Synthesis and detailed characterization of a newly synthesized chalcone, 3-(2,5-dimethoxyphenyl)-1-(naphthalen-2-yl)prop-2-en-1-one European Journal of Chemistry 12 (1) (2021) 69-76 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.12.1.69-76.2067 European Journal of Chemistry View Journal Online View Article Online Synthesis and detailed characterization of a newly synthesized chalcone, 3-(2,5-dimethoxyphenyl)-1-(naphthalen-2-yl)prop-2-en-1-one Madhu Kumar Dogganal Jayappa 1, Prabhuswamy Akhileshwari 2, Mandayam Anandalwar Sridhar 2,*, Lohith Tumakuru Nagarajappa 2, Shivegowda Nagaraju 3, Subrayachar Raghavendra 3 and Manasa Dogganal Jayappa 4 1 Faculty of Pharmacy, Ramaiah Institute of Applied Sciences, Bengaluru 560 054, India madhuvandj@gmail.com (M.K.D.J.) 2 Department of Studies in Physics, Manasagangotri, University of Mysore, Mysuru 570 006, India akhila@uomphysics.net (P.A.), mas@physics.uni-mysore.ac.in (M.A.S.), lohith@uomphysics.net (L.T.N.) 3 Department of Engineering Physics, Adichunchanagiri Institute of Technology, Chikkamagaluru 577 102, India nagubss@gmail.com (S.N.), raghuphotonics@gmail.com (S.R.) 4 Department of Applied Botany, Davanagere University, Davanagere 577 007, India manasadj310@gmail.com (M.D.J.) * Corresponding author at: Department of Studies in Physics, Manasagangotri, University of Mysore, Mysuru 570 006, India. e-mail: mas@physics.uni-mysore.ac.in (M.A. Sridhar). 10.5155/eurjchem.12.1.69-76.2067 Received: 12 January 2021 Received in revised form: 11 February 2021 Accepted: 18 February 2021 Published online: 31 March 2021 Printed: 31 March 2021 Chalcones are the main component of some natural compounds. The title compound, 3-(2,5- dimethoxyphenyl)-1-(naphthalen-2-yl)prop-2-en-1-one, was synthesized and characterized. The compound (C21H18O3) crystallizes in the triclinic system with the space group of P-1 (no. 2), a = 7.7705(4) Å, b = 10.2634(6) Å, c = 11.2487(6) Å, α = 79.655(5)°, β = 81.500(5)°, γ = 68.039(5)°, V = 815.28(9) Å3, Z = 2, T = 293(2) K, μ(MoKα) = 0.086 mm-1, Dcalc = 1.297 g/cm3, 9126 reflections measured (4.318° ≤ 2Θ ≤ 52.728°), 3302 unique (Rint = 0.0466, Rsigma = 0.0528) which were used in all calculations. The final R1 was 0.0568 (I > 2σ(I)) and wR2 was 0.1667 (all data). The crystal structure is stabilized by both short C-H···O inter- and intra- molecular interactions. In addition, the crystal structure is reinforced by π-π interactions. Hirshfeld surface analysis confirmed the presence of C-H···O intermolecular interactions. The two-dimensional fingerprint plots are used to visualize the individual interactions present in the molecule. DFT calculations were performed to know the energy levels of the frontier molecular orbitals (HOMO-LUMO). The energy gap between the frontier molecular orbitals shows the kinetic stability of the molecule. The chemical reactive sites are observed by generating MEP surface. Non-covalent interactions (NCIs) are analyzed using reduced density gradient (RDG) analysis. Chalcone Single crystal structure Reduced density gradient Hirshfeld surface analysis Frontier molecular orbitals Molecular electrostatic potential Cite this: Eur. J. Chem. 2021, 12(1), 69-76 Journal website: www.eurjchem.com 1. Introduction Chalcone is an aromatic ketone that forms the central core for a variety of important biological compounds [1,2]. The term “chalcone” is used to describe compounds with the 1,3- diphenylprop-2-en-1-one framework. They are naturally occurring compounds found in various plant species like Angelica, Glycyrrhiza, Humulus, and Scutellaria, which are widely used in folk remedies [3-6]. The products used daily as fruits, spices, tea, vegetables, and soybean-based food items contain derivatives of chalcone [7]. Chalcones are interme- diates in the biosynthesis of flavonoids, substances which are widespread in compounds, exhibiting an array of biological activities [8]. The chalcone derivatives have attracted increa- sing attention due to their diverse biological activities such as anti-malarial, anticancer, anti-inflammatory, antioxidant, anti- protozoal, antiulcer, and antibacterial [9-11]. Some biological compounds with embedding chalcone core are shown in Figure 1. They also exhibit many pharmacological activities such as cytotoxic agents, antiviral, anesthetics, mydriaties, etc. [12]. In view of the varied biological and pharmacological applications, the title compound was synthesized. The single crystal X-ray diffraction studies revealed the structure parameters. Quantum chemical computations were done to know the properties of the molecule. 2. Experimental 2.1. Synthesis of 3-(2,5-dimethoxyphenyl)-1-(naphthalen-2- yl)prop-2-en-1-one A mixture of equimolar amount 1-(naphthalen-2- yl)ethenone (0.1 mol) was dissolved in methanol followed by ABSTRACT RESEARCH ARTICLE KEYWORDS https://dx.doi.org/10.5155/eurjchem.12.1.69-76.2067 https://www.eurjchem.com/ https://dx.doi.org/10.5155/eurjchem.12.1.69-76.2067 mailto:madhuvandj@gmail.com mailto:akhila@uomphysics.net mailto:mas@physics.uni-mysore.ac.in mailto:lohith@uomphysics.net mailto:nagubss@gmail.com mailto:raghuphotonics@gmail.com mailto:manasadj310@gmail.com mailto:mas@physics.uni-mysore.ac.in http://www.eurjchem.com/ https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.12.1.69-76.2067&domain=pdf&date_stamp=2021-03-31 70 Jayappa et al. / European Journal of Chemistry 12 (1) (2021) 69-76 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.1.69-76.2067 O Core structure of a chalone O O O O O O O O HO O Sofalcone, Antiulcer drug Metochalcone, Choleretic drug OH O O A O OH O O OH HO HO O O OH OH Hesperidin methyl chalcone, Venous disease Figure 1. Some biological compounds with embedding chalcone core. CH3 O O O O O O O + CH3OH 40% NaOH H Figure 2. Synthesis of 3-(2,5-dimethoxyphenyl)-1-(naphthalen-2-yl)prop-2-en-1-one. addition of 10 mL of 40% sodium hydroxide (NaOH) solution under stirring and a solution of 2,5-dimethoxy benzaldehyde (0.1 mol) in methanol was added. Stirring was continued for 6- 8 hours [13]. The completion of the reaction was monitored by thin layer liquid chromatography (TLC) method and the reaction mixture was cooled and poured into ice-cold water. The precipitate was filtered, washed, and recrystallized from hot ethanol and little dimethylformamide (DMF). The crystals obtained were used for single crystal X-ray diffraction studies. The reaction scheme for the synthesized compound is shown in Figure 2. 2.2. X-ray diffraction analysis A white colored rectangular block of the crystal with approximate dimensions of 0.31 × 0.24 × 0.23 mm was selected for the X-ray diffraction study. The X-ray intensity data for the compound were collected at the temperature of 293(2) K on a Rigaku Saturn 724 diffractometer using graphite monochromat ed MoKα radiation. All frames were indexed using the triclinic system in the space group P-1. The complete data set was processed using CrystalClear [14]. The structure was solved by direct methods and refined by full-matrix least-squares on F2 using SHELXS and SHELXL [15] programs, respectively. The ORTEP [16] and packing diagrams were generated using the MERCURY [17] software. All non-hydrogen atoms were revealed in the first Fourier map itself. The hydrogen atoms were positioned geometrically and were allowed to ride on their parent atoms. 219 parameters were refined with 3302 unique reflections. The final residual value converged to R = 0.0568 with a goodness of fit 1.050. 3. Results and discussion 3.1 Molecular structure description The unit cell parameters are a = 7.7705(4) Å, b = 10.2634(6) Å, c = 11.2487(6) Å, α = 79.655(5)° , β = 81.500(5)° γ = 68.039(5)° with Z = 2. The asymmetric unit contains one molecule. The details of the crystal structure and data refinement are given in Table 1. The bond lengths and bond angles are in good agreement with the standard values [18]. The list of selected bond lengths, bond angles, and torsion angles are given in Tables 2-3, respectively. The ORTEP of the molecule with thermal ellipsoids drawn at 50% probability is shown in Figure 3. The structure consists of 2,5-dimethoxyphenyl and a naphthalene moiety, connected via a propenone chain. The rings in the molecule are sp2 hybridized. The dihedral angle between the phenyl ring (C14-C15-C16-C17-C18-C19) and the naphthalene ring (C1-C2-C3-C4-C5-C6-7-C8-C9-C10) bridged by propenone is 78.83(9)°. The naphthalene ring is nearly planar with a maximum rms deviation of 0.003(2) Å for C2 atom. The torsion angles of 174.9(2)° for the atoms C11-C12- C13-C14 indicate that the propenone chain is oriented in a +anti-periplanar conformation. The methoxy groups are substituted at the C16 and C19 positions of the phenyl ring. Jayappa et al. / European Journal of Chemistry 12 (1) (2021) 69-76 71 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.1.69-76.2067 Table 1. Crystal data and structure refinement details for the compound. Empirical formula C21H18O3 Formula weight 318.35 Temperature (K) 293(2) Crystal system Triclinic Space group P-1 a (Å) 7.7705(4) b (Å) 10.2634(6) c (Å) 11.2487(6) α (°) 79.655(5) β (°) 81.500(5) γ (°) 68.039(5) Volume (Å3) 815.28(9) Z 2 ρcalc (g/cm3) 1.297 μ (mm-1) 0.086 F(000) 336.0 Crystal size (mm3) 0.310 × 0.240 × 0.230 Radiation MoKα (λ = 0.71073) 2Θ range for data collection (°) 4.318 to 52.728 Index ranges -9 ≤ h ≤ 9, -11 ≤ k ≤ 12, -14 ≤ l ≤ 14 Reflections collected 9126 Independent reflections 3302 [Rint = 0.0466, Rsigma = 0.0528] Data/restraints/parameters 3302/0/219 Goodness-of-fit on F2 1.050 Final R indexes [I≥2σ (I)] R1 = 0.0568, wR2 = 0.1350 Final R indexes [all data] R1 = 0.0938, wR2 = 0.1667 Largest diff. peak/hole (e Å-3) 0.17/-0.20 Table 2. Comparison of bond lengths of selected non-hydrogen atoms. Atoms Length (Å) Atoms Length (Å) XRD DFT XRD DFT O1-C11 1.229(2) 1.198 C10-C11 1.500(3) 1.508 O2-C19 1.366(2) 1.353 C12-C13 1.330(3) 1.328 O3-C16 1.379(3) 1.352 C14-C15 1.395(3) 1.392 C4-C5 1.419(3) 1.423 C14-C19 1.394(3) 1.393 C7-C8 1.359(3) 1.359 C16-C17 1.378(3) 1.386 C9-C10 1.365(3) 1.362 C18-C19 1.388(3) 1.388 Table 3. Comparison of bond angles of selected non-hydrogen atoms. Atoms Angle (°) Atoms Angle (°) XRD DFT XRD DFT C19-O2-C20 118.16(17) 119.7 O1-C11-C10 120.26(18) 120.4 C2-C1-C6 121.0(2) 120.9 O1-C11-C12 119.26(19) 119.2 C1-C2-C3 120.5(2) 120.3 C10-C11-C12 120.46(18) 120.3 C4-C5-C6 118.29(19) 118.3 C11-C12-C13 125.4(2) 125.2 C1-C6-C5 119.1(2) 119.4 O2-C19-C18 124.29(19) 124.3 C9-C10-C11 119.10(19) 119.3 C14-C19-C18 119.8(2) 119.4 Figure 3. The ORTEP of the molecule with thermal ellipsoids drawn at 50% probability. The bond length of C11-O1 is 1.228(3) Å, which shows similar bond length with the other chalcone derivatives [19]. The torsion angles of 177.8(2)° and 179.7(2)° for the atoms C20-O2-C19-C14 and C14-C15-C16-O3 showed that they were oriented in +anti-periplanar conformations, respectively. The structure exhibits C-H···O intermolecular and intramolecular interaction. The hydrogen bond interaction is listed in Table 5. The packing of the molecules when viewed down a axis is shown in Figure 4. Further, the structure is stabilized by π-π interactions. Cg is the centroid of the ring C14-C15-C16-C17- C18-C19 with Cg⋯Cg distance of 4.080(14) Å, and perpendicular distance of Cg on itself is -3.5138(9) Å with a slippage value of 2.073 Å. The symmetry code for the Cg⋯Cg interaction is 1-x, -y, 2-z. The π⋯π interaction is shown in Figure 5. 3.2. Hirshfeld surface analysis Hirshfeld surface analysis is used to study the inter- connectivity of the molecules. It uses ‘Stockholder partitioning’ scheme to define the atoms in a molecule. Spackman and Byron introduced a new method to partition the electron densities into fragment contributions based on the Hirshfeld Stockholder partitioning scheme [20,21]. 72 Jayappa et al. / European Journal of Chemistry 12 (1) (2021) 69-76 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.1.69-76.2067 Table 4. Comparison of torsion angles of selected non-hydrogen atoms. Atoms Angle (°) Atoms Angle (°) XRD DFT XRD DFT C20-O2-C19-C14 177.80(18) -178.4 C7-C8-C9-C10 1.6(3) 1.2 C20-O2-C19-C18 −1.0(3) 0.9 C11-C12-C13-C14 174.87(19) 175.1 C2-C1-C6-C7 −179.5(2) -179.9 C13-C14-C15-C16 179.52(19) -179.4 C4-C5-C6-C7 178.15(18) -179.8 C14-C15-C16-O3 179.73(18) 179.4 C1-C6-C7-C8 179.5(2) 179.0 C16-C17-C18-C19 -0.1(3) 0.04 C5-C6-C7-C8 −0.8(3) -0.7 C17-C18-C19-O2 179.04(19) -179.9 Table 5. Hydrogen bond interactions. D-H···A D-H (Å) H···A (Å) D-A (Å) ∠ D-H···A (°) C18-H13···O1i 0.93 2.53 3.453(3) 172 i 1-x, -y, 2-z. Figure 4. Packing of the molecules viewed along a axis. Figure 5. The molecules showing π⋯π interactions in the crystal structure. Figure 6. Hirshfeld surface mapped with normalized contact distance dnorm. The resulting surfaces are called Hirshfeld surfaces. They help to identify the intermolecular interactions that are responsible for the connectivity of the molecules in the crystal structure. Hirshfeld surface study is a powerful tool which is used to visualize the intermolecular interactions by a 3-D color coding system. This can further be resolved into 2D fingerprint plots, which quantitatively summarize the nature and type of intermolecular contacts in the crystal [22]. The surfaces generated using dnorm function are illustrated for a clear visualization of the molecules. The high resolution Hirshfeld surfaces are mapped with the function dnorm, where dnorm is the normalized contact distance which is surface property and is given by Jayappa et al. / European Journal of Chemistry 12 (1) (2021) 69-76 73 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.1.69-76.2067 Figure 7. Fingerprint plot of the individual contacts to the total Hirshfeld surface. (a) (b) Figure 8. Comparison of the experimental structure (a) with optimized structure (b) of the title compound. dnorm = 𝑑𝑑𝑖𝑖−𝑟𝑟𝑖𝑖 𝑣𝑣𝑣𝑣𝑣𝑣 𝑟𝑟𝑖𝑖 𝑣𝑣𝑣𝑣𝑣𝑣 + 𝑑𝑑𝑒𝑒−𝑟𝑟𝑒𝑒 𝑣𝑣𝑣𝑣𝑣𝑣 𝑟𝑟𝑒𝑒𝑣𝑣𝑣𝑣𝑣𝑣 (1) where di and de are the distances from the nearest nucleus inside and outside of the molecule from the Hirshfeld surface, respectively, and rivdW and revdW are the van der Waals radii. Hirshfeld surface and 2D fingerprint plots were generated using CrystalExplorer17 [23]. The Hirshfeld surface mapped over dnorm is shown in Figure 6. The bright red spot on the dnorm surface is due to the presence of intermolecular C-H···O interactions. The fingerprint plots show the various contri- butions to the total Hirshfeld surface area with individual contacts H···H (51.9%), C···H/H⋯C (22.0%), O···H/H⋯O (16.4%), C⋯C (7.4%), C⋯O/O⋯C (2.3%) (Figure 7). The major contribution is from H⋯H contacts and the least is from O···H contacts. 3.3. Density functional theory (DFT) DFT is a computational approach to know the electronic properties of the molecule. The molecular structure is optimized in the gas phase using Gamess software [24] with B3LYP functional with the 6-31G(d, p) basis set. Comparisons of bond lengths, bond angles, and torsion angles of optimized structure with the X-ray crystallographic structure are drawn (Tables 3-4). In addition, the experimental and theoretical structures are shown in Figure 8. The small deviation observed can be ascribed to the gas phase calculation. 3.4. Frontier molecular orbitals The frontier molecular orbitals Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) are used to predict the energy level, kinetic stability, and chemical reactivity of a molecule. The energy of HOMO and LUMO gives the values of electron affinity and ionization potential of the molecule, respectively. The energy difference between the HOMO and LUMO is termed as energy gap. The DFT calculations were performed with B3LYP/6-31 G (d, p) basis set. The energy gap predicts the kinetic stability and chemical reactivity of the molecule [25]. The energy gap for the molecule is found to be 5.486 eV. The Energy level of frontier molecular orbitals is shown in Figure 9. 74 Jayappa et al. / European Journal of Chemistry 12 (1) (2021) 69-76 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.1.69-76.2067 Table 6. Molecular descriptors and their energies. Descriptor Value (eV) HOMO -7.540 LUMO 2.054 Energy gap (ΔE) 5.486 Ionization potential (I) 7.540 Electron affinity (E) 2.054 Chemical potential (μ) -4.797 Electronegativity (χ) 4.797 Global hardness (σ) 0.364 Global softness (η) 2.743 Electrophilicity (ω) 4.194 LUMO, 2.054 eV HOMO, -7.540 eV Figure 9. Energy levels of frontier molecular orbitals. Figure 10. The MEP plot of the title compound. Electronegativity, softness, hardness, chemical potential, and other chemical properties are derived from the energies of HOMO and LUMO. The electronegativity (χ) is the average of the ionization potential and electron affinity of the molecule. Its measure of the tendency of attracting electrons. The idea of hardness and softness of the molecule was introduced by Pearson et al. [26]. Molecules with small size, high electronegativity are referred as hard molecules, while molecules large in size and low electronegativity are known as soft molecules [27]. The molecular properties are calculated using the formulae, I = - EHOMO, A = ELUMO, χ = 1/2(I + A), μ = -χ, η = ΔE/2, σ = 1 /η, and ω = μ2/2η. The calculated values of molecular descriptors are listed in Table 6. 3.5. Molecular electrostatic potential (MEP) The molecular behavior can be understood by generating the electrostatic potential surface around the molecule. The MEP surface is defined as, at any point r(x, y, z) in the vicinity of a molecule, the potential energy is generated by the nuclei, electrons, and molecules and a proton [28]. At any point r, V(r) is given by V(r) = ZA / (RA – r) (2) where V(r) is the potential energy at r, ZA is the charge on the nucleus. The molecular electrostatic potential maps were generated using Multiwfn software [29] with the B3LYP/631- G(d, p) basis set. The MEP surface is shown in Figure 10. Jayappa et al. / European Journal of Chemistry 12 (1) (2021) 69-76 75 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.1.69-76.2067 (a) (b) Figure 11. The 2D scattered plot and RDG isosurface of the title molecule. The MEP map is useful to understand the chemical reactive sites in the molecule. The red and blue colored regions on the MEP indicate of electrophilic sites and nucleophilic sites, respectively. Figure 10 shows that the electrophilic sites are around the oxygen atoms while the nucleophilic sites are concentrated over hydrogen atoms. 3.6. Reduced density gradient (RDG) Reduced density gradient R(r) is a topological method employed to visualize the non-covalent interactions (NCIs) like hydrogen bond interactions, van der Waals interaction and steric effects in a molecule. It is a function of electron density ρ(r) and its gradient. The equation for (R(r)) is given by, R(r) = 1 2(3𝜋𝜋2)1 3⁄ |𝛻𝛻𝛻𝛻(𝑟𝑟)| 𝛻𝛻(𝑟𝑟)4 3⁄ (3) RDG is a dimensionless quantity of the inhomogeneity of the density at a point of space r [30]. To analyze the reduced density gradient, DFT calculations were performed using Gamess software [24] with B3LYP/6-31G(d,p) basis set. The RDG plot was generated by Multiwfn [29] and VMD [31] software. The RDG was analyzed by plotting R(r) against the product of the density and the sign of the second eigenvalue of the electron density of Hessian matrix (sign(λ2)ρ(r)). The 2D scattered plot and the corresponding RDG isosurface of the title molecule is shown in Figure 11. The region at the center of the ring with red color shows a strong steric effect, and the green color indicates the van der Waals interaction (Figure 11b). The sign of λ2 is used to distinguish between the regions of strong attraction (λ2 < 0) and strong repulsion (λ2 > 0). Figure 11b shows the van der Waals interaction between H14 of the naphthalene ring and O3 atom. A strong hydrogen bond is absent in the molecule. The right peak (Figure 11a) with red color corresponds to the stearic repulsion at the center of the naphthalene ring with the sign(λ2)ρ(r) value in the range 0.01- 0.02 a.u. The van der Waals interactions and steric clash are represented by the isosurface value 0.6. 4. Conclusion The synthesized compound crystallizes in the triclinic crystal system with the space group P-1. The structure was reinforced by C-H···O interaction. The Hirshfeld surface analysis confirmed the presence of intermolecular interactions. The fingerprint plots show the major contribution to the total molecular surface was from H···H contacts (51%). The calculated energy difference between the frontier molecular orbitals gives an energy gap of 5.486 eV which shows the kinetic stability of the molecule. The MEP map shows the chemical reactive sites of the molecule are around the oxygen (electronegative) and hydrogen (electropositive) atoms. The RDG analysis revealed the presence of van der Waals interactions and steric clashes in the molecule. Acknowledgments Prabhuswamy Akhileshwari thanks Department of Science and Technology - Karnataka Science and Technology Promotion Society (DST-KSTePS), Government of Karnataka, for providing the fellowship. Supporting information CCDC-2054693 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. https://www.ccdc.cam.ac.uk/structures/ mailto:data_request@ccdc.cam.ac.uk 76 Jayappa et al. / European Journal of Chemistry 12 (1) (2021) 69-76 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.1.69-76.2067 Disclosure statement Conflict of interests: The authors declare that they have no conflict of interest. Author contributions: All authors contributed equally to this work. Ethical approval: All ethical guidelines have been adhered. Sample availability: Samples of the compounds are available from the author. ORCID Madhu Kumar Dogganal Jayappa https://orcid.org/0000-0002-9391-4252 Prabhuswamy Akhileshwari https://orcid.org/0000-0003-0716-3542 Mandayam Anandalwar Sridhar https://orcid.org/0000-0002-3065-3630 Lohith Tumakuru Nagarajappa https://orcid.org/0000-0003-1808-740X Shivegowda Nagaraju https://orcid.org/0000-0001-6001-068X Subrayachar Raghavendra https://orcid.org/0000-0002-9633-953X Manasa Dogganal Jayappa https://orcid.org/0000-0002-6584-1922 References [1]. Rammohan, A.; Reddy, J. S.; Sravya, G.; Rao, C. N.; Zyryanov, G. V. Environ. Chem. Lett. 2020, 18 (2), 433–458. [2]. Budhiraja, A.; Kadian, K.; Kaur, M.; Aggarwal, V.; Garg, A.; Sapra, S.; Nepali, K.; Suri, O. P.; Dhar, K. L. Med. Chem. Res. 2011, 21 (9), 2133– 2140. [3]. Nishimura, R.; Tabata, K.; Arakawa, M.; Ito, Y.; Kimura, Y.; Akihisa, T.; Nagai, H.; Sakuma, A.; Kohno, H.; Suzuki, T. Biol. Pharm. Bull. 2007, 30 (10), 1878–1883. [4]. Chen, J. J.; Cheng, M. J.; Shu, C. W.; Sung, P. J.; Lim, Y. P.; Cheng, L. Y.; Wang, S. 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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). https://orcid.org/0000-0002-9391-4252 https://orcid.org/0000-0003-0716-3542 https://orcid.org/0000-0002-3065-3630 https://orcid.org/0000-0003-1808-740X https://orcid.org/0000-0001-6001-068X https://orcid.org/0000-0002-9633-953X https://orcid.org/0000-0002-6584-1922 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 of 3-(2,5-dimethoxyphenyl)-1-(naphthalen-2-yl)prop-2-en-1-one 2.2. X-ray diffraction analysis 3. Results and discussion 3.1 Molecular structure description 3.2. Hirshfeld surface analysis 3.3. Density functional theory (DFT) 3.4. Frontier molecular orbitals 3.5. Molecular electrostatic potential (MEP) 3.6. Reduced density gradient (RDG) 4. Conclusion Acknowledgments Supporting information Disclosure statement ORCID References PrintField10: PrintField11: PrintField12: PrintField13: PrintField14: PrintField15: PrintField16: PrintField17: PrintField20: PrintField21: PrintField22: PrintField23: PrintField24: PrintField25: PrintField26: PrintField27: