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American Chemical Science Journal 
4(1): 117-137, 2014 
SCIENCEDOMAIN international 
www.sciencedomain.org 
Synthesis, Cha...
American Chemical Science Journal, 4(1): 117-137, 2014 
complexes have been tested in vitro against a number of microorgan...
American Chemical Science Journal, 4(1): 117-137, 2014 
2. EXPERIMENTAL 
The hydrated lanthanide chlorides as well as 2-hy...
American Chemical Science Journal, 4(1): 117-137, 2014 
120 
Table 1. Analytical data and physical properties of the ligan...
American Chemical Science Journal, 4(1): 117-137, 2014 
2.2 Synthesis of the Sodium Salt of the Ligands 
Sodium metal was ...
American Chemical Science Journal, 4(1): 117-137, 2014 
2.4 Biological Activity 
2.4.1 Antifungal activity 
The antifungal...
American Chemical Science Journal, 4(1): 117-137, 2014 
2.4.2 Antibacterial activity 
Both of the ligands and their corres...
American Chemical Science Journal, 4(1): 117-137, 2014 
Sm(III) metal complexes of ligand (HPHCBESH2), respectively. The a...
American Chemical Science Journal, 4(1): 117-137, 2014 
125 
 = (1- βav)/ βav .100 
Where βav is the average value of the...
American Chemical Science Journal, 4(1): 117-137, 2014 
126 
Table 2. Electronic spectral data of Ln(III)complexes 
Comple...
American Chemical Science Journal, 4(1): 117-137, 2014 
3.3 1H NMR Spectra 
The 1H NMR spectra of both the ligands and the...
American Chemical Science Journal, 4(1): 117-137, 2014 
128 
Table 3. IR (cm-1) spectral data of the ligands and their cor...
American Chemical Science Journal, 4(1): 117-137, 2014 
129 
Table 5. Thermogravimetrical analysis data for the metal comp...
American Chemical Science Journal, 4(1): 117-137, 2014 
been assigned to each d value and 2θ angles are reported in Table ...
American Chemical Science Journal, 4(1): 117-137, 2014 
3.9 Biological Results and Discussion 
Antimicrobial activity of t...
American Chemical Science Journal, 4(1): 117-137, 2014 
The results of antifertility showed that administration of ligand ...
American Chemical Science Journal, 4(1): 117-137, 2014 
133 
Table 9. Effects of ligand and its complexes on body and repr...
American Chemical Science Journal, 4(1): 117-137, 2014 
134 
Table 11. Testicular biochemistry and serum testosterone leve...
American Chemical Science Journal, 4(1): 117-137, 2014 
4. CONCLUSION 
On the basis of the analytical data and spectral st...
American Chemical Science Journal, 4(1): 117-137, 2014 
11. Ali MA, Mirza AH, Tan AL, Wei LK, Bernhardt PV. The preparatio...
American Chemical Science Journal, 4(1): 117-137, 2014 
30. Joshi SC, Goyal R, Jain S. Effect of organochlorine pesticide ...
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Synthesis, Characterization, Spectral (FT-IR, 1H, 13C NMR, Mass and UV) and Biological Aspects of the Coordination Complexes of Sulfur Donor Ligands with Some Rare Earth Elements

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Bio-potent ligands, 2-hydroxy-N-phenylbenzamide hydrazinecarbothioamide(HPHTSCZH2) and 2-hydroxy-N-phenylbenzamide hydrazine carbodithioic benzyl ester (HPHCBESH2) have been synthesized by the condensation of 2-hydroxy-N-phenylbenzamide with hydrazinecarbothioamide and hydrazine carbodithioic benzyl ester, respectively and reacted with hydrated lanthanide chlorides. The coordination moieties of the ligands have been confirmed by various spectral studies. - See more at: http://www.sciencedomain.org/abstract.php?iid=271&id=16&aid=2488#sthash.6v3aFQIi.dpuf

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Synthesis, Characterization, Spectral (FT-IR, 1H, 13C NMR, Mass and UV) and Biological Aspects of the Coordination Complexes of Sulfur Donor Ligands with Some Rare Earth Elements

  1. 1. American Chemical Science Journal 4(1): 117-137, 2014 SCIENCEDOMAIN international www.sciencedomain.org Synthesis, Characterization, Spectral (FT-IR, 1H, 13C NMR, Mass and UV) and Biological Aspects of the Coordination Complexes of Sulfur Donor Ligands with Some Rare Earth Elements R. V. Singh1*, Pradeep Mitharwal1, Ritu Singh1 and S. P. Mital2 1Department of Chemistry, University of Rajasthan, Jaipur, 302 004, India. 2Department of Chemistry, D.A.V. P.G. College, Dehradun-248001, India. Authors’ contributions This work was carried out in collaboration between all authors. Author RVS designed the study, performed the statistical analysis, wrote the protocol, and wrote the first draft of the manuscript. Authors PM and RS managed the analyses of the study. Author SPM managed the literature searches. All authors read and approved the final manuscript. Received 17th September 2013 Accepted 16th October 2013 Published 9th November 2013 Original Research Article ABSTRACT Bio-potent ligands, 2-hydroxy-N-phenylbenzamide hydrazinecarbothioamide(HPHTSCZH2) and 2-hydroxy-N-phenylbenzamide hydrazine carbodithioic benzyl ester (HPHCBESH2) have been synthesized by the condensation of 2-hydroxy-N-phenylbenzamide with hydrazinecarbothioamide and hydrazine carbodithioic benzyl ester, respectively and reacted with hydrated lanthanide chlorides. The coordination moieties of the ligands have been confirmed by various spectral studies. Elemental analyses suggested that the complexes have 1:2 stoichiometry which were characterized further by magnetic moment, infrared, EPR, electronic, 1H NMR, 13C NMR and mass spectral studies. TGA studies were also conducted for one of the representative compound to analyze the presence of water molecule. The spectral studies confirmed the proposed framework of the new lanthanide complexes and indicated an octahedral geometry around the central metal atom. On the basis of X-ray powder diffraction study one of the representative Sm complex was found to have Hexagonal Lattice type, having Lattice Parameters: a = 18.528 Aº, b = 18.528 Aº and c = 20.675 Aº and α = 90º, β = 90º and γ =120º. The free ligands and their metal ____________________________________________________________________________________________ *Corresponding author: Email: rvsjpr@hotmail.com;
