Synthesis, characterization, structural features and cytotoxicity of innovative zinc(II) complex derived from ONS-donor thio-Schiff base of acyl pyrazolone European Journal of Chemistry 10 (2) (2019) 131-138 European Journal of Chemistry View Journal Online View Article Online Synthesis, characterization, structural features and cytotoxicity of innovative zinc(II) complex derived from ONS-donor thio-Schiff base of acyl pyrazolone Irfan Shaikh 1, Aliasgar Vohra 2, Ranjitsinh Devkar 2 and Rajendrasinh Jadeja 1 1 Department of Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara-390002, India irfan.chemistry7@gmail.com (I.S.), rjadeja-chem@msubaroda.ac.in (R.J.) 2 Department of Zoology, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara 390 002, India aliasgarvohra@rocketmail.com (A.V.), phyto_met@yahoo.com (R.D.) * Corresponding author at: Department of Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara-390002, India. Tel: +91.0265.2795552 Fax: +91.0265.2795552 e-mail: rjadeja-chem@msubaroda.ac.in (R. Jadeja). 10.5155/eurjchem.10.2.131-138.1858 Received: 29 March 2019 Received in revised form: 09 May 2019 Accepted: 10 May 2019 Published online: 30 June 2019 Printed: 30 June 2019 Novel acyl pyrazolone and thio-Schiff base of acyl pyrazolone ligand HL (2-((4- chlorophenyl)(1-(3-chlorophenyl)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)methylene) hydrazine-1-carbothioamide) has been synthesised and characterized by FT-IR and 1H NMR techniques. This unusual coordinated complex [Zn(L)(CH3C00)(H2O)]CH3CH2OH has been synthesized and characterized by FT-IR, thermogravimetric analysis (TGA), UV-Vis spectroscopy and single crystal X-ray diffraction. 1H NMR confirms the structure of the thio- Schiff base used in the study. The structural data reveal that mononuclear Zn(II)complex has distorted square pyramidal geometry. S-S interaction, Inter molecular and intra molecular H-Bond found in crystal packing of the complex. The complex has been screened for MTT assay against A549 cell lines. The Zn(II) complex is cytotoxic against the screened cell line at low concentration. ONS donors Cytotoxicity Zn(II) complex Thio-Schiff base Single crystal structure Acyl pyrazolone derivatives Cite this: Eur. J. Chem. 2019, 10(2), 131-138 Journal website: www.eurjchem.com 1. Introduction The Schiff based ligands of acyl pyrazolones paying attention in recent time due to its coordination ability and decent biological activities [1-6]. Reaction between ketones (or aldehydes) and a thiosemicarbazide that gives thiosemi- carbazones and which are called thio-Schiff and owing to their good binding capacity to metal they are very suitable in coordination chemistry [7]. Tautomer thione (-C=S) and thiol (-C-SH) forms (Figure 1) of thiosemicarbazone act as neutral or anionic bidentate ligands from the donor sites of azomethine N and S(thione/thiol) [8,9]. R1 R2 N HN NH2 S R1 R2 N N NH2 SH R1,R2 = Aryl or alkyl group (same or different) Figure 1. Thione, thiol tautomer of thiosemicarbazone. Their Zn (II) complexes show prospective fluorescence properties [10,11]. Several metal complexes showed respectable biological activities with significant thiosemicar- bazone of acyl pyrazolone [12]. Selected metal complexes of thiosemicarbazone are octahedral, square planer, square pyramidal and trigonal bipyramidal are reported in recent time [12,13].Very unique binding from three different molecules, penta coordinated square pyramidal geometry of thio-Schiff Zn(II) complex is reported in this article. Metal complexes of thio-Schiff base ligands appreciated because of their antimicrobial, antifungal, antioxidant and catalytic activities [14-17]. Metal complexes of tridentate acyl pyrazolone based thiosemicarbazone showed some decent results of several bioactivities [12]. Herein, zinc(II) complex of thio-Schiff base of biological active acyl pyrazolone synthe- sized and reported sound result of cytotoxicity againstA549 cells by MTT assay. 