. It has been suggested that the stereochemistries and activities of complexes often depend upon the nature of N(4) substituents and on groups attached to N (1). Recently, a number of papers have also appeared/4/on bis(thiosemicarbazone) derivatives (derived from dialdehyde or diketons) in which two thiosemicarbazone moieties are connected by their imine nitrogens, to N(1) carbon skeleton. However, very few reports are available on

Reactions of Cp2MCI and CpTiCI3 with dithiosemicarbazones
To a solution of bis(cyclopentadienyl)titanium(IV)/zirconium(IV) dichloride or mono(cyclopentadienyl)titanium(IV) trichloride (20 mmol) in dry THF (ca. 40 cma) was added the appropriate dithiosemicarbazone (10 mmol). To the resulting clear solution, EtaN (20 retool) was added and the mixture was stirred for ca. 12-22 h at room temperature. Precipitated EtaNHCl was removed by filtration and the volume of the solution was reduced to ca. 15 cm under reduced pressure. Light petroleum (b.p. 60-80 C) (10 cm3) was then added. The colored precipitate thus obtained was thoroughly washed with Et20 and recrystallized from 1"1 THF: Et20.
The details and important physical characteristics of new compounds are recorded in Table 1. The nuclear magnetic resonance spectra of ligands and the complexes were recorded on a Bruker 400 spectrometer. Chemical shifts are expressed relative to an internal reference TMS (1% by volume).

RESULTS AND DISCUSSION
A systematic study of the reactions of bis(cyclopentadienyl)titanium(IV)/zirconium(IV) dichloride and mono(cyclopentadienyl)titanium(IV) trichloride with piperazine dithiosemicarbazones (molar ratio 2:1, respectively) in anhydrous THF in the presence of triethylamine may be represented by the following In formulas for the complexes, L is the symbol for the dianion when both of the thiosemicarbazone moieties have lost their amide proton N(2)H in the piperazine dithiosemicarbazone ligands derived from benzaldehyde, 2-chlorobenzaldehyde and 4-nitrobenzaldehyde. L represents the loss of both amide protons and phenolic protons from the salicylaldehyde piparazine dithiosemicarbazone.
Colours, elemental analyses and molar conductivities are listed in Table 1. Complexes are soluble in dimethylformamide, dimethylsulphoxide, nitrobenzene, tetrahydrofuran. The molar conductances of the complexes in DMF are in the range 6.0-10.0 ohmcm mol , which are well below the range observed for uni-univalent electrolytes in this solvent. Magnetic susceptibility measurements show that they are diamagnetic. The electronic spectra of the complexes show a broad band in the 22200-23800 cm , region which can be assigned /12/ to charge-transfer, a result in accord with their (n-1)dns electronic configuration. The ligands show bands at ca. 35000 cm and 28000 cm , which are assigned to n---* transitions associated with imine and thioamide functions of the thiosemicarbazone moieties, respectively. In their respective complexes, these bands shift slightly to higher frequencies.

I.R.Spectra
Absorption bands occurring at ca. 3000 cm for v (C-H), ca. 1420 cm for v (C-C) and ca. 1020 cm "1 for v (C-H) in all the complexes are assigned to the cyclopentadienyl group and indicate that these groups are nbonded to the metal/13/.
The i.r. spectral bands most useful for determining the coordination mode for the dithiosemicarbazones are listed in Table 2. These ligands can exist either as a thione or the thiol tautomeric forms or as an equilibrium mixture of both forms, since they have a thioamide, -NH-C(=S) function. The i.r. spectra in the solid state do not show any v(S-H) band but exhibit a medium v(N-H) band at ca. 3150 cm -, indicating that in the solid state, they remain mainly in the thione form. However in solution they readily convert to the thiol tautomeric form with the concomitant formation of titanium(IV) zirconium(IV) complexes of the protonoted mercapto form of the ligands. This is indicated by the absence of-NH band in the complexes. The i.r. spectra of the complexes also show a new band at ca. 600-620 cm owing to conversion/4/of C=S to C-S-. The new band in the complexes at ca. 380-400 cm "l is assigned/13/to v(M-S) and shows that sulfur is bonded to titanium/zirconium atom. The v(C=N) shift of the dithiosemicarbazones from 1570-1560 cm " to lower energy in the spectra of complexes indicates coordination of the imine nitrogens N(1). However, the loss of N(2)H's from the two dithiosemicarbazone moieties, by thione thiol tautomerism produces additional carbon-nitrogen double bonds, N(2)=C(S) which is indicated by the appearance of a band at ca. 1590 cm in the complexes. Bands in the 460-475 cm region are assigned /13/to v(M-N) and support coordination of the imine nitrogens. The v(M-CI) bands have been assigned in the 330-315 cm region. l'kdume 1, No. I, 2003 S.wtthesis, Spectral and Antibacterial &udies of Binuclear Titanium(IV) Zirconimn(1V) Complexes of Piperazine Dithiosemicarbazones Table 2 IR spectral data of titanium(iv)/zirconium(iv) derivatives with piparazine dithiosemicarbazones  (Table 3)  The 3C n.m.r spectra of ligands and the corresponding .complexes were recorded in DMSO ( Table 3). The 3C resonance signals are assigned according to chemical shift theory. The compounds show cyclopentadienyl peak at ca. 8 117 (relative to TMS). A considerable shift takes place in the position of-C-S (ca. 165 ppm, ligands) and C N (ca. 150 ppm, ligands) indicating coordination through the azomethine nitrogen and the thiol group. The signal for piperazine group appears at ca. 8 62.8 in the ligands, which shift, slightly downfield in the complexes.   13 12 Antibacterial Activity The antibacterial activity of the complexes together with the parent ligands has been screened/14/against Gram-positive Bacillus subtilis and Gram-negative Escherichia coli by the paper disk plate method at 1000 ppm conc. The inhibition zone (mm) around each disk was measured after 24 h and the results of these studies are listed in "Fable 4. 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 complexes. (c) Mono(cyclopentadienyl)titanium(IV) derivatives possess better activity than bis(cyclopentadienyl)titanium(IV) derivatives.
(d) The best activity was recorded with mono(cyclopentadienyl)titanium(IV) derivatives with ligand L_Hz i.e. containing-CI group at phenyl ring of the thiosemicarbazone moieties.
On the basis of elemental analysis, electrical conductance and spectral data, the following structures for the complexes are proposed. 42