Disulfide-Unit Conjugation Enables Ultrafast Cytosolic Internalization of Antisense DNA and siRNA.

Development of intracellular delivery methods for antisense DNA and siRNA is important. Previously reported methods using liposomes or receptor-ligands take several hours or more to deliver oligonucleotides to the cytoplasm due to their retention in endosomes. Oligonucleotides modified with low molecular weight disulfide units at a terminus reach the cytoplasm 10 minutes after administration to cultured cells. This rapid cytoplasmic internalization of disulfide-modified oligonucleotides suggests the existence of an uptake pathway other than endocytosis. Mechanistic analysis revealed that the modified oligonucleotides are efficiently internalized into the cytoplasm through disulfide exchange reactions with the thiol groups on the cellular surface. This approach solves several critical problems with the currently available methods for enhancing cellular uptake of oligonucleotides and may be an effective approach in the medicinal application of antisense DNA and siRNA.

A crystalline porous coordination polymer decorated with nitroxyl radicals catalyzes aerobic oxidation of alcohols.

A porous coordination polymer (PCP) has been synthesized employing an organic ligand in which a stable free radical, isoindoline nitroxide, is incorporated. The crystalline PCP possesses one-dimensional channels decorated with the nitroxyl catalytic sites. When O2 gas or air was used as the oxidant, this PCP was verified to be an efficient, recyclable, and widely applicable catalyst for selective oxidation of various alcohols to the corresponding aldehydes or ketones.

Indium-catalyzed [1 + n] annulation reaction between beta-ketoester and alpha,omega-diyne.

A catalytic amount of In(NTf(2))(3) effects the inter- and intramolecular addition of a beta-ketoester to an alpha,omega-diyne to produce a 1,3-dimethylenecycloalkane derivative in a single step. This [1 + n] annulation reaction shows good functional group tolerance and allows the synthesis of five- to seven-membered carbo- and heterocyclic as well as spirocyclic structures in moderate to excellent yields.

Efficient formation of ring structures utilizing multisite activation by indium catalysis.

Lewis acidic indium(III) salts, in particular In(NTf(2))(3), effect the conversion of alpha-(omega'-alkynyl)-beta-ketoesters and omega-alkynyl-beta-ketoesters to the corresponding cyclic products in a manner known as the Conia-ene reaction. This reaction can lead to the creation of five- to fifteen-membered-ring carbocycles and heterocycles in good to excellent yields. The synthetic features of the reaction are a relatively low catalyst loading, as low as 0.01 mol % in the best case, as well as no requirement of solvent for five-membered-ring formation and the requirement of only moderately dilute reaction conditions for medium-sized-ring formation. The high reactivity of indium salts is due to the double activation of the beta-ketoester substrate containing an acetylene function. The indium metal activates the beta-ketoester moiety by the formation of an indium enolate, and this indium metal electrophilically activates the alkyne moiety. Such a strong push-pull activation of the substrate by a single metal circumvents the disadvantage of entropic and enthalpic factors generally associated with the formation of medium- and large-sized rings. The reaction allows the ready formation of a fifteen-membered-ring carbocycle, from which dl-muscone has been synthesized.