Synthesis, X-ray structure, and DFT analysis of a binary complex of 3,3'-[(3-benzimidazolyl)methylene]bis(4-hydroxy-2H-1-benzopyran-2-one): 5-Methyl-1,3-thiazol-2(3H)-imine European Journal of Chemistry 11 (4) (2020) 324-333 European Journal of Chemistry ISSN 2153-2249 (Print) / ISSN 2153-2257 (Online) – Copyright © 2020 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.11.4.324-333.2028 European Journal of Chemistry View Journal Online View Article Online Synthesis, X-ray structure, and DFT analysis of a binary complex of 3,3'-[(3-benzimidazolyl)methylene]bis(4-hydroxy-2H-1-benzopyran-2-one): 5-Methyl-1,3-thiazol-2(3H)-imine Gopal Sharma 1, Anshul Uppal 1, Sumati Anthal 1, Madhukar Baburao Deshmukh 2, Priyanka Pandharinath Mohire 2, Tanaji Ramchandra Bhosale 2, Chellappanpillai Sudarsanakumar 3 and Rajni Kant 1,* 1 X-ray Crystallography Laboratory, Department of Physics, University of Jammu, Jammu Tawi, 180006, India gopalgulshan1992@gmail.com (G.S.), anshuluppal629@gmail.com (A.U.), sumatianthal@gmail.com (S.A.), rkant.ju@gmail.com (R.K.) 2 Department of Chemistry, Shivaji University, Kolhapur, 416004, India m_deshmukh1@rediffmail.com (M.B.D.), mohire.priyanka258@gmail.com (P.P.M.), trbhosale2013@gmail.com (T.R.B.) 3 School of Pure and Applied Physics, Mahatma Gandhi University, Kerala, 686560, India c.sudarsan.mgu@gmail.com (C.S.) * Corresponding author at: X-ray Crystallography Laboratory, Department of Physics, University of Jammu, Jammu Tawi, 180006, India. e-mail: rkant.ju@gmail.com (R. Kant.). 10.5155/eurjchem.11.4.324-333.2028 Received: 18 August 2020 Received in revised form: 16 October 2020 Accepted: 22 October 2020 Published online: 31 December 2020 Printed: 31 December 2020 A combined theoretical and experimental investigation on a pharmaceutically important binary complex 3,3'-[(3-benzimidazolyl)methylene]bis(4-hydroxy-2H-1-benzopyran-2-one): 5-methyl-1,3-thiazol-2(3H)-imine is presented in this manuscript. The compound crystallizes in the monoclinic crystal system with space group Cc with unit cell parameters: a = 19.8151(8) Å, b = 15.2804(6) Å, c = 8.3950(4) Å, β = 94.0990(10)°, V = 2535.36(19) Å3, Z = 4, T = 296(2) K, μ(MoKα) = 0.184 mm-1, Dcalc = 1.490 g/cm3, 35833 reflections measured (5.332° ≤ 2Θ ≤ 56.678°), 6168 unique (Rint = 0.0467, Rsigma = 0.0388) which were used in all calculations. The final R1 was 0.0435 (I > 2σ(I)) and wR2 was 0.1073 (all data). The crystal structure has been determined by the conventional X-ray diffraction method, solved by direct methods and refined by the full matrix least squares procedure. Intramolecular hydrogen bonding of the type C–H⋅⋅⋅O and O–H⋅⋅⋅O is present and the crystal structure stabilizes via N–H…O, C–H…N and O–H…N intermolecular interactions. The optimized structural parameters have been compared and the parameters like ionization potential, electron affinity, global hardness, electron chemical potential, electronegativity, and global electrophilicity based on HOMO and LUMO energy values were calculated at B3LYP/6- 311G(d,p) level of theory for a better understanding of the structural properties of the binary complex. DFT Direct methods X-ray diffraction Crystal structure Benzopyran derivatives Intermolecular interactions Cite this: Eur. J. Chem. 2020, 11(4), 324-333 Journal website: www.eurjchem.com 1. Introduction Coumarin derivatives, i.e., molecules containing the benzo- pyran-2-one or chromen-2-one ring system, are widely distributed throughout nature, occurring as secondary metabolites of plant species, notably in the tonka bean and Melilotus species [1]. Natural coumarins play an important role in plant biochemistry and physiology and act as antioxidants, enzyme inhibitors, and precursors of toxic substances [2]. These are also involved in the actions of plant growth hormones and growth regulators, the control over respiration and photosynthesis, as well as in the defense against various infections [3]. Substitutions on the benzopyrone ring influence the chemical, structural [4], and biological properties of coumarins [5-7]. Coumarin heterocyclic derivatives exhibit diverse biological activities, as reviewed recently [8]. The biological activities of coumarin derivatives, in particular their therapeutic application as antifungal, antibacterial [9], anti- tubercular [10], antiacetylcholinesterase, anticancer [11,12] anticoagulant, antimutagenic, anti-hepatites C, anti-inflam- matory [13], and analgesic [14] agents. Moreover, many coumarin derivatives are used as non-peptidic proteases [15], heat shock proteins [16,17], and monoamine oxidase [18]. The interest in coumarins has