Elucidating of new hydrazide-based complexes derived from Pd(II), Cu(II) and Cd(II) ions: studies concerning spectral, DFT, Hirshfeld-crystal, biological screening beside Swiss-ADME verification

Abstract

A new hydrazide ligand (HL) was characterized to be used for synthesis of some bivalent complexes via a green approach that free from hazard solvents. All synthesizes were analytically, spectrally and computationally characterized by using all available techniques. A bis-ligands were coordinated with Pd(II) and Cd(II) ions through neutral bidentate mode of C=O and C=N groups. While, a mono-ligand was coordinated with Cu(II) ion through a mono-negative tridentate mode. Such mode of bonding was suggested based on IR and NMR analysis and then confirmed computationally. The charges on N(10), O(12) and N(13) atoms in the ligand indicate their high nucleophilicity. The complexes were suggested in octahedral or square-planer geometry according to UV-Vis spectra and ESR spectrum of Cu(II) complex. The g-factors and anisotropic parameters supported the square planer geometry of [CuCl(L)] complex. The thermogravimetric (TGA) and kinetic analyses were studied for all complexes and supporting their freedom from water molecules and non-spontaneity of degradation stages. Some physical properties were estimated from modelling study and the superiority of most complexes over HL was noticed. Furthermore, all the compounds were tested in vitro against microbial strains and the Cu(II) complex showed high activity. Also, the antioxidant activity was tested by two methods as well as the cytotoxicity was tested against Ehrlich ascites cells and the Cu(II) or Pd(II) complex plays excellent. It is worthy to note that, the in-vitro results were supported by utilizing Swiss-ADME link. The pharmacokinetics of the small molecules (HL & [CuCl(L)]) were calculated to rank their bioavailability via such in-silico way that navigating at various Swiss Drug Design tools. The BOILED-Egg was also obtained to evaluate HIA and BBB as the indicators of passive gastrointestinal absorption and brain penetration barrier, respectively. The blue point appeared in Cu(II) complex egg indicates its effective effluxes by P-glycoprotein (P-gp), whereas the red point appeared in HL egg points to the non-substrate role of HL versus P-gp. Moreover, the ligand appeared oriented mainly towards MAP kinase and mixed lineage kinase 7 by 53.3%, while, the Cu(II) complex appeared oriented mainly towards GABA-A receptors as ligand-gated ion channel by 42.9%.