Delocalized quinolinium-macrocyclic peptides, an atypical chemotype for CNS penetration.

Macrocyclic drugs can address an increasing range of molecular targets but enabling central nervous system (CNS) access to these drugs has been viewed as an intractable problem. We designed and synthesized a series of quinolinium-modified cyclosporine derivatives targeted to the mitochondrial cyclophilin D protein. Modification of the cation to enable greater delocalization was confirmed by x-ray crystallography of the cations.

Discovery of human hexosaminidase inhibitors by in situ screening of a library of mono- and divalent pyrrolidine iminosugars.

Two libraries of mono- and dimeric pyrrolidine iminosugars were synthesized by CuAAC and (thio)urea-bond-forming reactions from the respective azido/aminohexylpyrrolidine iminosugar precursors. The resulting monomeric and dimeric compounds were screened for inhibition of β-N-acetylglucosaminidase from Jack beans, the plant ortholog of human lysosomal hexosaminidases. A selection of the best inhibitors of these libraries was then evaluated against human lysosomal β-N-acetylhexosaminidase B (hHexB) and human nucleocytoplasmic β-N-acetylglucosaminidase (hOGA).

Discovery of a Potent α-Galactosidase Inhibitor by in Situ Analysis of a Library of Pyrrolizidine-(Thio)urea Hybrid Molecules Generated via Click Chemistry.

The parallel synthesis of a 26-membered-library of aromatic/aliphatic-(thio)urea-linked pyrrolizidines followed by in situ biological evaluation toward α-galactosidases has been carried out. The combination of the (thio)urea-forming click reaction and the in situ screening is pioneer in the search for glycosidase inhibitors and has allowed the discovery of a potent coffee bean α-galactosidase inhibitor (IC = 0.37 μM, K = 0.

Harnessing pyrrolidine iminosugars into dimeric structures for the rapid discovery of divalent glycosidase inhibitors.

The synthesis of three libraries (1a-l, 1a'-l' and 2a-l) of dimeric iminosugars through CuAAC reaction between three different alkynyl pyrrolidines and a set of diazides was carried out. The resulting crude dimers were screened in situ against two α-fucosidases (libraries 1a-l and 1a'-l') and one β-galactosidase (2a-l). This method is pioneer in the search of divalent glycosidase inhibitors.

Integrated carboxylic carbon nanotube pathways with membranes for voltage-activated humidity detection and microclimate regulation.

This work describes some single walled carboxylic carbon nanotubes with outstanding transport properties when assembled in a 3D microarray working like a humidity membrane-sensor and an adjustable moisture regulator. Combined nano-assembly approaches are used to build up a better quality pathway through which assisted-charge and mass transport synchronically takes place. The structure-electrical response relationship is found, while controllable and tunable donor-acceptor interactions established at material interfaces are regarded as key factors for the accomplishment of charge transportation, enhanced electrical responses and adjustable moisture exchange.

Functional carbon nanotubes for high-quality charge transfer and moisture regulation through membranes: structural and functional insights.

Functional single walled carbon nanotubes (SWCNTs) are assembled onto porous supports by using layer-by-layer (LBL) approaches. Directed nano-assembly of nanotubes is identified as a crucial factor for controlling the combined functions of hybrid-composite membranes, including charge and moisture transport. In both the cases, donor-acceptor interactions are indicated to be responsible for the rearrangement of nanotubes inside the LBL multilayer and their related properties.

Transport properties of alkali-doped multi walled carbon nanotubes.

In this work we propose a study on electrical properties of multiwalled carbon nanotubes (MWCNT) doped with the most commonly used alkali metals. We report resistivity measurements of MWCNT exposed to doping with Li, Na, K and Cs. Our results show that, increasing the alkali exposure, the resistance of the doped sample decreases denoting a progressive sample metallization.

Cathode-luminescence from extrinsic impurities in bundles of carbon nanotubes: a possible role.

Luminescence spectra obtained by electron bombardment of carbon nanotubes bundles show an UV signal centered at about 380 nm. We show that these transitions are extrinsic to nanotubes, in the sense that they are not linked to any carbon compound or structure, but are caused by the residual catalyst material used in the growth process. A possible role of such luminescence attributable to impurities is also discussed.