Crystal structure, Hirshfeld surface analysis, and DFT studies of N-(2-chlorophenylcarbamothioyl)cyclohexanecarboxamide European Journal of Chemistry 12 (4) (2021) 439-449 European Journal of Chemistry ISSN 2153-2249 (Print) / ISSN 2153-2257 (Online) – Copyright © 2021 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. https://dx.doi.org/10.5155/eurjchem.12.4.439-449.2196 European Journal of Chemistry View Journal Online View Article Online Crystal structure, Hirshfeld surface analysis, and DFT studies of N-(2-chlorophenylcarbamothioyl)cyclohexanecarboxamide Cemal Koray Ozer 1, Ummuhan Solmaz 2,* and Hakan Arslan 1 1 Department of Chemistry, Faculty of Arts and Science, Mersin University, Mersin, TR 33343, Turkey c.korayozer@gmail.com (C.K.O.), hakan.arslan@mersin.edu.tr (H.A.) 2 Department of Chemistry and Chemical Processing Technologies, Technical Science Vocational School, Mersin University, Mersin, TR 33343, Turkey ummuhansolmaz@mersin.edu.tr (U.S.) * Corresponding author at: Department of Chemistry and Chemical Processing Technologies, Technical Science Vocational School, Mersin University, Mersin, TR 33343, Turkey. e-mail: ummuhansolmaz@mersin.edu.tr (U. Solmaz). 10.5155/eurjchem.12.4.439-449.2196 Received: 22 October 2021 Received in revised form: 14 November 2021 Accepted: 20 November 2021 Published online: 31 December 2021 Printed: 31 December 2021 N-(2-Chlorophenylcarbamothioyl)cyclohexanecarboxamide was characterized by a single crystal X-ray diffraction study. Crystal data for this compound, C14H17ClN2OS; Monoclinic, space group P21/n with Z = 4, a = 5.2385(10) Å, b = 17.902(4) Å, c = 15.021(3) Å, β = 90.86(3)°, V = 1408.5(5) Å3, T = 153(2) K, μ(MoKα) = 0.413 mm-1, Dcalc = 1.400 g/cm3, 9840 reflections measured (7.082° ≤ 2Θ ≤ 50.378°), 2519 unique (Rint = 0.0406, Rsigma = 0.0335) which were used in all calculations. The final R1 was 0.0397 (I > 2σ(I)) and wR2 was 0.0887 (all data). The puckering parameters (q2 = 0.019(3) Å, q3 = 0.578(3) Å, θ = 1.0(3)° and φ = 51(8)°) of the title compound show that the cyclohexane ring adopts a chair conformation. The molecular conformation of the title compound is stabilized by intramolecular hydrogen bonds (N2-H2⋅⋅⋅Cl1, N2-H2⋅⋅⋅O1, and C2-H2A⋅⋅⋅S1) and intermolecular hydrogen bonds (N1- H1⋅⋅⋅S1i and C9-HA⋅⋅⋅S1i i: 2-x, 2-y, 1-z). The intramolecular hydrogen bonds (N2-H2⋅⋅⋅O1 and C2-H2A⋅⋅⋅S1) are also form two pseudo-six-membered rings. Density functional theory optimized structure in the gaseous phase at B3LYP/6-311G(d,p) level of theory has been compared with the experimentally defined molecular structure. The molecular orbitals HOMO and LUMO with the energy gap for the title compound are calculated and the estimated energy gap (ΔE) between the HOMO and LUMO energies levels of the title compound is 3.5399 eV, which implies that the title molecule is very reactive. The Hirshfeld surface analysis reveals that the most important contributions to crystal packing are from H···H (49.0%), H···C/C···H (12.5%), H···Cl/Cl···H (10.9%), and H···S/S···H (10.0%) interactions. The energy-framework calculations are used to analyze and visualize the three- dimensional topology of the crystal packing. The intermolecular energy analysis confirmed a significant contribution of dispersion to the stabilization of molecular packings in the title compound. Benzoylthiourea Chair conformation Cyclohexanecarboxamide Crystal structure analysis Hirshfeld surface analysis Density Functional Theory (DFT) Cite this: Eur. J. Chem. 2021, 12(4), 439-449 Journal website: www.eurjchem.com 1. Introduction Coordination compounds have attracted a great deal of attention due to their structural variety, interesting physical and chemical properties, and promising applications in many fields [1,2]. Coordination compounds consist of a central atom and a ligand attached to the central atom. Among these, the N- benzoyl thiourea derivatives are versatile ligands that coor- dinate to form stable compounds. These derivatives