Uptake mechanism of oppositely charged fluorescent nanoparticles in HeLa cells

The endocytotic mechanisms involved in the uptake of charged polystyrene nanoparticles into HeLa cells were investigated. Uptake experiments were done in the presence or absence of drugs known to inhibit various factors in endocytosis. Independent of the particle charge, endocytosis is highly dependent on dynamin, F-actin, and tyrosine-specific protein kinases, which suggests a dynamin-dependent and lipid raft-dependent mechanism. However, cholesterol depletion did not hinder particle uptake. Regarding positively charged particles, macropinocytosis, the microtubule network, and cyclooxygenases are also involved. The clathrin-dependent pathway plays a minor role.     

Computer-assisted identification of small-molecule Bcl-2 modulators

Apoptosis, the programmed cell death, is a highly regulated process, necessary for normal development and homeostasis of the functions of organisms. The Bcl-2 inhibitors BH3I-1 and BH3I-2 were used as lead compounds to find possible Bcl-2 or Bcl-X_L inhibitors by using computer-assisted screening with our in-house database, containing more than four million commercially available molecules. Identified compounds were further investigated regarding their possible application as a drug.     

Ligand-free nickel catalyzed perfluoroalkylation of arenes and heteroarenes

We describe a “ligand-free” Ni-catalyzed perfluoroalkylation of heteroarenes to produce a diverse array of trfiluoromethyl, pentafluoroethyl and heptafluoropropyl adducts. Catalysis proceeds at room temperature via a radical pathway. The catalytic protocol is distinguished by its simplicity, and its wide scope demonstrates the potential in the late-stage functionalization of drug analogues and peptides.

A ligand-free, room temperature, Ni-catalyzed perfluoroalkylation of heteroarenes produced a diverse array of polyfluorinated adducts; potential in the late-stage functionalization of drugs and peptides is also demonstrated.     

Soft-landing of peptides onto self-assembled monolayer surfaces

Mass-selected peptide ions produced by electrospray ionization were deposited as ions by soft-landing (SL) onto fluorinated and hydrogenated self-assembled monolayer (FSAM and HSAM) surfaces using a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially designed for studying collisions of large ions with surfaces. Analysis of modified surfaces was performed in situ by combining 2 keV Cs(+) secondary ion mass spectrometry with FT-ICR detection of the sputtered ions (FT-ICR-SIMS). Similar SIMS spectra obtained following SL at different collision energies indicate that peptide fragmentation occurred in the analysis step (SIMS) rather than during ion deposition. The effect of the surface on SL was studied by comparing the efficiencies of SL on gold, FSAM, HSAM, and COOH-terminated SAM surfaces. It was found that FSAM surfaces are more efficient in retaining ions than their HSAM analogues, consistent with their larger polarizability. The efficiency of soft-landing of different peptides on the FSAM surface increases with the charge state of the ion, also consistent with an ion-polarizable molecule model for the initial stage of soft-landing on SAM surfaces. The gradual decrease of peptide ion deposition efficiency with an increase in collision energy found experimentally was quantitatively rationalized using the hard-cube model.     

Photoelectron spectroscopy of S1 toluene: II. Intramolecular dynamics of selected vibrational levels in S1 toluene studied by nanosecond and picosecond time-resolved photoelectron spectroscopies

We present results which suggest that the photophysics of S(1) toluene is significantly more complicated than that of the related molecules p-fluorotoluene or p-difluorobenzene. We have measured a range of photoelectron spectra for a number of S(1) internal energies, on different time scales and at different temperatures, in an attempt to unravel the competing processes, but the final conclusion remains outstanding.     

Gut microbiota, diet, and heart disease

Modulation of the gut microbiota is an area of growing interest, particularly for its link to improving and maintaining the systemic health of the host. It has been suggested to have potential to reduce risk factors associated with chronic diseases, such as elevated cholesterol levels in coronary heart disease (CHD). Diets of our evolutionary ancestors were largely based on plant foods, high in dietary fiber and fermentable substrate, and our gut microbiota has evolved against a background of such diets. Therapeutic diets that mimic plant-based diets from the early phases of human evolution may result in drug-like cholesterol reductions. In contrast, typical Western diets low in dietary fiber and fermentable substrate, and high in saturated and trans fatty acids, are likely contributors to the increased need for pharmacological agents for cholesterol reduction. The gut microbiota of those consuming a Western diet are likely underutilized and depleted of metabolic fuels, resulting in a less than optimal gut microbial profile. As a result, this diet is mismatched to our archaic gut microbiota and, therefore, to our genome, which has changed relatively little since humans first appeared. While the exact mechanism by which the gut microbiota may modulate cholesterol levels still remains uncertain, end products of bacterial fermentation, particularly the short chain fatty acids (i.e., propionate), have been suggested as potential candidates. While more research is required to clarify the potential link between gut microbiota and CHD risk reduction, consuming a therapeutic diet rich in plant foods, dietary fiber, and fermentable substrate would be a useful strategy for improving systemic health, possibly by altering the gut microbiota.     

Crystal growth, structure, and physical properties of LnCu2(Al,Si)5 (Ln = La and Ce)

LnCu(2)(Al,Si)(5) (Ln = La and Ce) were synthesized and characterized. These compounds adopt the SrAu(2)Ga(5) structure type and crystallize in the tetragonal space group P4/mmm with unit cell dimensions of a ≈ 4.2 ? and c ≈ 7.9 ?. Herein, we report the structure as obtained from single crystal X-ray diffraction. Additionally, we report the magnetic susceptibility, magnetization, resistivity, and specific heat capacity data obtained for polycrystalline samples of LnCu(2)(Al,Si)(5) (Ln = La and Ce).     

Formation of the imide [Ta(NMe2)3(μ-NSiMe3)]2 through an unprecedented α-SiMe3 abstraction by an amide ligand

Ta(NMe(2))(4)[N(SiMe(3))(2)] (1) undergoes the elimination of Me(3)Si-NMe(2) (2), converting the -N(SiMe(3))(2) ligand to the ═NSiMe(3) ligand, to give the imide "Ta(NMe(2))(3)(═NSiMe(3))" (3) observed as its dimer 4. CyN═C═NCy captures 3 to yield guanidinates Ta(NMe(2))(3-n)(═NSiMe(3))[CyNC(NMe(2))NCy](n) [n = 1 (5), 2 (6)]. The kinetic study of α-SiMe(3) abstraction in 1 gives ΔH(?) = 21.3(1.0) kcal/mol and ΔS(?) = -17(2) eu.     

Samarium(II) iodide reduction of isoxazolidines

SmI₂ was used as reducing agent for the N-O bond cleavage in isoxazolidines. The procedure revealed is general and particularly useful for the transformation of 5-spirocyclopropane isoxazolidines to the corresponding β-aminocyclopropanols, a troublesome transformation with other known reagents.     

A novel catalytic adsorptive stripping voltammetric method for the determination of germanium ultratraces in the presence of chloranilic acid and the V(IV)·HEDTA complex

A novel, sensitive catalytic adsorptive stripping voltammetric procedure which can be used to determine trace amounts of germanium is described. The method is based on the interfacial accumulation of the complex formed by Ge(IV) and the product of the reduction of chloranilic acid on the hanging mercury drop electrode or the renewable silver amalgam film electrode, and its subsequent reduction from the adsorbed state followed by the catalytic action of the V(IV)·HEDTA complex. The presence of V(IV)·HEDTA greatly enhances the adsorptive stripping response of Ge. The reduction of the Ge(IV) in the presence of chloranilic acid and V(IV)·HEDTA was investigated in detail and the effects of pH, electrolyte composition, and instrumental parameters were studied. Under optimal conditions, the catalytic peak current of germanium exhibited good linearity for Ge(IV) concentrations in the range of 0.75–60 nM (for 60 s of accumulation at −0.1 V, r² = 0.995) and a low limit of detection (LOD = 0.085 nM). The procedure was successfully applied to determine Ge in water samples.