2. Experimental 2.1. Materials ABSTRACT RESEARCH ARTICLE KEYWORDS European Journal of Chemistry ISSN 2153-2249 (Print) / ISSN 2153-2257 (Online) – Copyright © 2019 The Authors – Atlanta Publishing House LLC – Printed in the USA. This work is published and licensed by Atlanta Publishing House LLC – CC BY NC – Some Rights Reserved. http://dx.doi.org/10.5155/eurjchem.10.2.131-138.1858 http://dx.doi.org/10.5155/eurjchem.10.2.131-138.1858 https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.10.2.131-138.1858&domain=pdf&date_stamp=2019-06-30 http://www.eurjchem.com/ http://dx.doi.org/10.5155/eurjchem.10.2.131-138.1858 mailto:irfan.chemistry7@gmail.com mailto:rjadeja-chem@msubaroda.ac.in mailto:aliasgarvohra@rocketmail.com mailto:phyto_met@yahoo.com mailto:rjadeja-chem@msubaroda.ac.in http://www.eurjchem.com/ https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.10.2.131-138.1858&domain=pdf&date_stamp=2019-06-30� 132 Shaikh et al. / European Journal of Chemistry 10 (2) (2019) 131-138 N N Cl O O Cl NN Cl N NH NH2 O Cl S NN N NH NH2 S OH Cl N N N N NH2 SH O Cl (II) (III) Cl Cl Schiff base reaction (Thiosemicarbazide) (I) Scheme 1. Synthesis route of ligand (HL). The compound 1-(3-chlorophenyl)-3-methyl-1H-pyrazol- 5(4H)-one (MCPMP) was obtained from Nutan Dye Chem., Sachin, Surat, India as free gift sample. 1,4-Dioxane and methanol were obtained from SD Fine Chem. Limited, Chennai, India. Calcium hydroxide, sodium acetate and zinc acetate dehydrate were obtained from LOBA Chem. Pvt. Ltd., Mumbai (India). Thiosemicarbazide obtained from Sisco Research Lab. Pvt. Ltd., Mumbai (India). Absolute ethanol was obtained from Baroda Chem. Industry Ltd. and was used after distillation. 2.2. Characterization techniques The synthesized compounds were characterized using FT- IR and UV-visible spectroscopy, molar conductance and X-ray crystallography. Infrared spectra (4000-400 cm-1, KBr pellets) of the samples were recorded on a model Bruker alpha FT-IR spectrophotometer with 4 scan number. The 1H NMR spect- rum of the ligand was recorded with a Bruker AV 400 MHz spectrometer using CDCl3 as the solvent and TMS as an internal reference. Electronic spectra (in DMSO at room temperature) in the range 400-800 nm were recorded on a model Perkin Elmer Lambda 35 UV-VIS spectrophotometer. TGA analysis has been done on SII TG/DTA A6300 instrument. The molar conductivity of a 1×10-3 M solution of the complex in DMSO was measured at room temperature with a model Elico CM 180 digital direct reading deluxe digital conductivity meter. The zinc content was determined by using EDTA in volumetric analysis after decomposing the complex with HNO3. 2.3. Synthesis 2.3.1. Synthesis of 4-(4-chlorobenzoyl)-2-(3-chlorophenyl)- 5-methyl-2,4-dihydro-3H-pyrazol-3-one [PCBMCPMP] The acylation reaction of pyrazolone (MCPMP) was carried out by reported method [18]. Color: Yellow. Yield: 58%. M.p.: 105-107 °C. 1H NMR (400 MHz, CDCl3, δ, ppm): 2.14 (s, 3H, pyrazolone C–CH3), 7.28-7.30 (m, 1H, Ar-H), 7.39-7.43 (m, 1H, Ar-H), 7.51-7.63 (m, 4H, Ar-H), 7.83-7.85 (m, 1H, Ar-H), 7.963- 7.968 (m, 1H, Ar-H),11.65 (s, 1H, OH). FT-IR (KBr, ν, cm-1): 1625 (s) (C=O, amide of pyrazolone), 1590 (m) (C=O, p-chloro ph), 966 (s) (N-N), 1486 (m) (Ar-C-C). Anal. calcd. for C17H12Cl2N2O2 : C, 58.81; H, 3.48; N, 8.07 Found: C, 58.70; H, 3.37;N, 8.22%. Λm (S.cm2.mol-1): 7.0. 2.3.2. (Z)-2-((4-chlorophenyl)(1-(3-chlorophenyl)-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-4-yl)methylene)hydrazine-1- carbothioamide [HL] PCBMCPMP (0.347 g, 1 mmol) and thiosemicarbazide (0.091 g, 1 mmol) in ethanol (50 mL) were refluxed for 6 h in round bottom flask. During the reflux a microcrystalline yellow compound [HL] separated out, which was isolated by filtration, dried in air and finally crystallized in the suitable solvent (Scheme 1). Color: Yellow. Yield: 82.34 %. M.p.: 188- 190 °C. 1H NMR (400 MHz, CDCl3, δ, ppm): 2.14 (s, 3H, pyra- zolone C-CH3), 2.24 (s, 2H, NH2-tsc), 3.50 (s, 1H, NH-tsc), 7.28- 7.31 (m, 1H, Ar-H), 7.39-7.43 (m, 1H, Ar-H), 7.52-7.63 (m, 4H,Ar-H), 7.96-7.97 (m, 1H,Ar-H), 7.84-7.85 (m, 1H, Ar-H), 10.19 (s, 1H, OH). FT-IR (KBr, ν, cm-1): 3331 (b) (NH2), 3168 (b) (NH-tsc), 1662 (C=O, pyrazolone), 1014 (m) (C=S), 1602 (m) (C=N, cyclic), 958 (s) (N-N), 1481 (m) (Ph-C-C), 2960 (b) (Ph-C-H). Anal. calcd. for C18H15Cl2N5OS: C, 51.44; H, 3.60; N, 16.66. Found: C, 51.25; H, 3.56; N, 16.57%. UV/Vis (DMSO, λmax, nm, (ε)): 271 (1.83). Λm (S.cm2.mol-1): 8.8. 2.4. Synthesis of complex [Zn(L)(CH3COO)(OH2)]CH3CH2OH To a solution of Zn(CH3COO)2·2H2O (0.2195 g, 1 mmol) in methanol (5 mL), a solution of HL (0.420 g, 1 mmol) in methanol (10 mL) was added while stirring. After half an hour add a methanolic solution of sodium acetate. The reaction mixture was refluxed for 4 h. After the reflux, the clear reaction mixture was placed for a week at 4 °C temperature. After a week light yellow crystalline product was obtained. The synthesis of the complex can be summarized by Scheme 2. Color: Yellowish white. Yield: 65 %. M.p.: 200-202 °C. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.2.131-138.1858 Shaikh et al. / European Journal of Chemistry 10 (2) (2019) 131-138 133 Table 1. Crystal data and structure refinement for [Zn(L)(H20)(CH3COO)]CH3CH2OH. Identification code [Zn(L)(H20)(CH3COO)]CH3CH2OH Empirical formula C22H25Cl2N5O5SZn Formula weight 607.80 Temperature (K) 273.0 Crystal system Triclinic Space group P-1 a (Å) 8.1030(7) b (Å) 12.1220(10) c (Å) 14.9628(12) α (°) 72.777(7) β (°) 75.541(7) γ (°) 88.486(7) Volume (Å3) 1357.6(2) Z 2 ρcalc (g/cm3) 1.487 μ (mm-1) 1.219 F(000) 624.0 Crystal size (mm3) 0.3 × 0.2 × 0.2 Radiation MoKα (λ = 0.71073) 2Θ range for data collection (°) 6.128 to 57.92 Index ranges -10 ≤ h ≤ 10, -14 ≤ k ≤ 15, -11 ≤ l ≤ 20 Reflections collected 6488 Independent reflections 5415 [Rint = 0.0196, Rsigma = 0.0554] Data/restraints/parameters 5415/0/330 Goodness-of-fit on F2 1.026 Final R indexes [I≥2σ (I)] R1 = 0.0484, wR2 = 0.1086 Final R indexes [all data] R1 = 0.0698, wR2 = 0.1231 Largest diff. peak/hole(e Å-3) 0.94/-0.84 N N N HN NH2 S Cl O Cl EtOH Zn(CH3COO)2 2H2O CH3COONa Reflux N N N H N NH2 S Cl O Cl Zn H2O O O CH3CH2OH Scheme 2. Synthesis route of zinc (II) complex. FT-IR (KBr, ν, cm-1): 3408 (b) (NH-), 1160 (C=N, azomethine), 862 (s) (N-N), 1474 (m) (Ph-C-C), 1612 (s) (C=N, cyclic), 1139 (m) (N-N), 3159 (b) (NH2), 1589 (m) (C=N, cyclic), 2927 (b) (Ph–C–H), 1015 (m) (C=S), 511 (s) (Zn–N), 480 (s) (Zn–O), 445 (s) (S-O). Anal. calcd. for C22H25Cl2N5O5SZn: C, 43.47; H, 4.15; N, 11.52. Found: C, 43.36; H, 3.95; N, 11.75%. UV/Vis (DMSO, λmax, nm, (ε)): 288 (1.40). Λm (S.cm2.mol-1): 3.3. 2.5. X-ray structure determination Single-crystal X-ray diffraction measurement for one of the Zn(II) complex was carried out. X-ray intensity data of Reflections collected 6488 (Independent reflections 5415) were collected on Bruker CCD area-detector diffractometer equipped with graphite monochromated MoKα radiation (λ = 0.71073). The crystal used for data collection was of dimensions 0.30 mm × 0.20 mm × 0.20 mm. The structure was solved by methods using SHELXS97 [19]. All non-hydrogen atoms of the molecule were located in the best E-map. Full- matrix least-squares refinement was carried out using SHELXL97[19]. The final refinement cycles converged to an R1 = 0.0698 and wR2 = 0.1231 for the observed data. Residual electron densities ranged from 0.94/-0.84 e.A−3. The crystallographic data are summarized in Table 1. An ORTEP [20] view of the complex with 50% possibility is shown in Figure 2 [21]. The geometry of the molecule has been calculated using the software PLATON [22] and PARST [23]. 2.6. MTT cell viability assay A549 (human lung carcinoma) cells were procured from National Centre of Cell Sciences, Pune, India. Cells were maintained at 37 °C and 5% CO2. Cells were seeded (1×105 cells) in a T25 flask and cultured in DMEM containing 10% FBS and 1% antibiotic-antimycotic solution with trypsinization at every third day and sub-culturing with a TPVG solution. 1 mg test complex was dissolved in 5 μL DMSO solvent and later, 1, 5, 10, 25, 50, 100, 200, 500 and 1000 μg/mL doses were tested against A549 cells for cytotoxicity using 3-(4,5-dimethyl- thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cyto- toxicity assay. A549 cells (7×103 cells/well) were seeded in 96-well culture plates (Tarson India Pvt. Ltd.) for 24 h in absence or presence of complex. Later, 10 μL MTT (5 mg/mL) was added to the wells and plates were incubated at 37 °C for 4 h to form the formazan crystals. The culture media was discarded and wells were washed with PBS. The resultant formazan was dissolved in 150 μL of DMSO and absorbance was read at 540 nm in Synergy HTX-Multimode Reader (Biotek, USA). 2.7. Statistical analysis The data was analysed for statistical significance using one way analysis of variance (ANOVA) followed by Dunnett’s multiple comparison test and the results were expressed as 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.2.131-138.1858 134 Shaikh et al. / European Journal of Chemistry 10 (2) (2019) 131-138 Figure 2. Crystal structure of Zn(II) complex. Figure 3. UV-Vis spectroscopy of ligand and complex. mean±SEM using Graph Pad Prism version 5.0 for Windows, Graph Pad Software, San Diego, California, USA. 3. Result and discussion 3.1. IR spectroscopy IR spectroscopy study and comparison between ligand complex indicating that ligand HL is reacted as monoionic tridentate ligand in zinc(II) complex with thionesulphur, azomethine nitrogen and amidic -C=O to -C-O- in pyrazolone moiety. The IR spectra of the ligand display sharp band at 3331 cm-1 as indicated NH2 group remain unchanged and just slightly shifted to 3159 cm-1 in complex IR-spectrum [24]. Medium intensity bands in the region 2960-2926 cm-1 due to - N-H vibration changed in complex 2968-2927 cm-1 and IR stretching of C=S is 1014 cm-1 in the ligand (HL) that showed in complex at 1015 cm-1. These bands of IR spectra clearly indicating –N-H and -C=S remain unchanged in complex [12,24]. In comparison between IR spectra of ligand and complex indicating unchanged thione-sulphur and azomethine nitrogen in coordination zinc(II) complex. Carbonyl bond (C=O) band observed at 1625 cm-1 of ligand disappear in complex and new bond (-C-O-) a sharp intense band appeared at 1160 cm-1the complex, where shift to higher frequency region is seen, due to de-protonation of enol (-C-OH) form (Scheme 1) of ligand and the appearance of new bond of (-C-O-) in complex indicating the ONS monoionic tridentate behaviour of the ligand (HL).Bonds between metal and ligand showed bands at 511, 480 and 445 cm−1 recognized to (Zn–N), (Zn–O) and (Zn–S), respectively. 3.2. Electronic spectroscopy The transfer of an electron from one atom to another called charge transfer (C.T.). The UV-Vis bands are related with C.T. of metal to ligand and ligand to metal in metal complex. The visible spectrum for the complex under examination was measured in DMSO (Figure 3). Two bands were observed around wavelength 280 and 350 nm indicated charge transfer in complex [18]. As expected, there was no any d-d band for Zinc complex due to the completely filled 3d orbital in d10 metal complex [18]. 3.3. Thermogravimetric analysis (TGA) The thermogravimetric analysis (TGA) is an analytical method used to define thermal stability of a compound and its division of volatile decomposition products by monitoring the mass loss that occurs as sample is heated. TGA of complex has been completed under nitrogen atmosphere from 27 to 500 °C. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.2.131-138.1858 Shaikh et al. / European Journal of Chemistry 10 (2) (2019) 131-138 135 Table 2. Important bond lengths and bond angles. Atom-Atom Length (Å) Atom- Atom-Atom Angle (˚) Zn1-S12 2.3293(10) O26-Zn1-S12 145.25(8) Zn1-O26 1.977(2) O26-Zn1-O29 107.39(10) Zn1-O29 2.010(2) O26-Zn1-O32 87.18(10) Zn1-O32 2.090(2) O26-Zn1-N9 86.48(9) Zn1-N9 2.198(3) O29-Zn1-S12 107.01(7) S12-C11 1.695(3) O29-Zn1-O32 95.93(10) Cl14-C5 1.747(4) O29-Zn1-N9 100.82(10) Cl28-C19 1.740(5) O32-Zn1-S12 94.09(8) O26-C22 1.287(4) O32-Zn1-N9 163.19(10) O32-C31 1.271(4) N9-Zn1-S12 82.43(7) O30-C31 1.232(5) C11-S12-Zn1 99.24(12) N9-N10 1.384(4) C22-O26-Zn1 122.7(2) N9-C8 1.305(4) C31-O32-Zn1 123.8(2) N10-C11 1.347(4) N10-N9-Zn1 114.31(19) N21-N25 1.393(3) C8-N9-Zn1 127.6(2) N21-C22 1.367(4) C8-N9-N10 117.9(3) N21-C15 1.415(4) C11-N10-N9 120.3(3) N25-C24 1.317(4) N25-N21-C15 119.6(3) O34-C35 1.411(5) C22-N21-N25 110.8(3) N13-C11 1.318(4) C22-N21-C15 129.2(3) C24-N25-N21 105.7(3) N10-C11-S12 123.2(3) N13-C11-S12 119.7(3) N13-C11-N10 117.0(3) C24-C23-C8 130.2(3) C22-C23-C24 104.6(3) C22-C23-C8 124.8(3) N25-C24-C23 112.1(3) N25-C24-C27 118.2(3) C23-C24-C27 129.6(3) Figure 4. TG-DTA of complex. The first mass loss was observed up to 150 °C probably is due to loss of coordinated one molecule of water. Second mass loss observed between 160-260 °C that indicating the coordinated acetate group [25]. Thus the thermogravimetric curve of the Figure 4 indicate that thermal properties of Zn(II) complex is completely approving its thermal stability. After two mass losses there is one continuous mass loss displayed in complex TGA study. That above 300 °C to more than 500 °C, the complexes decompose slowly due to fragmentation and thermal degradation of the organic moiety of thio-Schiff based thiosemicarbazone of acyl pyrazolone. 3.4. Conductance measurement The conductivities of zinc(II) metal complex and ligand in DMSO were measured with a calibrated conductivity cell at room temperature. The low conductivity values in DMSO reveal Complexes are non-electrolytic in nature. The conductivity of each solution (1×10-3 M) was measured and used for further calculations where possible, specific conductivities and molar conductivities. Ligand (HL) and its zinc(II) complex molar conductance values are 8.8 and 3.3 ohm-1cm2mol-1, respectively. Sp. conductivity = cell constant × conductivity (1) Sp. conductivity 1000Molar conductivity Molarity of solution × = (2) 3.5. Crystallographic data The molecular structure of zinc complex and the atom labelling scheme is shown in Figure 2. The main bond distances and angles are listed in Table 2. As shown in Figure 1, the Zn(II) ion is penta-coordinated by three oxygen atoms of one acyl pyrazolone ligand, one oxygen atom of water molecule and one oxygen atom of acetate group. The one oxygen, one thione-sulphur and one azomethine nitrogen of ligand (L) and one oxygen of acetate molecules occupy the basal sites of the square pyramidal structure, whereas the water molecule binds the zinc at the apical site. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.2.131-138.1858 136 Shaikh et al. / European Journal of Chemistry 10 (2) (2019) 131-138 Figure 5. Intra molecule H-Bond in complex. Figure 6. Intermolecule H-bond, S-S interactions. In this complex, the combination of the solvent EtOH into the outer-sphere of the complex without coordination bond. The geometry around the metal is now distorted square pyramidal. The zinc atom of complex occupies a distorted square- pyramidal environment (SP), formed by three oxygen atoms [O(26), O(29) and O(32)] supplied by one pyrazolone based ligand, water molecule and acetate molecule, respectively. The fourth and fifth coordination site is occupied by one nitrogen atom and sulphur atom of ligand molecule. The Zn-O distances are Zn(1)-O(26) = 1.977(2) Å and Zn(1)-O(29) = 2.010(2) Å and Zn(1)-O(32) is 2.090(2) Å. Where the distance between Zn(1)-S(12) = 2.3293(10) Å [26] and Zn(1)-N(9) = 2.198(3) Å. In the complex, displayed intra-moleculer hydrogen bond (O34-H34···O32) between H34-O34 of EtOH solvent and O32 of acetate, and additional one is H29-O29 of water molecule and O30 of acetate (Figure 5). Furthermore in inter molecule hydrogen bond observed between H13-N13···O30 where H13-N13 of thio-Schiff base of acyl pyrazolone. Another one is H29-O29···N25 H-bond where H29-O29 of coordinated water molecule and N25 of pyrazolone ring. In the Figure 6, very interesting illustrated that the struc- ture of zinc(II) complex exhibiting a sulphur-sulphur (S···S) interaction of 3.581 Å in identical complex molecules found within the crystallographic cell. The C=S bond is formally a double bond (1.695(3) Å) and the adjacent C-N(H) bond (C11- N10 =1.347(4) Å) was consistent with a thioamide tautomer (Table 2, Figure 2) [27]. 3.6. Cell culture and cell viability assay Cytotoxicity of the synthesized metal complex was asses- sed against A549 cells by MTT assay. Doses 1, 5 and 10 μg/mL accounted for a weak cytotoxicity response with more than 70% cells being viable at the end of 24 h. But the subsequent doses of 325-1000 μg/mL accounted for 11% viability thus indicating at significant toxicity induced by the metal complex. These results are in agreement with previous report on anticancer potential of pyrazolone based complexes [28-30]. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.2.131-138.1858 Shaikh et al. / European Journal of Chemistry 10 (2) (2019) 131-138 137 Figure 7. Cytotoxicity of complex [Zn(H2O)(CH3COO)]C2H5OH (DC=DMSO control). It is hypothesized in the present study that Zn(II) chelation by pyrazolone based ligand accounts for cytotoxicity observed herein. MTT assay is focused at reporting the viability of a cell as a result of mitochondrial function and loss of viability is implicated on mitochondrial dysfunction [31,32]. Results obtained herein suggest mitochondrial dysfunction induced by metal complexes results in loss of cell viability of A549 cells (Figure 7). 4. Conclusion The acyl pyrazolone and its Schiff based with thiosemicar- bazide has been synthesised and characterized by FT-IR, 1H NMR and UV-Vis spectroscopy. The ligand typically behaved as monoionic tridentate in nature coordinated through thione sulphur, azomethine nitrogen and amidic -C=O to –C-O- in pyrazolone moiety. Zinc(II) complex of thio-Schiff ligand synthesised and characterised by FT-IR, single crystal X-ray diffraction, UV-vis spectroscopy and conductance measure- ment. The Zn(II) enjoys square pyramidal environment. The complex was also screened for the cytotoxicity against the A549 lung cancer cell lines and found active. Disclosure statement Conflict of interests: The authors declare that they have no conflict of interest. Author contributions: All authors contributed equally to this work. Ethical approval: All ethical guidelines have been adhered. Sample availability: Samples of the compounds are available from the author. Acknowledgment The authors are thankful to Head, Department of Chemistry for providing necessary facilities required to carry out this work. Supporting information CCDC-1906438 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge viahttps://www.ccdc.cam.ac.uk/structures/, or by e-mailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(0)1223-336033. Disclosure statement Conflict of interests: The authors declare that they have no conflict of interest. Author contributions: All authors contributed equally to this work. Ethical approval: All ethical guidelines have been adhered. Sample availability: Samples of the compounds are available from the author. ORCID Irfan Shaikh http://orcid.org/0000-0002-0403-2566 Aliasgar Vohra http://orcid.org/0000-0002-4845-084X Ranjitsinh Devakar http://orcid.org/0000-0002-9863-7418 Rajendrasinh Jadeja http://orcid.org/0000-0002-2228-8653 References [1]. Zhang, Y. P.; Li, Y.; Xu, G. C.; Li, J. Y.; Luo, H. Y.; Li, J. Y.; Zhang, L.; Jia, D. Z. Appl. Organomet. Chem. 2019, 33(3), 4668-4672. [2]. Li, H.; Xu, G. C.; Zhang, L.; Guo, J. X.; Jia, D. Z. Polyhedron 2013, 55, 209-215. [3]. Parmar, N.; Teraiya, S.; Patel, R.; Barad, H.; Jajda, H.; Thakkar, V. J. Saudi Chem. Soc. 2015, 19(1), 36-41. [4]. Liu, L.; Jia, D. Z.; Ji, Y. L.; Yu, K. B. J. Photochem. Photobiol. A 2003, 154(2), 117-122. [5]. Joseph; V. A.; Vyas, K. M.; Pandya, J. H.; Gupta, V. K.; Jadeja, R. N. J. Coord. Chem. 2013, 66(6), 1094-1106. [6]. Nakum, K.; Jadeja, R. N. Z. Naturforsch. B 2018, 73(10), 677-747. [7]. Lo, K. Inorganic and organometallic transition metal complexeswith biological molecules and living cells, Academic Press: Hong Kong, 2017. [8]. Novak, P.; Piculjan, K.; Biljan, T.; Hrenar, T.; Cindric, M.; Rubcic, M.; Meic, Z. Croat. Chem. Acta 2007, 80, 575-581. [9]. Campbell, M. J. M.; Morrison, E.; Rogers, V.; Baker, P. K. Polyhedron 1987, 6(8), 1703-1705. [10]. Lu, J.; Zhang, L.; Liu, L.; Liu, G.; Jia, D.; Wu, D.; Xu, G. Spectrochim. Acta A 2008, 71(3), 1036-1041. [11]. Xu, G. C.; Zhang, L.; Zhang, Y. H.; Guo, J. X.; Shi, M. Q.; Jia, D. Z. CrystEngComm 2013, 15(15), 2873-2880. [12]. Vyas, K. M.; Joshi, R. G.; Jadeja, R. N.; Prabha, C. R.; Gupta, V. K. Spectrochim. Acta A 2011, 84, 256-268. [13]. Yadav, R. J.; Vyas, K. M.; Jadeja, R. N. J. Coord. Chem. 2010, 63(10), 1820-1831. [14]. Singh, R. V.; Chaudhary, P.; Chauhan, S.; Swami, M. Spectrochim. Acta A 2009, 72(2), 260-268. [15]. Abou-Hussein, A. A.; Linert, W. Spectrochim. Acta A 2014, 117, 763- 771. [16]. Bal-Demirci, T.; Sahin, M.; Kondakci, E.; Ozyurek, M.; Ulkuseven, B.; Apak, R. Spectrochim. Acta A 2015, 138, 866-872. [17]. Datta, S.; Seth, D. K.; Butcher, R. J.; Bhattacharya, S. Inorganica Chim. Acta 2011, 377(1), 120-128. [18]. Jadeja, R. N.; Chhatrola, M.; Gupta, V. K. Polyhedron 2013, 63, 117- 126. [19]. University of Gottingen. G. M. Sheldrick, SHELXS97 and SHELXL97; Germany, 1997. [20]. Johnson, C. K. ORTEP II; Report ORNL-5138;Oak Ridge, TN, 1976. [21]. Farrugia, L. J. J. Appl. Crystallogr. 1997, 30, 565-566. [22]. Spek, A. L. PLATON for Windows,September.; University of Utrecht: 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.2.131-138.1858 https://www.ccdc.cam.ac.uk/structures/ mailto:data_request@ccdc.cam.ac.uk http://orcid.org/0000-0002-0403-2566 http://orcid.org/0000-0002-4845-084X http://orcid.org/0000-0002-9863-7418 http://orcid.org/0000-0002-2228-8653 138 Shaikh et al. / European Journal of Chemistry 10 (2) (2019) 131-138 Netherlands, 1999. [23]. Nardelli, M. J. Appl. Crystallogr. 1995, 28(5), 659-665. [24]. Malik, S.; Kumari, M.; Sharma, D. J. Indian Chem. Soc. 2010, 87, 539- 549. [25]. Korosec, R. C.; Bukovec, P. Thermochim. Acta 2004, 410, 65-71. [26]. Turkkan, B.; Ulkuseven, B.; Eroglu, E. Phosphorus, Sulfur Silicon Relat. Elem. 2015, 190(1), 53-65. [27]. Stacy, A. E.; Palanimuthu, D.; Bernhardt, P. V; Kalinowski, D. S.; Jansson, P. J.; Richardson, D. R. J. Med. Chem. 2016, 59(10), 4965- 4984. [28]. Field, J. B.; Dolendo, E. C.; Mireles, A.; Ershoff, B. H. Cancer Res. 1966, 26(7), 1371-1375. [29]. Vyas, K. M.; Jadeja, R. N.; Patel, D.; Devkar, R. V; Gupta, V. K. Polyhedron 2014, 80, 20-33. [30]. Vyas, K. M.; Jadeja, R. N.; Patel, D.; Devkar, R. V; Gupta, V. K. Polyhedron 2013, 65, 262-274. [31]. Thounaojam, M. C.; Jadeja, R. N.; Valodkar, M.; Nagar, P. S.; Devkar, R. V; Thakore, S. Food Chem. Toxicol. 2011, 49(11), 2990-2996. [32]. Upadhyay, K. K.; Jadeja, R. N.; Thadani, J. M.; Joshi, A.; Vohra, A.; Mevada, V.; Patel, R.; Khurana, S.; Devkar, R. V. Toxicol. Appl. Pharmacol. 2018, 360, 99-108. Copyright © 2019 by Authors. This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at http://www.eurjchem.com/index.php/eurjchem/pages/view/terms and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0). By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License (http://www.eurjchem.com/index.php/eurjchem/pages/view/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry). 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.2.131-138.1858 http://www.eurjchem.com/index.php/eurjchem/pages/view/terms http://creativecommons.org/licenses/by-nc/4.0 http://www.eurjchem.com/index.php/eurjchem/pages/view/terms 1. Introduction 2. Experimental 2.1. Materials 2.2. Characterization techniques 2.3. Synthesis 2.3.1. Synthesis of 4-(4-chlorobenzoyl)-2-(3-chlorophenyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-one [PCBMCPMP] 2.3.2. (Z)-2-((4-chlorophenyl)(1-(3-chlorophenyl)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)methylene)hydrazine-1-carbothioamide [HL] 2.4. Synthesis of complex [Zn(L)(CH3COO)(OH2)]CH3CH2OH 2.5. X-ray structure determination 2.6. MTT cell viability assay 2.7. Statistical analysis 3. Result and discussion 3.1. IR spectroscopy 3.2. Electronic spectroscopy 3.3. Thermogravimetric analysis (TGA) 3.4. Conductance measurement 3.5. Crystallographic data 3.6. Cell culture and cell viability assay Disclosure statement Acknowledgment Supporting information Disclosure statement ORCID References PrintField10: PrintField11: PrintField12: PrintField13: PrintField14: PrintField15: PrintField16: PrintField17: PrintField20: PrintField21: PrintField22: PrintField23: PrintField24: PrintField25: PrintField26: PrintField27: