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1.
Cancers (Basel) ; 11(12)2019 Dec 07.
Article in English | MEDLINE | ID: mdl-31817924

ABSTRACT

While first discovered in immunoreceptor signaling, the Syk protein kinase behaves as a tumor and metastasis suppressor in epithelial cells. Its reduced expression in breast and other carcinomas is correlated with decreased survival and increased metastasis risk, but its action mechanism remains largely unknown. Using phosphoproteomics we found that Syk phosphorylated E-cadherin and α-, ß-, and p120-catenins on multiple tyrosine residues that concentrate at intercellular junctions. Increased Syk expression and activation enhanced E-cadherin/catenin phosphorylation, promoting their association and complex stability. In human breast cancer cells, Syk stimulated intercellular aggregation, E-cadherin recruitment and retention at adherens junctions, and promoted epithelial integrity, whereas it inhibited cell migration and invasion. Opposite effects were obtained with Syk knockdown or non-phosphorylatable mutant E-cadherin expression. Mechanistically, Syk stimulated the interaction of the E-cadherin/catenin complex with zonula occludens proteins and the actin cytoskeleton. Conditional Syk knockout in the lactating mouse mammary gland perturbed alveologenesis and disrupted E-cadherin localization at adherens junctions, corroborating the observations in cells. Hence, Syk is involved in the maintenance of the epithelial integrity of the mammary gland via the phosphorylation and stabilization of the E-cadherin/catenin adherens junction complex, thereby inhibiting cell migration and malignant tumor invasion.

2.
J Org Chem ; 83(4): 1891-1897, 2018 02 16.
Article in English | MEDLINE | ID: mdl-29308637

ABSTRACT

We report the first example of a dihydrodinaphthoheptacene derivative and the mechanistic investigations of the regioselective electrophilic intramolecular cyclization reaction involved in the synthesis. The structural, electrochemical, and photophysical properties have been investigated.

3.
Chemistry ; 21(26): 9426-39, 2015 Jun 22.
Article in English | MEDLINE | ID: mdl-26012479

ABSTRACT

New families of donor/acceptor semiconductors based on dihydroindeno[1,2-a]fluorene and dihydroindeno[2,1-b]fluorene are reported. Due to the spiro bridges, this new generation of dihydroindenofluorenes allows a spatial separation of HOMO and LUMO, which retains the high ET value of the dihydroindenofluorene backbone and excellent physical properties. This control of the electronic and physical properties has allowed a second generation of dihydroindeno[1,2-a]fluorene to be obtained with strongly enhanced performance in green and sky-blue phosphorescent organic light-emitting diodes (PhOLEDs) relative to the first generation of materials. To date, this is the highest performance ever reported for a blue PhOLED by using a dihydroindenofluorene derivative. Through this structure-property relationship study, a remarkable difference of performance between syn and anti isomers has also been highlighted. This surprising behaviour has been attributed to the different symmetry of the two molecules, and highlights the importance of the geometry profiles in the design of host materials for PhOLEDs.

4.
Angew Chem Int Ed Engl ; 54(4): 1176-80, 2015 Jan 19.
Article in English | MEDLINE | ID: mdl-25469476

ABSTRACT

This work reports the first structure-properties relationship study of ortho [2,1-c]-, meta [1,2-a]-, and para [1,2-b]dihydroindenofluorenes, highlighting the influence of bridge rigidification on the electronic properties. This study has made it possible to devise an extended π-conjugated molecule with both a high triplet state energy level and excellent thermal and morphological stability. As a proof of concept, dihydroindenofluorenes were used as the host in sky-blue phosphorescent organic light-emitting diodes (PhOLEDs) with high performance.

5.
Chem Commun (Camb) ; 51(7): 1313-5, 2015 Jan 25.
Article in English | MEDLINE | ID: mdl-25482246

ABSTRACT

A new high triplet organic semi-conductor based on a donor-spiro-acceptor design has been synthesised and used as a host material in high performance (EQE = 11.4%) sky blue phosphorescent organic light emitting diodes.

7.
Dalton Trans ; 42(24): 8838-47, 2013 Jun 28.
Article in English | MEDLINE | ID: mdl-23648521

ABSTRACT

Herein we describe the synthesis and characterization of a neutral heteroleptic iridium complex bearing an unusual 2-pyridyl-6-methylthiazine dioxide ligand (pythdo). X-ray crystallographic analysis reveals that in the complex, the pythdo ligand is twisted and puckered, resulting in very low photoluminescent quantum efficiency. The emission profile is structured. Excited state lifetime measurements along with oxygen quenching studies point to a rare case of dual emission from different excited states whereby the high energy bands possess significant ligand-centered ((3)LC) character while the lower energy bands are predominantly characterized as a mixture of charge transfer ((3)CT) states. A detailed computational analysis corroborates the unusual photophysical behavior.

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