Synthesis, Molecular Modeling, and Biological Activity of Zinc(II) Salts with 1,4-Bis(benzimidazol-2-yl)benzene

Zinc(II) halides and perchlorate react with 1,4-bis(benzimidazol-2-yl)benzene (L) in 1 : 2 molar ratio in n-butanol/2-methoxy ethanol (10mL) at re�uxing temperature to produce white/pale yellow-colored complexes of the formulae [ZnCl2L]H2O, [ZnBr2L]3H2O, and [Zn(OClO3)2L]HOCH2CH2CH2CH3. Zinc(II) iodide also reacts with L in 1 : 2 molar ratio in n-butanol (HOCH2CH2CH2CH3) to yield white-colored complex of the formula [ZnL2(OCH2CH2CH2CH3)2]. e complexes were characterized by elemental analysis, molar conductance measurements, thermal analysis, and IR, H-, C-NMR spectral studies. e complexes showed signi�cant anthelmintic activity. e minimum energy con�guration has been obtained for the zinc complexes using molecular modeling Pro Plus; a tool developed by ChemSW, inc, USA.

1.1. Reagents. e hydrated zinc(II) chloride was used as supplied (BDH). Terephthalic acid and o-phenylenediamine were from Merck Chemicals. e solvents used were from Merck Chemicals and they were puri�ed according to literature methods [14]. Hydrated zinc(II) bromide, zinc(II) iodide, and zinc(II) perchlorate salts were prepared by dissolving the metal in hydrobromic acid, hydroiodic, acid and perchloric acid, respectively, followed by �ltration of obtained precipitate and careful evaporation nearly to dryness under reduced pressure.
Drugs: Albendazole (BANDY, Mankind Pharma Ltd., New Delhi),Piperazine citrate, Tween 80. 1.2. Measurements. C, H, and N analyses were carried out on a Carlo Erba Microanalyser. IR spectra (in nujol) were recorded on a Nicolet 4000D spectrophotometer. Molar conductivity measurements were made with 10 −3 M solution in dimethylformamide (DMF) using a digital (SYSTRON-ICS) conductivity meter-304 with a conventional dip-type conductivity cell with a cell constant 1.00 cm −1 . NMR spectra were recorded (in DMSO-d 6 ) on a Bruker WH-270 or AMX-400 MHz spectrometer using TMS as the internal standard. e thermograms were recorded on a Shimadzu ermal Analyzer DT30 at a heating rate of 5 ∘ C/minute. (1,benzene). e ligand was prepared according to the literature method [15]. Terephthalic acid (10 mmole) was stirred with o-phenylenediamine (20 mmole) in syrupy phosphoric acid (20 mL) at 240 ∘ C for 4 h. e coloured melt was poured into cold water (500 mL) with stirring to obtain a blue-green-coloured precipitate. e precipitate 2 Journal of Chemistry  was neutralized with 10% aqueous sodium carbonate solution. e resulting solid was recovered by �ltration and recrystallized from ethanol to obtain a pale-pink compound ( Figure 1). (yield 50%).

Preparation of the Complexes
. To a solution of zinc(II) halide (1 mmol) dissolved in 2methoxyethanol/n-butanol (10 mL), the ligand (2 mmol) in the same solvent (15 mL) was added and the mixture was re�uxed for 6-8 h, followed by concentration of the mixture under reduced pressure, during which time a buff/white/paleyellow solid separated. is was �ltered, washed with petroleum benzene 40-60 ∘ C (20 mL), and dried in a vacuum (yield 65%).

[Zn(OClO
1.5. Procedure for Anthelmintic Activity. e anthelmintic assay was carried out as for the method of Ajaiyeoba et al. [16]. Indian adult earthworms Pheretima posthuma. e worms were procured from local supplier at Shimoga at the time of carrying out the experiment. e worms were washed with normal saline to remove all fecal matter used for the anthelmintic study. e earthworms of 4-6 cm in length and 0.3-0.4 cm in width were used for all experimental protocol due to its anatomical and physiological resemblance with intestinal roundworms parasite of human beings. e cleaned and uniform-size worms were kept in 6% dextrose solution for acclimating. e worms with normal motility were selected for the activity. In a separate Petri dish a, 2 mL of each test compound (5 mg/mL) in 0.1% Tween-20 suspension were placed and the volume was made up to 25 mL with an aqueous solution of dextrose (6%). e albendazole solution was served as standard. In each petri dish, one earth worm was placed. e time taken by the worm for paralysis was noted and the paralysis of worm was tested by placing the worm in water maintained at 50 ∘ C. Nonmotility at 50 ∘ C was taken as the death of the worm and correspondingly the time taken for the death was recorded.
Synthesized complexes were dissolved separately in minimum amount of Tween 80 and then volume was adjusted to 25 mL with dextrose solution. All solutions were freshly prepared before starting the experiment. Four groups of six earthworms each were released into 25 mL of desired formulation as follows: (1) vehicle: 5% Tween 80 in dextrose solution, (2) albendazole,

Results and Discussion
e physical properties and analytical data of the complexes are listed in Table 1.e complexes are insoluble in common organic solvents but are soluble in DMF and DMSO and show low conductivity in DMF at room temperature (25 ∘ C). is may arise from the replacement of the halide by DMF in solution and the existence an equilibrium of the type below [17]: Journal of Chemistry 3 T 3: 13 C-NMR spectral data of the ligand and complexes (in p.p.m). e IR spectra (in nujol mull) of the complexes are similar to the spectra of the uncoordinated N-heterocycle except for minor shis in the positions of some of the bands and some changes in their intensities due to coordination. e complexes displayed N-H band in the range 3150-3180 cm −1 and this increased by 10-30 cm −1 as compared to that of the uncoordinated ligand. e C=N and C=C vibrations are very close to each other and occur around 1616 cm −1 as weak bands in the spectra of uncoordinated heterocycle and have been observed to shi by about 10-15 cm −1 on complexation. e shi in the position of C=N and C=C is suggestive of coordination of the N-heterocycle via the tertiary nitrogen of the imidazole moiety [18,19]. e O-H of water of hydration [20] is observed around 3400 cm −1 . A strong band at 1574 cm −1 and a band around 1550 cm −1 are assigned to N-H in-plane bending vibrations of ligand and the complexes, respectively. e C-N and N-H vibrations are probably very close to one another and occur at 1320 cm −1 . e band due to p-disubstituted benzene ring vibrations occurs around 1300, 1250, and 760 cm −1 . e bands due to benzimidazole ring vibrations are located around 1280, 1010, and 960 cm −1 . e assignments are tentative and are based on the literature reports on related compounds [18,19]. However, in the infrared spectrum of [Zn(OClO 3 ) 2 L]HO(CH 2 ) 3 CH 3 complex, in addition to the ligand bands, the peaks around 1100 and 622 cm −1 of 3 and 4 of perchlorate are also observed. e former band is split indicating the presence of at least one perchlorate coordinated to the metal ion [21]. e 1 H NMR spectra of the complexes recorded in DMSO-d 6 exhibit resonances due to coordinated Nheterocycle. e spectral data of the complexes along with the assignments are compiled in Table 2. e spectra of the complexes are almost similar to those of the ligand, except for a slight shi in the positions of the signals. e X-ray crystal structure study of the ligand has been established by Bei and coworkers [15] that it has centrosymmetry. e molecule is twisted in such a way that the part of the molecule is in the plane opposite to the plane of the other part. e N-H resonance signal occurs at 13.0 ppm. e protons of the benzene ring, which are almost equivalent, give resonance signal at 8.3 ppm, the protons of benzimidazole ring resonances are found in the range 7.2-7.8 ppm [22,23]. In addition to the ligand resonance signals, the resonance signals due to the protons of nbutanol are also observed in [ZnL 2 (OCH 2 CH 2 CH 2 CH 3 ) 2 ] and [Zn(OClO 3 ) 2 L]HOCH 2 CH 2 CH 2 CH 3 complexes. e resonance signal of -CH 3 protons of n-butanol are located at 0.86 ppm and signal due to -CH 2 -protons are observed at 1.3 ppm. e protons of -O-CH 2 -group show resonance signal at 4.31 ppm. e presence of solvent molecules in the complexes was con�rmed by comparison with the spectrum complex, and [ZnL 2 (OCH 2 CH 2 CH 2 CH 3 ) 2 ] complex recorded in DMSOd 6 reveal distinct resonances that are in agreement with the expected carbon environments and the data are collected in Table 3. e assignments of the signals are compared with the reported values for benzimidazole and substituted benzimidazoles [24,25]. e 13 C spectra for the chloro and bromo complexes could not be recorded due to their poor solubility in DMSO-d 6 . e resonance signal due to C-1 � carbon is observed around 135.0 ppm. e resonance signal at 126.0 ppm is assigned to C-2 � and C-6 � carbons. e resonances due to aromatic carbons of benzimidazole ring are found in the range 119.0 to 150.6 ppm. e resonance due to C-8 is observed around 150.0 ppm and has shown positive coordination induced shi of 6.0 ppm. e C-9 carbon resonance signal is observed around 130.0 ppm.
In addition to the ligand resonance signals, the peaks of n-butanol are also observed. e resonance signal found at 13.8 ppm indicates the presence of -CH 3 group. e carbon atoms of the two -CH 2 groups of n-butanol resonate at 18.6 and 34.6 ppm. e carbon of -CH 2 -O-is observed at 60.3 ppm. Both positive and negative coordination-induced shis are observed in the spectra of the complexes due to the ligand to metal -donation and metal-to-ligand -donation, respectively [26].
ermogravimetric analysis data of complex [ZnL 2 (OCH 2 CH 2 CH 2 CH 3 ) 2 ] has shown that there is a loss of a part of the solvent molecule (CH 3 CH 2 CH 2 -) (0.58%, theoretical value 4.4% and found 5.1%) around 419 ∘ C. e weight loss due to 1.42% solvent molecule (OCH 2 -and OCH 2 CH 2 CH 2 CH 3 ) and two molecules of N-heterocycle takes place in the temperature around 600 ∘ C, which corresponds to a theoretical loss of 92.1% (found 93.4%). e �nal step of the decomposition corresponds to the formation of ZnO [27,28]: Molecular modeling studies were carried out with an interactive graphics molecular program [29]. Energy minimization was repeated several times to obtain the global minimum. e Leonnard-Jones equation was applied on M-N bond to obtain a con�guration with minimum repulsion and hence minimum steric strain. A representative example of the structure of the complex [ZnCl 2 L]H 2 O, with minimum energy con�guration, is shown in molecular model I ( Figure  2). Aer global minimum con�guration is attained, the total energy of the molecule in kJ/mol, percentage strain on the metal atom, and selected bond lengths, bond angles have been computed. e lowest energy of the complex is indicative of more stability; the values are given in Tables 4 and 5.
Based on the above discussion, the chloro-, bromo-, and perchlorate-complexes are proposed to possess tetrahedral geometry. In the case of the perchlorate complex, at least one perchlorate monodentately coordinated to the metal ion as supported by IR spectrum. e molecular modeling suggests that the N-heterocycles act as bridging ligand and, therefore, have a polymeric structure. In the case of [ZnL 2 (OCH 2 CH 2 CH 2 CH 3 ) 2 ] complex, 1 H and 13 C NMR spectral studies and the thermogravimetric data show the presence of two solvent molecules, that is, n-butanol, which are coordinated to the metal ion through oxygen atom, and the complex is also proposed to have tetrahedral geometry around the metal ion.

Anthelmintic Activities of Synthesized Complex
e results revealed that synthesized complexes have sig-ni�cant anthelmintic activity at 5 mg�mL concentrations. e results are comparable with standard drugs albendazole and piperazine citrate at the same concentration.  Figure 3).