  2. 2. American Chemical Science Journal, 4(1): 117-137, 2014 complexes have been tested in vitro against a number of microorganisms in order to assess their antimicrobial properties and in vivo for antifertility activity on male albino rats. Both the ligands and their complexes were found to possess appreciable fungicidal, bactericidal and antifertility activities. Keywords: Rare earth elements; thiosemicarbazone; hydrazine carbodithioic acid; 2- hydroxy-N-phenylbenzamide; microorganisms; antifertility activity; TGA; spectral studies. 1. INTRODUCTION Nowadays, the complexes of the rare earth ions are a subject of increasing interest in bioinorganic and coordination chemistry [1]. A sustained research activity has been devoted to lanthanide complexes, because of their successful application in the form of diagnostic tools in biomedical analysis as MRI contrast agents [2,3]. The coordination chemistry of lanthanide elements and important role of their complexes in chemical, medical and industrial processes are enough to recognize them as worthwhile for the synthesis of the new complexes. Apart from the structural diversities and bonding interactions, the multitude applications of lanthanide complexes make it an exciting arena in coordination chemistry [4,5]. Imines are important class of ligands due to their synthetic flexibility, their selectivity and sensitivity towards the central metal atom, structural similarities with natural biological substances and also due to the presence of the imine group (>C=N) which imparts in elucidating the mechanism of transformation and racemisation reaction in biological system [6]. The chemistry of thiosemicarbazones has received considerable attention in view of their variable bonding modes, promising biological implications, structural diversity, and ion-sensing ability [7-8]. They have been used as drugs and are reported to 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 [9,10]. Metal complexes of imines derived from S-alkyl/aryl esters of dithiocarbazoic acid [11] have received considerable attention because of the presence of both hard nitrogen and soft sulfur donor atoms in the backbones of these ligands. It is well known that lanthanide ions have high affinity to hard donor atoms, and thus ligands containing oxygen or nitrogen atoms have been extensively used in the synthesis of lanthanide complexes [12]. Recently, there has been a growing interest in the lanthanide imines complexes owing to the important applications of both metals and ligands. Hirayama, et al. [13] extracted the trivalent lanthanide selectively as anionic imine complexes. Bastida, et al. [14] studied the lanthanide complexes with macrocyclic Schiff base ligands and obtained complexes of 18 and 15- membered macrocycles. Exhibiting a broad spectrum of biological activities and outstanding optical properties, complexes of rare-earth metals with imines derived from amino acids attract a great interest of researchers in recent years [15]. Keeping all these facts under consideration, during the present investigations we have synthesized, characterized and screened the biologically potent ligands and their lanthanide complexes against a variety of pathogenic fungal and bacterial strains. Further, the complexes were also tested for their antifertility activity in male albino rats and the results were indeed positive. 118
  3. 3. American Chemical Science Journal, 4(1): 117-137, 2014 2. EXPERIMENTAL The hydrated lanthanide chlorides as well as 2-hydroxy-N-phenylbenzamide were purchased from Alfa Aesar and used as such. All the chemicals and solvents used were of analytical grade. Hydrazine carbodithioic acid was prepared in the laboratory by the literature method [16]. All the solvents were dried and distilled before use. The metal contents were estimated complexometrically with EDTA using Erichrome Black T as an indicator. Sulfur and nitrogen were estimated by the Messenger’s and Kjeldahl’s method, respectively. IR spectra were recorded on a Perkin-Elmer model 577 grating spectrophotometer, in the range 4000–200 cm-1 in KBr discs. 1H NMR and 13C NMR spectra were recorded on a JEOL-AL-300 FT NMR spectrometer in DMSO-d6 using TMS as the internal standard. EPR spectra of the complexes were monitored on Varian E- 4X band spectrometer. The electronic spectra were recorded on a Varian–Cary/5E spectrophotometer and mass spectra were recorded on JEOL GCmate spectrometer. Molecular weight determinations were carried out by the Rast Camphor Method. Magnetic susceptibility measurements were made at room temperature with the Faraday balance using Hg[Co(NCS)4] as calibrant. 2.1 Synthesis of the Ligands Both of the ligands, 2-hydroxy-N-phenylbenzamide hydrazinecarbothioamide (HPHTSCZH2) and hydroxy-N-phenyl benzamide hydrazine carbodithioic benzyl ester (HPHCBESH2) were prepared as reported in the literature [17]. Their physical properties and analytical data are given in Table 1. Synthetic route and structures of the ligands are given in Fig. 1. 119 C O HN OH H2N C NH NH2 S H2N C NH SCH2C6H5 S C N HN OH NH C NH2 S HPHTSCZH2 C N HN OH NH C SCH2C6H5 S HPHCBESH2 Ethanol, H2O Ethanol, H2O Fig. 1. Synthesis and structures of the ligands