recently increased significantly because it was found that they inhibit HIV (human immune- deficiency virus), by affecting integrase and reverse trans- criptase, which play a critical role in the replicative cycle of HIV [19-21]. Compounds containing a thiazole ring are known to have versatile pharmacological roles [22]. Substituted benz- imidazoles also possess many biological activities, which is why benzimidazole derivatives are considered as an important moiety for the development of molecules of pharmaceutical interest [23,24]. ABSTRACT RESEARCH ARTICLE KEYWORDS http://dx.doi.org/10.5155/eurjchem.11.4.324-333.2028 http://www.eurjchem.com/ http://dx.doi.org/10.5155/eurjchem.11.4.324-333.2028 mailto:gopalgulshan1992@gmail.com mailto:anshuluppal629@gmail.com mailto:sumatianthal@gmail.com mailto:rkant.ju@gmail.com mailto:m_deshmukh1@rediffmail.com mailto:mohire.priyanka258@gmail.com mailto:trbhosale2013@gmail.com mailto:c.sudarsan.mgu@gmail.com mailto:rkant.ju@gmail.com http://www.eurjchem.com/ https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.11.4.324-333.2028&domain=pdf&date_stamp=2020-12-31 Sharma et al. / European Journal of Chemistry 11 (4) (2020) 324-333 325 2020 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.11.4.324-333.2028 O O OH + O H N H H N + S N NH2 O O OH O OH O NH HN S H N H3C NH Reflux LTMM H Scheme 1. Reaction scheme of 3,3'-[(3-benzimidazolyl)methylene]bis(4-hydroxy-2H-1-benzopyran-2-one):5-methyl-1,3-thiazol-2(3H)-imine. With the importance of both coumarin and thiazole pharmaceuticals in mind, we were interested in developing a synthetic route to a binary complex that contains both entities with the aim of exploring whether or not the effects of the two units would work in concert in a pharmaceutical sense in the combined molecules [4,25]. The present study is focused on synthesis, X-ray structure, and DFT analysis of a binary complex of 3,3'-[(3-benzimi- dazolyl)methylene]bis(4-hydroxy-2H-1-benzopyran-2-one):5- methyl-1,3-thiazol-2(3H)-imine. Studies on single crystal structure, crystal packing, molecular electrostatic potential map, and HOMO-LUMO plots provide supportive information about the crystal. The calculated optimized structural para- meters were compared and the parameters like ionization potential, electron affinity, global hardness, electron chemical potential, electronegativity, and global electrophilicity based on HOMO and LUMO energy values were calculated at B3LYP/6- 311G(d,p) level of theory for a better understanding of the structural properties. 2. Experimental 2.1. Materials and instrumentations All chemicals were purchased from Alfa Aesar and Spectrochem (PVT. Ltd, Mumbai, India), Sigma Aldrich and used without purification. The reaction was monitored by TLC. The desired structures of the synthesized compounds were confirmed by their relevant spectral data. The melting points were determined by the open glass capillary method and are uncorrected. The compounds were confirmed by IR and 1H NMR spectral data. The IR spectra were recorded on a JASCO FT-IR spectrophotometer (FTIR-4600) and the values are expressed as νmax (cm-1). The 1H NMR spectra were recorded on Bruker Avance II 300 MHz using DMSO-d6 as a solvent and TMS as an internal standard. 2.2. Synthesis of 3,3'-[(3-benzimidazolyl)methylene]bis(4- hydroxy-2H-1-benzopyran-2-one):5-methyl-1,3-thiazol- 2(3H)-imine A mixture of 4-hydroxycoumarin (1 mmole) and dihydro benzimidazole 5-carbaldehyde (1 mmole), with 5 mL low transition temperature mixture was taken in a 50 mL round bottomed flask at room temperature to form the Knoevenagel condensation product, monitored by TLC and then 2-amino 5- methyl thiazole (1 mmole) was added and the same reaction mixture refluxed for 20 min. The 2-amino 5-methyl thiazole is not involved in the Knoevenagel condensation, however, it forms a conglomerate with the chiral product formed by the condensation of two molecules of 4-hydroxy coumarin with 5- formyl dihydrobenzimidazole which separates in the form of transparent crystals. The progress of the reaction was monitored by TLC using petroleum ether:ethyl acetate (8:2, v:v). After the completion of the reaction, the mixture was cooled to room temperature and the product collected by simple filtration, washed with ethanol and diethyl ether. Finally, the crude product was recrystallized from ethanol to obtain the pure product. The Reaction scheme of the title compound is shown in Scheme 1. 3, 3'-[(3-Benzimidazolyl)methylene] bis(4-hydroxy-2H-1-ben zopyran-2-one):5-Methyl-1,3-thiazol-2(3H)-imine: Yield: 60%. M.p. 208-210 ᵒC. FT-IR (KBr, ν, cm-1): 3300-3150(NH), 2930(C- H), 1670 (C=O), 1605 ( C=C). 1H NMR (300 MHz, DMSO-d6, δ, ppm): 2.1 (s, 3H, CH3), 3.8 (d, 2H, CH2), 4.6 (t, 2H, 2×NH of imidazole ring), 4.8 (s, 1H, NH of thiazole ring), 6.25 (s, 1H, CH benzylic proton), 6.8-8.1 (m, 12H, Aromatic protons & proton of thiazole ring ), 8.6 (s, 1H, C=NH), 14.5 (s br, 2H, 2×OH enolic). 2.3. Crystal structure determination and refinement X-ray intensity data of the crystal of dimensions 0.25×0.30×0.35 mm3 were collected on a Bruker APEX-II CCD area detector diffractometer [26] equipped with graphite monochromated MoKα radiation (λ = 0.71073 Å). The data were collected at 296(2) K and 6168 reflections were found as unique. The intensities were measured by ϕ/ω scan mode for θ range 2.67 to 27.46°. A total of 4717 reflections with I > 2σ(I) were treated as observed. Data was corrected for Lorentz- polarization and absorption factors. The structure was solved by direct methods using SHELXS [27] and was refined using SHELXL [28]. All non-hydrogen atoms of the binary complex were located from the best E-map. All hydrogen atoms were geometrically fixed (except N4 hydrogen atom) and allowed to ride on their parent carbon atoms with C-H = 0.93-0.97 Å, N-H = 0.86 Å. The final refinement cycles converged to an R-factor of 0.044 and wR(F2) = 0.107 for 4717 observed reflections. The residual electron density ranges from -0.32 to 0.28 e.Å-3. The geometry of the binary complex was calculated using the WinGX [29], PARST [30], and PLATON [31] software. Crystallographic information file (CIF) has been deposited at the Cambridge Crystallographic Data Centre with CCDC-1948179. A precise description of the crystallographic data of the X-ray structure is given in Table 1. 2.4. Theoretical calculation The optimized structure of the compound 3,3'-[(3- benzimidazolyl)methylene]bis(4-hydroxy-2H-1-benzopyran-2- one):5-methyl-1,3-thiazol-2(3H)-imine has been obtained by using Hartree-Fock (HF) method and is the same got re- optimized by using Becke’s three-parameter hybrid function (B3) [32,33] for the exchange part and the Lee-Yang-Parr (LYP) correlation function [34] using 6-311G basis set. The natural bond orbital (NBO) analyses, frontier molecular orbitals, atomic charges, and molecular electrostatic potential surface calculations were carried out by using Gaussian 09W [35] program. 326 Sharm et al. / European Journal of Chemistry 11 (4) (2020) 324-333 2020 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.11.4.324-333.2028 Table 1. Crystal data and experimental details. Empirical formula C26H18N2O6·C4H6N2S Formula weight 568.59 Temperature (K) 296(2) Crystal system Monoclinic Space group Cc a (Å) 19.8151(8) b (Å) 15.2804(6) c (Å) 8.3950(4) β (°) 94.0990(10) Volume (Å3) 2535.36(19) Z 4 ρcalc (g/cm3) 1.490 μ (mm-1) 0.184 F(000) 1184.0 Crystal size (mm3) 0.350 × 0.300 × 0.250 Radiation MoKα (λ = 0.71073) 2Θ range for data collection (°) 5.332 to 56.678 Tmin, Tmax 0.938, 0.955 Index ranges -25 ≤ h ≤ 26, -20 ≤ k ≤ 20, -11 ≤ l ≤ 10 Reflections collected 35833 Independent reflections 6168 [Rint = 0.0467, Rsigma = 0.0388] Data/restraints/parameters 6168/2/379 Goodness-of-fit on F2 1.021 Final R indexes [I≥2σ (I)] R1 = 0.0435, wR2 = 0.0967 Final R indexes [all data] R1 = 0.0700, wR2 = 0.1073 Largest diff. peak/hole (e Å-3) 0.28/-0.32 Flack parameter 0.03(10) CCDC Number 1948179 Figure 1. ORTEP view of the binary complex with displacement ellipsoids drawn at 40% probability level. 3. Results and discussion 3.1. Single crystal structure analysis The structure containing atom numbering scheme is shown in Figure 1 [36]. The bond distances, bond angles which play an important role in collating the structural properties of the binary complex with the related structures are presented in Table 2. The values of bond distance [37] and angles of all the rings are within the normal range. The C2-O1 = 1.213 Å and C26-O5 = 1.211 Å bond distances of the title compound are comparable with the values observed for some analogous structure [38,39]. In fact, the distances C9-O4 = 1.310 Å and C19-O3 = 1.295 Å is smaller than the values observed for some analogous structure [38,39]. The bond angles O1-C2-O2 = 114.7(3)°, O1-C2-C1 = 127.0(3)°, O5-C26-O6 = 114.0(3)° and O5-C26-C18 = 126.8(3)° are comparable with the values observed in some related structure. The atoms in the coumarin moiety deviate slightly from the planarity maximum deviation observed for C1 [-0.0342] and C23 [-0.0693] atoms. The imidazole ring in the molecule adopts an envelope conformation with a single mirror plane of symmetry passing through the C13-C14 bond (asymmetry parameter ΔCs = 0.474). The packing of the molecules in the unit cell is governed by both the intra and intermolecular interactions. In the crystal structure, adjacent molecules are interconnected through N1- H1···O1, N1-H1···O5, N4-H4A···O1, C23-H23···N2 and O3- H3A…N4 intermolecular hydrogen bonds. Here, the atoms O1, O5, N2, and N4 and nitrogen atom N1 of the five-membered thiazole ring act as hydrogen bond acceptors while the atoms N4, C23 and O3 act as hydrogen bond donors. In addition to the intermolecular hydrogen bonding network, C17-H17···O1, C17- H17···O5 and O4-H4C···O3 intramolecular interactions have also been observed which results in the formation of two (virtual five-membered rings) with a graph-set motif S(5) (Figure 1). The supramolecular assembly is formed by the intermolecular interactions of the type N-H···O and O-H…N which links the molecules to form a chain running parallel to a- axis, whereas hydrogen bond of the type C-H···N having atom C23 as the donor links the molecules to form a chain parallel to b-axis. The N1 atom of thiazole ring is the hydrogen bond donor that forms bifurcated hydrogen bonds with two different carbonyl groups [N1-H1···O1 (2.966 Å), N1-H1···O5 (2.724 Å) give rise to 𝑅𝑅21(6) motif. Intermolecular hydrogen bonds of the type N-H···O and O-H…N are mainly responsible for stabilizing the crystal packing. Sharma et al. / European Journal of Chemistry 11 (4) (2020) 324-333 327 2020 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.11.4.324-333.2028 Table 2. Comparison between experimental and calculated selected bond lengths (Å) and bond angles (°) of C26H18N2O6·C4H6N2S using HF and DFT/6-311G basis set. Bond Bond lengths Bond Bond lengths Experimental Calculated Experimental Calculated HF/6-311G DFT/6-311G HF/6-311G DFT/6-311G C13-N3 1.387(5) 1.401 1.398 C26-O5 1.211(4) 1.212 1.234 C14-N2 1.387(5) 1.318 1.342 C26-O6 1.387(4) 1.370 1.421 C10-C17 1.533(4) 1.508 1.508 C19-O3 1.295(4) 1.339 1.349 N2-C16 1.425(5) 1.470 1.479 C25-O6 1.366(4) 1.368 1.387 C2-O2 1.375(4) 1.391 1.427 C28-C27 1.317(6) 1.323 1.343 C2-O1 1.213(4) 1.277 1.293 C28-S1 1.755(4) 1.845 1.856 C17-C1 1.526(5) 1.541 1.553 C28-C29 1.500(6) 1.488 1.489 C9-O4 1.310(4) 1.450 1.486 C27-N1 1.373(6) 1.387 1.393 C17-C18 1.527(5) 1.512 1.514 C30-N1 1.326(5) 1.361 1.374 C13-C14 1.367(6) 1.455 1.459 C30-S1 1.717(4) 1.845 1.890 C3-O2 1.369(4) 1.377 1.402 C30-N4 1.317(5) 1.267 1.285 N3-C16 1.418(6) 1.452 1.460 Bond Bond angles HF/6-311G DFT/6-311G Bond Bond angles HF /6-311G DFT/6-311G S1-C28-C29 121.5(4) 120.3 120.5 C17-C18-C19 124.2(3) 127.9 127.5 C17-C1-C2 115.9(3) 129.3 128.5 C18-C19-O3 122.6(3) 123.9 123.8 C17-C1-C9 123.6(3) 104.0 104.0 O5-C26-C18 126.8(3) 125.1 126.2 C20-C19-O3 119.6(3) 114.7 115.2 O6-C26-O5 114.0(3) 117.0 115.8 C1-C2-O1 127.0(3) 129.4 130.1 C26-C18-C17 114.8(3) 113.1 112.5 O2-C2-O1 114.7(3) 111.9 111.0 C15-C10-C17 118.7(3) 127.8 127.4 C8-C9-O4 C1-C9-O4 115.0(3) 125.3(3) 109.2 111.9 109.4 111.5 C10-C17-C18 C7-C8-C9 115.1(3) 123.6(3) 117.3 121.8 118.8 121.4 C11-C10-C17 121.3(3) 108.2 109.1 C27-C28-C29 128.9(4) 130.5 130.0 O2-C3-C4 116.1(3) 116.5 116.2 O6-C25-C24 115.8(3) 118.1 117.7 S1-C30-N4 124.6(3) 128.3 129.0 N1-C30-N4 125.3(4) 124.6 124.6 Table 3. Hydrogen bonding geometry (e.s.d’s in parentheses). D–H...A D–H (Å) H...A (Å) D...A (Å) ∠ D–H...A (°) O4-H4C···O3 0.82 1.67 2.462(3) 162 C17-H17···O1 0.98 2.33 2.871(4) 114 C17-H17···O5 0.98 2.33 2.826(4) 110 N1-H1···O1 i 0.86 2.27 2.966(4) 138 N1-H1···O5 i 0.86 2.12 2.724(5) 127 N4-H4A···O1 i 0.83(5) 2.21(4) 2.956(4) 150(4) C23-H23···N2 ii 0.93 2.58 3.468(5) 160 O3-H3A…N4 iii 0.82 2.26 2.839(4) 128 Symmetry code: (i) 1/2 + x, 1/2 - y, -1/2 + z (ii) x, -y, -1/2 + z. (iii) x, y, z. Figure 2. Packing of the molecules viewed down the c-axis. The molecular packing in the unit cell as viewed down the c-axis is shown in Figure 2 [36] and the geometry of intra- and inter-molecular hydrogen bonds is given in Table 3. 3.2. Theoretical calculation 3.2.1. Molecular geometry The optimized structure of 3,3'-[(3-benzimidazolyl) methylene]bis(4-hydroxy-2H-1-benzopyran-2-one):5-methyl- 1,3-thiazol-2(3H)-imine is shown in Figure 3. The optimized geometrical parameters (bond lengths and bond angles) calculated with HF and DFT methods using 6-311G basis set have been compared with the corresponding ones as obtained by X-ray diffraction method and are presented in Table 2. 3.2.2. Molecular electrostatic potential (MEP) The molecular electrostatic potential is a physically observable property that can be measured experimentally by diffraction approaches [40,41]. It is also used to illustrate the wide-ranging electronic and nuclear charge distribution, which is an appropriate feature for understanding the reactivity of various species [42]. The potential, V(r), is typically written in terms of atomic units (a.u) and has the following form [43]. 328 Sharm et al. / European Journal of Chemistry 11 (4) (2020) 324-333 2020 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.11.4.324-333.2028 Figure 3. Optimized structure of 3,3'-[(3-benzimidazolyl)methylene]bis(4-hydroxy-2H-1-benzopyran-2-one):5-methyl-1,3-thiazol-2(3H)-imine. Figure 4. Molecular electrostatic potential map of 3,3'-[(3-benzimidazolyl)methylene]bis(4-hydroxy-2H-1-benzopyran-2-one):5-methyl-1,3-thiazol-2(3H)- imine. V(r) = ∑ ZA |RA−r|A − ∫ ρ�r′� |r′−r| d3r′ (1) where 𝑍𝑍𝐴𝐴 is the charge of the nucleus A located at 𝑅𝑅𝐴𝐴, 𝜌𝜌(𝑟𝑟’) is the electronic density function of the molecule, and 𝑟𝑟’ is the dummy integration variable. MEP has been constructed using DFT/6-311G level of theory for 3, 3'-[(3-benzimidazolyl)methylene] bis(4-hydroxy- 2H-1-benzopyran-2-one): 5-methyl-1, 3-thiazol-2(3H)-imine and is shown in Figure 4. In the color scheme of MEPs, red represents the electron rich, partially negative charge which is the preferred site for electrophilic attack, blue corresponds to electron deficient, partially positive charge which is the preferred site for nucleophilic attack, yellow for slightly electron rich region; green for neutral respectively. The color code of 3,3'-[(3-benzimidazolyl)methylene]bis(4-hydroxy-2H- 1-benzopyran-2-one) : 5-methyl-1,3-thiazol-2(3H)-imine is in the range between -9.703×10-2 (deepest red) to 9.703×10-2 (deepest blue). It can be seen that the negative regions are mainly over the oxygen atoms and the positive potential sites are around the hydrogen atoms. 3.2.3. HOMO-LUMO analysis The highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) are known as frontier molecular orbitals (FMOs). The FMOs plays an important role in the optical and electrical properties as well as in quantum chemistry [44]. The HOMO represents electron- donating ability, while LUMO represents the electron accepting ability [45]. The pictorial representation of the energies of molecular orbitals is shown in Figure 5, the positive phase is represented by the red color and negative phase represented in green color). The HOMO lies at -4.82 eV and spreads over the thiazole ring whereas the LUMO is located at -3.36 eV which shows that the charge transfer to imidazole ring within the molecule and the energy gap is 1.46 eV. The energy difference between the HOMO and the LUMO orbital is called as energy gap that is important for the stability of structures. Both the HOMO and LUMO orbitals help describe the chemical reactivity and kinetic stability of the binary complex. By using HOMO and LUMO energy values for a molecule, the electronegativity and chemical hardness can be calculated as follows [46]: 𝜒𝜒 = -(EHOMO + ELUMO)/2 = 4.09 (2) 𝜂𝜂 = (ELUMO - EHOMO)/2 = 0.73 (3) 𝑆𝑆 = 1/2𝜂𝜂 = 0.68 (4) 𝐼𝐼 = -𝐸𝐸HOMO = 4.82 (5) 𝐴𝐴 = -𝐸𝐸LUMO = 3.36 (6) Sharma et al. / European Journal of Chemistry 11 (4) (2020) 324-333 329 2020 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.11.4.324-333.2028 Table 4. HOMO-LUMO and other related molecular properties of 3,3'-[(3-benzimidazolyl)methylene]bis(4-hydroxy-2H-1-benzopyran-2-one):5-methyl-1,3- thiazol-2(3H)-imine. Molecular parameters (eV) B3LYP/6-311G ELUMO -3.36 EHOMO -4.82 ELUMO- EHOMO 1.46 Ionization potential (I) 3.36 Electron affinity (A) 4.82 Electronegativity (χ) 4.09 Global hardness (ɳ) 0.73 Chemical potential (μ) -4.09 Global Electrophilicity (ω) 2.04 Figure 5. HOMO-LUMO plot of 3,3'-[(3-benzimidazolyl)methylene]bis(4-hydroxy-2H-1-benzopyran-2-one):5-methyl-1,3-thiazol-2(3H)-imine. The HOMO and LUMO energies, the energy gap (∆E), the ionization potential (I), the electron affinity (A), global hardness (ɳ), chemical potential (μ), global electrophilicity (ω) for the investigated binary complex have been calculated at DFT/6- 311G level and the results are given in Table 4. 3.2.4. Atomic net charges The charge distribution on the molecule has an important influence on the vibrational spectrum. The total atomic charges of 3, 3'-[(3-benzimidazolyl)methylene] bis(4-hydroxy-2H-1-ben- zopyran-2-one): 5-methyl-1, 3-thiazol-2(3H)-imine obtained by Mulliken [47] methods using HF/6-311G and B3LYP/6-311G level of theory are shown in Table 5. The atomic Mulliken charge values have been obtained by the Mulliken population analysis. It is based on the linear combination of atomic orbitals and therefore the wave function of the molecule. The range of hydrogen atom charge in the case of HF/6-311G is from 0.161 to 0.488, whereas the range of hydrogen atom charges in the case of B3LYP/6-311G(d,p) is from 0.149 to 0.432. All hydrogen atoms exhibit positive charge, which is an acceptor atom. The charge distribution for the oxygen atoms (O1, O2, O3, O4, O5, and O6) and nitrogen atoms (N1, N2, N3, and N4) present in the molecule have negative charge values which are donor atoms and their magnitudes decrease as we go from HF to DFT level of theory whereas sulphur atom has positive charge both in HF and DFT theory which is an acceptor atom. 3.2.5. Natural bond orbital analysis Natural bond analysis provides an efficient method for studying intra- and inter-molecular bonding interactions among bonds and provides a convenient source for investi- gating charge transfer or conjugative interactions in molecular systems. It gives useful information about interactions in both filled virtual orbital spaces which could enhance the analysis of intra- and inter-molecular interactions [48]. The natural bond orbital (NBO) calculation was performed using NBO program implemented in the Gaussian 09 package at the DFT/B3LYP level in order to understand various second-order interactions between the filled orbitals of one subsystem and vacant orbitals of another subsystem, which is a measure of the delocalization or hyperconjugation. The hyperconjugative interaction energy was deduced from the second-order perturbation approach [49]. For each donor NBO (i) and acceptor NBO (j), the stabilization energy E(2) associated with electron delocali- zation between donor and acceptor is estimated as 𝐸𝐸(2) = ∆𝐸𝐸𝑖𝑖𝑖𝑖 = 𝑞𝑞𝑖𝑖 𝐹𝐹(𝑖𝑖,𝑖𝑖)2 𝐸𝐸𝑗𝑗 −𝐸𝐸𝑖𝑖 (7) where qi is the donor orbital occupancy, Ei, Ej are diagonal elements (orbital energies), and F(i,j) is the off-diagonal NBO Fock matrix element. Larger the E(2) value, the more intensive is the interaction between the electron donor and electron acceptor, i.e, the more donating tendency from the electron donor to electron acceptors and the extent of electron delocalization is greater. The results of second-order perturbation theory analysis of Fock matrix at B3LYP/6-311G level of theory are collected in Table 6. In this compound, the strong intra-molecular hyperconju- gation interaction of the π electrons from C18-C19 to the π* antibonding orbitals of C26-O5 and σ (C6-C5) to the σ* antibonding orbital C8-C7 leads to the stabilization energy of 30.36 and 23.44 kJ/mol, respectively. The most important interaction energy related to the resonance in the binary complex is the electron donating from the lone pair LP O1 atom to σ* (C1-C2) and LP N3 atom to σ* (C13-C12) which leads to a stabilization energy of 56.98 and 39.65 kJ/mol, respectively. 330 Sharm et al. / European Journal of Chemistry 11 (4) (2020) 324-333 2020 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.11.4.324-333.2028 Table 5. Mulliken charges using HF and DFT theory. Atom no Mulliken (HF/6-311G) Mulliken (B3LYP/6-311G) C13 0.251087 0.314476 C14 0.485383 0.258599 C15 -0.039955 0.049746 C10 0.287460 0.103562 C11 -0.438188 -0.320469 C12 0.110025 0.055399 H15 0.225850 0.211357 H12 0.215910 0.190972 N3 -0.946875 -0.820857 N2 -0.964970 -0.774947 C16 0.182368 0.069975 H3 0.361921 0.348392 H2 0.399899 0.368059 H16B 0.210958 0.217518 H16A 0.208974 0.220085 C17 -0.493542 -0.480255 C1 -0.084671 0.018405 C2 0.820503 0.583461 C9 0.094619 -0.071655 C8 0.021775 0.037947 C3 0.305067 0.236978 H11 0.297138 0.268804 O2 -0.789026 -0.616687 O1 -0.797180 -0.596030 O4 -0.738375 -0.591135 H4C 0.408051 0.368489 C7 -0.149051 -0.113887 C6 -0.175219 -0.157784 C5 -0.157243 -0.151340 C4 -0.182099 -0.162701 H7 0.178553 0.161375 H6 0.161152 0.147715 H5 0.164646 0.149822 H4 0.289050 0.249553 C18 -0.233884 -0.105957 C26 0.743513 0.496077 C19 0.616685 0.388833 C20 -0.213317 -0.156950 C25 0.387685 0.289643 O6 -0.687697 -0.509336 H17 0.309773 0.265387 O5 -0.514493 -0.371347 C21 -0.079446 -0.068824 C22 -0.187771 -0.165099 C24 -0.191184 -0.163029 C23 -0.103081 -0.110996 H21 0.213159 0.183199 H22 0.169470 0.153234 H23 0.170681 0.154871 H24 0.201202 0.180110 O3 -0.819505 -0.633236 H3A 0.488926 0.398229 C28 -0.409296 -0.380254 C27 0.382935 0.317406 C30 0.368787 0.216696 N1 -0.866889 -0.704579 S1 0.192235 0.200104 C29 -0.568555 -0.595302 N4 -0.670799 -0.546805 H29C 0.187736 0.192695 H29A 0.188584 0.192440 H29B 0.190970 0.196152 H4A 0.264622 0.254694 H1 0.485942 0.432944 H27 0.259014 0.226059 3.2.6. Fukui function Density Functional Theory is a powerful tool for the study of reactivity and selectivity in a molecule [50]. The most basic and commonly used local reactivity parameter is the Fukui function, which indicates the tendency of the electron density to deform at a given position upon accepting or donating electrons [51,52]. Fukui function gives us information about the electrophilic/nucleophilic power of a given atomic site in a molecule. The condensed Fukui functions on the jth atom site can be expressed as: fj+ = qj(N + 1) − qj(N) (8) fj0 = 1 2 [qj(N + 1) − qj(N − 1)] (9) fj− = qj(N) − qj(N − 1) (10) where fj+ for nucleophilic attack, fj- for electrophilic attack and fj0 for free radical. In these equations, qj is the atomic charge at the jth atomic site in the neutral (N), anionic (N+1), or cationic (N-1) chemical species. Sharma et al. / European Journal of Chemistry 11 (4) (2020) 324-333 331 2020 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.11.4.324-333.2028 Table 6. Second-order perturbation theory analysis of Fock matrix of 3,3'-[(3-benzimidazolyl)methylene]bis(4-hydroxy-2H-1-benzopyran-2-one):5-methyl-1,3- thiazol-2(3H)-imine by NBO method at B3LYP/6-311G(d,p) level. Donor (i) ED(i)(e) Acceptor (j) ED(j)(e) E(2) (KJ/mol) a E(j) - E(i) (a.u) b F(i,j) (a.u) c σ (C13-C14) 1.96134 σ* (C14-C15) 0.02290 3.07 1.21 0.055 σ (C13-C14) 1.96134 σ* (N2-H2) 0.01427 4.44 1.06 0.062 σ (C13-C12) 1.97402 σ* (C13-C14) 0.03863 4.61 1.18 0.066 σ (C13-N3) 1.98467 σ* (C13-C12) 0.01793 3.99 1.43 0.068 σ (C14-C15) 1.97009 σ * (C15-C10) 0.02433 4.33 1.31 0.067 σ (C15-C10) 1.97414 σ* (C14-N2) 0.02208 5.27 1.18 0.070 σ (C15-H15) 1.97052 σ* (C10-C11) 0.02635 5.98 0.92 0.066 σ (C17-C1) 1.92065 σ* (C15-C10) 0.18601 8.82 0.58 0.065 σ (C1-C2) 1.84116 σ* (C9-O4) 0.08400 8.38 0.48 0.057 σ (C9-O4) 1.98372 σ* (C8-C3) 0.03647 1.11 1.34 0.034 σ (C8-C7) 1.66693 σ* (C3-C4) 0.37020 22.55 0.28 0.072 σ (C3-C4) 1.61133 σ *(C8-C7) 0.40517 22.43 0.28 0.070 σ (C6-C5) 1.64673 σ * (C8-C7) 0.40517 23.44 0.27 0.072 π (C18-C19) 1.76968 π* (C26-O5) 0.33748 30.36 0.26 0.082 σ (C26-O6) 1.99290 σ * (C18-C26) 0.05865 2.63 1.49 0.057 LP (1) N(3) 1.79677 σ* (C13-C12) 0.22058 39.65 0.30 0.098 LP (3) O(1) 1.68771 σ* (C1-C2) 0.34221 56.98 0.30 0.117 LP (2) O(5) 1.83576 σ* (C26-O6) 0.12214 37.44 0.50 0.124 LP (2) O(3) 1.83601 π* (C18-C19) 0.28696 18.84 0.39 0.079 σ* (C15-C10) 0.18601 σ* (C1-C2) 0.34221 9.73 0.03 0.028 σ* (C8-C7) 0.40517 σ* (C9-O4) 0.08400 4.62 0.18 0.052 π * (C26-O5) 0.33748 π* (C18-C19) 0.28696 72.06 0.03 0.075 σ * (C20-C25) 0.42731 σ* (C21-C22) 0.29231 236.10 0.01 0.080 a E(2) means energy of hyperconjugative interactions. b Energy difference between donor and acceptor i and j NBO orbitals. c F(i,j) is the Fock matrix element between i and j NBO orbitals. Table 7. Fukui indices for nucleophilic and electrophilic attacks on atoms calculated from natural population analysis at DFT-B3LYP/6-311G. Atom Fj+ Fj- ∆f(r) C13 0.00937 -0.02345 0.03282 C14 0.00770 0.17867 -0.17097 C15 0.01838 -0.02978 0.04816 C10 -0.00923 0.18086 -0.19009 C11 0.00155 -0.03583 0.03738 C12 -0.00392 0.11262 -0.11654 H15 0.00865 0.03557 -0.02692 H12 0.00621 0.03251 -0.02630 N3 0.01043 0.01413 -0.00370 N2 0.02034 0.07698 -0.05664 H3 0.00775 0.02548 -0.01773 H2 0.00862 0.03421 -0.02559 C17 -0.01082 -0.00694 -0.00388 C1 0.13197 0.00373 0.12824 C2 -0.00424 0.02333 -0.02757 C9 -0.01389 0.01428 -0.02817 O2 0.00736 0.01525 -0.00789 O1 0.04897 0.04419 0.00478 O4 0.02437 0.00377 0.02060 C26 0.00096 0.00381 -0.00285 C19 0.00509 0.01274 -0.00765 O6 0.01021 0.01182 -0.00161 O5 0.01342 0.00746 0.00596 O3 0.00191 -0.00265 0.00456 N1 0.06728 -0.00373 0.07101 S1 0.14188 0.02853 0.11335 N4 0.13501 -0.01195 0.14696 H4A 0.02133 0.00729 0.01404 H1 0.01244 -0.01152 0.02396 The atomic charges either calculated by natural population analysis (NPA) or by Mulliken population analysis (MPA) have been used to calculate the Fukui function. In the present study the values of Fukui Function calculated from the NBO charges. The dual descriptor ∆f(r) [53] for the calculation of nucleo- philicity and electrophilicity is defined as the difference between the nucleophilic and electrophilic Fukui functions and is given by the Equation (11): ∆f(r) = fj+ − fj− (11) If ∆f(r) > 0, then the site is favored for nucleophilic attack, whereas if ∆f(r) < 0, then the site is favored for an electrophilic attack. According to the dual descriptor, ∆f(r) gives a transparent distinction between nucleophilic and electrophilic attacks at a particular site with their sign. From the values reported in Table 7, according to the condition for dual descriptor, nucleophilic site in our title molecule is C1, C13, C15, C11, O1, O3, O4, O5, N1, N4, S1, H4A and H1 are positive values (i.e. ∆f(r) > 0). Similarly, the electrophilic site is C10, C12, C14, C2, C9, C19, C26, C17, N2, N3, O2, O6, H2, H3, H12 and H15 negative values (i.e. ∆f(r) < 0). 4. Conclusion In this present investigation, the synthesis and the molecular structure analysis of 3,3'-[(3-benzimidazolyl) methyl ene]bis(4-hydroxy-2H-1-benzopyran-2-one):5-methyl-1,3-thia zol-2(3H)-imine has been reported by X-ray crystallographic techniques and NBO, HOMO-LUMO, Fukui function, atomic net charge analysis by HF and DFT-B3LYP methods at 6-311G basis set. In the crystal structure, the presence of coumarine and 5- methyl-1,3-thiazol-2(3H)-imine promotes the formation of 332 Sharm et al. / European Journal of Chemistry 11 (4) (2020) 324-333 2020 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.11.4.324-333.2028 intermolecular hydrogen bond network. The molecular packing in the unit cell is stabilized via N–H⋅⋅⋅O and C–H⋅⋅⋅N intermolecular interactions. The computed geometric parameters (bond length, bond angle) have been compared with their corresponding experimental data. The molecular electrostatic potential map indicates that the negative potential sites are on electronegative atoms and the positive potential sites are around the hydrogen atoms. These sites provide information concerning the region from where the structure may result into the formation of intra- and intermolecular interactions. Acknowledgements Rajni Kant acknowledges the Research Grants as sanctioned under Rashtriya Uchchatar Shiksha Abhiyan (RUSA) 2.0 Project (Ref. No: RUSA/JU/2/2019-20/111/3588-3636). Supporting information CCDC-1948179 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 interest: 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 Gopal Sharma http://orcid.org/0000-0003-4780-2804 Anshul Uppal http://orcid.org/0000-0001-8203-616X Sumati Anthal http://orcid.org/0000-0001-7947-7335 Madhukar Baburao Deshmukh http://orcid.org/0000-0001-7097-2356 Priyanka Pandharinath Mohire http://orcid.org/0000-0003-4644-1111 Tanaji Ramchandra Bhosale http://orcid.org/0000-0002-0372-7702 Chellappanpillai Sudarsanakumar http://orcid.org/0000-0003-2750-7795 Rajni Kant http://orcid.org/0000-0001-8043-2329 References [1]. Kontogiorgis, C.; Detsi, A.; Hadjipavlou-Litina, D. Exp. Opin. Therap. Pat. 2012, 22, 437-454. [2]. Kostova, I. Curr. Med. Chem. Anti-Cancer Agents 2005, 5, 29-46. [3]. Weinmann, I. Coumarins: Biology, Applications and Mode of Action, John Wiley & Sons, USA, 1997, pp. 1-22. [4]. 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Chem. 2000, 65, 405-410. https://www.ccdc.cam.ac.uk/structures/ mailto:data_request@ccdc.cam.ac.uk http://orcid.org/0000-0003-4780-2804 http://orcid.org/0000-0001-8203-616X http://orcid.org/0000-0001-7947-7335 http://orcid.org/0000-0001-7097-2356 http://orcid.org/0000-0003-4644-1111 http://orcid.org/0000-0002-0372-7702 http://orcid.org/0000-0003-2750-7795 http://orcid.org/0000-0001-8043-2329 Sharma et al. / European Journal of Chemistry 11 (4) (2020) 324-333 333 2020 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.11.4.324-333.2028 [46]. Pearson, R. G. Proceed. Nat. Acad. Sci. USA 1986, 83, 8440-8841. [47]. Mulliken, R. S. J. Chem. Phys. 1955, 23, 1833-1840. [48]. Choo, J.; Kim, S.; Joo, H.; Kwon, Y. J. Mol. Struct. 2002, 587, 1-8. [49]. Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem. Rev. 1988, 88, 899-926. [50]. Parr, R. G.; Yang, W. Density Functional Theory of Atoms and Molecules, Oxford University Press, New York, 1989. [51]. Ayers, P. W.; Parr, R. G. J. Am. Chem. Soc. 2000, 122, 2010-2018. [52]. Parr, R. G.; Yang, W. J. Am. Chem. Soc. 1984, 106, 511-516. [53]. Morell, C.; Grand, A.; Toro-Labbe, A. J. Phys. Chem. 2005, 109, 205-212. Copyright © 2020 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). 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 and instrumentations 2.2. Synthesis of 3,3'-[(3-benzimidazolyl)methylene]bis(4-hydroxy-2H-1-benzopyran-2-one):5-methyl-1,3-thiazol-2(3H)-imine 2.3. Crystal structure determination and refinement 2.4. Theoretical calculation 3. Results and discussion 3.1. Single crystal structure analysis 3.2. Theoretical calculation 3.2.1. Molecular geometry 3.2.2. Molecular electrostatic potential (MEP) 3.2.3. HOMO-LUMO analysis 3.2.4. Atomic net charges 3.2.5. Natural bond orbital analysis 3.2.6. Fukui function 4. Conclusion Acknowledgements Supporting information Disclosure statement ORCID References PrintField10: PrintField11: PrintField12: PrintField13: PrintField14: PrintField15: PrintField16: PrintField17: PrintField18: PrintField19: PrintField20: PrintField21: PrintField22: PrintField23: PrintField24: PrintField25: PrintField26: PrintField27: PrintField28: PrintField29: