Complexation of some d-metals with N-benzyl-N-nitrosohydroxylamine derivatives. Crystal and molecular structure of diaquabis[N-benzyl-N-nitrosohydroxylaminato-κ2O,O′]cobaltl(II) and in silico target fishing

• Published in: Inorganic chemistry communications 2023-11, Vol.157, p.111295, Article 111295
• Main Authors: Alabada, Rusul, Utenyshev, Andrey, Mohammad, Layth Jasim, Shilov, Gennadiy, Zyuzin, Igor, Bostanabad, Ali Sheikh, Abdulhussein, Jasim Mohammed, Karimi, Isaac, Kovalchukova, Olga
• Format: Article
• Language: English
• Subjects: ADMET; Antibacterial; In silico drug discovery; N-nitrosohydroxylamine; Target fishing
• ISSN: 1387-7003; 1879-0259
• DOI: 10.1016/j.inoche.2023.111295

[Display omitted] •The complexation of bivalent metals with N-benzyl-N-nitrosohydroxylamine (L1) and N-(2F-benzyl)-N-nitrosohydroxylamine (L2) were reported.•The crystal structure of Co(L1)2(H2O)2 showed that the organic species act as bidental chelating ligands occupying cis-positions in the coordination sphere of Co(II) cation.•These ligands obeyed Lipinski’s and Veber’s rules of drug discovery pipeline.•L2 showed different target preference in comparison to that of its parent molecule, L1.•Glutaminyl-tRNA synthetase and lumazine synthase were top-scored targets. N-nitrosohydroxylamine derivatives are dubbed as chelating agents. The complexation of bivalent metals with N-benzyl-N-nitrosohydroxylamine (L1) and N-(2F-benzyl)-N-nitrosohydroxylamine (L2) were studied with DFT B3LYP modeling, electronic spectroscopy, and X-Ray diffraction. The 3d-metal cations showed good affinity to N-nitroso-N-hydroxylamine derivatives and formed complex compounds with high degree of covalence. Their absorption bands shifted towards the spectra of neutral forms of the non-coordinated ligands. The value of the shift increased in a series of Mn2+ < Co2+ < Ni2+ < Cu2+ > Zn2+ > Cd2+. The determined formation constants of the complexes lied in the range of 9.86 – 11.58. The crystal structure of Co(L1)2(H2O)2 showed that the organic species act as bidental chelating ligands occupying cis-positions in the coordination sphere of Co(II) cation. In the lattice, the molecules of the compound formed parallel layers which arranged in columns stabilized using a set of intermolecular hydrogen bonds. These ligands obeyed Lipinski’s and Veber’s rules of drug discovery pipeline. Besides, L1 and L2 also had half-life values of 0.7and 0.4 h, oral bioavailability score of 0.55, and positive blood–brain barrier permeability indicating their potential as therapeutic lead-like compounds. Further, potential targets were screened out computationally. L1 predominantly interacted with family A of G-protein coupled receptors and enzymes while L2 also interacted with protease and nuclear receptors in addition to the targets of its parent molecule, L1. Essentially, glutaminyl-tRNA synthetase and lumazine synthase were suggested as top-scored targets. In sum up, these ligands may be antimicrobial lead-like molecules suitable to be submitted to the in vitro validation.