  4. 4. American Chemical Science Journal, 4(1): 117-137, 2014 120 Table 1. Analytical data and physical properties of the ligands and their complexes Compound Colour Melting point (ºC) Found (Calcd.) (%) μeff (B.M) Mol. wt. found (Calcd.) Yield (%) N S Ln HPHTSCZH2 Light pink 124 19.51 (19.57) 11.13 (11.20) - - 267.46 (286.35) 80 HPHCBESH2 Grey 133 10.56 (10.68) 16.34 (16.30) - - 407.70 (393.53) 82 [La(HPHTSCZH)(HPHTSCZ)].3H2O Black 210-218 14.39 (14.63) 7.67 (7.96) 19.34 (18.14) .00 751.01 (762.63) 72 [Pr(HPHTSCZH)(HPHTSCZ)].3H2O Dirty yellow 160-165 14.43 (14.59) 8.52 (8.35) 17.22 (18.35) 3.53 747.98 (764.62) 74 [Nd(HPHTSCZH)(HPHTSCZ)].3H2O Sandy brown 178-180 11.65 (11.76) 6.69 (6.70) 14.99 (15.50) 3.47 779.06 (767.96) 76 [Sm(HPHTSCZH)(HPHTSCZ)].3H2O Sandy brown 140-142 14.23 (14.47) 8.12 (8.28) 18.35 (19.42) 1.44 768.56 (774.07) 70 [La(HPHCBESH)(HPHCBES)].3H2O Light brown 150-158d 8.78 (8.85) 13.42 (13.51) 13.87 (14.63) .00 967.53 (948.93) 75 [Pr(HPHCBESH)( HPHCBES)].3H2O Brown 230-240d 8.96 (8.83) 13.60 (13.48) 13.99 (14.81) 3.71 932.86 (950.93) 71 [Nd(HPHCBESH)( HPHCBES).3H2O Grey 90-100 8.57 (8.80) 13.34 (13.44) 14.98 (15.11) 3.62 947.49 (954.26) 68 [Sm(HPHCBESH)(HPHCBES)].3H2O Chocolate brown 100-110 8.81 (8.75) 13.42 (13.35) 14.79 (15.65) 1.52 956.14 (960.37) 71
  5. 5. American Chemical Science Journal, 4(1): 117-137, 2014 2.2 Synthesis of the Sodium Salt of the Ligands Sodium metal was taken corresponding to the weight of the ligand in 2:1 molar ratios. Now both the sodium metal and ligand were dissolved in minimum amount of methanol separately. Ultimately these two solutions had been dissolved to prepare sodium salt of the ligand. In this process the sodium metal first reacts with methanol and form sodium methoxide. This sodium methoxide in the next step reacts with the ligand and replaces acidic proton from the enolic form of the ligand with the sodium metal and form sodium salt of the particular ligand (Fig. 2). The ligands may be used as such but the rate of reaction will be slow as compared to the sodium salt. Removal of chloride from the metal chloride is easy with sodium as compared to hydrogen. 2.3 Synthesis of the Lanthanide (III) Complexes The methanolic solution of the hydrated lanthanide chloride LnCl3.6H2O (2 g, 5.48 - 5.66 mmol) was mixed with methanolic solution (50 mL) of the sodium salt of the ligand (3.13 – 4.45 g, 10.96 – 11.32 mmol) in 1:2 molar ratios. The mixture was then heated under reflux for about 13-16 h. On cooling, the sodium chloride which formed in this reaction was filtered through the alkoxy funnel and the excess of solvent from mother liquor was removed under reduced pressure. The physical properties and analytical data of these complexes are recorded in Table 1. The suggested structure of the complexes is given in Fig. 2. 121 C N HN O N S C R C N NH O R C N SH Ln .3H2O Fig. 2. Structure of the metal complexes Where, Ln = La, Pr, Nd and Sm , R = -NH2 or –SCH2C6H5
  6. 6. American Chemical Science Journal, 4(1): 117-137, 2014 2.4 Biological Activity 2.4.1 Antifungal activity The antifungal activity of both the ligands and the synthesized complexes was evaluated against Aspergillus fumigatus and Aspergillus niger using Czapek’s agar medium having the composition, glucose 20g, starch 20g, agar-agar 20g and distilled water 1000 mL. To this medium was added requisite amount of the compounds after being dissolved in dimethylformamide so as to get a certain concentrations (50, 100 and 200 ppm). The medium then was poured into petri plates and the spores of fungi were placed on the medium with the help of inoculum’s needle. These petri plates were wrapped in polythene bags containing a few drops of alcohol and were placed in an incubator at 30 + 2ºC. The controls were also run and three replicates were used in each case. The linear growth of the fungus was recorded by measuring the diameter of the fungal colony after 96 h and the percentage inhibition was calculated by the equation: 122 % Inhibition = (C-T)100 / C Where C and T are the diameters of the fungal colony in the control and the test plates, respectively [18]. Fig. 3. Antifungal activity of the ligands and their complexes .
  7. 7. American Chemical Science Journal, 4(1): 117-137, 2014 2.4.2 Antibacterial activity Both of the ligands and their corresponding metal complexes were tested for their antibacterial activity against Escherichia coli and Salmonala typhi using the paper disc plate method [19]. The nutrient agar medium (peptone, beef extract, NaCl and agar-agar) and 5mm diameter paper discs of Whatman filter paper No.1 were used. The compounds were dissolved in methanol for obtaining the concentrations of 500 and 1000 ppm. The filter paper discs were soaked in these solutions, dried and then placed in the petri plates previously seeded with the test organisms. The plates were incubated for 24 h at 28 + 2ºC and inhibition zone around each disc was measured. 123 Fig. 4. Antibacterial activity of the ligands and their complexes 2.4.3 Antifertility activity The activity of the synthetic products towards the biological systems is an important feature of the current research, and the Schiff base metal complexes play a significant role in this direction. In view of such potential interest in these biologically active compounds, the antifertility activity of some selected compounds has been studied on male albino rats. Healthy adult male albino rats (Ratus norvegicus) of an average body weight 190-200 g were used for experimentation. The animals were kept in clean polypropylene cages covered with chrome plates grills and maintained in an airy room with controlled room temperature (20 ± 5ºC) with 12:12 hours light and dark cycle. The animals were fed with food pellet procured from Ashirwad Industries, Chandigarh as well as germinated/sprouted gram and wheat seeds as an alternative feed. Tap water was supplied ad libitum. Animals were divided into six groups containing 6 animals each. Group A animals were kept control and were administered olive oil only. The animals in group B received ligand (HPHCBESH2) whereas the animals in groups C, D, E and F received La(III), Pr(III), Nd(III),
  8. 8. American Chemical Science Journal, 4(1): 117-137, 2014 Sm(III) metal complexes of ligand (HPHCBESH2), respectively. The animals were maintained under perfect supervision and in accordance to the guidelines of committee for the purpose of control and supervision of experiment on animals (CPCSEA) for the regulations of scientific experiments on animals. The experimental protocol has approval of the institutional ethical committee Dept of zoology UOR Jaipur. In the group B, the ligand 30 mg/kg body weight suspended in olive oil was given orally through the mouth by pearl point needle for a period of 60 days. The animals of groups C, D, E and F received same doses of respective compound for the same period. It was then administered orally through the mouth by pearl point needle. No rat mortality occurred during the study period. The mating exposure test was done on day 55th of the experiment. The rats were sacrificed after 24 h of the last dose (61st day) to perform various tests. At the end of experiment, the rats were weighed and sacrificed under light ether anesthesia. The male reproductive organs were removed, washed with distilled water, dried, weighed and processed for biochemical studies. Sperm mobility in cauda epididymis and sperm density in testes and cauda epididymis were assessed. The protein, sialic acid, testicular glycogen acid and alkaline phosphatase of testes, and serum testosterone were determined by standard laboratory techniques. Results were analysed statistically using student’s t-test. 3. RESULTS AND DISCUSSION The reactions of hydrated lanthanide chlorides with bibasic tridentate ligands have been shown by the following general equation: 124 MeOH LnCl3.6H2O+ 2LH2 + 4Na [Ln(L) (LH)].3H2O + 3NaCl + NaOH + 3H2O Where, Ln = La, Pr, Nd and Sm, L= HPHTSCZ and HPHCBES The newly synthesized complexes have been obtained as coloured solids which exhibit their solubility in methanol, DMSO and DMF. The monomeric nature of these products has been confirmed by the molecular weight determinations. 3.1 Electronic Spectra The electronic spectra of the ligands and their metal complexes have been recorded in dry methanol. The electronic spectra of the ligands exhibit three bands in the regions 238-242, 272-277 and 330-355 nm. The bands in the regions 238-242 nm and 272-277 nm are assignable to -* transitions of the azomethine group. The considerable hypsochromic shifting of the third band viz. 330-355 nm in the spectra of the metal complexes attributed to the coordination of the azomethine nitrogen to the metal atom. The electronic spectra of the complexes are dominated by the ligands bands with the slight shift of spectral bands to the lower energy level. This slight shift was attributed to the effects of crystal field upon the interelectronic repulsion of 4f electrons. The absorption bands appear in the spectra of Pr(III), Nd(III) and Sm(III) are due to transitions from the ground levels 3H4, 4I9/2 and 6H5/2 to the excited ‘J’ levels of 4f configuration, respectively. The nephelauxetic parameter (β) [20], bonding parameter (b1/2) [21] and Sinha’s covalency parameter () [22] and angular covalency (η) for the Pr(III), Nd(III) and Sm(III) complexes are presented in Table 2. The Sinha’s parameter () suggests the degree of covalency and is obtained by the equation,
  9. 9. American Chemical Science Journal, 4(1): 117-137, 2014 125  = (1- βav)/ βav .100 Where βav is the average value of the ratio of vcomplex/ vaquo. The magnitude of the bonding parameters (b1/2) suggests the degree of involvement of 4f orbitals in metal–ligand bonding and is related to nephelauxetic ratio (β) by the equation, b1/2 = [(1-βav)/2]1/2 Angular covalency (η) = (1-βav)1/2/ βav 1/2 The intensity of the f–f transitions presents an interesting observation. The intensity of the normal f–f transitions does not show much change. However, the hypersensitive transitions (environment sensitive transitions) are found to show large changes in intensity. According to Karraker [23] the shape and intensity of these transitions indicate the geometry of the complex. In the present complexes, nephelauxetic ratio (β) being less than one and positive values of b1/2 and  indicate slight covalent bonding between metal and ligand. 3.2 Infrared Spectra The infrared spectra of the ligands show the most significant band in the region 1622-1618 cm-1 assignable to (C=N) group which shifted to the lower frequency in the complexes suggesting the coordination of the azomethine nitrogen to the metal atom (Table 3). The band in the region 3200-3050 cm-1 due to the (NH/OH) mode disappears in the complexes. The coordination of the azomethine nitrogen, phenolic oxygen and bonding of the thiolic sulfur to the metal ion is supported by the appearance of three absorption bands in the regions 530-515, 620-580 and 420–355 cm-1 in the complexes which may be assigned to (MN), (M-O) and (M-S) vibrations, respectively. However, two strong bands in the regions 3475-3460 and 3365-3350 cm-1 due to the asymmetric and symmetric vibrations of NH2 group remain unaltered in the spectra of the complexes indicating the non-involvement of this group in the coordination. In the ligand HPHCBESH2, a doublet at 2895 and 2945 cm-1 is assigned to symmetric and asymmetric vibrations of S-CH2-C6H5 grouping and is reduced to a weak doublet in the spectra of the complexes. The characteristic band due to v(SH) at 2610–2540 cm-1 present in spectra of the ligands was also seen in the complexes showing that one ligand moiety of both type of ligands form coordinate bond in place of simple covalent bond to the metal atom. The broad band present in the region 3600-3568 cm-1 may be assigned to (OH) stretching indicating the presence of water molecules.
