Connectivity mapping of glomerular proteins identifies dimethylaminoparthenolide as a new inhibitor of diabetic kidney disease.

While blocking the renin angiotensin aldosterone system (RAAS) has been the main therapeutic strategy to control diabetic kidney disease (DKD) for many years, 25-30% of diabetic patients still develop the disease. In the present work we adopted a systems biology strategy to analyze glomerular protein signatures to identify drugs with potential therapeutic properties in DKD acting through a RAAS-independent mechanism. Glomeruli were isolated from wild type and type 1 diabetic (Ins2Akita) mice treated or not with the angiotensin-converting enzyme inhibitor (ACEi) ramipril.

Gold(I)/Gold(III) Catalysis that Merges Oxidative Addition and π-Alkene Activation.

Heteroarylation of alkenes with aryl iodides was efficiently achieved with a (MeDalphos)AuCl complex through Au /Au catalysis. The possibility to combine oxidative addition of aryl iodides and π-activation of alkenes at gold is demonstrated for the first time. The reaction is robust and general (>30 examples including internal alkenes, 5-, 6-, and 7-membered rings).

A non-symmetric sulfur-based O,C,O-chelating pincer ligand leading to chiral germylene and stannylene.

New chiral heteroleptic germanium(ii) and tin(ii) metallylenes were obtained using 1-(para-tolylsulfinyl)-3-tosyl-5-tert-butyl-benzene as a non-symmetric O,C,O-chelating pincer ligand. Crystallographic analysis and DFT calculations indicate that the non-symmetric sulfinyl-sulfonyl pincer ligand acts as an O,C,O-coordinating pincer-type-ligand with predominant sulfinyl intramolecular S[double bond, length as m-dash]O coordination to germanium(ii) and tin(ii) centers.

Bare histidine-serine models: implication and impact of hydrogen bonding on nucleophilicity.

A new family of 2-hydroxyalk(en/yn)ylimidazoles has been evaluated as serine-histidine bare dyad models for the ring-opening reaction of L-lacOCA, a cyclic O-carboxyanhydride. These models were selected to unravel the implication of intramolecular hydrogen bonding and to substantiate its influence on the nucleophilicity of the alcohol moiety, as it is suspected to occur in enzyme active sites. Although designed to exclusively facilitate the preliminary step of proton transfer during the studied ring-opening reaction, these minimalistic models depicted a measureable increase in reactivity relative to the isolated fragments.

Y-shaped mPEG-PLA cabazitaxel conjugates: well-controlled synthesis by organocatalytic approach and self-assembly into interface drug-loaded core-corona nanoparticles.

A well-defined poly(ethylene glycol) methyl ether-b-poly(lactic acid) copolymer (mPEG-PLA) featuring a new, Y-shaped, architecture with a hydroxyl functional group between the two blocks has been prepared and thoroughly characterized. The functional copolymer was then readily coupled to diglycolyl-cabazitaxel. The resulting copolymer conjugates assembled into stable and monodisperse nanoparticles (NPs) in aqueous suspension.

Organo-catalyzed ring opening polymerization of a 1,4-dioxane-2,5-dione deriving from glutamic acid.

The (3S)-[(benzyloxycarbonyl)ethyl]-1,4-dioxan-2,5-dione (BED) was prepared in four steps starting from glutamic acid and bromoacetyl bromide. According to X-ray diffraction analysis, the pendant functional group is located in equatorial position and points away from the six-membered ring. The organo-catalyzed ring-opening polymerization of BED was promoted with 4-dimethylaminopyridine (DMAP) and the combination of thiourea TU(Cy) and (-)-sparteine.

(1-Naphthyl)(trifluoromethyl) O-carboxy anhydride as a chiral derivatizing agent: eclipsed conformation enforced by hydrogen bonding.

The preparation of the (1-naphthyl)(trifluoromethyl) O-carboxy-anhydride 1 and its use as a chiral derivatizing agent with several alpha-chiral primary amines are reported. The very large Delta delta(RS) values observed in (1)H NMR have been correlated with a marked preference of the corresponding alpha-hydroxy-amides for the eclipsed conformation. In comparison, the related O-methylated amides are shown to adopt staggered conformations, which substantiates the critical role of intramolecular hydrogen bonding in maximizing the anisotropic effect.

Functionalized polyesters from organocatalyzed ROP of gluOCA, the O-carboxyanhydride derived from glutamic acid.

Well-controlled poly(alpha-hydroxyacids) featuring pendant carboxylic acid groups were prepared under mild conditions via DMAP-catalyzed ROP of the O-carboxyanhydrides derived from glutamic and lactic acids.

An activated equivalent of lactide toward organocatalytic ring-opening polymerization.

The alpha-lactone equivalent lacOCA exhibits remarkable reactivity compared with lactide in nucleophile-catalyzed ROP. PLAs of controlled molecular weights and narrow polydispersities are typically obtained under mild conditions using DMAP and various protic initiators.