Syntheses, Characterization, Thermal, and Antimicrobial Studies of Lanthanum(III) Tolyl/Benzyldithiocarbonates

Lanthanum(III) tris(O-tolyl/benzyldithiocarbonates), [La(ROCS2)] (R = o-, m-, p-CH3C6H4 and C6H5CH2), were isolated as yellow solid by the reaction of LaCl3 ·7H2O with sodium salt of tolyl/benzyldithiocarbonates, ROCS2Na (R = o-, m-, p-CH3C6H4 and C6H5CH2), in methanol under anhydrous conditions in 1 : 3 molar ratio. These complexes have formed adducts with nitrogen and phosphorus donor molecules by straightforward reaction of these complexes with donor ligands, which have the composition of the type [La(ROCS2)3 ·nL] (where n = 2, L = NC5H5 or P(C6H5)3 and n = 1, L = N2C12H8 or N2C10H8). Elemental analyses, mass, IR, TGA, and heteronuclear NMR (1H, 13C and 31P) spectroscopic studies indicated bidentate mode of bonding by dithiocarbonate ligands leading to hexacoordinated and octacoordinated geometry around the lanthanum atom. Antimicrobial (antifungal and antibacterial) activity of the free ligands and some of the complexes have also been investigated which exhibited significantly more activity for the complexes than the free ligands.


Introduction
Alkyldithiocarbonates, more commonly referred to as xanthates, were first prepared by Semeniuc et al. [1]. Their applications as vulcanizers [2], fungicides [3], and flotation agents [4,5] in metallurgy have been described in the literature. The synthetic and structural chemistry of xanthates witnessed increased attention through the pioneering work of Winter [6], Tiekink and Winter [7], Hoskins and Pannan [8], and Dakternieks et al. [9]. Subsequently, extensive structural analyses were performed by Tiekink and Haiduc [10], which showed that these ligands can coordinate to metal atoms in a monodentate, isobidentate, or anisobidentate fashion. More recent applications of xanthates and other thio compounds are in the production of nanoparticles of metal sulphides [11,12] and NLO properties [13,14]. Metal xanthates are extensively used as pesticides [15], corrosion inhibitors [16], agricultural reagents [17], and quite recently in therapy for HIV infections [18]. Moreover, xanthates are also known to show antitumor properties [19,20] and their antioxidant properties could be of importance for treating Alzheimer's disease [21]. These have extensively been used as intermediates in organic synthesis, in free radical polymerization, for rechargeable lithium ion batteries, and so forth [22,23]. Sodium and potassium ethyl xanthate have antidotal effects on acute mercurial poisoning [24]. Much progress has recently been achieved in the coordination chemistry of lanthanides [25]. The design and synthesis of lanthanide(III) complexes with chelating ligands have many potential applications such as light-emitting devices, sensors, liquid crystalline materials, and chelate lasers [26]. Both lanthanum and xanthate find their applications in the field of medicinal chemistry [27,28]. In spite of years of chemistry of the extensive and long term use of alkyl xanthates as ligands [29][30][31][32][33][34][35], structural and spectroscopic characterization have been rather limited with regard to the aryl xanthates [36,37]. Fackler et al., however, reported the synthesis of thallium aryl xanthates which are in turn used for the metathetical synthesis of other metal derivatives [36]. We report herein for the first time the synthesis and characterization of O-tolyl/benzyl xanthates of lanthanum(III) and their adducts with nitrogen and phosphorus donor ligands like pyridine (NC 5 H 5 ), triphenylphosphine [P(C 6 H 5 ) 3 ], 1,10-phenanthroline (N 2 C 12 H 8 ), and 2,2 -bipyridyl (N 2 C 10 H 8 ).

Materials and Methods.
Stringent precautions were taken to exclude moisture during the preparation of ligands. Moisture was carefully excluded throughout the experimental manipulations by using standard Schlenk techniques. Sodium salts of dithiocarbonates were obtained using literature procedures [2]. Toluene (Thomas Baker, B.P. 110 ∘ C) and n-hexane (Thomas Baker, B.P. 68-69 ∘ C) were freshly dried over sodium wire. Methanol (Thomas Baker, B.P. 64 ∘ C) was dried over P 2 O 5 and CaCO 3 , respectively. Cresols (ortho-, meta-, and para-) and benzyl alcohol (Thomas Baker, B.P. 191 ∘ C, 203 ∘ C, 202 ∘ C, and 205 ∘ C) were purified by distillation prior to use.

Physical Measurements.
Lanthanum was estimated gravimetrically as lanthanum oxide [38]. Elemental analyses (C, H, N, and S) were carried out on CHNS-932 Leco Elemental analyzer and ESI mass spectra of the compounds were recorded on ESQUIRE 3000-00037 spectrophotometer from Indian Institute of Integrative Medicine (IIIM), Jammu. The IR spectra were recorded in KBr pallets in the range of 4000-200 cm −1 on a Perkin Elmer spectrum RX1-FT IR spectrophotometer and multinuclear ( 1 H, 13 C, and 31 P) NMR spectra were recorded in CDCl 3 on a Brucker Avance II 400 MHz spectrometer using TMS as internal reference for 1 H and 13 C and 85% H 3 PO 4 as external reference for 31 P NMR at Sophisticated Analytical Instrumentation Facility (SAIF), Punjab University, Chandigarh. The thermogram was analyzed by using Perkin Elmer, diamond TG/DTA instrument. The thermogram was recorded in the temperature range from 30 ∘ C to 1000 ∘ C under nitrogen atmosphere from National Chemical Lab (NCL), Pune. Also the antifungal and antibacterial activity were tested under laboratory condition in the Bioassay Lab, Department of Chemistry, University of Jammu, Jammu, using classical poison food technique and agar well diffusion method.

Synthetic Procedures
(1.00 g, 4.84 mmol) was added to methanolic solution of lanthanum chloride (0.60 g, 1.61 mmol) with constant stiring at room temperature. Subsequently, the contents were refluxed for eight hours. The turbidity created by the byproduct (sodium chloride) was filtered off using alkoxy funnel fitted with G-4 sintered disc and volatiles were removed from the filtrate under reduced pressure. The solid thus obtained was extracted with chloroform (∼20 cm 3 ) by stirring overnight. Again the insoluble's were filtered off and the desired product [La(o-CH 3 C 6 H 4 OCS 2 ) 3 ] (5) was obtained from the filtrate as yellow solid.
The compounds 6-8 reported herein were synthesized by using similar methodology and required stoichiometric weights. The relevant synthetic and analytical data are given in Table 1.

Synthesis of [La(o-CH
Pyridine (0.11 g, 1.39 mmol) was added with constant stirring to a methanolic (∼15 mL) solution of [La(o-CH 3 C 6 H 4 OCS 2 ) 3 ] (0.50 g, 0.72 mmol). The mixture was refluxed for two hours. The solvent was evaporated in vacuo and the product was washed with dry n-hexane for the sake of purity and finally dried under reduced pressure that resulted in the formation of the compound [La(o-CH 3 C 6 H 4 OCS 2 ) 3 ⋅2NC 5 H 5 ] (9) in 89% yield.
The compounds 10-24 reported herein were synthesized by using similar methodology and required stoichiometric weights. The relevant synthetic and analytical data are given in Table 1.

Antimicrobial Activity
2.4.1. Antifungal Activity. Potato dextrose medium (PDA) was prepared in a flask and sterilized. Now, 100 L of each sample was added to the PDA medium and poured into each sterilized petri plate. Mycelial discs taken from the standard culture (Fusarium oxysporum) of fungi were grown on PDA medium for 7 days. These cultures were used for aseptic inoculation in the sterilized petri dish. Standard cultures, inoculated at 28±1 ∘ C, were used as the control. The efficiency of each sample was determined by measuring the radial fungal growth. The radial growth of the colony was measured in two directions at right angles to each other and the average of two replicates was recorded in each case. Data were expressed as percent inhibition over the control from the size of the colonies. The percent inhibition was calculated using the formula % Inhibition = (( − )/ ) × 100, where is the diameter of the fungus colony in the control plate after 96hour incubation and is the diameter of the fungus colony in the tested plate after the same incubation period.

Antibacterial
Activity. Test samples were prepared in different concentrations (250, 500, and 1000 ppm) in DMSO. Agar medium (20 mL) was poured into each petri plate. The plates were swabbed with broth cultures of the respective microorganisms Klebsiella pneumonia and Bacillus cereus and kept for 15 minutes for adsorption to take place. About 6 mm diameter holes were created in the seeded agar plates using a punch and 100 L of the DMSO solution of each test compound was poured into the wells. DMSO was used as the control for all the test compounds. After holding the plates at room temperature for 2 hrs to allow diffusion of the compounds into the agar then the plates were incubated at 37 ∘ C for 24 hrs. The antibacterial activity was determined by measuring the diameter of the inhibition zone. The entire tests were made in triplicates and the mean of the diameter of inhibition was calculated.

IR Spectra.
The characteristic stretching bands in the IR spectra (4000-200) cm −1 were assigned by comparison with literature data [2,14,39,40]. The IR spectra of these complexes exhibited band in the region 1260-1238 cm −1 for V(C-O-C). The bands observed in the region 3059-3012 and 1601-1560 cm −1 were ascribed to ring vibrations in the cyclic dithiocarbonates. The presence of one strong band for V(C-S) in the region 1044-1034 cm −1 without a shoulder favors the bidentate linkage of the dithiocarbonate ligands with lanthanum atom. The presence of a new band ascribed to V(La-S) was present in the region 331-310 cm −1 , which is indicative of formation of La-S bond in these complexes. The IR spectra of the adducts (9-24) have showed all the bands observed in the parent lanthanum-dithiocarbonates and bands characteristic of donor ligands (NC 5 H 5 , P(C 6 H 5 ) 3 , N 2 C 12 H 8 and N 2 C 10 H 8 ) in the regions 455-442 and 402-399 cm −1 , which may be assigned to V(La-N) and V(La-P) bonding modes, respectively. The IR spectral values of the complexes are given in Table 3.

1 H NMR Spectra.
In 1 H NMR spectra, the signals for the -CH 3 (tolyl ring) and -CH 2 (benzyl ring) protons were observed at 2.22-2.33 and 4.50-4.61 ppm as singlet. The protons of the C 6 H 4 (tolyl) and C 6 H 5 (benzyl ring) gave signals in the range 6.22-7.23 and 7.10-7.64 ppm as multiplets. This chemical shift has no deviation either to lower or higher field side compared to the parent ligands. There were two resonances for the ring protons of para complexes whereas four resonances were observed for ortho-and metaderivatives. 1  The presence of all characteristic chemical shifts in the 1 H NMR spectra favors the formation of these complexes. The 1 H NMR spectral data of these complexes are given in Table 4.   16 ppm. The 13 C NMR spectra of the addition complexes exhibited the signals of the carbon nucleus of the donor moieties in addition to the characteristic chemical shifts indicated above. The aryl carbon nuclei of the pyridine (11)(12) and triphenylphosphine (14-15) resonated at 118.71-148.02 ppm and 127.02-138.01 ppm, respectively. The aryl carbon nuclei of the phenanthroline (17-18) and bipyridine (21)(22)(23)(24) gave their resonance at 120.02-150.00 ppm and 120.12-153.80 ppm, respectively. The 13 C NMR spectral data of the complexes are given in the Table 5.
3.1.6. Thermogravimetric Analysis. The thermal properties of the complexes were studied by TGA in the temperature ranging from 30-1000 ∘ C under nitrogen atmosphere. The content of a particular component in a complex changes with its composition and structure. These can be determined based on mass losses of these components in the thermogravimetric plots of the complexes. The thermogravimetric analysis of the complex, [La(p-CH 3 C 6 H 4 OCS 2 ) 3 ] (5) displayed a thermolysis step that covers a temperature range from 150 to 900 ∘ C. The thermogram (Figure 1)     antifungal screening data are given in Table 6, which shows that complexes have higher activity than free ligands. The colony diameter of the fungus decreases on enhancing the concentration of the complex; that is, all the complexes inhibited the growth of fungus significantly. This shows a linear relationship between concentration and percent inhibition. The increase in antifungal activity may be attributed to faster diffusion of metal complexes as a whole through the cell membrane or due to combined activity effect of the metal and the ligand. It is also evident from the antifungal  screening data that adducts of nitrogen and phosphorous donor ligands are more potent than the parent complex. The chelation theory accounts for the increased activity of the metal complexes [41]. On chelating, the polarity of the metal ion will be reduced to a greater extent due to overlap of the ligand orbital and the partial sharing of the positive charge of the metal ion with donor group. The comparison of antifungal activity of all the ligands and some of the complexes is described diagrammatically in Figure 2.
(2) Antibacterial Activity. Antibacterial in vitro studies against two bacterial strains involve Gram-negative Klebsiella pneumonia and Gram-positive Bacillus cereus using penicillin as standard antibacterial drug. Antibacterial screening data are given in Table 7. These studies revealed that free ligands are inactive against the bacterial strains but metal complexes shows higher activity than free ligands but lower activity than reference drug that is, penicillin. However, the complex [La(C 6 H 4 CH 2 OCS 2 ) 3 ⋅N 2 C 12 H 8 ] (20) shows pronounced activity against Klebsiella pneumonia and Bacillus cereus even more than reference drug.