  10. 10. American Chemical Science Journal, 4(1): 117-137, 2014 126 Table 2. Electronic spectral data of Ln(III)complexes Complex Assignment Vmax of Ln+3 ion (cm-1) Vmax of complexes (cm-1) β 1-β b1/2 δ η [Pr(HPHTSCZH)(HPHTSCZ)].3H2O 3H4 – 1D2 - 3P0 - 3P1 - 3P2 17401 20945 21450 22820 17241 20833 21276 22727 .9908 .9946 .9918 .9959 .0092 .0054 .0082 .0041 .0678 .0519 .0640 .0452 .9285 .5429 .8267 .4116 .0963 .0736 .0908 .0641 [Nd(HPHCBESH)(HPHCBES).3H2O 4I9/2 - 4G5/2,2G7/2 - 2G9/2 - 4G11/2 16830 19795 21913 16666 19607 21739 .9902 .9905 .9920 .0098 .0095 .0080 .0700 .0689 .0632 .9896 .9591 .8064 .0993 .0978 .0897 [Sm(HPHCBESH)(HPHCBES)].3H2O 6H5/2 – 4I13/2 - 4F9/2 - 4I9/2 - 6P3/2 21450 25825 26520 28733 21276 25641 26315 28571 .9918 .9928 .9922 .9943 .0082 .0072 .0078 .0057 .0640 .0600 .0624 .0533 .8267 .7252 .7256 .5732 .0908 .0851 .0886 .0756
  11. 11. American Chemical Science Journal, 4(1): 117-137, 2014 3.3 1H NMR Spectra The 1H NMR spectra of both the ligands and their La(III) complexes were recorded in DMSO-d6 (Table 4). In the ligands, the signal in the region 10.05-12.10 ppm due to -OH disappears in the complexes and this confirms the deprotonation and complexation through this functional group. The signal due to the -NH proton attached to the phenyl ring remains unaltered in the complexes. In the spectra of La(III) complex, the -NH2 signal remains unpurturbed at  2.58-2.60 ppm indicating the non involvement of this group in the complexation. The signal of -NH proton in the ligands in the range  8.59-8.78 ppm disappears in the spectra of the corresponding complexes. The free ligands show multiplets in the region  6.70-8.32 ppm attributable to aromatic protons, which appear almost in the same position in their respective complexes. The signals appearing at 5.50-4.51 ppm are due to the SH proton. The appearance of this signal in the complexes showing that one ligand moiety of both type of ligands form coordinate bond in place of simple covalent bond to the metal atom. 3.4 13C NMR Spectra The 13C NMR spectra of the ligands and their lanthanum complexes were recorded in DMSO-d6 and the assignments are shown in Table 4. The signals due to azomethine carbon appeared at δ152.81-153.43 ppm and on complexation they have shown downfield shift to δ156.26-158.05 ppm due to the resonance and also have given proof that nitrogen is involved in coordination. The spectra of the ligands exhibit a strong peak at δ175.02-176.24 ppm due to C=S group which undergoes downfield shift in metal complexes suggesting the involvement of sulfur in coordination to the metal atom. 3.5 Magnetic Properties and EPR Spectra The La(III) complexes are diamagnetic as expected. The room temperature magnetic moments of the complexes do not show much deviation from Van Vleck values [24] indicating that there is no significant participation of the 4f electrons in bonding since they are well shielded by the 5s2 5p6 octet. However in case of Sm(III) complexes a slight variation from Van Vleck values was observed [25]. Due to the low J–J separation, the energy level between the ground state and the next higher level being only of the order of KT, the excited states are also populated leading to anomalous magnetic moments. This is known as the first order Zeeman Effect [26]. The EPR spectra (both at RT and LNT) were broad having similar 'g' value of 1.98, which is nearly equal to the free electron value (g = 2.00277). Similar line widths at both the temperatures indicate spin–lattice and spin– spin relaxation processes contribute equally to line width. 3.6 Thermogravimetrical Analysis (TGA) The TGA method was conducted to demonstrate the nature and number of the H2O molecules in the complexes. Table 5 listed the losses in mass (Found and Calculated) of the [Pr(HPHTSCZH)( HPHTSCZ)].3H2O complex. 127
  12. 12. American Chemical Science Journal, 4(1): 117-137, 2014 128 Table 3. IR (cm-1) spectral data of the ligands and their corresponding complexes Compound ν(C=N) (NH/OH) v(NH2) (SCH2C6H) v(SH) v(OH) ν(M→N) ν(M→O) ν(M→S) vsym vasym vsym vasym HPHTSCZH2 1618 3050 3350 3475 - - 2540 - - - - HPHCBESH2 1622 3200 3365 3460 2895 2945 2610 - - - - [La(HPHTSCZH)(HPHTSCZ)].3H2O 1600 - 3348 3472 - - 2535 3600 530 620 420 [Pr(HPHTSCZH)( HPHTSCZ)].3H2O 1598 - 3342 3469 - - 2532 3572 524 615 412 [Nd(HPHTSCZH)(HPHTSCZ)].3H2O 1610 - 3339 3470 - - 2538 3585 518 586 358 [Sm(HPHTSCZH)(HPHTSCZ)].3H2O 1608 - 3345 3465 - - 2536 3591 515 580 360 [La(HPHCBESH)(HPHCBES)].3H2O 1602 - 3362 3452 2890 2940 2608 3576 526 618 417 [Pr(HPHCBESH)(HPHCBES)].3H2O 1607 - 3356 3458 2885 2940 2600 3598 529 584 414 [Nd(HPHCBESH)(HPHCBES).3H2O 1594 - 3363 3453 2889 2935 2598 3583 523 596 355 [Sm(HPHCBESH)(HPHCBES)].3H2O 1612 - 3359 3457 2878 2936 2605 3568 520 585 356 Table 4. 1H NMR and 13 CNMR (, ppm) spectral data of the ligands and their La(III) complexes. Compound 1HNMR 13CNMR -OH (s) -NH (bs) -SH (bs) -NH2 (s) -S-CH2 (s) -NH (s) Aromatic proton (m) Thiolo carbon >C=N Aromatic carbon HPHTSCZH2 10.05 8.59 - 2.60 - 10.64 6.75-8.32 175.02 152.81 159.76, 136.99, 129.15, 127.79, 126.98, 125.58, 122.44, 119.68, 117.94, 116.89 HPHCBESH2 12.10 8.78 - - 1.92 10.75 6.70-8.19 176.24 153.43 158.72, 137.74, 133.81, 127.82 [La(HPHTSCZH) (HPHTSCZ)].3H2O - - 4.51 2.58 - 10.59 6.61-8.03 179.74 156.26 160.66, 138.89, 130.08, 127.99, 129.85, 123.58, 120.94, 120.48, 118.99, 118.09 [La(HPHCBESH) (HPHCBES)].3H2O - - 5.50 - 1.89 10.69 6.99-7.68 182.64 158.05 160.62, 137.84, 130.81, 127.94
