Cooperative Effects In Heterometallic Complexes

About 8% of the human genome is covered with candidate cis-regulatory elements (cCREs). Disruptions of CREs, described as “cis-ruptions” have been identified as being involved in various genetic diseases. Thanks to the development of chromatin conformation study techniques, several long-range cystic fibrosis transmembrane conductance regulator (CFTR) regulatory elements were identified, but the regulatory mechanisms of the CFTR gene have yet to be fully elucidated. The aim of this work is to improve our knowledge of the CFTR gene regulation, and to identity factors that could impact the CFTR gene expression, and potentially account for the variability of the clinical presentation of cystic fibrosis as well as CFTR-related disorders. Here, we apply the robust GWAS3D score to determine which of the CFTR introns could be involved in gene regulation. This approach highlights four particular CFTR introns of interest. Using reporter gene constructs in intestinal cells, we show that two new introns display strong cooperative effects in intestinal cells. Chromatin immunoprecipitation analyses further demonstrate fixation of transcription factors network. These results provide new insights into our understanding of the CFTR gene regulation and allow us to suggest a 3D CFTR locus structure in intestinal cells. A better understand of regulation mechanisms of the CFTR gene could elucidate cases of patients where the phenotype is not yet explained by the genotype. This would thus help in better diagnosis and therefore better management. These cis-acting regions may be a therapeutic challenge that could lead to the development of specific molecules capable of modulating gene expression in the future.

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Self-Assembled Heterometallic Complexes by Incorporation of Calcium or Strontium Ion into a Manganese(II) 12-Metallacrown-3 Framework Supported by a Tripodal Ligand with Pyridine-Carboxylate Motifs: Stability in Their Manganese(III) Oxidized Form

Inorganic Chemistry ◽

10.1021/acs.inorgchem.1c00457 ◽

2021 ◽

Author(s):

Eric Gouré ◽

Bertrand Gerey ◽

Catalina N. Astudillo ◽

Jacques Pécaut ◽

Selim Sirach ◽

...

Keyword(s):

Heterometallic Complexes ◽

Tripodal Ligand ◽

Pyridine Carboxylate ◽

Self Assembled ◽

Strontium Ion

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Towards a Paradigm Shift in Polar Organometallic Chemistry

CHIMIA International Journal for Chemistry ◽

10.2533/chimia.2020.681 ◽

2020 ◽

Vol 74 (9) ◽

pp. 681-688 ◽

Cited By ~ 1

Author(s):

Eva Hevia

Keyword(s):

Organometallic Chemistry ◽

Synergistic Effects ◽

Chemical Properties ◽

Deep Eutectic Solvents ◽

Chemical Transformations ◽

Organometallic Reagents ◽

Cooperative Effects ◽

Bond Forming ◽

Synthetic Methodologies ◽

Metal Reagents

Core tools of synthetic chemistry, polar organometallic reagents (typified by organolithium and Grignard reagents) are used worldwide for constructing compounds, especially aromatic compounds, which are ubiquitous in organic chemistry and thus in numerous commodities essential to everyday life. By isolation and characterisation of key organometallic intermediates, research in our group has led to the design of polar mixed-metal reagents imbued with synergistic effects that display chemical properties and reactivity profiles far exceeding the limits of traditional single-metal reagents. These studies have improved existing, or established new fundamentally important, synthetic methodologies based on either stoichiometric or catalytic reactions. Bimetallic cooperative effects have been demonstrated in an impressive array of important bond forming reactions including deprotonative metallation, transition metal-free C–C bond formation and metal–halogen exchange to name just a few. Towards greener, more sustainable, safer chemical transformations, our group has also pioneered the use of polar organometallic reagents under air and/or with water present using biorenewable solvents such as Deep Eutectic Solvents (DES) and 2-methyl THF. Herein we summarize some of our recent efforts in this intriguing area, which we believe can make inroads towards a step change in the practice and future scope of polar organometallic chemistry.

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