TY - JOUR

T1 - «Green-Ligand» in Metallodrugs Design—Cu(II) Complex with Phytic Acid: Synthetic Approach, EPR-Spectroscopy, and Antimycobacterial Activity

AU - Koshenskova, Kseniya A

AU - Makarenko, Natalia V

AU - Dolgushin, Fedor M

AU - Yambulatov, Dmitriy S

AU - Bekker, Olga B

AU - Fedin, Matvey V

AU - Dementev, Sergei A

AU - Krumkacheva, Olesya A

AU - Eremenko, Igor L

AU - Lutsenko, Irina A

N1 - The work was supported by the Ministry of Science and Higher Education of Russia as part of the state assignment of Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences.

PY - 2025/1/15

Y1 - 2025/1/15

N2 - The interaction of sodium phytate hydrate C6H18O24P6·xNa·yH2O (phytNa) with Cu(OAc)2·H2O and 1,10-phenanthroline (phen) led to the anionic tetranuclear complex [Cu4(H2O)4(phen)4(phyt)]·2Na+·2NH4+·32H2O (1), the structure of the latter was determined by X-ray diffraction analysis. The phytate 1 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 Cu2+ 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 1 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 (1 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 1 in vitro against the non-pathogenic (model for Mycobacterium tuberculosis) strain of Mycolicibacterium smegmatis is comparable to the first-line drug for tuberculosis treatment, rifampicin.

AB - The interaction of sodium phytate hydrate C6H18O24P6·xNa·yH2O (phytNa) with Cu(OAc)2·H2O and 1,10-phenanthroline (phen) led to the anionic tetranuclear complex [Cu4(H2O)4(phen)4(phyt)]·2Na+·2NH4+·32H2O (1), the structure of the latter was determined by X-ray diffraction analysis. The phytate 1 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 Cu2+ 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 1 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 (1 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 1 in vitro against the non-pathogenic (model for Mycobacterium tuberculosis) strain of Mycolicibacterium smegmatis is comparable to the first-line drug for tuberculosis treatment, rifampicin.

KW - EPR spectra

KW - antimycobacterial activity

KW - copper(II) compounds

KW - crystal structure

KW - phytic acid

UR - https://www.mendeley.com/catalogue/cfb9a03d-09aa-3e8d-b59f-02637eeb2ab0/

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85216077024&origin=inward&txGid=75486613e3d8c76c1a5751785039b534

U2 - 10.3390/molecules30020313

DO - 10.3390/molecules30020313

M3 - Article

C2 - 39860183

JO - Molecules

JF - Molecules

SN - 1420-3049

M1 - 313

ER -