Design and synthesis of stereochemically defined novel spirocyclic P2-ligands for HIV-1 protease inhibitors

The synthesis of a series of stereochemically defined spirocyclic compounds and their use as novel P2-ligands for HIV-1 protease inhibitors are described. The bicyclic core of the ligands was synthesized by an efficient nBu 3SnH-promoted radical cyclization of a 1,6-enyne followed by oxidative cleavage. Structure-based design, synthesis of ligands, and biological evaluations of the resulting inhibitors are reported.     

Ultra-Small Air-Stable Triplet-Triplet Annihilation Upconversion Nanoparticles for Anti-Stokes Time-Resolved Imaging

Image contrast is often limited by background autofluorescence in steady-state bioimaging microscopy. Upconversion bioimaging can overcome this by shifting the emission lifetime and wavelength beyond the autofluorescence window. Here we demonstrate the first example of triplet-triplet annihilation upconversion (TTA-UC) based lifetime imaging microscopy. A new class of ultra-small nanoparticle (NP) probes based on TTA-UC chromophores encapsulated in an organic–inorganic host has been synthesised. The NPs exhibit bright UC emission (400–500 nm) in aerated aqueous media with a UC lifetime of ≈1 μs, excellent colloidal stability and little cytotoxicity. Proof-of-concept demonstration of TTA-UC lifetime imaging using these NPs shows that the long-lived anti-Stokes emission is easily discriminable from typical autofluorescence. Moreover, fluctuations in the UC lifetime can be used to map local oxygen diffusion across the subcellular structure. Our TTA-UC NPs are highly promising stains for lifetime imaging microscopy, affording excellent image contrast and potential for oxygen mapping that is ripe for further exploitation.     

An optical sensor for reactive oxygen species: encapsulation of functionalised silica nanoparticles into silicate nanoprobes to reduce fluorophore leaching

Sol-gel nanoprobes, also known as Photonic Explorer for Bioanalysis with Biologically Localised Embedding (PEBBLE), capable of performing in-vitro intracellular monitoring of reactive oxygen species have been developed using a modified form of 5(6)-carboxyfluorescein diacetate. A sol-gel matrix was selected for the design of the probes as it is photostable, optically transparent and chemically inert, and to minimise leaching of the dye from the porous matrix it was covalently immobilised to silica nanoparticles (15 nm). Using this approach, 0.1% of the dye was found to leach over a typical analysis time of 5 h and minimal photobleaching was observed. In addition, the nanoprobes were shown to respond to hydrogen peroxide, hydroxyl anions, nitric oxide, peroxynitrile and superoxide anions, obtaining limits of detection of 2.2, 1.1, 3.2, 1.1 and 1.1 nM respectively. The nanoprobes were subsequently introduced into bovine oviducts using a lipid transfection reagent (Escort IV) and fluorescence was observed.     

Colorimetric detection and fingerprinting of bacteria by glass-supported lipid/polydiacetylene films

Glass-supported films of lipids and polydiacetylene were applied for visual detection and colorimetric fingerprinting of bacteria. The sensor films comprise polydiacetylene domains serving as the chromatic reporter interspersed within lipid monolayers that function as a biomimetic membrane platform. The detection schemes are based on either visible blue-red transitions or fluorescence transformations of polydiacetylene, induced by amphiphilic molecules secreted by proliferating bacteria. An important feature of the new film platform is the feasibility of either naked-eye detection of bacteria or color analysis using conventional scanners. Furthermore, we find that the degrees of bacterially induced color transformations depend both on the bacterial strains examined and the lipid compositions of the films. Accordingly, bacterial fingerprinting can be achieved through pattern recognition obtained by recording the chromatic transformations in an array of lipid/PDA films having different lipid components.     

Design and synthesis of C2-symmetric N-heterocyclic carbene precursors and metal carbenoids

Chiral, C(2)-symmetric imidazolium and imidazolinium ions, as well as the corresponding copper- or silver-bound carbenoids, have been prepared. Structural study of these compounds by X-ray crystallography reveals a chiral pocket that surrounds the putative carbene site or the metal-carbene bond, at carbon 2, in three of the four ligands prepared. Preliminary investigation into the application of these complexes has shown one of them to be highly enantioselective in the hydrosilylation of acetophenone.     

Dihydropyranone formation by ipso C-H activation in a glucal 3-carbamate-derived rhodium acyl nitrenoid

By using (N-tosyloxy)-3-O-carbamoyl-D-glucal 10, which removes the need for a hypervalent iodine(III) oxidant, we provide evidence for rhodium nitrenoid-mediated ipso C-H activation as the origin of a C3-oxidized dihydropyranone product 3. This system may be especially susceptible to such a pathway because of the ease of forming a cation upon hydride transfer to the rhodium-complexed acyl nitrene.     

Behavior of β-amyloid 1-16 at the air-water interface at varying pH by nonlinear spectroscopy and molecular dynamics simulations

The adsorption and aggregation of β-amyloid (1-16) fragment at the air-water interface was investigated by the combination of second harmonic generation (SHG) spectroscopy, Brewster angle microscopy (BAM), and molecular dynamics simulations (MD). The Gibbs free energy of surface adsorption was measured to be -10.3 kcal/mol for bulk pHs of 7.4 and 3, but no adsorption was observed for pH 10-11. The 1-16 fragment is believed not to be involved in fibril formation of the β-amyloid protein, but it exhibits interesting behavior at the air-water interface, as manifested in two time scales for the observed SHG response. The shorter time scale (minutes) reflects the surface adsorption, and the longer time scale (hours) reflects rearrangement and aggregation of the peptide at the air-water interface. Both of these processes are also evidenced by BAM measurements. MD simulations confirm the pH dependence of surface behavior of the β-amyloid, with largest surface affinity found at pH = 7. It also follows from the simulations that phenylalanine is the most surface exposed residue, followed by tyrosine and histidine in their neutral form.     

A renewable, chemoselective, and quantitative ligand density microarray for the study of biospecific interactions

Novel renewable microarray technology has been developed to immobilize and release carbohydrates and proteins from self-assembled monolayers (SAMs) of electroactive quinone-terminated alkanethiolates on gold surfaces. This method may be applied to a variety of research fields for use in biosensor technology and the generation of renewable and tailored microarrays for biospecific cell-based assays.     

Magnetic and thermoelectric properties of REMoN3 (RE = La,Ce, Pr,Nd, and Sm): A first-principles study

We investigated the magnetic and thermoelectric properties of REMoN₃ (RE = La, Ce, Pr, Nd, Sm) perovskites using the full potential linearized augmented plane wave (FP-LAPW) method. To overcome the problem of underestimation of electronic interaction, we employed the DFT + U approach to accurately map the electronic structure of these compounds. Our study shows an increasing trend in the magnetic moments with the increasing number of unpaired electrons in RE. Among these compounds, SmMoN₃ possesses a large magnetic moment, which is suitable for applications such as memory devices and sensors. Interestingly, all these perovskites display ferromagnetic behavior except CeMoN₃, which exhibits an antiferromagnetic nature. Furthermore, our analysis indicates n-type thermoelectric behavior in all these materials. The compound, namely PrMoN₃, exhibits a high figure of merit among REMoN₃, which can be improved by modifying the lattice sites.     

Nickel-catalyzed Negishi alkylations of styrenyl aziridines

A nickel-catalyzed cross-coupling reaction between N-sulfonyl aziridines and organozinc reagents is reported. The catalytic system comprises an inexpensive and air-stable Ni(II) source and dimethyl fumarate as ligand. Regioselective synthesis of β-substituted amines is possible under mild and functional-group-tolerant conditions. The stereoselectivity of the reaction is consistent with a stereoconvergent mechanism wherein the sulfonamide directs C-C bond formation.