Synthesis, Characterization, X‑ray Crystal Structure, DFT Calculations, and Catalytic Properties of a Dioxidovanadium(V) Complex Derived from Oxamohydrazide and Pyridoxal: A Model Complex of Vanadate-Dependent Bromoperoxidase

A vanadium­(V) complex with the formula [Et₃NH]­[V^VO₂(sox-pydx)] with a new tridentate ligand 2-[2-[[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]­methylene]­hydrazinyl]-2-oxoacetamide (soxH-pydxH), obtained by condensation of oxamohydrazide and pyridoxal (one of the forms of vitamin B₆), has been synthesized. The compound was characterized by various analytical and spectroscopic methods, and its structure was determined by single-crystal X-ray diffraction technique. Density functional theory (DFT) and time-dependent DFT calculations were used to understand the electronic structure of the complex and nature of the electronic transitions observed in UV–vis spectra. In the complex, vanadium­(V) is found to be pentacoordinated with two oxido ligands and a bianionic tridentate ONO-donor ligand. The vanadium center has square-pyramidal geometry with an axial oxido ligand, and the equatorial positions are occupied by another oxido ligand and a phenolato oxygen, an imine nitrogen, and a deprotonated amide oxygen of the hydrazone ligand. A DFT-optimized structure of the complex shows very similar metrical parameters as determined by X-ray crystallography. The O₄N coordination environment of vanadium and the hydrogen-bonding abilities of the pendant amide moiety have a strong resemblance with the vanadium center in bromoperoxidase enzyme. Bromination experiments using H₂O₂ as the oxidizing agent, with model substrate phenol red, and the vanadium complex as a catalyst show a remarkably high value of <i>k</i>_cat equal to 26340 h^–1. The vanadium compound also efficiently catalyzes bromination of phenol and salicylaldehyde as well as oxidation of benzene to phenol by H₂O₂

The plant alkaloid chelerythrine binds to chromatin, alters H3K9Ac and modulates global gene expression

<p>Chelerythrine (CHL), a plant alkaloid, possesses antimicrobial, anti-inflammatory, and antitumor properties. Although CHL influences several key signal transduction pathways, its ability to interact directly with nucleoprotein complex chromatin, in eukaryotic cells has so far not been looked into. Here we have demonstrated its association with hierarchically assembled chromatin components, viz. long chromatin, chromatosome, nucleosome, chromosomal DNA, and histone H3 and the consequent effect on chromatin structure. CHL was found to repress acetylation at H3K9. It is more target-specific in terms of gene expression alteration and less cytotoxic compared to its structural analog sanguinarine.</p

DNA Damage and Apoptosis Induction in Cancer Cells by Chemically Engineered Thiolated Riboflavin Gold Nanoassembly

Herein we have engineered a smart nuclear targeting thiol-modified riboflavin-gold nano assembly, <b>RfS@AuNPs</b>, which accumulates selectively in the nucleus without any nuclear-targeting peptides (NLS/RGD) and shows photophysically in vitro DNA intercalation. A theoretical model using Molecular Dynamics has been developed to probe the mechanism of formation and stability as well as dynamics of the <b>RfS@AuNPs</b> in aqueous solution and within the DNA microenvironment. The <b>RfS@AuNPs</b> facilitate the binucleated cell formation that is reflected in the significant increase of DNA damage marker, γ-H2AX as well as the arrest of most of the HeLa cells at the pre-G1 phase indicating cell death. Moreover, a significant upregulation of apoptotic markers confirms that the cell death occurs through the apoptotic pathway. Analyses of the microarray gene expression of <b>RfS@AuNPs</b> treated HeLa cells show significant alterations in vital biological processes necessary for cell survival. Taken together, our study reports a unique nuclear targeting mechanism through targeting the riboflavin receptors, which are upregulated in cancer cells and induce apoptosis in the targeted cells