Synthesis, Structure, DFT Investigation, and In Silico Anticancer Activity of N‐(4‐Methoxyphenyl)‐N′‐Methyl Thiourea

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AbstractThe molecule of N‐(4‐methoxyphenyl)‐N′‐methyl thiourea (NMTU) was synthesized and characterized through FT‐IR, UV–vis, and 1H, 13C NMR analyses. Its absolute structure was established using single‐crystal X‐ray diffraction (SC‐XRD). The compound crystallizes in the P21/c space group of the monoclinic crystallographic system. Additionally, theoretical evaluations were performed using the density functional theory (DFT) with the B3LYP functional at the 6‐311G(d,p) basis set in the gas phase, showing that the theoretical geometry is in agreement with the X‐ray structural parameters. The analysis of the 3D structure, including dihedral angles, revealed that the compound was non‐planar. The HOMO and LUMO energy values, the global chemical reactivity descriptors, and the molecular electrostatic potential (MEP) were calculated, highlighting the molecule's positive and negative regions, as well as its stability and several electronic characteristics. Hirshfeld surface and 2D fingerprint plots were used to study intermolecular interactions within the crystal. The identified predominant interactions were H⋅⋅⋅H (58.1%), S⋅⋅⋅H/H⋅⋅⋅S (19%), and C⋅⋅⋅H/H⋅⋅⋅C (18.4%). Non‐bonded and weak interactions were investigated using the reduced density gradient (NCI‐RDG). Also, Mulliken charge distribution and natural bond orbital (NBO) analysis for electron transfer were performed at the same theoretical level. Finally The absorption, distribution, metabolism, excretion, and toxicity (ADMET) assessment followed by molecular docking studies were conducted to explore the toxicity and the biological activity of NMTU against mitochondria‐related disease and binding energies with the target protein (PDB ID: 1NTK).