  13. 13. American Chemical Science Journal, 4(1): 117-137, 2014 129 Table 5. Thermogravimetrical analysis data for the metal complex Complex formula Dehydration stage Start of decom-position Oxide formation metallic residues/% Temperature range /ºC H2O loss Temp. /ºC Calc. Found Calc. Found [Pr(HPHTSCZH) (HPHTSCZ)].3H2O 120-200 7.0683 7.0687 300 700 18.42 18.38 The complex decomposes in three steps. The initial mass loss within the range 120-200ºC corresponds to the removal of three H2O molecules resulting in anhydrous complexes. The facts that the water molecule was lost at a low temperature suggest that the water is a crystal hydrate. The second and third subsequent decomposition steps start at 300ºC and continue upto 650ºC. Based on the above TGA results, the following three steps of the thermal decomposition may be proposed for the lanthanide imine complex. [Pr(HPHTSCZH)( HPHTSCZ)].3H2O Dehydration at [Pr(HPHTSCZH)(HPHTSCZ )] + 3H2O [Pr(HPHTSCZH)(HPHTSCZ) 120-200 0C Partialdecomposition 300-450 0C Intermediate Intermediate Final decomposition 500-650 0C Metal Oxide Step - 1 Step - 2 Step - 3 3.7 Mass Spectra The elemental analyses data of Nd(III) and Pr(III) complexes obtained are in agreement with the formula [Nd(HPHCBESH)(HPHCBES)].3H2O and [Pr(HPHCBESH)(HPHCBES)].3H2O. The suggested formulae were further confirmed by mass-spectral fragmentation analysis. Many lanthanides possess several isotopes and the MS peak patterns are therefore characteristic of the nature of the cation present. Neodymium and Praseodymium have several isotopes and the peak pattern of the compounds containing these metals therefore much more complicated. The spectra (although with low intensity) showed isotopic patterns centered around m/z (%) 954.26 and 950.93 for Nd and Pr, respectively, corresponding to the mass weights of the complexes. The results thus obtained are in agreement with metal: ligand ratio, 1:2. 3.8 X-ray Powder Diffraction Studies The possible geometry of the finely powdered product has been deduced on the basis of X-ray powder diffraction studies. The observed interplanar spacing values (’d’ in Å), have been measured from the diffractogram of these compounds and the Miller indices h, k and l have
  14. 14. American Chemical Science Journal, 4(1): 117-137, 2014 been assigned to each d value and 2θ angles are reported in Table 6 and Fig. 5. The results show that the compound belongs to ‘Hexagonal’ crystal system having unit cell parameters as a = 18.528 Aº, b =18.528 Aº and c = 20.675 Aº maximum deviation of 2θ = 0.04 and α = 90º, β = 90º and γ =120º. 130 Fig. 5. XRD-diffraction pattern of [Sm(L1H)(L1)].3H2O Table 6. X-ray spectral data of [Sm(L1H)(L1)].3H2O. H K l 2Theta (Exp.) 2Theta (Calc.) 2Theta (Diff.) d( Exp.) d( Calc.) Intensity (Exp.) 3 0 4 30.190 30.193 -.003 3.71720 3.71680 30.23 4 1 2 33.898 33.942 -.044 3.32056 3.31639 40.34 4 0 5 39.287 39.292 -.005 2.87958 2.87920 64.48 5 1 4 45.227 45.235 -.009 2.51755 2.51708 12.96 6 1 0 46.608 46.607 .001 2.44689 2.44695 15.62 4 4 5 57.265 57.249 .016 2.02011 2.02064 53.13 7 2 2 60.304 60.346 -.042 1.92720 1.92597 16.60 6 2 7 65.997 66.005 -.009 1.77744 1.77723 11.57 8 2 1 67.370 67.408 -.038 1.74535 1.74449 15.47 5 2 9 68.862 68.840 .022 1.71207 1.71254 11.05 8 1 6 71.901 71.893 .008 1.64885 1.64900 44.81 5 1 11 75.865 75.887 -.022 1.57471 1.57431 26.92 5 5 8 80.019 80.011 .008 1.50567 1.50580 12.45 9 0 8 82.525 82.543 -.017 1.46778 1.46753 13.86 7 6 1 85.902 85.919 -.017 1.42069 1.42046 19.73 7 6 3 87.943 87.932 .011 1.39424 1.39438 22.59
  15. 15. American Chemical Science Journal, 4(1): 117-137, 2014 3.9 Biological Results and Discussion Antimicrobial activity of the synthesized ligands and their corresponding metal complexes (Tables 7 and 8) on selected fungi, Aspergillus fumigatus and Aspergillus niger and two bacteria Escherichia coli and Salmonala typhi, were carried out (Figs. 3 and 4) [27]. The results of antimicrobial activity show that the metal complexes exhibit antimicrobial properties and it is important to note that they show enhanced inhibitory activity compared to the parent ligand. It has been suggested [28] that the ligands with nitrogen and sulfur donor systems might inhibit enzyme production, since the enzymes which require these groups for their activity appear to be especially more susceptible to deactivation by the metal ions upon chelation. Chelation reduces the polarity [29] of the metal ion mainly because of the partial sharing of its positive charge with the donor groups and possibly the π-electron delocalization within the whole chelate ring system thus formed during coordination. This process of chelation thus increases the lipophilic nature of the central metal atom, which in turn favours its permeation through the lipid layer of the membrane. 131 Table 7. Antifungal activity of the ligands and their complexes Compound Diameter of inhibition zone (mm) Aspergillus fumigates, Aspergillus niger 50 100 200 50 100 ppm ppm ppm ppm ppm 200 ppm HPHTSCZH2 27 33 45 31 39 47 HPHCBESH2 33 39 49 35 41 52 [La(HPHTSCZH)(HPHTSCZ)].3H2O 48 58 69 46 60 65 [Pr(HPHTSCZH)( HPHTSCZ)].3H2O 46 55 62 52 61 68 [Nd(HPHTSCZH)(HPHTSCZ)].3H2O 41 48 56 51 58 66 [Sm(HPHTSCZH)(HPHTSCZ)].3H2O 40 45 53 50 64 61 [La(HPHCBESH)(HPHCBES)].3H2O 57 65 74 54 63 66 [Pr(HPHCBESH)( HPHCBES)].3H2O 50 62 68 56 64 70 [Nd(HPHCBESH)( HPHCBES).3H2O 43 50 60 52 60 68 [Sm(HPHCBESH)(HPHCBES)].3H2O 42 48 59 53 66 63 Flucanazole 90 100 100 95 100 100 Table 8. Antibacterial activity of the ligands and their complexes Compound Diameter of inhibition zone (mm) E. coli, S. typhi 500 ppm 1000 ppm 500 ppm 1000 ppm HPHTSCZH2 4 8 5 8 HPHCBESH2 6 9 6 9 [La(HPHTSCZH)(HPHTSCZ)].3H2O 8 9 7 9 [Pr(HPHTSCZH)( HPHTSCZ)].3H2O 7 10 6 10 [Nd(HPHTSCZH)(HPHTSCZ)].3H2O 9 9 6 11 [Sm(HPHTSCZH)(HPHTSCZ)].3H2O 6 8 8 11 [La(HPHCBESH)(HPHCBES)].3H2O 10 11 9 12 [Pr(HPHCBESH)( HPHCBES)].3H2O 9 13 10 12 [Nd(HPHCBESH)( HPHCBES).3H2O 13 12 8 10 [Sm(HPHCBESH)(HPHCBES)].3H2O 11 14 11 13 Tetracyclin 16 20 15 18
  16. 16. American Chemical Science Journal, 4(1): 117-137, 2014 The results of antifertility showed that administration of ligand and its metal complexes did not affect the body weights of treated groups. However, a significant reduction in the weight of testes, epidydymis, seminal vesicle and ventral prostate was observed after treatment with ligand (HPHCBESH2) and its La(III), Pr(III), Nd(III), Sm(III) metal complexes. (Table 9) A significant decrease in motility of spermatozoa in cauda epidydymis and sperm density in cauda epidydymis and testes have been observed in rats treated with ligand and its metal complexes. (Table 10) The reduction in the weights of these sex accessory organs may be due to the decreased production of androgen [30]. Oral administration of ligand and its metal complexes caused a significant reduction in testicular glycogen and sialic acid contents where as cholesterol, sialic acid and alkaline phosphatase contents of testes were increased after treatment with in ligand and metal complexes (Table 11). Sialic acids are concerned with changing the membrane Surface of maturing spermatozoa as well as with the development of their fertilizing capacity [31]. The results demonstrate a marked decrease in testicular glycogen, which may be due to interference during glucose metabolism [32]. Inhibition of glycogen synthesis eventually affects the protein synthesis and thus inhibits spermatogenesis [33].The serum testosterone concentrations were decreased significantly (P ≤ .01 to .001) after treatment with ligand (HPHCBESH2) and its La(III), Pr(III), Nd(III) and Sm(III) metal complexes (Table 11). A marked reduction in testosterone content, in association with a highly reduced circulating level of this hormone, confirmed alterations in the reproductive physiology of the rats. These results suggested that the ligand and its complexes exert inhibitory effects on testicular function and lead to the infertility in male rats. Further, addition of a metal ion to the ligand enhances the activity. 132
  17. 17. American Chemical Science Journal, 4(1): 117-137, 2014 133 Table 9. Effects of ligand and its complexes on body and reproductive organ weight of male rats Group Treatment Body Weight Organ Weight (mg/100 g b.wt.) Initial Final Testes Epidydymis Seminal Vesicle Ventral Prostrate A Control (olive oil) 221.0±16.4 231.0±14.5 1280.0±30.2 470.0±12.9 461.0±14.3 451.0±21.7 B HPHCBESH2 226.0±10.3 237.0±13.3ns 1010.0±25.3a 359.0±13.2a 394.0±25.4a 398.0±19.7a C [La(HPHCBESH)(HPHCBES)].3H2O 204.0±12.4 228.0±11.9ns 722.0±15.8b 281.0±11.2b 253.0±26.5b 279.0±17.9b D [Pr(HPHCBESH)(HPHCBES)].3H2O 216.0±13.4 231.0±16.3ns 800.0±19.4b 293.0±14.1b 231.0±27.3b 251.0±30.3b E [Nd(HPHCBESH)(HPHCBES).3H2O 218.0±15.4 238.0±16.5ns 710.0±20.4b 270.0±14.3b 222.0±26.9b 261.0±30.2b F [Sm(HPHCBESH)(HPHCBES)].3H2O 209.0±9.8 225.0±14.3ns 652.0±30.2b 275.0±10.5b 228.0±28.3b 267.0±15.2b Values are mean ± SEM of 6 determinations a = p ≤ .01 b= p ≤ .001 ns = p= Non Significant Group B, C, D, E and F compared with Group A Table 10. Altered sperm dynamics and fertility of ligand and its various complexes treated male rats Group Treatment Sperm Mortility (%) Sperm Density (million/mL) Fertility (%) Cauda Epidydymis Testes Cauda Epidydymis A Control (olive oil) 71.5±4.5 4.78±0.7 60.4±3.70 100(+ve) B HPHCBESH2 58.5±4.7 a 3.20±.5 a 52.4±2.90 a 40(-ve) C [La(HPHCBESH)(HPHCBES)].3H2O 34.0±6.5 b 1.97±.3 b 25.0±2.10 b 82(-ve) D [Pr(HPHCBESH)(HPHCBES)].3H2O 31.0±5.4 b 1.80±.3 b 28.0±2.20 b 85(-ve) E [Nd(HPHCBESH)(HPHCBES).3H2O 33.0±5.1 b 1.50±.4 b 20.0±1.90 b 88(-ve) F [Sm(HPHCBESH)(HPHCBES)].3H2O 32.0±3.9 b 1.30±.3 b 22.3±2.10 b 85(-ve) Values are mean± SEM of 6 determinations a = p ≤ .01 b= p ≤ .001 Group B, C, D, E and F compared with Group A
  18. 18. American Chemical Science Journal, 4(1): 117-137, 2014 134 Table 11. Testicular biochemistry and serum testosterone levels of ligand and its various complexes treated rats Group Treatment Protein Sialic Acid Cholesterol Glycogen Acid Phosphatase Alkaline Phosphatase Serum Testosterone (mg/ml) A Control(olive oil) 228.5±10.5 4.24±.70 8.0±.90 3.24±.39 3.21±.19 10.2±.60 2.90±.67 B HPHCBESH2 281.0±5.3 a 3.18±.75 a 11.2±.70 a 2.71±.19 a 4.81±.20 a 14.1±.20 b 2.20±.72 a C [La(HPHCBESH) (HPHCBES)].3H2O 336.0±2.9 b 1.91±.72 a 13.8±.39 b 1.48±.11 b 5.34±.16 b 17.2±.20 b 1.35±.10 b D [Pr(HPHCBESH) (HPHCBES)].3H2O 332.0±3.6 a 1.82±.69 b 13.2±.35 a 1.42±.17 b 6.11±.32 b 17.6±.30 b 1.60±.30 b E [Nd(HPHCBESH) (HPHCBES).3H2O 339.0±4.3 b 1.6±.75 b 13.6±.31 b 1.31±.13 b 6.22±.39 b 17.3±.40 b 1.28±.10 b F [Sm(HPHCBESH) (HPHCBES)].3H2O 327.0±4.5 a 1.7±.60 b 13.7±.43 b 1.34±.14 b 5.74±.12 b 16.5±.35 b 1.15±.15 b Values are mean ± SEM of 6 determinations a = p ≤ .01 b= p ≤ .001 Group B, C, D, E and F compared with Group A
  19. 19. American Chemical Science Journal, 4(1): 117-137, 2014 4. CONCLUSION On the basis of the analytical data and spectral studies, it has been observed that the ligands coordinated to the metal atoms in a bibasic tridentate manner and thus possess octahedral geometry. On the basis of X-Ray powder diffraction study [Sm(L1H)(L1)].3H2O complex was found to have hexagonal lattice type. The biological screening data of the ligands and their complexes indicate that the complexes are more potent than the parent ligands. ACKNOWLEDGMENTS The authors are thankful to CSIR, New Delhi, India through grant no. 09/149(0594)/2011/EMR-I for financial assistance. COMPETING INTERESTS Authors have declared that no competing interests exist. REFERENCES 1. Kostova I, Momekov G, Tzanova T, Karaivanova M. Synthesis, characterization, and cytotoxic activity of new lanthanum(III) complexes of bis-coumarins. Bioinorg. Chem. Appl., 2006; Article ID 25651:1. 2. Picard C, Geum N, Nasso I, Mestre B, Tisnès P, Laurent S, Muller RN, Elst LV. A dual lanthanide probe suitable for optical (Tb3+ luminescence) and magnetic resonance imaging (Gd3+ relaxometry). Bioorg. Med Chem Lett. 2006;16:5309. 3. Aime S, Crich SG, Gianolio E, Giovenzana GB, Tei L, Terreno E. High sensitivity lanthanide (III) based probes for mr-medical imaging. High Coord Chem Rev. 2006;250:1562-1579. 4. Mohanan K, Devi SN. Synthesis, characterization, thermal stability, reactivity, and antimicrobial properties of some novel lanthanide(III) complexes of 2-(N-salicylideneamino)- 3-carboxyethy l-4,5,6,7-tetrahydrobenzo [b] thiophene. Russian J 135 Coord Chem. 2006;32:600. 5. McCleverty JA, Meyer TJ. Comprehensive Coord. Chem. II, Eds., Oxford: Pergamon 2004;3:93. 6. Elzahany EA, Khaled HH, Safaa K, Khalil H, Youssef NS. Synthesis, characterization and biological activity of some transition Metal complexes with Schiff bases derived from 2-formylindole, Salicyladehyde, and N-amino Rhodanine. Australian J Basic Appl Sci. 2008;2:210. 7. Casas JS, Garcia-Tasende MS, Sordo. Corrigendum to main group metal complexes of semicarbazone and thiosemicarbazone. J Coord Chem Rev. 2000;209:197. 8. Mishra D, Naskar S, Drew, MGB, Chattopadhyay SK. Synthesis, spectroscopic and redox properties of some ruthenium(II) thiosemicarbazone complexes: Structural description of four of these complexes. Inorg Chim Acta. 2006;359:585-592. 9. Chandra S, Tyagi M, Refat MS. Spectroscopic, thermal and antibacterial studies on Mn(II) and Co(II) complexes derived from thiosemicarbazone J .of Serbin Chem Soc. 2009;74:907-915. 10. Singh NK, Singh SB, Shrivastav A, Singh SM. Spectral, magnetic and biological studies of 1,4-dibenzoyl-3-thiosemicarbazide complexes with some first row transition metal ions. Proceed Indian Acad of Sci Chem Sci. 2001;113:257.
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  21. 21. American Chemical Science Journal, 4(1): 117-137, 2014 30. Joshi SC, Goyal R, Jain S. Effect of organochlorine pesticide Methoxychlor (1,1,1- trichloro-2,2-bis (4-methoxypheny1) ethane) on reproductive function of male albino rat. Asian J Exp Sci. 2005;19(2):23. 31. Verma RJ, Chinoy NJ. Effect of papaya seed extract on microenvironment of cauda 137 epididymis. Asian J Androl. 2001;3(2):143. 32. Yeung CH, Oberlander G, Cooper TG. Effects of the male antifertility agent ornidazole on sperm function in vitro and in the female genital tract. J Reprod. Fertil. 1995;103(2):257. 33. Cooper TG, Yeung CH, Skupin R, Haufe G. Antifertility potential of ornidazole analogues in rats. J Androl. 1997;18(4):431. _________________________________________________________________________ © 2014 Singh et al.; This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Peer-review history: The peer review history for this paper can be accessed here: http://www.sciencedomain.org/review-history.php?iid=271&id=16&aid=2488

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