Spectroscopic Rationalization of Selective Colorimetric Chemosensing of Fe(lll) in Aqueous Medium by a New Mono-Substituted Dibenzodiaza-Crown Ether Macrocyclic Ligand Appended with Mono 2-Benzimidazole N-Pendant Side Arm.

Optical chemosensor L comprising of a new mono-N-substituted derivative of dibenzodiaza-crown ether macrocyclic ligand bearing a 2-benzimidazole (2Bim) side arm was synthesized, and characterized by FT-IR, elemental microanalyses, 1H NMR, and 13C NMR, UV-visible, fluorescence (FL) spectroscopy. The colorimetric chemosensing behavior of L toward the library metal ions was examined, wherein L represented a prompt and selective yellow-to-purple color change for Fe(III) cation in a 25µM solution with LOD as 0.23 µM in ethanol:water (9:1, v/v), even in the presence of the other library metal ions (LMI). Based on the 1H NMR, UV-visible, and FL observations the coordination sphere of Fe(III) was shared with two 2-benzoimidazole (2Bim) side arms which were also confirmed by the elemental microanalyses (in the solid state) and the Job plot method (in the solution) of the complex. Moreover, the above-mentioned color change was attributed to the presence of a strong charge transfer (LMCT) band for the Fe(III)/L interaction in the solution. Furthermore, the viscosity measurement in the presence of Fe(III) uncovered an increase at 0.5-1.0 ratios for Fe(III)/L, attributable to the formation of a self-assembly in the solution. A TLC paper strip was impregnated by L for selective detection of Fe(III), demonstrating a live color change for Fe(III) at 0-5 mM in the presence of LMI.

Integrative genomic analyses identify candidate causal genes for calcific aortic valve stenosis involving tissue-specific regulation.

There is currently no medical therapy to prevent calcific aortic valve stenosis (CAVS). Multi-omics approaches could lead to the identification of novel molecular targets. Here, we perform a genome-wide association study (GWAS) meta-analysis including 14,819 cases among 941,863 participants of European ancestry. We report 32 genomic loci, among which 20 are novel. RNA sequencing of 500 human aortic valves highlights an enrichment in expression regulation at these loci and prioritizes candidate causal genes. Homozygous genotype for a risk variant near TWIST1, a gene involved in endothelial-mesenchymal transition, has a profound impact on aortic valve transcriptomics. We identify five genes outside of GWAS loci by combining a transcriptome-wide association study, colocalization, and Mendelian randomization analyses. Using cross-phenotype and phenome-wide approaches, we highlight the role of circulating lipoproteins, blood pressure and inflammation in the disease process. Our findings pave the way for the development of novel therapies for CAVS.