Synthesis, structure, computational and molecular docking studies of asymmetrically di-substituted ureas containing carboxyl and phosphoryl hydrogen bond acceptor functional groups

Abstract

Abstract Two asymmetrically substituted ureas N,N -(2-carboxylphenyl)phenyl urea (L1) and diethyl 4-(3-phenylureido)benzylphosphonate (L2) were synthesized and characterized by spectroscopic and X-ray crystallographic analysis. The two compounds crystallized in the centrosymmetric monoclinic crystal system and P21/n space group. The carboxyl substituted urea L1 crystallized with one molecule in the asymmetric unit. A hydrogen-bonded dimer is formed between the carboxyl group of the urea and a second molecule of the compound. The urea functional group is involved in both intramolecular and intermolecular hydrogen bonding with the carboxyl and carbonyl oxygens, respectively. The interplay of intermolecular and intramolecular hydrogen bonding in the compound results in a 2-D hydrogen-bonded structure. The phosphoryl-substituted urea L2, on the other hand, crystallized with two molecules in the asymmetric unit, resulting in a hydrogen-bonded tetramer in the crystal lattice. Non-covalent interactions (NCI) analysis of the two compounds revealed the presence of competitive interactions between the urea functional group and the carboxyl and phosphoryl substituents in L1 and L2, respectively. Molecular docking calculations predicted favorable binding interactions between the ureas and the two anticancer protein targets EGFR kinase (2J5F) and anaplastic lymphoma kinase (5J7H).