Document Type : Original Research Article
- Ruchika Sharma 1
- Mulveer Singh 1
- Kamal K 2
- Nitin G Ghatpande 3, 4
- Mahidansha M Shaikh 3, 4
- Jagannath S Jadhav 5
- Saminathan Murugavel 6
- Rajni Kant 1
1 Chemical Crystallography Laboratory, Department of Physics, University of Jammu, Jammu Tawi-180006, India.
2 Department of Chemistry, Indian Institute of Technology, Jammu, 181221, India.
3 Department of pharmaceutical Chemistry, School of Health Science, University of KwaZulu- Natal, Durban-4041, South Africa.
4 Unique Med Chem Laboratories, L-64, Chincholli MIDC, Solapur-413255, M. S., India.
5 Department of Chemistry, Shivaji University, Kolhapur-416004, M.S., India.
6 Department of Physics, Thanthai Periyar Government Institute of Technology, Vellore-632002, Tamil Nadu, India.
(2,6-dimethoxyphenyl)acetic acid exists in the triclinic crystal system having space group P-1 and lattice dimensions = 7.66(4) Å, b = 8.16(4) Å, c = 8.65(3) Å, V = 503(4) Å3 and Z = 2. The molecular and crystal structure was elucidated using X-ray crystallographic techniques. The refinement of all the structural parameters was done using the full-matrix least-squares method and it yielded the final R-factor as 0.0579 for 1711 observed reflections. In the crystal packing, molecules are consolidated by intermolecular O-H....O and intramolecular C-H....O interactions. The O-H….O interaction makes a dimer corresponding to R22 (8) graph-set motif. Hirshfeld surface (HS) analysis has been complemented to envisage the conformity of the molecular structure. The void-volume analysis has been made to obtain the mechanical strength of the crystal structure. The energy frameworks have been constructed to know the stability of the structure and the kind of dominant energy present in it. The optimized structure using density functional theory (DFT), HOMO–LUMO energy and the charge on the atoms has been examined using B3LYP method. The inhibitory activity of (2,6-dimethoxyphenyl)acetic acid against microbial targets has been assessed using the docking process.
- (2,6-dimethoxyphenyl)acetic acid (DMPAA) has been synthesized by a standard procedure and its three-dimensional structure analyzed using crystallographic techniques.
- The crystal structure has been reinforced by hydrogen bond interactions.
- Hirshfeld surface analysis and DFT calculations have been performed.
- HOMO-LUMO frontier molecular orbitals have been examined (Egap = 5.87 eV)
- Molecular docking of DMPAA with DNA gyrase and CYP51protein has been analyzed and reported.
- Castellari, and S. Ottani, Anti-Inflammatory Drugs. II. Salt of 2-(2,6-Dichlorophenylamino) phenylacetic Acid with Diethanolamine. Acta Crystallographica, C51 (1995) 2612-2615.
- P. Deshpande, V.B. Nanduri, A. Pullockaran, H. Christie, R.H. Mueller and R.N. Patel, Microbial hydroxylation of o-bromophenylacetic acid: synthesis of 4-substituted-2,3-dihydrobenzofurans. Journal of Industrial Microbiology and Biotechnology, 35 (2008) 901–906.
- J. Jackson, H. Kobayashi, S.D. Steffens and A. Zakarian, 10‐Step Asymmetric Total Synthesis and Stereochemical Elucidation of (+)‐Dragmacidin D. Angewandte Chemie International Edition, 54 (2015) 9971-9975.
- L. Priebbenow and C. Bolm, Recent advances in the Willgerodt–Kindler reaction. Chemical Society Reviews, 42 (2013) 7870-7880.
- Hachuła, M. Nowak and J. Kusz, Hydrogen-bonding interactions in (3, 4-dimethoxyphenyl) acetic acid monohydrate. Acta Crystallographica, C64 (2008) o357–o360.
- J. Friedhoff and E.Van Winkle, Isolation and Characterization of a Compound from the Urine of Schizophrenics. Nature (London), 194 (1962a) 897–898.
- J. Friedhoff and E. Van Winkle , The characteristics of an amine found in the urine of Schizophrenic patients. The Journal of Nervous and Mental Disease, 135 (1962b) 550–555.
- Barbeau, J.A. De Groot, J.G. Joly, D.R. Tremblay and J. Donaldson, Urinary excretion of a 3-4, dimethoxyphenylethylamine-like substance in Parkinson''s disease. Revue Canadienne de Biologie, 22 (1963) 469–472.
- Szawkało and Z. Czarnocki, Enantioselective Synthesis of Some Tetracyclic Isoquinoline Alkaloids by Asymmetric Transfer Hydrogenation Catalysed by a Chiral Ruthenium Complex. Monatshefte für Chemie, 136 (2005) 1619–1627.
- Leiserowitz, Molecular packing modes. Carboxylic acids. Acta Crystallographica, B32 (1976) 775–802.
- Das and G.R. Desiraju, Packing Modes in Some Mono- and Disubstituted Phenylpropiolic Acids: Repeated Occurrence of the Rare syn,antiCatemer. Chemistry, an Asian Journal, 1–2 (2006) 231–244.
- R. Spackman, M.J. Turner, J.J. McKinnon, S.K. Wolff, D.J. Grimwood, D. Jayatilaka and M.A. Spackman. CrystalExplorer: a program for Hirshfeld surface analysis, visualization and quantitative analysis of molecular crystals. Journal of Applied Crystallography 54 (2021) 1006-1011.
- J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G.A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H.P. Hratchian, A.F. Izmaylov, J. Bloino, G. Zheng, J.L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J.A. Montgomery Jr., J.E. Peralta, F. Ogliaro, M. Bearpark, J.J. Heyd, E. Brothers, K.N. Kudin, V.N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J.M. Millam, M. Klene, J.E. Knox, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, R.L. Martin, K. Morokuma, V.G. Zakrzewski, G.A. Voth, P. Salvador, J.J. Dannenberg, S. Dapprich, A.D. Daniels, O. Farkas, J.B. Foresman, J.V. Ortiz, J. Cioslowski and D.J. Fox, Gaussian 09, Revision A.1, Gaussian, Inc., Wallingford, CT. 2013.
- Wehenkel, P. Fernandez, M. Bellinzoni, V. Catherinot, N. Barilone, G. Labesse,M. Jackson and P.M. Alzari, The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria. FEBS Letters, 580 (2006) 3018-3022.
- Aoumeur, N. Tchouar, S. Belaidi, M. Ouassaf, T. Lanez and S. Chtita, Molecular docking studies for the identifications of novel antimicrobial compounds targeting of staphylococcus aureus. Moroccan Journal of Chemistry, 9(2) (2021) 274-289.
- M. El-Feky, L.A. Abou-Zeid, M.A. Massoud, S.G. Shokralla1 and H.M. Eisa, Computational Design, Molecular Modeling and Synthesis of New 1,2,4 – Triazole Analogs with Potential Antifungal Activities. SMU Medical Journal, 1(2) (2014) 224-242.
- Jorda and S. Puig, Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae. Genes, 11 (2020) 795.
- R. Shinde and D.B. Muley. Synthesis, Characterization and Evaluation of Antioxidant and Antimicrobial activity of Spirochromones Derivatives. Anti-Infective Agents, 18 (2020) 352 - 361.
- M. Sheldrick, A Short History of SHELX. Acta Crystallographica, A64, (2008) 112-122.
- M. Sheldrick, SHELXT– Integrated space-group and crystal-structure determination. Acta Crystallographica, C71 (2015) 3-8.
- J.C. Wilson, International Tables for Crystallography Volume C: Mathematical, Physical and Chemical Tables. Acta Crystallographica, A51 (1995) 441-444.
- F. Macrae, I.J. Bruno, J.A. Chisholm, P.R. Edgington, P. McCabe, E. Pidcock, L. Rodriguez-Monge, R. Taylor, J. Van De Streek, and P.A. Wood, New Features for the Visualization and Investigation of Crystal Structures. Journal of Applied Crystallography, 41 (2008) 466-470.
- L. Spek, Structure validation in chemical crystallography. Acta Crystallographica, D65 (2009) 148-155.
- Nardelli, PARST: a system of Fortran routines for calculating molecular structure parameters from the results of crystal structure analyses. Journal of Applied Crystallography, 28 (1995) 659-659.
- Trott and A.J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. Journal of Computational Chemistry, 31 (2010) 455-461.
- H. Allen, O. Kennard, D.G. Watson, L. Brammer, A.G. Orpen and R.J. Taylor. Tables of Bond Lengths determined by X-Ray and Neutron Diffraction. Part I. Bond Lengths in Organic Compounds. Journal of the Chemical Society, Perkin Transactions 2, 2 (1987) 1-19.
- Hachula, M. Nowak and J. Kusz, Hydrogen-bonding interactions in (3,4-dimethoxyphenyl)acetic acid monohydrate. Acta Crystallographica, C64 (2008) o357-o360.
- Chopra, A.R. Choudhury and T.N. Guru Row, 3, 4-Dimethoxyphenylacetic acid. Acta Crystallographica, E59 (2003) o433-o434.
- J. Turner, S. Grabowsky, D. Jayatilaka and M.A. Spackman, Accurate and Efficient Model Energies for Exploring Intermolecular Interactions in Molecular Crystals. The Journal of Physical Chemistry Letters, 5 (2014) 4249-4255.
- J. Edwards, C.F. Mackenzie, P.R. Spackman, D. Jayatilaka and M.A. Spackman, Intermolecular interactions in molecular crystals: what’s in a name?. Faraday Discussions, 203 (2017) 93-112.
- Sangeetha, M. Govindarajan, N. Kanagathara, M.K. Marchewka, M. Drozd and G. Anbalagan, Vibrational, DFT, and thermal analysis of 2,4,6-triamino-1,3,5-triazin-1-ium 3-(prop-2-enoyloxy) propanoate acrylic acid monosolvate monohydrate. Journal of molecular structure, 1054-1055 (2013) 307-320.
- Ji Aihara, Weighted HOMO-LUMO energy separation as an index of kinetic stability for fullerenes. Theoretical chemistry accounts, 102 (1999) 134–138.
- Murugavel, S. Sundramoorthy, D. Lakshmanan, R. Subashini, P. Pavan Kumar, Synthesis, crystal structure analysis, spectral (NMR, FT-IR, FT-Raman and UV-Vis) investigations, molecular docking studies, antimicrobial studies and quantum chemical calculations of a novel 4-chloro-8-methoxyquinoline-2(1H)-one: an effective antimicrobial agent and an inhibition of DNA gyrase and lanosterol-14α-demethylase enzymes. Journal of molecular structure, 1131 (2017) 51-72.