Synthesis, crystal structure, molecular docking, lattice energy and Hirshfeld surface analysis of an antituberculosis drug of (E)-2-methoxy-5-(((6-methoxypyridin-3yl)imino)methyl)phenol

Abstract

Synthesis, X-ray structure, molecular docking, lattice energy and Hirshfeld surface analysis of (E)-2-methoxy-5-(((6-methoxypyridin-3yl)imino)methyl)phenol (MMPIMP) is presented in this paper. The compound crystallizes in the monoclinic space group P2₁/c with unit cell parameters: a = 5.6149 (2), b = 14.5520 (5), c = 29.9813 (8) Å, β = 94.795 (3) and Z = 8. The asymmetric unit contains two crystallographically independent molecules (A and B) and the structure was solved by direct methods using single-crystal X-ray diffraction data and refined by full-matrix least-squares procedure to a final value of R = 0.050 and wR₂ = 0.1231 for 3536 observed reflections. The molecular packing in the unit cell is stabilized via O – H… N and C – H… O intermolecular hydrogen bonds. In the crystal packing, pairs of intermolecular hydrogen bonds of the type O–H…N links the molecules into dimers, forming $R_2^2$(20) ring motif. To understand the nature and strength of intermolecular interaction in terms of its energy and their quantitative contributions toward the molecular packing, lattice energy analysis was carried out by using PIXEL software. Molecular docking studies were executed to realize the inhibitory activity of the compound MMPIMP against DprE1 (PDB code: 4KW5). The analysis of the Hirshfeld surface and its associated two dimension fingerprint plots has been carried out to examine the intermolecular contacts in the crystal structure.

Keywords:

• Crystal structure
• Direct methods
• Intermolecular hydrogen bonding
• lattice energy
• Molecular docking
• Hirshfeld surface

Additional information

Funding

Rajni Kant acknowledges the Research Grants as sanctioned under the RUSA 2.0 Project (Ref. No: RUSA/JU/2/2019-20/111/3588-3636). Akhileshwari thanks KSTePS, DST and the Government of Karnataka for providing the fellowship in the paper.