possess very strong donor groups (Carbonyl and thioamide) that allow the preparation of different transition metal complexes, either monoanionic bidentate form by deprotonation that forms neutral homoleptic or heteroleptic complexes with S,O coordination or in neutral form only through the S atom [3-21]. Several benzoyl thiourea derivatives and their metal complexes are also associated with various types of biological activities such as insecticidal, herbicidal, antibacterial, antifungal, anti- tubercular, antithyroid, anthelmintic, rodenticidal, and plant growth regulator properties [22-25]. Our colleagues have pursued investigations on the synthesis, characterization, thermal behavior, antimicrobial activity, and catalytic activity of benzoyl thiourea derivatives [26-35]. Based upon the literature search, we could find no crystal structure characterization of N-(2-chlorophenyl- carbamothioyl)cyclohexanecarboxamide compound except reference [28]. In this work, in continuation of our ongoing interest in structural studies of thiourea derivative molecules [26-35], we re-refined and report the single-crystal X-ray diffraction study of the title compound. In addition, density functional theory optimized structure in the gaseous phase at B3LYP/6-311G(d,p) level has been compared with the experimentally defined new re-refined molecular structure. A Hirshfeld surface analysis and energy framework study was also performed to complement the experimental results to attempt to understand the nature of the described noncovalent ABSTRACT RESEARCH ARTICLE KEYWORDS https://dx.doi.org/10.5155/eurjchem.12.4.439-449.2196 https://www.eurjchem.com/ https://dx.doi.org/10.5155/eurjchem.12.4.439-449.2196 mailto:c.korayozer@gmail.com mailto:hakan.arslan@mersin.edu.tr mailto:ummuhansolmaz@mersin.edu.tr mailto:ummuhansolmaz@mersin.edu.tr http://www.eurjchem.com/ https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.12.4.439-449.2196&domain=pdf&date_stamp=2021-12-31 440 Ozer et al. / European Journal of Chemistry 12 (4) (2021) 439-449 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.4.439-449.2196 O Cl O N C S KSCN - KCl Cl NH2 O N H S N H ClO N C S Scheme 1. Synthesis of the title compound (H2L). Figure 1. The molecular structure of the title compound. interactions in the supramolecular network of the title compound. 2. Experimental 2.1. Instrumentation The X-ray single-crystal diffraction data were recorded on a Rigaku Mercury AFC8S system with a Mercury CCD detector. A suitable crystal was selected and mounted onto a Nylon loop on a Rigaku Mercury system. The crystal was kept at T = 153(2) K during data collection. Data were collected with graphite- monochromated MoKα radiation (λ = 0.71073 Å). Using Olex2 [36], the structure was solved with the Superflip [37-39] structure solution program, using the Charge Flipping solution method, and refined by the full-matrix least squares technique on F2 using SHELXL [40] with refinement of F2 against all reflections. All non-H atoms were refined anisotropically. ORTEP views were drawn using OLEX2 software [36]. 2.2. Synthesis The compound was reported in a previous study in the literature [27]. A solution of cyclohexanecarbonyl chloride (0.005 mole) in acetone (50 mL) was added dropwise to a suspension of potassium thiocyanate (0.005 mole) in acetone (50 mL). The reaction mixture was heated under reflux for 30 min and then cooled to room temperature. A solution of 2- chloro benzylamine (0.005 mole) in acetone (30 mL) was added to the mixture for 15 min at room temperature and stirred for 2 h. Hydrochloric acid (0.1 N, 300 mL) was added and the solution was filtered. The solid product was washed with water and purified by recrystallization from an ethanol:dichloro methane mixture (1:2, v:v) (Scheme 1). Color: White. Yield: 93 %. M.p.: 136-138 °C. 2.3. Computational studies The density functional theory calculations for the title compound were performed using Gaussian 16 software [41]. They were carried out with Becke three parameters for the exchange with correlation functional of Lee-Yang-Parr (B3LYP) for 6-311G(d,p) basis set [42,43]. The Gauss View 06 program [44] was used to visualize the calculated parameters. All the parameters were allowed to relax, and all the calculations converged to an optimized geometry. The local minima were confirmed by the absence of an imaginary mode in the vibrational analysis calculations. Hirshfeld surfaces [45,46] was performed with the aid of CrystalExplorer 17.5 software [47] to verify the contributions of different intermolecular interac- tions. The two-dimensional fingerprint plots [48] were calculated using the crystallographic information file as input for analysis. Electrostatic potentials were calculated using Gaussian 16 and TONTO [41,49,50] and mapped on Hirshfeld surfaces using the 6-311G(d,p) basis set at the B3LYP level of theory. On the surfaces, donors with positive potential (blue regions) and acceptors with negative potential (red regions) are represented. The proposed molecular structure’s with Hirshfeld surfaces (Shape index and curvedness), map over the shape index region −1.000 to 1.000 Å and the curvedness region −4.000 to +0.400 Å. For the generation of fingerprint plots, the bond lengths of hydrogen atoms involved in the interactions were normalized to standard neutron values [51]. The 2D fingerprint plots were displayed using the standard view with the de and di distance scales displayed on the graph axes. The energies of intermolecular interaction of the molecular pairs in the crystal packing were calculated using 3D energy framework analysis, at B3LYP/6-311G(d,p) level of theory, in a cluster of radius 3.8 Å around the molecule. The neighboring molecules in the shell around the central molecule were generated by applying crystallography symmetry operations. 3. Result and discussion 3.1. Crystal structure analysis The title compound was prepared and characterized previously [27]. To the best of our knowledge, no reports on the single crystal of this molecule exist except reference [28]. As a follow-up to the synthesis and characterization, a recrystallize- tion of an authenticated this molecule with dichloromethane and ethanol was undertaken. A suitable single crystal of the title compound for the X-ray diffraction study was obtained by slow evaporation of a dichloromethane:ethanole (1:2, v:v) solution [27,28]. The re-refined molecular structure of the compound in crystal form with the corresponding atom numbering scheme is shown in Figure 1 and the crystal packing of the compound is viewed along the crystal a-axis and c-axis in Figure 2. Ozer et al. / European Journal of Chemistry 12 (4) (2021) 439-449 441 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.4.439-449.2196 Table 1. Crystallographic data and refinement parameters for the title compound. Parameters H2L Empirical formula C14H17ClN2OS Formula weight 296.81 Temperature (K) 153(2) Crystal system Monoclinic Space group P21/n a, (Å) 5.2385(10) b, (Å) 17.902(4) c, (Å) 15.021(3) β, (°) 90.86(3) Volume (Å3) 1408.5(5) Z 4 ρcalc (g/cm3) 1.400 μ (mm-1) 0.413 F (000) 624.0 Crystal size (mm3) 0.72 × 0.19 × 0.12 Radiation MoKα (λ = 0.71073) 2Θ range for data collection (°) 7.082 to 50.378 Index ranges -6 ≤ h ≤ 6, -21 ≤ k ≤ 20, -15 ≤ l ≤ 17 Reflections collected 9840 Independent reflections 2519 [Rint = 0.0406, Rsigma = 0.0335] Data/restraints/parameters 2519/0/240 Goodness-of-fit on F2 1.137 Final R indexes [I≥2σ (I)] R1 = 0.0397, wR2 = 0.0844 Final R indexes [all data] R1 = 0.0503, wR2 = 0.0887 Largest diff. peak/hole (e Å-3) 0.26/-0.27 Table 2. The experimental and theoretical bond lengths of the title compound. Atom Atom Length (Å) Atom Atom Length (Å) Experimental (X-ray) Theoretical (DFT) Experimental (X-ray) Theoretical (DFT) O1 C8 1.227(3) 1.2230 C3 C4 1.384(4) 1.3916 Cl1 C6 1.739(2) 1.7596 C4 C5 1.383(4) 1.3908 S1 C7 1.669(2) 1.6729 C5 C6 1.381(3) 1.3887 N1 C7 1.389(3) 1.4082 C8 C9 1.512(3) 1.5205 N1 C8 1.376(3) 1.3827 C9 C10 1.525(3) 1.5457 N2 C1 1.410(3) 1.4094 C9 C14 1.539(3) 1.5442 N2 C7 1.346(3) 1.3501 C10 C11 1.526(3) 1.5345 C1 C2 1.398(3) 1.4002 C11 C12 1.519(4) 1.5344 C1 C6 1.409(3) 1.4066 C12 C13 1.522(4) 1.5345 C2 C3 1.392(3) 1.3896 C13 C14 1.525(3) 1.5347 Table 3. The experimental and theoretical bond angles of the title compound. Atom Atom Atom Angle (°) Atom Atom Atom Angle (°) Experimental (X-ray) Theoretical (DFT) Experimental (X-ray) Theoretical (DFT) C8 N1 C7 129.53(19) 130.1560 N2 C7 S1 128.15(17) 129.1519 C7 N2 C1 131.0(2) 129.7756 N2 C7 N1 114.21(19) 113.8546 C2 C1 N2 124.84(19) 123.5793 O1 C8 N1 122.65(19) 122.7877 C2 C1 C6 118.0(2) 117.8269 O1 C8 C9 123.03(19) 121.9433 C6 C1 N2 117.15(19) 118.5297 N1 C8 C9 114.31(18) 115.2666 C3 C2 C1 120.2(2) 120.7162 C8 C9 C10 112.12(18) 109.4879 C4 C3 C2 121.0(2) 120.6465 C8 C9 C14 109.75(17) 110.0766 C5 C4 C3 119.3(2) 119.5372 C10 C9 C14 110.99(18) 110.8440 C6 C5 C4 120.4(2) 119.8060 C9 C10 C11 110.06(18) 111.5439 C1 C6 Cl1 120.24(17) 120.1909 C12 C11 C10 110.8(2) 111.6577 C5 C6 Cl1 118.70(18) 118.3458 C11 C12 C13 111.8(2) 111.2614 C5 C6 C1 121.0(2) 121.4632 C12 C13 C14 110.9(2) 111.7023 N1 C7 S1 117.64(15) 116.9900 C13 C14 C9 110.75(19) 111.5024 Crystallographic data and new refinement parameters are summarized in Table 1, and the bond length and angle para- meters are tabulated in Tables 2 and 3. In the molecular structure of the title compound, the bond lengths of carbonyl (C8-O1) and thiocarbonyl are 1.227(3) and 1.669(2) Å, which are found in the range of typical double bonds for the C=O and C=S groups, respectively [26-28,52,53]. The C- N bond lengths for this molecule (C8-N1: 1.376(3) Å, C7-N1: 1.389(3) Å, C7-N2: 1.346(3) Å, C1-N2: 1.410(3) Å) are all shorter than the average single C–N bond length of 1.48 Å, thus showing varying degrees of double bond character in these C-N bonds [54-58]. The bond lengths within the cyclohexane ring (C9-C14) lie in the expected lengths (C9-C10: 1.525(3), C10- C11: 1.526(3), C11-C12: 1.519(4), C12-C13: 1.522(4), C13-C14: 1.525(3), C9-C14: 1.539(3) Å). The bond angles in cyclohexane ring (C9-C14) are in the range between 110.06(18) and 111.8(2)° and these obtained bond angle values agree with the literature values [26-28]. The puckering parameters are q2 = 0.019(3) Å, q3 = 0.578(3) Å, θ = 1.0(3)°, and φ = 51(8)°. The conformation of the cyclohexane ring slightly deviates from the ideal chair (θ = 1.0(3)°) for the title compound. These ring puckering parameters show that the cyclohexane ring has a chair conformation [59,60]. The crystal packing of the title compound is stabilized by a combination of intramolecular and intermolecular hydrogen bonds (Table 4). The intramolecular hydrogen bonds cause the formation of the two fused S(6) ring motifs in the title compound (Figure 3). 3.2. Computational studies The bond angles and bond lengths of the experimental XRD and DFT optimized title compound are listed in Tables 2 and 3. The theoretical and experimental parameters differ somewhat, which may be explained by the fact that the DFT calculation was performed on an isolated molecule in the gaseous phase, whereas the X-ray parameters were calculated on molecules in the solid-state (Figure 4). 442 Ozer et al. / European Journal of Chemistry 12 (4) (2021) 439-449 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.4.439-449.2196 Table 4. Intra- and inter-molecular hydrogen bonds for the title compound (Å, °). D-H⋯A d(D-H) d(H⋯A) d(D⋯A) ∠ D-H⋯A Symmetry N(1)-H(1)⋯S(1) 0.77(3) 2.71(3) 3.4679(19) 166(2) 2-x, 2-y, 1-z N(2)-H(2)⋯Cl(1) 0.84(3) 2.44(3) 2.9389(19) 116(2) - N(2)-H(2)⋯O(1) 0.84(3) 1.91(3) 2.646(2) 145(2) - C(2)-H(2A)⋯S(1) 0.92(3) 2.58(3) 3.192(2) 125(2) - C(9)-H(9)⋯S(1) 0.99(2) 2.82(2) 3.561(2) 132.2(16) 2-x, 2-y, 1-z (a) (b) Figure 2. The unit cell packing of the title compound viewed along the a-axis (a) and c-axis (b). Figure 3. Intramolecular hydrogen bonds cause the formation of two fused S(6) ring motifs in the title compound. Figure 4. Optimized geometric structure of the title compound obtained at B3LYP/6-311G(d,p) level. Figure 5. Atom-by-atom superimposition of the structures calculated (blue) over the X-ray structure (red) for the title compound. The experimental geometries determined by the X-ray diffraction technique and the theoretically derived geometries overlapped in the current study (Figure 5). In the bond length calculations, the correlation was found at the B3LYP/6- 311G(d,p) level of theory as r = 0.9987, and the maximum difference between the theoretical and experimental bond lengths (C9-C10) was 0.0207 Å. In the bond angle calculations, the correlation was found as r = 0.9888, and the maximum difference between the theoretical and experimental bond angles (C8-C9-C10) was 2.632°. The RMS value resulting from the superposition of the experimental and theoretically structure was found to be 0.452 Å for B3LYP/6-311G(d,p) level. According to this result, the DFT method has minor level error and we can use for the future calculations for the character- rization of the three-dimensional structure of molecular geometry. Ozer et al. / European Journal of Chemistry 12 (4) (2021) 439-449 443 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.4.439-449.2196 Table 5. Calculated energy values and quantum molecular descriptors of the title compound. Parameters Values SCF energy (a.u.) -1587.13 Total energy (Thermal) Etotal (kcal/mol) 195.16 Heat capacity at const. volume, Cv (cal/mol.K) 67.377 Vibrational energy, Evib (kcal/mol) 193.383 Zero-point vibrational energy, Eo (kcal/mol) 184.102 Entropy (cal/mol.K) Translational 42.954 Rotational 34.633 Vibrational 63.660 Total 141.247 Rotational constant (GHz) A 0.62251 B 0.14267 C 0.12408 Dipole moment (Debye) µx -2.2665 µy -0.5163 µz 1.0532 µTotal 2.5520 LUMO energy (eV) -2.1701 HOMO energy (eV) -5.7100 Energy gap (eV) 3.5399 Ionization potential (eV) 5.7100 Electron affinity (eV) 2.1701 Chemical hardness (eV) 1.7700 Global softness (1/eV) 0.2825 Electronegativity (eV) 3.9401 Chemical potential (eV) -3.9401 Electrophilicity (eV) 4.3854 ELUMO = -2.1701 eV ↕ ∆E = 3.5399 eV EHOMO = -5.7100 eV Figure 6. HOMO-LUMO energy levels and energy gap of the title compound. In addition, the global chemical reactivity descriptors enable us to know the chemical properties of the title compound. Therefore, DFT/B3LYP/6-311G(d,p) platform was used to obtain the quantum mechanical molecular energy data and the data obtained are incorporated in Table 5. The frontier molecular orbitals highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of the title compound were generated. The energy gap between the molecular orbitals describes the chemical reactivity and chemical stability of the related molecule. It is clear that a molecule with a low-energy gap is expected to be more polarizable and associated with a high chemical reactivity [61]. The molecular orbitals HOMO and LUMO with the energy gap for the title compound are shown in Figure 6. The estimated energy gap (ΔE) between the HOMO and LUMO energies levels of the title compound is 3.5399 eV, which implies that the molecule is more chemically reactive and unstable. In addition, this lower energy gap explains the easy transfer of electrons taking place within the title molecule. Hirshfeld surface analysis has been conducted to verify the contributions of different intermolecular interactions in forming supramolecular structure. The intermolecular interactions in the re-refined crystal structure of the title compound have been examined using Hirshfeld surface analysis and fingerprint plots utilizing Crystal Explorer 17.5 [47]. Fingerprint plots with dnorm surfaces (where dnorm = di + de) for all intermolecular contacts, and the intermolecular energies of the molecular pairs in the crystal packing were calculated with molecular wavefunction at the B3LYP/6-311G(d,p) level of theory, cluster of radius 3.8 Å around the molecule. 444 Ozer et al. / European Journal of Chemistry 12 (4) (2021) 439-449 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.4.439-449.2196 (a) (b) (c) (d) (e) (f) Figure 7. Hirshfeld surfaces mapped with dnorm (a), de (b), di (c), shape index (d), curvedness (e) and fragment patch (f) for the title compound. Figure 8. dnorm map showing regions intermolecular contacts over the title compound. The Hirshfeld surfaces of the title compound have been mapped over dnorm, de, di, shape index, and curvedness (Figure 7). The dnorm value is positive for longer contacts (blue region, dnorm > VdW radii), negative for shorter contacts (red regions, dnorm < VdW radii) compared to van der Waals separation (white regions, dnorm = VdW radii). The calculated molecular Hirshfeld surface area is 322.08 Å2, which encloses the volume of 345.22 Å3. Other calculated shape descriptors are globularity G = 0.739 and asphericity Ω = 0.316. The term asphericity is a measure of structural anisotropy, and globularity is found as < 1, indicating that the molecular surface is more structured [62-64]. Figure 8 displays semitransparent dnorm-mapped the Hirshfeld surface for the title compound that form strong intermolecular contacts. The red regions in Figure 8 are apparent around the sulphur atom participating in the C-H···S and N-H···S contacts. The 2D fingerprint plot provides a precise two-dimensional graphical representation of the intermolecular interactions in the crystal. The contributions from different contacts to the total Hirshfeld surface area are H···H (49.0%), H···C/C···H (12.5%), H···Cl/Cl···H (10.9%), H···S/S···H (10.0%), H···O/O···H (7.0%), and H···N/N···H (1.6%). The general contributions of the different contacts to the total Hirshfeld surface area are shown in Figure 9. Ozer et al. / European Journal of Chemistry 12 (4) (2021) 439-449 445 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.4.439-449.2196 (a) (b) (c) (d) (e) (f) Figure 9. 2-Dimensional fingerprint plot of the main intermolecular interactions in the crystal structure of the title compound. Figure 10. Molecular pairs involved in the calculation of interaction energies of the title compound along the c axis. Table 6. Different interaction energies of molecular pairs in kJ/mol. Color * Symmetry Electron density R Eele Epol Edis Erep Etot x, y, z B3LYP/6-311G(d,p) 5.24 -17.60 -3.90 -60.10 55.20 -26.40 x+1/2, -y+1/2, z+1/2 B3LYP/6-311G(d,p) 9.47 -4.20 -1.00 -12.40 5.30 -12.30 x+1/2, -y+1/2, z+1/2 B3LYP/6-311G(d,p) 9.53 -1.50 -0.20 -5.60 4.10 -3.20 x+1/2, -y+1/2, z+1/2 B3LYP/6-311G(d,p) 11.97 0.20 -0.30 -6.70 4.20 -2.60 -x+1/2, y+1/2, -z+1/2 B3LYP/6-311G(d,p) 10.22 -2.10 -0.50 -11.50 7.90 -6.20 -x, -y, -z B3LYP/6-311G(d,p) 5.41 -31.30 -5.70 -45.70 58.70 -24.00 x+1/2, -y+1/2, z+1/2 B3LYP/6-311G(d,p) 9.87 -7.60 -0.50 -18.50 18.40 -8.20 -x, -y, -z B3LYP/6-311G(d,p) 7.12 -78.10 -10.40 -33.30 106.80 -15.00 -x, -y, -z B3LYP/6-311G(d,p) 12.60 -4.50 -0.50 -19.90 17.20 -7.70 * The color and compound relationship is given in Figure 10. Molecular pairs involved in the calculation of the interaction energies of the title compound along the c axis are shown in Figure 10 (Table 6). The pictorial representation of Coulomb energy, dispersion energy, and the total interaction energy of the molecule viewed along a, b, and c axis is shown in green, red, and blue colors, respectively, and are displayed in Figure 11. The total intermolecular interaction energy (Etot) is the sum of four energy terms: electrostatic (Eele), polarization (Epol), dispersion (Edisp) and exchange-repulsion (Erep) with scale factors of 1.057, 0.740, 0.871, and 0.618, respectively [65]. The different interaction energies viz., electrostatic, polari- zation, dispersion, and repulsion energies are -146.7, -23.0, - 213.7, and 277.8 kJ/mol, respectively. The total energy is -105.6 kJ/mol. The cylinders in the energy framework depict the relative strengths of the molecular packing and the associated energies between the molecular pairs in different directions, while the absence of cylinders along a particular direction is due to weak interactions below a threshold energy (5 kJ/mol) and they are omitted. 446 Ozer et al. / European Journal of Chemistry 12 (4) (2021) 439-449 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.4.439-449.2196 Figure 11. Representation of the Coulomb interaction energy, dispersion energy, and total energy in red, green, and blue colors along the a, b, and c axes, respectively. The dispersion energy framework is dominant over the electrostatic energy framework shown in Figure 11 and Table 6. This is due to the presence of a Cl atom, which has a large electron cloud in the title compound [66]. The study of a three-dimensional surface MEP plot is a method to map the electrostatic potential to the isoelectronic density’s surface, providing details of the reactive sites. The surface simultaneously shows the molecular size and shape and the electrostatic potential value. The red region indicates an electron-rich region with a partial negative charge and blue region as an electron-deficient region with a partial positive charge in the color scheme. The B3LYP/6-311G(d,p) method was used to obtain the MEP of the title compound. Figure 12 shows that the molecule has two potential electrophilic attack sites. The negative area is located on the carbonyl oxygen atom and the thiocarbonyl sulfur atom. According to Figure 12, the oxygen atom of the C=O group in the title compound is responsible for the nucleophilic attack due to the fact that it has the largest electronegativity among all types of atoms in the title compound. On the other hand, the positive potential sites of the compound are around hydrogen atoms and the most positive point or the blue point is focused around the hydrogen atom of the N-H group which is the most suitable region for susceptible nucleophilic attack [67]. So, the N-H groups in the title compound could act as hydrogen bonding donors. Ozer et al. / European Journal of Chemistry 12 (4) (2021) 439-449 447 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.4.439-449.2196 Table 7. Mulliken atomic charges for the title compound. Atom Charge Atom Charge Atom Charge Atom Charge O1 +0.39319 H10 +0.15875 C19 +0.42756 C28 –0.20717 Cl2 –0.06205 C11 –0.10340 C20 –0.24722 H29 +0.11390 S3 –0.22778 H12 +0.10229 H21 +0.11845 H30 +0.11013 N4 –0.39023 C13 –0.08152 C22 –0.17570 C31 –0.21145 H5 +0.27417 H14 +0.10284 H23 +0.11562 H32 +0.10408 N6 –0.45240 C15 +0.01610 H24 +0.13246 H33 +0.11804 H7 +0.28738 H16 +0.11894 C25 –0.21018 C34 –0.17510 C8 +0.31543 C17 –0.27016 H26 +0.11789 H35 +0.11680 C9 –0.04592 C18 +0.16527 H27 +0.10421 H36 +0.13316 (a) (b) Figure 12. (a) The contour map of electrostatic potential and (b) Molecular electrostatic potential (MEP) map calculated at the B3LYP/6-311G(d,p) level. The presence of a negative charge on the oxygen, sulphur and chlorine atoms and a positive site on the N–H bonds supports the configuration of H···O, H···S, and H···Cl contacts (Table 4). In the gas phase at the level of B3LYP/6-311G(d,p), the Mulliken atomic charge of all atoms of the title compound have been obtained by Mulliken atomic charge distribution analysis [68]. While positively charged atoms have the nucleophilic effect, negatively charged atoms are responsible for the electrophilic effect. The values of Mulliken atomic charges are given in Table 7. It is observed that the charge of the N6 atom in the title molecule has the lowest negative value (–0.45240) and the C19 atom has the highest positive value (+0.42756) due to the polarizability of the N-H and C=O groups. These calculated values are in agreement with the intermolecular and intramolecular interactions in the title compound. 5. Conclusions The title compound was synthesized according to the literature and characterized to confirm its structure. The obtained DFT geometries are in good agreement with the re- refined single crystal X-ray diffraction results. The low energy gap between the frontier molecular orbitals indicates that molecule is unstable with easy transfer of electrons from HOMO to LUMO. In addition, the HOMO-LUMO gap of 3.5399 eV implies that the title compound has good polarizability and high chemical reactivity. The molecular structure is stabilized by different hydrogen bond interactions. Hirshfeld surface studies reveal that the types of intermolecular interactions of the title compound molecule and 2D fingerprint plots present the percentage of each type of contact for it. From the energy 3D frameworks analysis, it is found that the dispersion energy is the dominant factor among all interaction energies, this is due to the presence of the Cl atom which has a large electron cloud in the title compound. Acknowledgements A part of this work was supported by the Mersin University Research Fund [Project No: BAP-SBETB (CKÖ) 2007-1]. We thank B. Arslan for allowing us to reuse and reinvestigation the crystal diffraction data. Supporting information CCDC-2120032 contains the supplementary crystallo- graphic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, 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. Ethical approval: All ethical guidelines have been adhered. Sample availability: Sample of the compound is available from the author. http://www.ccdc.cam.ac.uk/data_request/cif mailto:data_request@ccdc.cam.ac.uk 448 Ozer et al. / European Journal of Chemistry 12 (4) (2021) 439-449 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.4.439-449.2196 CRediT authorship contribution statement Conceptualization: Hakan Arslan; Methodology: Cemal Koray Ozer, Ummuhan Solmaz, Hakan Arslan; Software: Hakan Arslan; Validation: Ummuhan Solmaz, Hakan Arslan; Formal Analysis: Cemal Koray Ozer, Ummuhan Solmaz, Hakan Arslan; Investigation: Ummuhan Solmaz, Hakan Arslan; Resources: Cemal Koray Ozer; Data Curation: Cemal Koray Ozer, Ummuhan Solmaz, Hakan Arslan; Writing - Original Draft: Ummuhan Solmaz; Writing - Review and Editing: Cemal Koray Ozer, Ummuhan Solmaz, Hakan Arslan; Visualization: Ummuhan Solmaz, Hakan Arslan; Funding acquisition: Hakan Arslan; Supervision: Hakan Arslan; Project Administration: Hakan Arslan. Funding Mersin Üniversitesi http://dx.doi.org/10.13039/501100004172 ORCID Cemal Koray Ozer https://orcid.org/0000-0001-9957-4167 Ummuhan Solmaz https://orcid.org/0000-0002-3697-577X Hakan Arslan https://orcid.org/0000-0003-0046-9442 References [1]. Karakus, S.; Rollas, S. Farmaco 2002, 57 (7), 577–581. [2]. Solomon, V. R.; Haq, W.; Smilkstein, M.; Srivastava, K.; Puri, S. K.; Katti, S. B. Eur. J. Med. Chem. 2010, 45 (11), 4990–4996. [3]. Saeed, A.; Flörke, U.; Erben, M. F. J. Sulphur Chem. 2014, 35 (3), 318– 355. [4]. Beyer, L.; Hoyer, E.; Liebscher, J.; Hartmann, H. Z. Chem. 2010, 21 (3), 81–91. [5]. Mühl, P.; Gloe, K.; Dietze, F.; Hoyer, E.; Beyer, L. Z. Chem. 2010, 26 (3), 81–94. [6]. Duque, J.; Estevez-Hernandez, O.; Reguera, E.; Ellena, J.; Correa, R. S. J. Coord. Chem. 2009, 62 (17), 2804–2813. [7]. Estevez-Hernandez, O.; Duque, J.; Rodríguez-Hernandez, J.; Reguera, E. Polyhedron 2015, 97, 148–156. [8]. Yesilkaynak, T. J. Therm. Anal. Calorim. 2016, 124 (2), 1029–1037. [9]. 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In Topics in Current Chemistry Fortschritte der Chemischen Forschung; Springer Berlin Heidelberg: Berlin, Heidelberg, 2007; pp 95–170. [68]. Mulliken, R. S. J. Chem. Phys. 1955, 23 (10), 1833–1840. Copyright © 2021 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. Instrumentation 2.2. Synthesis 2.3. Computational studies 3. Result and discussion 3.1. Crystal structure analysis 3.2. Computational studies 5. Conclusions Supporting information Disclosure statement Funding ORCID References PrintField10: PrintField11: PrintField12: PrintField13: PrintField14: PrintField15: PrintField16: PrintField17: PrintField18: PrintField19: PrintField110: PrintField20: PrintField21: PrintField22: PrintField23: PrintField24: PrintField25: PrintField26: PrintField27: PrintField28: PrintField29: PrintField210: