Pd2+ and Cu2+ catalyzed oxidative cross-coupling of mercaptoacetylenes and arylboronic acids

An oxidative thiolate scavenging concept in a metal catalyzed reaction is presented and demonstrated on the aerobic Pd and Cu catalyzed cross-coupling of mercaptoacetylenes with arylboronic acids. Synthetic value of the chemistry as the complementary tool to the Sonogashira protocol has been demonstrated on a series of functionalized mercaptoacetylene substrates.     

First Distance-of-Flight Instrument: Opening a New Paradigm in Mass Spectrometry

A new instrumental concept, distance-of-flight mass spectrometry (DOFMS), is demonstrated experimentally. In DOFMS the mass-to-charge ratio of ions is determined by the distance each ion travels during a fixed time period; the mass spectrum is then recorded with a position-sensitive detector. The DOF approach provides a new way to separate and quantify components of complex samples. Initial results are demonstrated with a glow discharge ion source and a microchannel plate–phosphor screen detector assembly for atomic ion determination. This detection system demonstrated mass spectral peak widths of approximately 0.65 mm, corresponding to resolving powers of approximately 400–600 for a number of elemental samples.     

Switchable Lipids: Conformational Change for Fast pH‐Triggered Cytoplasmic Delivery

We report the use of switchable lipids to improve the endosomal escape and cytosolic delivery of cell‐impermeable compounds. The system is based on a conformational reorganization of the lipid structure upon acidification, as demonstrated by NMR spectroscopic studies. When incorporated in a liposome formulation, the switchable lipids triggered bilayer destabilization through fusion even in the presence of poly(ethylene glycol). We observed 88 % release of sulforhodamine B in 15 min at pH 5, and the liposome formulations demonstrated high stability at pH 7.4 for several months. By using sulforhodamine B as a model of a highly polar drug, we demonstrated fast cytosolic delivery mediated by endosomal escape in HeLa cells, and no toxicity.     

Effective χ and surface segregation in blends of star and linear polystyrene

The existence in blends of linear and star branched polystyrenes (PS) of a bulk thermodynamic interaction due to differences in macromolecular architecture has been demonstrated with small angle neutron scattering measurements. It has also been demonstrated that a regularly star‐branched polystyrene material segregates preferentially to the surface of a blend of star and linear molecules.     

Low-voltage electromembrane extraction of basic drugs from biological samples

The present work has for the first time demonstrated electromembrane extraction (EME) at voltages obtainable by common batteries. Five basic drugs were extracted from acidified aqueous sample solutions, across a supported liquid membrane (SLM) consisting of 1-isopropyl-4-nitrobenzene impregnated in the walls of a hollow fiber, and into an acidified aqueous acceptor solution present inside the lumen of the hollow fiber with potential differences of 1-10 V applied over the SLM. Extractions from 1 ml standard solutions prepared in 10mM HCl for 5 min and with a potential of 10 V demonstrated analyte recoveries of 50-93% in 25 microl of 10mM HCl as acceptor solution. This corresponds to enrichment factors of 20-37. Similar results were obtained with a common 9 V battery as power supply. Recoveries from low-voltage EME on human plasma, urine, and breast milk diluted with acetate buffer (pH 4) demonstrated recoveries in the range of 37-55% after 5 min of extraction. Excellent selectivity was demonstrated as no interfering peaks were detected. Standard curves in the range of 0.0625-0.62 5 microg/ml demonstrated correlation coefficients of 0.994-0.999. Extraction recoveries from human plasma, urine or breast milk were not found to be sensitive towards individual variations. The results show that low-voltage EME has a future potential as a simple, selective, and time-efficient sample preparation technique of biological fluids.     

Room temperature reversible C-H activation mediated by a Pt(0) center, and stoichiometric biphenyl formation via solvent activation

Room temperature reversible C-H activation mediated by a designed diphosphine platinum complex is presented. These findings are demonstrated through mechanistic studies involving kinetics, isotopic effects, and corroborated by DFT calculations. The coupling between two unactivated aromatic derivatives is also demonstrated.     

