Detailed analytical studies of 1,2,4-triazole derivatized quinoline European Journal of Chemistry 10 (4) (2019) 281-294 European Journal of Chemistry View Journal Online View Article Online Detailed analytical studies of 1,2,4-triazole derivatized quinoline Shilpa Mallappa Somagond 1, Manjunath Ningappa Wari 2, Saba Kauser Jaweed Shaikh 1, Sanjeev Ramchandra Inamdar 2, Madan Kumar Shankar 3, Dasappa Jagadeesh Prasad 4 and Ravindra Ramappa Kamble 1,* 1 Department of Chemistry, Karnatak University, Dharwad, Karnataka 580003, India shilpasomagond@gmail.com (S.M.S.), saba9805@gmail.com (S.K.J.S.), kamchem9@gmail.com (R.R.K.) 2 Department of Physics, Karnatak University Dharwad, Karnataka 580003, India sm5wari@gmail.com (M.N.W.), him_lax3@yahoo.com (S.R.I.) 3 Department of Science and Technology, PURSE Laboratory, Mangalore University, Mangalagangothri, Karnataka 574199, India madan.mx@gmail.com (M.K.S.) 4 Department of Chemistry, Mangalore University, Konaje, Mangalore, Karnataka 574199, India jprasad2003@gmail.com (D.J.P.) * Corresponding author at: Department of Chemistry, Karnatak University, Dharwad, Karnataka 580003, India. Tel: +91.836.2445998 Fax: +91.836.2747884 e-mail: kamchem9@gmail.com (R.R. Kamble). 10.5155/eurjchem.10.4.281-294.1844 Received: 07 March 2019 Received in revised form: 25 July 2019 Accepted: 30 July 2019 Published online: 31 December 2019 Printed: 31 December 2019 The present study describes, the X-ray single crystal analysis of 4-((2-chloro-6- methoxyquinolin-3-yl)methyl)-2-phenyl-2H-1,2,4-triazol-3(4H)-one (TMQ). The crystal data for C19H15ClN4O2: monoclinic, space group P21/n (no. 14), a = 7.3314(15) Å, b = 12.459(3) Å, c = 18.948(4) Å, β = 98.322(9)°, V = 1712.5(6) Å3, Z = 4, T = 296.15 K, μ(MoKα) = 0.245 mm-1, Dcalc = 1.423 g/cm3, 5082 reflections measured (3.926° ≤ 2Θ ≤ 38.556°), 1428 unique (Rint = 0.0545, Rsigma = 0.0574) which were used in all calculations. The final R1 was 0.0423 (I >2σ(I)) and wR2 was 0.1145 (all data). The Density functional theory optimized molecular geometries in TMQ agree closely with those obtained from crystallographic studies. The Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) energy levels and energy gap were calculated by experimental (UV absorption & Cyclic voltammetry) and theoretical studies in two different solvents. The natural bond orbital analysis was performed to understand the molecular interaction on the basis of stability of molecule arising from hyper-conjugative interaction and charge delocalization. Hirshfeld surface and their related fingerprint plots enabled the identification of significant intermolecular interaction. The molecular electrostatic potential analysis provides the visual image of the chemically active sites and comparable reaction of atoms. UV absorption Hirshfeld surface Cyclic voltammetry Single crystal structure Natural bond orbital (NBO) Time Dependent-Density Functional Theory Cite this: Eur. J. Chem. 2019, 10(4), 281-294 Journal website: www.eurjchem.com 1. Introduction Quinoline, an aza heterocycle, is pharmaceutically an important class of compound that exists as an emergence of pyridine ring and one benzene ring fused together at nearby two (side) carbon atoms [1]. These are widely used as a source compounds for the synthesis of numerous drugs. Many quinoline based drugs such as Captothecine (anticancer) [2] and Cryptolepine (antimalarial) [3] are available in the market. This skeleton also showed a broad spectrum of biological activities including antiasthmatic [4], antidiabetic [5], antibacterial [6], antitoxoplasma [7], antifungal [8] and anti- HIV [9] activities. Due to the presence of nitrogen, the quinoline moieties act as chelating agent as well as a weak base [10]. Some of thequinoline derivatives are often used as fluorescent materials and sensors due to their rigid structure, high fluorescent yield, and large energy gaps [11]. The 1,2,4-triazole scaffolds have attracted significant interest as chemotherapeutic agents, where they possess diverse pharmacological activities [12]. 1,2,4-Triazole nucleus is the main structural motif of many commercially available drugs including Fluconazole, Ribavirin, Letrozole and Itraconazole etc. [13-15]. 4-((2-Chloro-6-methoxyquinolin-3-yl)methyl)-2-phenyl- 2H-1,2,4-triazol-3(4H)-one (TMQ) was designed and mole- cular docking study was performed to explore the mechanism of anti-TB as well as anticancer activity and to study the intermolecular interactions between the targeted enzyme (Enoyl-acyl carrier protein) and TMQ. Based on impressive outcome of docking study (C-Score = 5.89) of the TMQ, the molecule was synthesized structure was characterized. Further, invitro study was carried out and it was found that this molecule is promising candidate for developing novel anticancer (GI50 = 63.15 µM) and anti-tubercular (MIC90 = 0.100 µM) agent [16]. 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.10.4.281-294.1844 http://dx.doi.org/10.5155/eurjchem.10.4.281-294.1844 https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.10.4.281-294.1844&domain=pdf&date_stamp=2019-12-31 http://www.eurjchem.com/ http://dx.doi.org/10.5155/eurjchem.10.4.281-294.1844 mailto:shilpasomagond@gmail.com mailto:saba9805@gmail.com mailto:kamchem9@gmail.com mailto:sm5wari@gmail.com mailto:him_lax3@yahoo.com mailto:madan.mx@gmail.com mailto:jprasad2003@gmail.com mailto:kamchem9@gmail.com http://www.eurjchem.com/ https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.10.4.281-294.1844&domain=pdf&date_stamp=2019-12-31� 282 Somagond et al. / European Journal of Chemistry 10 (4) (2019) 281-294 Table 1. Summary of the crystal structure, data collection, and crystallographic refinement data of TMQ. Parameter Values Empirical formula C19H15ClN4O2 Formula weight 366.80 Temperature (K) 296.15 Crystal system Monoclinic Space group P21/n a (Å) 7.3314(15) b (Å) 12.459(3) c (Å) 18.948(4) β (°) 98.322(9) Volume (Å3) 1712.5(6) Z 4 ρcalc(g/cm3) 1.423 μ(mm-1) 0.245 F(000) 760.0 Crystal size (mm3) 0.15 × 0.12 × 0.11 Radiation MoKα (λ = 0.71073) 2Θ range for data collection (°) 3.926 to 38.556 Index ranges -5 ≤ h ≤ 6, -11 ≤ k ≤ 10, -17 ≤ l ≤ 16 Reflections collected 5082 Independent reflections 1428 [Rint = 0.0545, Rsigma = 0.0574] Data/restraints/parameters 1428/0/236 Goodness-of-fit on F2 1.021 Final R indexes [I≥2σ (I)] R1 = 0.0423, wR2 = 0.1029 Final R indexes [all data] R1 = 0.0588, wR2 = 0.1145 Largest diff. peak/hole (e.Å-3) 0.23/-0.19 CCDC deposition number 1828103 The structural, spectroscopic and photophysical behavior of a molecule depends on function of its overall molecular structure and hence there is a scope in the synthesis of novel conjugate molecules by combining two different moieties together and studying their properties [17]. Also, the spectros- copic and structural behaviors of various molecules using both experimental and theoretical methods have fascinated the curiosity of researchers for many years. Density functional theory (DFT) has become a very useful tool for theoretical calculation in current years. The theoretical calculations using DFT have been utilized to study molecular properties such as structural, spectroscopic and photophysical properties [18- 21]. DFT is computationally less challenging than wave function as it also expresses small molecules more reliably than Hartree-Fock theory [22,23]. In the present work, a combined approach by X-ray crystallography (XRD) and DFT calculation was handled, which takes the benefit of both the reliability of the experi- mental technique and high interpretative influence of the theo- retical studies and the accuracy. The structural confirmation was done by XRD data. Since, X-ray diffraction study has become indispensable device in crystal chemistry as it assists in solving the molecular structure, magnitudes and directional characteristics. The exact results of molecular structure of compound TMQ will become important due to experimental facts which help in designing molecules for potential pharma- cological property. The theoretical structural predicttions have been carried out by using density functional theory. Ultraviolet (UV)-Visible spectra of TMQ in gaseous phase, ethanol, and acetonitrile are simulated using the Time-dependent density functional theory (TD-DFT). The HOMO and LUMO are analyzed to describe the electronic transition properties of the systems investigated. The theoretically predicted UV Visible spectra of TMQ are compared with the observed experimental results, and discussed. The HOMO and LUMO are also deter- mined by using cyclic voltammetry technique and these are in good agreement with the theoretical results. The general structural features and to predict the reactivity of a molecule, natural bond orbital (NBO) analysis has been carried out which provides important information regarding orbital interactions and electron density among them [24]. 2. Experimental 2.1. Synthesis 4-((2-Chloro-6-methoxyquinolin-3-yl)methyl)-2-phenyl- 2H-1,2,4-triazol-3(4H)-one was synthesized according to reported method [16]. TMQwas dissolved in DMSO and heated until the moisture is eliminated. The saturated solution was filtered through the Whatman filter paper into a clean and dry beaker and kept aside for slow evaporation for a period of 15 days at room temperature. Purple colored rectangular shaped crystals of TMQwere collected. Good diffraction quality single crystals were studied further for structural analysis. 2.2. X-ray crystallography A single crystal of dimensions 0.11 × 0.12 × 0.15 mm of TMQ was chosen for X-ray diffraction study. The X-ray intensity data were collected at a temperature of 293 K on a Rigaku Saturn724 diffractometer using graphite monochro- mated MoKα radiation. A complete data set was processed using CrystalClear [25]. The structure was solved by direct method and refined by full-matrix least squares method on F2 using SHELXS and SHELXL programs [26]. All the non- hydrogen atoms were revealed in the first difference Fourier map itself. All the hydrogen atoms were positioned geometrically and refined using a riding model. After ten cycles of refinement, the final difference Fourier map showed peaks of no chemical significance. The geometrical calculations were carried out using the program PLATON [27]. The molecular and packing diagrams were generated using the software MERCURY [28]. The details of the crystal structure and data refinement are given in Table 1. The ORTEP [28] of the molecule with thermal ellipsoids are drawn at 50% probability is shown in Figure 1. 2.3. Hirshfeld surface calculations Three-dimensional (3D) molecular Hirshfeld surfaces and the two-dimensional (2D) fingerprint plots represent a new way of visualizing and analysing intermolecular interactions in molecular crystals, and are basically different from conven- tional methods of crystal structure analysis. The molecular Hirshfeld surface [29] in the crystal of organic compounds is created by dividing space in the crystal into regions where the electron distribution as the sum of atoms for the molecule dominates the corresponding sum over the crystal. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.281-294.1844 Somagond et al. / European Journal of Chemistry 10 (4) (2019) 281-294 283 Figure 1. ORTEP of TMQ showing the atomic numbering system. Displacement ellipsoids are drawn with 50% probability. Hirshfeld surfaces and their related fingerprint plots are generated using the program Crystal Explorer 3.0 [30]. The crystallographic information file (.cif) is given as input to the Crystal Explorer program. The Hirshfeld surface is unique for a given crystal structure and for a set of spherical atomic electron densities. Each point on the Hirshfeld surface is specified with two distances: the distance from the Hirshfeld surface to the nearest nucleus inside the surface is diand to the nearest nucleus outside the surface is de. Then dnorm is the normalized contact distance which is defined in terms of di, deand the van der Waals radii (vdW) of the atoms. The electrostatic potential is mapped on Hirshfeld surface using STO-3G (Slater-type-orbitals simulated by 3 Gaussians) basis set at the Hartree-Fock theory over the range −0.069 au (red), through 0 (white) to 0.043 au (blue). Crystal geometries were used as input to the TONTO [31] integrated with Crystal Explorer. The acceptor atoms in these interactions are shown with negative electrostatic potentials (red regions) and donor atoms are shown with positive electrostatic potentials (blue regions) [32]. 2.4. UV absorption spectroscopy Absorption spectra of TMQ was recorded using UV-Vis, NIR (JASCO V-670, Japan) spectrophotometer at room temperature, keeping the concentrations of compound 1×10-5 M in ethanol and acetonitrile. 2.5. Cyclic voltammetry (CV) Cyclic voltammetry (CV) study of TMQ was carried out using an Electrochemicalanalyzer / Work station (model 600E series, USA) at room temperature. CV consists of three electrode system that is Ag/AgCl reference electrode (RE), platinum counter electrode (CE) and glassy carbon working electrode (WE). The CV measurements of TMQ (1×10-3 M concentration) were obtained at 0.1 M with tetrabutyl ammonium perchlorate as supporting electrolyte in dimethyl- sulphoxide (Acetonitrile) solvent with a scan rate 100 mV/s. 2.6. Density functional theory (DFT) calculations The DFT calculations were performed using Gaussian 09 software package [33]. The potential energy surface scan has been carried out with (Hartree-Fock) HF/6-31G level to place the molecule at local minima. The geometry at local minima has been assumed as starting point for the calculation by utilizing Becke’s three parameter hybrid model with the Lee- Yang-Parr correlation functional (B3LYP) method [34,35]. The geometry is optimized with 6-31++G(d,p) and 6-311++G(2d,p) basis sets for comparison with XRD data. The HOMO (EHOMO), LUMO (ELUMO) energy levels and energy gap (Eg) were calculated by TD-DFT in gas phase and in two different solvents using 6-311++G(2d,p) basis set. The NBO analysis was performed using NBO 3.1 program [36] as implemented in the Gaussian 09 package at the DFT/B3LYP level using 6- 311++G(2d,p) basis set.The molecular electrostatic potential surfaces (MEPs) and the Mulliken charge distributions of the title molecule were obtained from the population analysis calculations and visualized using Gauss View 5 [37]. 2.7. Molecular electrostatic potential The molecular electrostatic potential (MEP) surface was determined by DFT level in order to know the relative polarity of the molecule. MEP is formed by the nuclei and the electrons (treated as static distribution of charge) and is typically visualized through its values on the molecular electron density. MEP mapping is very helpful descriptor in under- standing sites for relative reactivity towards electrophilic and nucleophilic [38] attacks, in studies of biological identification as well as hydrogen bonding interactions [39,40]. The electrostatic potential V(r) has been mainly useful as sign of the regions or sites of a molecule to which an approaching electrophile is primarily attracted, and is also well matched for analyzing processes based on the “recognition” of one molecule by another, as in enzyme-substrate, drug-receptor, and interactions, since it is through their potentials that the two species initially “see” each other [41,42]. 3. Results and discussion 3.1. Description of the crystal structure The ORTEP of TMQ with thermal ellipsoids are drawn at 50% probability shown in Figure 1. The title molecule crystallizes in monoclinic crystal system (space group P21/n) with unit cell dimensions a = 7.3314(15) Å, b = 12.459(3) Å, c = 18.948(4) Å, β = 98.322(9)° and Z = 4. Crystallographic data, details of the data collections and structure refinement parameters of the compoundTMQ were determined. The resulted all bond lengths, bond angles and dihedral angles are in good agreement with the calculated values, and tabulated in Tables 2-4, respectively. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.281-294.1844 284 Somagond et al. / European Journal of Chemistry 10 (4) (2019) 281-294 Table 2. Experimental and calculated bond lengths (Å) for TMQ. Atoms Experimental Calculated (B3LYP/6-31 ++G(d,p)) Calculated (B3LYP/6-311 ++G(2d,p)) Cl1-Cl1 1.742(4) 1.778 1.778 O2-C19 1.420(5) 1.425 1.422 O2-C17 1.358(5) 1.361 1.358 N4-C11 1.294(5) 1.299 1.291 N4-C12 1.354(4) 1.363 1.359 O1-C7 1.215(4) 1.229 1.220 N1-N2 1.395(4) 1.387 1.385 N1-C7 1.374(5) 1.389 1.386 N1-C6 1.412(5) 1.422 1.418 N2-C8 1.275(4) 1.298 1.291 C17-C18 1.360(5) 1.383 1.376 C17-C16 1.403(5) 1.425 1.420 C18-C13 1.407(5) 1.422 1.416 C13-C14 1.401(5) 1.417 1.411 C13-C12 1.411(5) 1.427 1.421 C14-C10 1.358(5) 1.382 1.375 C10-C9 1.502(5) 1.515 1.511 C10-C11 1.410(5) 1.426 1.420 C9-N3 1.452(4) 1.463 1.460 N3-C7 1.372(4) 1.398 1.395 N3-C8 1.355(4) 1.372 1.367 C6-C5 1.367(5) 1.403 1.397 C6-C1 1.379(5) 1.402 1.396 C5-C4 1.379(5) 1.397 1.390 C4-C3 1.362(5) 1.396 1.389 C3-C2 1.361(5) 1.398 1.391 C12-C15 1.408(5) 1.422 1.416 C15-C16 1.354(5) 1.372 1.365 C2-C1 1.375(5) 1.394 1.388 Table 3. Experimental and calculated bond angles (°) for TMQ. Atoms Experimental Calculated (B3LYP/6-31 ++G(d,p)) Calculated (B3LYP/6-311 ++G(2d,p)) C17-O2-C19 116.8(3) 118.491 118.275 C11-N4-C12 117.5(4) 118.555 118.630 N2-N1-C6 119.1(4) 120.009 120.134 C7-N1-N2 111.3(3) 111.745 111.594 C7-N1-C6 129.4(4) 128.243 128.271 C8-N2-N1 104.0(3) 105.004 105.087 O2-C17-C18 125.6(4) 125.123 125.192 O2-C17-C16 114.4(4) 114.486 114.519 C18-C17-C16 119.9(4) 120.391 120.288 C17-C18-C13 119.9(4) 119.545 119.611 C18-C13-C12 120.3(4) 120.063 120.041 C14-C13-C18 122.3(4) 122.972 122.968 C14-C13-C12 117.4(4) 116.966 116.990 C10-C14-C13 120.8(4) 121.064 121.060 C14-C10-C9 120.5(4) 120.246 120.289 C14-C10-C11 116.3(4) 116.026 116.051 C11-C10-C9 123.2(4) 123.724 123.657 N3-C9-C10 113.6(3) 113.281 113.484 C7-N3-C9 123.0(4) 122.496 122.555 C8-N3-C9 129.2(4) 129.702 129.630 C8-N3-C7 107.8(4) 107.794 107.803 O1-C7-N1 128.6(4) 130.655 130.712 O1-C7-N3 128.1(4) 126.309 126.286 N3-C7-N1 103.4(4) 103.035 103.000 C5-C6-N1 120.6(4) 120.736 120.797 C5-C6-C1 120.1(4) 120.352 120.169 C1-C6-N1 119.3(4) 118.912 119.033 C6-C5-C4 119.2(4) 119.151 119.262 C3-C4-C5 120.6(4) 121.026 121.005 C2-C3-C4 120.3(4) 119.213 119.217 N4-C11-Cl1 115.4(4) 115.611 115.700 N4-C11-C10 126.0(4) 125.473 125.470 C10-C11-Cl1 118.6(4) 118.915 118.827 N4-C12-C13 122.1(4) 121.912 121.791 N4-C12-C15 119.9(4) 119.152 119.304 C15-C12-C13 118.0(4) 118.936 118.904 C16-C15-C12 120.6(4) 120.273 120.279 C15-C16-C17 121.1(4) 120.792 120.874 N2-C8-N3 113.5(4) 112.417 112.512 C3-C2-C1 119.9(4) 120.728 120.711 C2-C1-C6 120.0(4) 119.530 119.634 The Cg1: N1/N2/C8/N3/C7 makes dihedral angles of 78.1(2) and 77.54(18)° with Cg3:C1-C6 and Cg5:N4/C11/ C10/C14/C13/C18/C17/C16/C15/C12, respectively. The dihedral angle between Cg3 and Cg5 is 81.31(17)°. In the crystal structure (Table 5 and Figure 2), the intermolecular hydrogen bonds (C(8)-H(8)···O(1)) and intermolecular interaction of the type C(9)-H(9A)[1] → Cg(3) are observed and also intramolecular hydrogen bonds (Table 5) of the type C-H···N and C-H···O are viewed. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.281-294.1844 Somagond et al. / European Journal of Chemistry 10 (4) (2019) 281-294 285 Table 4. Experimental and calculated dihedral angles (°). Atoms Experimental Calculated (B3LYP/6-31 ++G(d,p)) Calculated (B3LYP/6-311 ++G(2d,p)) O2-C17-C18-C13 178.8(3) -179.74 -179.7641 N1-N2-C8-N3 0.7(4) -0.2628 -0.221 N2-N1-C6-C1 -4.5(5) 0.61318 0.8157 N2-N1-C6-C5 175.5(3) -179.27 -179.9411 N2-N1-C7-O1 178.6(4) -179.83 -179.9411 N2-N1-C7-N3 -1.1(4) 0.40339 0.3116 N3-C9-C10-C11 72.1(4) 93.382 93.1891 N3-C9-C10-C14 -108.8(4) -85.798 -86.4007 N4-C12-C13-C14 -1.1(5) -0.3902 -0.4741 N4-C12-C13-C18 -179.9(3) 179.709 179.6304 N4-C12-C15-C16 178.7(3) -179.762 -179.7144 C1-C2-C3-C4 0.4(7) -0.00438 0.0114 C2-C1-C6-N1 -179.6(3) -179.933 -179.9218 C2-C1-C6-C5 0.4(6) -0.04305 0.0238 C2-C3-C4-C5 0.0(7) 0.00853 0.0119 C3-C4-C5-C6 -0.2(6) -0.02968 -0.0169 C4-C5-C6-N1 -180.0(3) 179.935 179.9436 C4-C5-C6-C1 0.0(6) 0.04691 -0.0011 C6-N1-N2-C8 -175.8(3) 179.782 179.8188 C6-N1-C7-O1 -5.9(6) 0.29240 0.1822 C6-N1-C7-N3 174.5(3) -179.471 -179.5652 C6-C1-C2-C3 -0.6(6) 0.02160 -0.0291 C7-N1-N2-C8 0.2(4) -0.1035 -0.0694 C7-N1-C6-C1 -179.7(4) -179.521 -179.3168 C7-N1-C6-C5 0.3(5) 0.5886 0.738 C7-N3-C8-N2 -1.4(5) 0.5289 0.4277 C7-N3-C9-C10 62.9(4) 87.4729 87.0644 C8-N3-C7-O1 -178.2(4) 179.684 179.8111 C8-N3-C7-N1 1.4(4) -0.5383 -0.4265 C8-N3-C9-C10 -117.4(4) -91.375 -92.2879 C9-N3-C7-O1 1.5(6) 0.6145 0.3349 C9-N3-C7-N1 -178.8(3) -179.607 -179.9026 C9-N3-C8-N2 178.8(3) 179.508 179.8543 C9-C10-C11-Cl1 -1.9(5) 0.62079 0.1931 C9-C10-C11-N4 177.4(4) 179.757 179.8796 C9-C10-C14-C13 -178.2(3) 179.259 179.5551 C11-N4-C12-C13 0.4(5) -0.08046 -0.0464 C11-N4-C12-C15 -179.3(3) 179.878 179.9016 C11-C10-C14-C13 1.0(5) 0.01812 -0.0649 C12-N4-C11-Cl1 -179.6(3) -179.792 -179.7365 C12-N4-C11-C10 1.1(6) 0.57460 0.5683 C12-C13-C14-C10 0.3(5) 0.40370 0.5128 C12-C13-C18-C17 0.8(5) 0.07475 0.1291 C12-C15-C16-C17 1.7(6) 0.0285 0.0353 C13-C12-C15-C16 -1.1(5) 0.1977 0.235 C14-C10-C11-Cl1 178.9(3) 179.833 179.7988 C14-C10-C11-N4 -1.8(6) -0.545 -0.5147 C14-C13-C18-C17 -177.9(3) -179.819 -179.7598 C15-C12-C13-C14 178.6(3) 179.650 179.5777 C15-C12-C13-C18 -0.2(5) -0.250 -0.3177 C15-C16-C17-O2 179.8(3) 179.702 179.6871 C15-C16-C17-C18 -1.1(6) -0.2094 -0.2302 C16-C17-C18-C13 -0.1(5) 0.15403 0.1437 C18-C13-C14-C10 179.1(3) -179.698 -179.595 C19-O2-C17-C16 -172.1(3) -179.189 -179.1433 C19-O2-C17-C18 8.9(5) 0.71771 0.7693 Table 5. Intermolecular and Intramolecular interactions of TMQ. D−H···A/Cg D−H H···A/Cg D···A D−H···A Symmetry C(1)-H(1)···N(2) 0.93 2.43 2.767(6) 102 C(5)-H(5)···O(1) 0.93 2.30 2.934(5) 125 C(8)-H(8)···O(1) 0.93 2.27 3.180(5) 167 1/2-x, 1/2+y, 1/2-z C(9)-H(9A)[1] → Cg(3) 2.68 3.499(4) 143 1+x, y, z 3.2. Hirshfeld surface calculations Hirshfeld surface analysis is a graphical tool for visualization and was carried out to comprehend relative contributions of various molecular contacts to intermolecular interactions in TMQ [43]. The Hirshfeld surface is a drawing of shape engaged by a molecule in the crystal structure and can be constructed from the electron division [44,45]. The 2D (two-dimensional) fingerprint plots [46,47] obtained by Hirshfeld surface analysis can classify each type of inter- molecular interactions, and their relative input can be obtained from the area of the surfaces. The 2D fingerprint plots are constructed based on de and di distances scales, displayed on the graph axes, in which the de represents the distance between the Hirshfeld surface and the nearest atomoutside, while the di represents the distance between this surface and the nearest atominside. The crystal structure packing of the C19H15N4ClO2compound was generated and quantified with Hirshfeld surface analysis and the associated 2D-fingerprint plots using Crystal Explorer package [48] which accepts a crystal structure input file in CIF format. The 2D fingerprint plot for all the intermolecular interact- tions are shown in Figure 3. The H···H interactions which show the most significant contribution of 34.6% to the total Hirshfeld surfaces are reflected in the middle of scattered points in the 2D fingerprint plot. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.281-294.1844 286 Somagond et al. / European Journal of Chemistry 10 (4) (2019) 281-294 Table 6. Percentage of various intermolecular contacts contributing to Hirshfeld surface. Intercontacts Contribution (%) Intercontacts Contribution (%) H···H 34.6 C···C 06.0 C···H/H···C 20.0 C···Cl/Cl···C 01.0 N···H/H···N 12.8 C···N/N···C 02.7 O···H/H···O 11.1 C···O/O···C 00.5 Cl···H/H···Cl 10.5 Cl···O/O···Cl 00.8 (a) (b) (c) Figure 2. Packing of the molecules viewed along the a-(a), b-(b) and c-axis (c). The C···H interactions appear as two wings and show a contribution of 20%. The N···H interaction is identified by sharp peaks which comprises 12.8% of the total Hirshfeld surface. The O···H intermolecular contact has covered 11.1% of total Hirshfeld surface area of the molecule apart from that, there aresmaller contributions of Cl…H (10.5%), C···C (6.0%), C···Cl (1.0%), C···N (2.7%), C···O (0.5%), and Cl···O (0.8%) (Table 6). Hence, Hirshfeld surface analysis and fingerprint plots illustrate that the crystal lattice is stabilized by four major interactions H···H, C···H, N···H, and O···H. In the dnorm surface intermolecular contacts relative to the van der Waals radii are represented by method of red-white- blue color scheme where red regions denote shorter contacts with a negative dnorm value (higher electron density regions), white regions indicate the distance of contacts exactly comparable to the Van der Waals separation with zero dnorm value and blue regions represent longer contacts with a positive dnorm value (lower electron density regions) [49]. The large circular deep red colored depressions visible on dnorm surfaces indicate hydrogen bonding contacts such asC-H···O and additional spots are due to H-H contacts. The intermolecular interactions are also revealed from the views of electro-static potential mapped over Hirshfeld surface, shown in Figure 4. The acceptor and donor atoms participating in these interactions are shown with respective negative (red regions) and positive electrostatic potentials (blue regions). 