Synthesis, X-ray crystal structure, DFT, Hirshfeld surfaces, energy frameworks, and molecular docking analysis of a bicyclic ortho-aminocarbonitrile derivative

Abstract

2-Amino-4-(2, 5-dimethoxyphenyl)-4a,5,6,7-tetrahydronaphthalene-1,3,3(4H)-tricarbonitrile has been synthesized and characterized by conventional spectroscopic techniques (FT-IR and 1H NMR) and the three-dimensional structure elucidated by single crystal X-ray diffraction studies (SC-XRD). It exists in monoclinic crystal system with space group P21/c and lattice parameters: a = 14.641(13) Å, b = 8.653(4) Å, c = 16.609(10) Å, β = 116.34(3)°, and Z = 4. In the crystal packing, molecules are connected through N-H···O and N-H···N intermolecular and intramolecular C-H···O interactions. The N1-H11···N2 interaction results in the formation of a dimer corresponding to R22(12) graph-set motif. The molecular structure has been theoretically optimized by using density functional theory (DFT) with the basis set B3LYP/6-311G (d,p). The optimized bond geometry shows consistency with the SC-XRD data. Besides this, the molecular electrostatic potential (MEP), Mulliken charges, and frontier molecular orbital analysis have been described. The dnorm, shape index, curvedness, crystal voids, 2D fingerprint (FP) plots, and 3D energy frameworks using Hirshfeld surface (HS) studies have also been computed and investigated. The molecular docking studies for 2-amino-4-(2, 5-dimethoxyphenyl)-4a,5,6,7-tetrahydronaphthalene-1,3,3(4H)-tricarbonitrile with DNA gyrase/lanosterol 14α-demethylase suggest that the compound may act as an active antimicrobial drug.

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“…Their mechanisms are nonselective, inhibiting both COX-I and COX-II isoforms [6,7]. Density-functional theory (DFT) is a computational quantum mechanical method widely used in modern medicinal chemistry to suggest the electronic 3D atoms or molecule structures compute the ground state energy in realistic models of bulky molecules and their surfaces [8,9]. On the other hand, a valuable and popular tool in drug design is molecular docking.…”

“…Docking of Anthranilic acid derivatives (compounds[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] …”