Carbohydrate-based heteronuclear complexes as topoisomerase Iα inhibitor: approach toward anticancer chemotherapeutics

<p>Due to the critical role of cellular enzymes necessary for cell proliferation by deciphering topological hurdles in the process of DNA replication, topoisomerases have been one of the major targets in the anticancer drug development area. A need, therefore, arises for new metallodrugs that specifically recognizes DNA and inhibits the activity of topoisomerase enzymes, herein, we report the synthesis and characterization of new metal-based glycoconjugate entities containing heterobimetallic core Cu^II–Sn^IV (<b>1</b>) and Ni^II–Sn^IV (<b>2</b>) derived from N-glycoside ligand (<b>L</b>). The optimized structure of complex <b>1</b> and other significant vibrational modes have been explained using dispersion corrected B3LYP/DFT calculations. <i>In vitro</i> DNA binding profile of the <b>L</b> and both the complexes <b>1</b> and <b>2</b> were done by various biophysical studies. Complex <b>1</b> breaks pBR322 DNA <i>via a</i> hydrolytic means which was validated by T4 DNA enzymatic assay. To get a mechanistic insight of mode of action topoisomerase I (Topo I) inhibition assay was carried out. Also, we have taken the help of molecular modeling studies in accordance with experimental findings. <i>In vitro</i> cytotoxicity of the complex <b>1</b> was evaluated against a panel of cancer cells which exhibited remarkably good anticancer activity (GI₅₀ values <10 μg/ml). Moreover, intracellular localization of the complex <b>1</b> was visualized by confocal microscopy against HeLa cells.</p

Metal vs Ligand Oxidation: Coexistence of Both Metal-Centered and Ligand-Centered Oxidized Species

A series of two-electron-oxidized cobalt porphyrin dimers have been synthesized upon controlled oxidations using halogens. Rather unexpectedly, X-ray structures of two of these complexes contain two structurally different low-spin molecules in the same asymmetric unit of their unit cells: one is the metal-centered oxidized diamagnetic entity of the type CoIII(por), while the other one is the ligand-centered oxidized paramagnetic entity of the type CoII(por•+). Spectroscopic, magnetic, and DFT investigations confirmed the coexistence of the two very different electronic structures both in the solid and solution phases and also revealed a ferromagnetic spin coupling between Co­(II) and porphyrin π-cation radicals and a weak antiferromagnetic coupling between the π-cation radicals of two macrocycles via the bridge in the paramagnetic complex

Probing Phosphorus Solubility and Its Effect on Critical Temperature (<i>T</i>_c) in the Helical Superconducting Magnet RbEuFe₄As_4–<i>x</i>P_<i>x</i>

RbEuFe4As4 exhibits a rare combination of high-temperature superconductivity and noncollinear magnetism, originating from the FeAs and Eu layers, respectively. In order to fine-tune its superconducting and magnetic properties, we studied P-doped RbEuFe4As4–xPx. To determine the value of x for which RbEuFe4As4–xPx exists, members of the series have been synthesized in the form of relatively large-sized single crystals by a high-temperature flux growth technique using RbAs flux as well as polycrystalline powder by direct combination reactions between RbFe2As2 and EuFe2As2–xPx. The flux crystal growth reactions indicate that RbEuFe4As4–xPx forms with the values of x ≤ 0.12, which is corroborated by the Rietveld refinement analysis on the products obtained from direct combination reactions. The solubility limit exists primarily due to the preferential site As(2) occupation by P in the RbEuFe4As4 crystal structure. As x increases in RbEuFe4As4–xPx, magnetization measurements reveal that the superconducting critical transition temperature (Tc) decreases, while the magnetic ordering temperature (TN) remains almost unchanged in comparison to undoped RbEuFe4As4