3.3. DFT Calculations The potential energy surface (PES) scan has been carried out on dihedral angles C1-C3-C12-H14, C30-N35-C12-H14 at HF/6- 31G level to examine all possible conformations of the title compound. The PES scan was done by minimizing the potential energy in all geometrical parameters by changing the dihedral angle for 360° rotation for both dihedral angles at steps of every 20°. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.281-294.1844 Somagond et al. / European Journal of Chemistry 10 (4) (2019) 281-294 287 Figure 3. 2D Finger print plots of TMQ. Figure 4. dnorm mapped over the Hirshfeld surface with color scale in the range -0.21 au (red) to 1.2 au (blue), green dotted lines show C-H···O intermolecular interaction. The acceptor and donor atoms are shown with respective negative (red) and positive electrostatic potentials (blue). The geometry of molecule at local minima is selected on the basis of results obtained in PES scan study. The geometry at local minima has been assumed as starting point for the optimization calculation by utilizing Becke’s three parameter hybrid model with the Lee-Yang-Parr correlation functional (B3LYP) method. The geometrical parameters (bond lengths, bond angles and dihedral angles) obtained by B3LYP/6- 31++G(d,p) and B3LYP/6-31++G(2d,p) methods are compared with experimental results and were found to be reasonably in good agreement with each other (Tables 1-3). Eventually the theoretical and experimental values differ slightly, as the experimental values of molecule have been recorded in solid phase while theoretical values were computed in gas phase. The optimized structure (Figure 5) from theoretical calculation (DFT) is superimposed with the molecular skeleton from XRD, giving a molecular overlay RMSD value of 0.09 Å (Figure 6). From the obtained results, it is concluded that the B3LYP calculations very well reproduced the geometry of TMQ. 3.4. Molecular electrostatic potential (MEP) The MEP plot of TMQ (Figure 5) provides a visual image of the chemically active sites and comparative reactivity of atoms. The negative electrostatic potential (red) regions are mainly localized of C=O and C=N group and are promising sites for electrophilic attack. The positive regions (blue) are localized on all the rings, representing possible sites for nucleophilic attack. 3.5. Frontier molecular orbitals The frontier molecular orbital, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) are key factors for quantum chemistry and the way of the molecule interacts with other species may be analyzed by knowing the HOMO and LUMO energy values. For organic derivatives, the HOMO-LUMO gap is very important because they relate to specific movements of electrons and may be most significant for single electron transfer. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.281-294.1844 288 Somagond et al. / European Journal of Chemistry 10 (4) (2019) 281-294 Figure 5. The optimized geometry andMEP plot of TMQ. Figure 6. Superimposition diagram TMQ, experimental (Yellow stick model) and theoretical (Green stick model). Figure 7. The molecular orbitals and energies for the HOMO and LUMO of TMQ. The value of HOMO, LUMO and HOMO-LUMO energy gap for the TMQ was calculated by DFT/B3LYP method with 6- 311++G(2d,p) basis set. The electron density plots of the HOMO and LUMO for the title molecule is presented in Figure 7. As can be seen from Figure 7 of TMQ, the HOMO is delocalized over the triazole and phenyl ring and LUMO localized over quinoline moiety.The energy values of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of TMQ are about -6.164 and -2.086 eV, respectively. In the present study, calculated (Eg = EHOMO-ELUMO) energy gap is found to be 4.078 eVwhich shows that there is a transfer of electrons from HOMO to LUMO. Accordingly, the HOMO–LUMO transition implied an electron density transfer from the triazole to quinoline. 3.6. Electronic absorption spectra Figure 8 showed the experimental absorption spectra of the compound TMQ. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.281-294.1844 Somagond et al. / European Journal of Chemistry 10 (4) (2019) 281-294 289 Table 7. Experimental and calculated absorption wavelength λ (nm), excitation energies E (eV), and oscillator strengths (f) of TMQ calculated by the B3LYP method using 6-311++G(2d,p)basis set. Experimental method TD-DFT B3LYP/6-311++G (2d,p) Ethanol Acetonitrile Gas Ethanol Acetonitrile λ (nm) Abs. λ (nm) Abs. λ (nm) E (eV) f λ (nm) E (eV) f λ (nm) E (eV) f 241 252 343.11 3.6135 0.0026 325.60 3.8079 0.0193 326.87 3.7931 0.0273 327 336 318.73 3.8900 0.0676 322.65 3.8427 0.0731 324.43 3.8216 0.0639 280.85 4.4146 0.0156 282.94 4.3820 0.0193 284.24 4.3619 0.0196 272.70 4.5465 0.0046 264.69 4.6842 0.0194 265.91 4.6626 0.0175 271.24 4.5710 0.0252 261.90 4.7340 0.2104 262.92 4.7156 0.2116 268.52 4.6173 0.0004 257.35 4.8178 0.1212 258.39 4.7983 0.0977 HOMO -6.3820 -6.3571 -6.1443 LUMO -2.1075 -2.0686 -2.0530 Energy gap 4.2745 4.2885 4.0913 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 200 250 300 350 400 Ab so rb an ce (a .u .) Wavelength (nm) (a) 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 200 250 300 350 400 Ab so rb an ce (a .u .) Wavelength (nm) (b) Figure 8. Experimental electronic absorption spectra of TMQ (1×10-5 M) in ethanol (a) and acetonitrile (b) at room temperature. From Figure 8 maximum absorption wavelength bands were observed at 241, 327 nm in ethanol and 252, 336 nm in acetonitrile for the compound TMQ. 3.6.1. The theoretical electronic absorption spectrum of TMQ In the UV absorption region, six absorptions at 343.11 nm (λ1), 318.73 nm (λ2), 280.85 nm (λ3) 272.70 nm (λ4), 271.24 nm (λ5), and 268.52 nm (λ6) were observed for the gas phase (Table 7). The oscillator strength (f) values corresponding to six wavelengths were 0.0026, 0.0676, 0.0156, 0.0046, 0.0252, 0.0004 oscillator strength value. In the ethanol environment, TMQ exhibited the following six wavelengths at 325.60, nm (λ1), 322.65 nm (λ2), 282.94 nm (λ3), 264.69, nm (λ4), 261.90 nm (λ5), and 257.35 nm (λ6), and the parallel oscillator strength (f) values were observed to be 0.0193, 0.0731, 0.0193, 0.0194, 0.2104, 0.1212, respectively. Acetonitrile environment of TMQ was absorbed at 326.87 nm (λ1), 324.43 nm (λ2), 284.24 nm (λ3), 265.91 nm (λ4), 262.92 nm (λ5), and 258.39 nm (λ6), and the equivalent oscillator strength (f) values were observed to be 0.0273, 0.0639, 0.0196, 0.0175, 0.2116, 0.0977. 3.7. Cyclic voltammetry (CV) In order to investigate the electrochemical properties (HOMO and LUMO) of TMQ, cyclic voltammetry (CV) measure- ments were carried out. Figure 9 shows cyclic voltammogram of TMQ. HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) energy levels were calculated by using the Equations (2) and (3), respectively [50- 52] and given in Table 8. Eg= 1240/λ (1) HOMO = -[4.44+EOXonset] (eV) (2) LUMO = [HOMO + EOpt] (eV) (3) where, EOXonset and EOpt are onset oxidation potential and optical band gap respectively. The HOMO energy levels of TMQwas determined and found to be in the range -5.052 eV (v/s. Ag/AgCl). 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.281-294.1844 290 Somagond et al. / European Journal of Chemistry 10 (4) (2019) 281-294 Table 8. Optical and electrochemical properties of TMQ. Compound EOpt/λOnset(eV/nm) EOXonset (V) HOMO (eV) (Expt.) LUMO (eV) (Expt.) TMQ 3.512/(353) 0.612 -5.052 -1.54 Figure 9. Cyclic voltammogram of TMQ in acetonitrile in the presence of tetrabutylammoniumhexafluorophosphate (Supporting electrolyte) at a scan rate of 100 mV/s. From Tables 7 and 8, it was observed that the band gaps, HOMO and LUMO values obtained experimentally are approximately in close agreement with values obtained using DFT. 3.8. Mulliken atomic charges and natural charges The calculation of atomic charges plays a vital role in the application of quantum mechanical calculations to molecular systems. Mulliken charges are evaluated by determining the electron population analysis of each atom as defined in the basic functions. The charge distributions calculated by the Mulliken [53] and NBO methods for the equilibrium geometry of TMQ are given in Table 7. Atomic charges particularly that of reactive ones are very important in defining the reactive nature of molecules under study [54]. This analysis was performed at DFT/B3LYP using two methods 6-31++G (d,p) and 6-311G++(2d,p) basis set. All the hydrogen atoms have positive charges, an acceptor atom for the studied molecule. The distribution of charge on the molecule has an important influence on the vibrational spectra.Mulliken atomic charge of the carbon atoms in the neighbourhood of C22, C23 and C36 become more positive, due to surrounded by more electronegative atoms and shows that the natural atomic charges are more sensitive to the changes in the molecular structure than Mulliken’s net charges [55]. C14, Cl1, N5, C17 were changed from negative to positive, due to the effect of Cl atom. Besides, C30, C31, C34 positive to negative most possibly due to electro negativity contribution from halogen (Table 9) [54]. Mulliken charges obtained by different basis sets have been compared and represented in Table 9 in order to examine the sensitivity of the calculated charges to alter in the selection of the basis set. It is interesting to note that change in the charge distribution value is observed with two different basis sets. These natural charge calculations showed the electronegative nature of the O, N and Cl atoms. The carbon (C22) of the triazole C=O group possess the highest positive value of 0.79993 e (6-31++G(d,p)) and 0.78821e (6-311G++ (2d,p)) resulting from its bonding to one electronegative oxygen atom. Of the N-atoms of the triazole ring, the first N- atom has the least negative charge of -0.29196. In addition, all carbon atoms are negatively charged except those attached to the strong electronegative N, O and Cl atom. The oxygen atom attached to aromatic ring (O2) has the lesser negative value - 0.53951 e / -0.52973 compared with the O4 (-0.66976 e) [6- 31++G (d,p)] / O4 (-0.66559 e) [6-311G++ (2d,p)] attached with the triazole ring. The electropositive nature of all the hydrogen atoms was observed. The nitrogen atom (N3) present in the quinoline ring system possesses more electronegative value -0.45714 and -0.43291. 3.9. NBO analysis Natural bond orbital (NBO) analysis provides the most precise possible ‘natural Lewis structure’ by utilizing details of all orbital that are mathematically chosen to consist of the highest probable percentage of the electron density (ED). NBO analysis helps us to understand the delocalization of electron density from ‘Lewis occupied donor’ NBOs to properly unoccupied ‘non-Lewis acceptor’ NBOs in the molecule. To explore the intra and inter-molecular interactions, the stabilization energies TMQ were calculated by using second- order perturbation theory. For each donor NBO (i) and acceptor NBO (j), the stabilization energy E(2) associated with electron delocalization between donor and acceptor is calculated as [56]. ( ) ( )2 2 ij i j i F i, j E E q e e =∆ = − (4) Where, qi → donor orbital occupancy, Ei, Ej → diagonal elements (orbital energies) and F(i,j) → the off-diagonal NBO Fock matrix element. The complete NBO analysis and second order Fock matrix perturbation theory analysis was carried for the title molecule under study using B3LYP/6-311++G(2d,p) level of theory. In NBO analysis, the greater the E(2) (stabilization energy) value, the more exhaustive is the interacttion between electron-donors and electron-acceptors i.e. the more donating tendency from electron donors to electron acceptors, and greater the extent of conjugation of the whole system. The stabilization energies [E(2)] of the donor- acceptor interactions with more than 5 kcal/mol determined by second order perturbation analysis of Fock matrix of TMQ is reported in the Table 10. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.281-294.1844 Somagond et al. / European Journal of Chemistry 10 (4) (2019) 281-294 291 Table 9. Mulliken and natural charges for TMQ. Atoms Atomic charges(Mulliken) 6-31++G(d, p) Natural charges 6-31++G(d, p) Atomic charges (Mulliken) 6-311++G(2d, p) Natural charges 6-311++G(2d, p) Cl1 0.026991 -0.02079 -0.063774 -0.01987 O2 -0.33771 -0.52973 -0.436535 -0.53951 N3 -0.0695 -0.43291 -0.200568 -0.45714 O4 -0.52227 -0.66559 -0.48729 -0.66976 N5 0.30345 -0.28286 0.118766 -0.29196 N6 -0.37689 -0.29664 -0.376311 -0.3006 C7 -0.201 -0.29866 -0.253533 -0.20103 H8 0.165256 0.20343 0.141882 0.171 H9 0.160746 0.22838 0.173438 0.19262 H10 0.167261 0.20492 0.145156 0.17253 C11 -0.34359 0.31909 0.060499 0.33368 C12 -0.21804 -0.28958 -0.371064 -0.2701 H13 0.09385 0.24587 0.166663 0.21371 C14 0.154984 -0.08152 0.535227 -0.08708 C15 0.300682 -0.14415 -0.222587 -0.0684 H16 0.18063 0.2638 0.235302 0.22128 C17 1.282312 -0.11966 0.939888 -0.12958 C18 -0.71334 -0.25643 -0.714541 -0.18742 H19 0.207724 0.27264 0.209468 0.23384 H20 0.198725 0.26297 0.199435 0.22845 N21 -0.32406 -0.47188 -0.032455 -0.47685 C22 -0.03983 0.78821 0.081885 0.79993 C23 -0.56993 0.14635 0.224346 0.15378 C24 0.34095 -0.25375 -0.131644 -0.2239 H25 0.198003 0.27427 0.213608 0.24405 C26 -0.37709 -0.22412 -0.203351 -0.18635 H27 0.118074 0.24002 0.133359 0.20402 C28 -0.23963 -0.24903 -0.366897 -0.21583 H29 0.105848 0.23851 0.121031 0.20374 C30 -0.17956 0.21024 -0.258584 0.22792 C31 -0.62352 0.15616 -0.09016 0.16325 C32 -0.34019 -0.20288 -0.263201 -0.16782 H33 0.15829 0.25759 0.154558 0.22198 C34 0.208713 -0.24031 0.074353 -0.20578 H35 0.147777 0.25651 0.157561 0.221 C36 0.322857 0.21428 0.125576 0.24812 H37 0.176487 0.24649 0.183568 0.21291 C38 0.073646 -0.2246 -0.085895 -0.18702 H39 0.121259 0.24003 0.134879 0.20421 C40 0.088516 -0.24848 -0.162534 -0.21785 H41 0.173131 0.26405 0.190477 0.23191 The orbital energy decreases due to the interaction between the doubly occupied orbitals and the unoccupied orbital, which is a suitable way to interpret the molecular structure in the electronic point of view. Several other types of parameters, such as hybridization, directionality and partial charges, can also be analysed from NBO tool. The possible intensive interaction among the whole system in title compound, there is an intermolecular hyper- conjugative interaction of N3-C30 from Cl1 of n(Cl1) → π*(N3- C30) which increases the electron density (0.36900 e) and weakens the respective bonds N3-C30 leading to stabilization of 14.45 kJ/mol. Also, there occurs predominant intermole- cular hyper-conjugative interaction of C11-C12 from O2 of π(O2) → π*(C11-C12) which increases the electron density (0.32263 e) that weakens the respective bonds C11-C12 leading to stabilization of 32.71 kJ/mol. There occurs an intermolecular hyper-conjugative interaction of C17-C30 with the electron density (0.04824 e) from N3 of σ(N3) → σ*(C17- C30) results in to weakening the respective bonds C17-C30 and leads to stabilization of 11.76 kJ/mol. These probable observed interactions occur as an increase in electron density in the C-C anti-bonding orbital that weakens the respective bonds. In addition another kind of hyper-conjugative interaction of N5-C22 from O4 of π(O4) → σ*(N5–C22) which increases the electron density (0.09490e) that weakens the respective bonds N5-C22 leading to stabilization of 26.76 kJ/mol and a hyper-conjugative interaction of O4-C22 with stabilization energy of 29.65 kJ/mol occurs from N5 of σ(N5) → σ*(O4-C22) which increases the electron density (0.34442 e) that weakens the respective bonds O4-C22. Moreover, there is also intermolecular hyper-conjugative interaction of N5-C22 from N6 of σ(N6) → σ*(N5-C22) which increases the electron density (0.09490 e) that weakens the respective bonds N5– C22 leading to stabilization of 3.5 kJ/mol. Also, there occurs an intermolecular hyper-conjugative interaction of O4-C22 from σ(N21) → σ*(O4-C22) which increases the electron density (0.34442 e) that weakens the respective bonds O4-C22 leading to stabilization of 26.6 kJ/mol. The successful approach of second-order perturbation theory to predict the hyper- conjugative interaction energy is adopted. Electron density delocalization between the occupied Lewis type (bond or lone pair) NBO orbital and formally unoccupied (anti bond or Rydberg) non-Lewis NBO orbital corresponds to a stabilizing donor-acceptor interaction. The NBO analysis also describes the bonding in terms of the natural hybrid orbital which occupy a higher energy orbital n3Cl1 (-0.33084 a.u.) with considerable p-character (100.0%) and low occupation number (1.92327) and the other n1(Cl1) occupy a lower energy orbital (-0.93632 a.u.) with p- character (16.83%) and high occupation number (1.99365). The NBO analysis also describes the bonding in terms of the natural hybrid orbital n2(O2), which occupy a higher energy orbital (-0.33302 a.u.) with considerable p-character (100.0%) and high occupation number (1.83506). The NBO analysis also describes the bonding in terms of the natural hybrid orbital n2(O4), which occupy a higher energy orbital (-0.26529 a.u.) with considerable p-character (100.0%) and high occupation number (1.83581). n1N5 which occupy a higher energy orbital (-0.28207 a.u.) with considerable p-character (100.0%) and high occupation number (1.60231). n1N21 which occupy a higher energy orbital (-0.28672 a.u.) 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.281-294.1844 292 Somagond et al. / European Journal of Chemistry 10 (4) (2019) 281-294 Table 10. Second order perturbation theory analysis of Fock matrix in NBO basis corresponding to the intra-molecular bonds of TMQusing B3LYP/6-311++G (2d,p) basis set. Donor (i) Type of bond orbital ED/e Occupancy Acceptor (j) Type of bond orbital ED/e Occupancy Energy E(2) kcal/mol E(i)-E(j)a.u. Energy difference F(i,j)a.u. Polarized energy N3-C30 σ 1.98627 N3-C31 σ* 0.02423 1.85 1.40 0.046 N3-C30 π 1.81489 C17-C30 σ* 0.04824 2.93 0.96 0.049 O4-C22 σ 1.98927 N5-C22 σ* 0.09490 0.99 0.96 0.028 O4-C22 π 1.98837 N5-N6 σ* 0.02298 0.93 1.21 0.030 N5-N6 σ 1.97933 N5-C23 σ* 0.03683 0.93 1.22 0.030 N5-C22 σ 1.98479 O4-C22 σ* 0.34442 0.68 0.97 0.025 N6-C36 σ 1.98244 N5-C23 σ* 0.03683 3.77 1.28 0.062 C11-C12 σ 1.97760 O2-C7 σ* 0.00935 1.77 0.86 0.035 C11-C12 π 1.73203 C14-C15 σ* 0.02000 0.58 0.51 0.016 C11-C34 σ 1.97116 O2-C7 σ* 0.00935 4.14 0.81 0.052 C14-C15 σ 1.96937 C11-C12 σ* 0.02684 1.74 1.29 0.042 C15-C17 π 1.71676 N3-C30 π * 0.36900 25.19 0.26 0.074 C17-C18 σ 1.97460 N3-C30 σ* 0.02398 2.98 1.24 0.054 C17-C30 σ 1.97742 N3-C30 σ* 0.02398 3.06 1.31 0.057 N21-C36 σ 1.98581 O4-C22 σ* 0.34442 1.38 0.98 0.036 C23-C24 σ 1.97099 N5-N6 σ* 0.02298 6.18 1.02 0.071 C23-C40 σ 1.97250 N5-N6 σ* 0.02298 1.42 1.02 0.034 C31-C32 σ 1.97425 N3-C30 σ* 0.02398 2.65 1.27 0.052 C32-C34 π 1.75559 C11-C12 π * 0.32263 18.81 0.28 0.067 C38-C40 σ 1.97611 N5-C23 σ* 0.03683 4.14 1.08 0.060 C38-C40 π 1.67977 C26-C28 π * 0.33949 18.74 0.29 0.066 LP Cl1 σ 1.99365 N3-C30 σ* 0.02398 0.62 1.51 0.027 LP O2 σ 1.96453 C11-C12 σ* 0.02684 6.99 1.15 0.080 LP N3 σ 1.89208 C17-C30 σ* 0.04824 11.76 0.83 0.090 LP O4 σ 1.97846 N5-C22 σ* 0.09490 2.37 1.10 0.046 LP N5 σ 1.60231 O4-C22 σ* 0.34442 29.65 0.42 0.101 LP N6 σ 1.94352 N5-N6 σ* 0.02298 0.94 0.71 0.023 LP N21 σ 1.61253 O4-C22 σ* 0.34442 26.60 0.42 0.096 Table 11. NBO results showing the formation of Lewis and non-Lewis orbitals. Donor(i) ED/e EDA% EDB% NBO S% P% σN3-C30 1.98627 59.54 40.46 0.7716(sp1.57)N+ 38.84 60.84 πN3-C30 1.81489 56.34 43.66 0.7506 (sp1.00)N+ 0.00 100.0 σO4-C22 1.98927 70.36 29.64 0.8388 (sp8.84)O+ 10.12 89.49 πO4-C22 1.98837 65.61 34.39 0.8100 (sp2.43)O+ 29.02 70.50 σN5-N6 1.97933 55.18 44.82 0.7428 (sp2.66)N+ 27.30 72.59 σN5-C22 1.98479 63.20 36.80 0.7950 (sp1.94)N+ 33.92 65.96 σN6-C36 1.98244 58.86 41.14 0.7672 (sp1.61)N+ 38.08 61.44 σC11-C12 1.97760 50.16 49.84 0.7082 (sp1.54)C+ 39.35 60.59 π C11-C12 1.73203 45.93 54.07 0.6777 (sp1.00)C+ 0.00 100.0 σC11-C34 1.97116 50.72 49.28 0.7122 (sp1.80)C+ 35.64 64.29 σC14-C15 1.96937 51.49 48.51 0.7176 (sp2.00)C+ 33.30 66.63 πC15-C17 1.71676 45.60 54.40 0.6752 (sp1.00)C+ 0.00 100.0 σC17-C18 1.97460 50.77 49.23 0.7125 (sp2.15)C+ 31.72 68.22 σC17-C30 1.97742 50.77 49.23 0.7125 (sp2.04)C+ 32.89 67.03 σN21-C36 1.98581 63.53 36.47 0.7970 (sp1.96)N+ 33.74 66.14 σC23-C24 1.97099 51.62 48.38 0.7184 (sp1.68)C+ 37.33 62.62 σC23-C40 1.97250 51.52 48.48 0.7178 (sp1.71)C+ 36.94 63.00 σC31-C32 1.97425 51.17 48.83 0.7154 (sp1.87)C+ 34.88 65.06 πC32-C34 1.75559 49.06 50.94 0.7004 (sp1.00)C+ 0.00 100.00 σC38-C40 1.97611 49.51 50.49 0.7036 (sp1.81)C+ 35.59 64.29 πC38-C40 1.67977 49.25 50.75 0.7018 (sp1.00)C+ 0.00 100.0 n1Cl1 1.99365 - - sp0.20 83.16 16.83 n2Cl1 1.96696 - - sp1.00 0.52 99.47 n3Cl1 1.92327 - - sp1.00 0.00 100.00 n1O2 1.96453 - - sp1.65 37.66 62.20 n2O2 1.83506 - - sp1.00 0.00 100.0 n1N3 1.89208 - - sp2.77 26.40 73.25 n1O4 1.97846 - - sp0.64 60.80 39.11 n2O4 1.83581 - - sp1.00 0.00 100.00 n1N5 1.60231 - - sp1.00 0.00 100.00 n1N6 1.94352 - - sp1.45 40.70 59.07 n1N21 1.61253 - - sp1.00 0.00 100.00 with considerable p-character (100.0%) and high occupation number (1.61253). Thus, a very close to pure p-type lone pair orbital participates in the electron donation to the n(Cl1) → π*(N3-C30), π(O2) → π*(C11-C12), σ(N3) → σ*(C17-C30), π(O4) → σ*(N5-C22), σ (N5) → σ*(O4-C22), σ(N6) → σ*(N5- C22), σ(N21) → σ*(O4-C22) interactions in the compound. The results are displayed in Table 11. 4. Conclusions In the present study, the single crystal X-Ray and DFT analysis of TMQ is reported. It is interesting to note that the optimized geometrical (DFT) results are found in good conformity with the obtained single X-ray diffraction results (XRD). MEP predicts the most reactive component in the molecule. The Hirshfeld surfaces and fingerprint plots predict- ted that TMQ molecule is stabilized by various intermolecular contacts such as H···H, C···C, C···H/ H···C, N···H/H···N, O···H/H···O, Cl···H/H···Cl, C···Cl/Cl···C, C···N/N···C, C···O/O···C, and Cl···O/O···Cl interactions. A complete molecular picture, stability of the molecule arising from hyper-conjugative interaction, charge delocalization and bond length have been investigated by using Natural Bond Orbital (NBO) analysis. Both experimental and theoretical HOMO and LUMO energies 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.281-294.1844 Somagond et al. / European Journal of Chemistry 10 (4) (2019) 281-294 293 determine the charge transfer within the molecule and the difference between HOMO and LUMO energy has supported the chemical and bioactivity properties of TMQ. Mulliken atomic charge of the carbon atoms in the neighborhood of C22, C23 and C36 become more positive indicating the direction of delocalization and also showed that the natural atomic charges are more sensitive to the changes in the molecular structure than Mulliken’s net charges. Acknowledgements Authors wish to thank the University Grants commission, New Delhi for providing financial assistants under UGC UPE FAR-I “Antitumor activity: An Integrated Approach” vide F. No. 14-3/2012 (NS/PE). The authors are grateful to University Scientific Instrumentation Centre (USIC), Karnataka University, Dharwad, for single X-ray diffractometer. Authors thank DST-PURSE Lab for single crystal X-ray diffractometer and other facilities, Karnatak Univeristy Dharwad and Mangalore University, Mangalore. Dr. Shilpa M. Somagond acknowledges the UGC, New Delhi for providing fellowship under project UPE FAR-I Program. Supporting information CCDC-1828103 contains the supplementary crystallo- graphic data for this paper. These data can be obtained free of charge via https://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: Sample of the compound is available from the author. Funding UGC UPE FAR-I “Antitumor activity: An Integrated Approach” vide F. No. 14-3/2012 (NS/PE), University Grants commission (UGC), New Delhi, India. ORCID Shilpa Mallappa Somagond http://orcid.org/0000-0002-0481-3426 ManjunathNingappa Wari http://orcid.org/0000-0003-0342-1284 Saba Kauser Jaweed Shaikh http://orcid.org/0000-0001-8839-9498 Sanjeev Ramchandra Inamdar http://orcid.org/0000-0003-3398-4897 Madan Kumar Shankar http://orcid.org/0000-0002-7944-1081 Dasappa Jagadeesh Prasad http://orcid.org/0000-0003-1333-028X Ravindra Ramappa Kamble http://orcid.org/0000-0002-0384-655X References [1]. Rastelli, E. J.; Truong, N. T.; Coltart, D. M. Org. Lett. 2016, 18, 5588- 5591. [2]. 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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.10.4.281-294.1844 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. Synthesis 2.2. X-ray crystallography 2.3. Hirshfeld surface calculations 2.4. UV absorption spectroscopy 2.5. Cyclic voltammetry (CV) 2.6. Density functional theory (DFT) calculations 2.7. Molecular electrostatic potential 3. Results and discussion 3.1. Description of the crystal structure 3.2. Hirshfeld surface calculations 3.3. DFT Calculations 3.4. Molecular electrostatic potential (MEP) 3.5. Frontier molecular orbitals 3.6. Electronic absorption spectra 3.6.1. The theoretical electronic absorption spectrum of TMQ 3.7. Cyclic voltammetry (CV) 3.8. Mulliken atomic charges and natural charges 3.9. NBO analysis 4. Conclusions Acknowledgements Supporting information Disclosure statement Funding ORCID References PrintField10: PrintField11: PrintField12: PrintField13: PrintField14: PrintField15: PrintField16: PrintField17: PrintField18: PrintField19: PrintField110: PrintField111: PrintField112: PrintField113: PrintField20: PrintField21: PrintField22: PrintField23: PrintField24: PrintField25: PrintField26: PrintField27: PrintField28: PrintField29: PrintField210: PrintField211: PrintField212: PrintField213: