«Green-Ligand» in Metallodrugs Design-Cu(II) Complex with Phytic Acid: Synthetic Approach, EPR-Spectroscopy, and Antimycobacterial Activity.

The interaction of sodium phytate hydrate CHOP·xNa·yHO (phytNa) with Cu(OAc)·HO and 1,10-phenanthroline (phen) led to the anionic tetranuclear complex [Cu(HO)(phen)(phyt)]·2Na·2NH·32HO (), the structure of the latter was determined by X-ray diffraction analysis. The phytate is completely deprotonated; six phosphate fragments (with atoms P1-P6) are characterized by different spatial arrangements relative to the cyclohexane ring (1a5e conformation), which determines two different types of coordination to the complexing agents-P1 and P3, P4, and P6 have monodentate, while P2 and P5 are bidentately bound to Cu cations. The molecular structure of the anion complex is stabilized by a set of strong intramolecular hydrogen bonds involving coordinated water molecules. Aromatic systems of phen ligands chelating copper ions participate in strong intramolecular and intermolecular π-π interactions, further contributing to their association. At the supramolecular level, endless stacks are formed, in the voids of which sodium and ammonium cations and water molecules are present. The stability of in the presence of human serum albumin (HSA) was investigated using Electron Paramagnetic Resonance (EPR) spectroscopy. Continuous wave (CW) EPR spectra in water/glycerol frozen solution clearly indicate a presence of an exchange-coupled Cu(II)-Cu(II) dimeric unit, as well as a Cu(II) monomer-like signal arising from spins sufficiently distant from each other, with comparable contributions of two types of signals. In the presence of albumin at a 1:1 ratio ( to albumin), the EPR spectrum changes significantly, primarily due to the reduced contribution of the S = 1 fraction showing dipole-dipole splitting. The biological activity of in vitro against the non-pathogenic (model for ) strain of is comparable to the first-line drug for tuberculosis treatment, rifampicin.