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

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. © 2023 Elsevier B.V.