The [1,5]-Brook rearrangement: an initial application in anion relay chemistry

The [1,5]-Brook rearrangement proceeds efficiently in a series of hydroxyl dithiane substrates with sodium and potassium bases; less effective are lithium bases. That the mode of silyl migration is intramolecular was demonstrated by a crossover experiment. Finally, the tricomponent anion relay chemistry (ARC) coupling tactic was demonstrated employing the [1,5]-Brook rearrangement.     

Nitrite‐Templated Synthesis of Lanthanide‐Containing [2]Rotaxanes for Anion Sensing

The first anion‐templated synthesis of a lanthanide‐containing interlocked molecule is demonstrated by utilizing a nitrite anion to template initial pseudorotaxane formation. Subsequent stoppering of the interpenetrated assembly allows for the preparation of a lanthanide‐functionalized [2]rotaxane in high yield. Following removal of the nitrite anion template, the europium [2]rotaxane host is demonstrated to recognize and sense fluoride selectively.     

A new trick (hydroxyl radical generation) for an old vitamin (B12)

Photolysis of hydroxocobalamin in the presence of plasmid DNA (pBR322) results in DNA cleavage. Temporal control of hydroxyl radical production and DNA strand scission by hydroxocobalamin was demonstrated using a 2-deoxyribose assay and a plasmid relaxation assay, respectively. The light-driven hydroxocobalamin-mediated catalytic formation of hydroxyl radicals was demonstrated using radical scavenging studies of DNA cleavage and via recycling of a hydroxocobalamin-resin conjugate several times without loss of efficacy.     

Ultra rapid prototyping of microfluidic systems using liquid phase photopolymerization

We present a method for the ultra rapid prototyping of microfluidic systems using liquid phase photopolymerization, requiring less than 5 min from design to prototype. Microfluidic device fabrication is demonstrated in a universal plastic or glass cartridge. The method consists of the following steps: introduction of liquid prepolymer into the cartridge, UV exposure through a mask to define the channel geometry, removal of unpolymerized prepolymer, and a final rinse. Rapidly fabricated masters for polydimethylsiloxane micromolding are also demonstrated. The master making process is compared to SU-8 50 photoresist processes. Press-on connectors are developed and demonstrated. All materials used are commercially available and low cost. An extension of these methods (mix and match) is presented that allows for maximal design flexibility and integration with a variety of existing fluidic geometries, components, and processes.     

The Grob/Eschenmoser fragmentation of cycloalkanones bearing β-electron withdrawing groups: a general strategy to acyclic synthetic intermediates

Introduction of a β-electron withdrawing group to cycloalkanones allows facile C-C bond fragmentation. The reaction has been demonstrated with a large range of ring sizes, bearing various leaving and electron withdrawing groups, and using a variety of nitrogen and oxygen containing nucleophiles (>30 examples). The application of fragmentation products to the preparation of substituted γ-lactones has been demonstrated. Mechanistic studies are reported which are suggestive of a Grob/Eschenmoser type reaction.     

Suppression of non-specific adsorption using sheath flow

The use of a confining sheath fluid within a microfluidic channel in order prevent non-specific adsorption of analytes to the walls of microchannels is demonstrated. A sheath-flow channel fabricated using laser cutting of Mylar films is developed. Numerical simulations of convective and diffusive mass transport within the channel are presented. The device is characterized experimentally using epifluorescence microscopy. It is demonstrated that the device is capable of preventing the adsorption of Rhodamine B to the walls of the channel for a period that would allow for adsorption-free T-sensor measurements to be made within the core of the flow channel. Generalized scaling rules based on the diffusion coefficient, sheath thickness and affinity of the potential adsorbant for the surface material are discussed. The controlled adsorption of the protein bovine serum albumin (BSA) to a gold surface is also demonstrated using SPR microscopy.     

Selective inhibition of engineered receptors via proximity-accelerated alkylation

A new approach for creating allele-specific inhibitors is demonstrated. In this approach, a receptor and ligand are engineered to contain complementary reactive groups that form a covalent bond via a proximity-accelerated reaction upon formation of the receptor-ligand complex, irreversibly modulating the biological function of the receptor. This approach is demonstrated in the cyclophilin-cyclosporin receptor-ligand system by introducing thiol and acrylamide functional groups in the receptor and ligand, respectively.     

A novel approach to evaluate the extent and the effect of cross-contribution to the intensity of ions designating the analyte and the internal standard in quantitative GC-MS analysis

In gas chromatography-mass spectrometry methods of analysis adopting the analyte's isotopic analog as the internal standard (IS), the cross-contribution (CC) phenomenon -- contribution of IS to the intensities of the ions designating the analyte, and vice versa -- has been demonstrated to affect the quantitation data. A novel approach based on the deviations of the empirically observed concentrations of a set of standards was developed to assess the accuracy of the empirically derived CC data. This approach demonstrated that normalization of ion intensities derived from the analyte and the IS generates reliable CC data. It further demonstrated that an ion-pair (designating the analyte and the IS) with approximately 5% or higher CC will result in a very limited linear calibration range.     

Determination of fatty acids in products of the vibromagnetic treatment of sapropel by chromatography-mass spectrometry

Lipids in the colloidal (micellar) form were isolated from sapropel of a lake of Karasevoe (Tomsk region) using the method of aqueous vibromagnetic extraction. It has been demonstrated that the yield of lipids in the vibromagnetic treatment of sapropel increases, and in the aqueous extract it is comparable to the yield of lipids isolated using organic solvents. The concentration of fatty acids in the studied samples was qualitatively and quantitatively evaluated by chromatography-mass spectrometry. It has been demonstrated that the total concentration of saturated and unsaturated fatty acids in the products of vibromagnetic treatment increases. The dispersion of sapropel particles has been demonstrated by scanning electron microscopy.     

Effects of Photobiomodulation on Functionality in Wistar Rats with Sciatic Nerve Injury

A peripheral nerve injury (PNI) can result in motor or sensory disorders. Low‐level laser therapy (LLLT) has demonstrated positive results as a treatment option for PNI. Wistar rats were divided into five groups: Control, Injury, Injury + LLLTn (nerve), Injury + LLLTm (muscle) and Injury + LLLTn + m (nerve and muscle irradiation). The groups were analyzed after one, two, three and four weeks. PNI was achieved by crushing the sciatic nerve. Laser treatment (780 nm, 3.2 J) was realized over the nerve and/or tibialis anterior muscle. In gait analyses, the groups irradiated over the nerve demonstrated an improvement after two weeks. In the analysis of mechanical sensitivity, the Injury + LLLTn demonstrated a reduction after one week in comparison with Injury group; the Injury + LLLTn + m and Injury + LLLTm demonstrated an increase after two weeks in comparison with Injury group; and the irradiated groups demonstrated a reduction in nociception after four weeks in comparison with Injury group. In the analysis of muscle atrophy, the Injury + LLLTn demonstrated more muscle mass after two weeks. LLLT improves functional aspects related to gait, mechanical sensitivity and muscle mass, with better results regarding motor aspects and muscle mass when administered over the injured nerve and better results regarding sensory aspects when administered over the muscle.     

Synthesis of Camalexin and Related Analogues

Camalexin is synthesized on a gram scale by coupling of thiazole and indole in an amidoalkylation–oxidation sequence. Several high‐yielding implementations of this two‐step approach are demonstrated with variation of either the intermediate acyliminium reagent or the oxidation conditions. Benzo‐analogues and aza‐analogues of the natural product are also obtained by this method. As a side result, a new formylation of indole is demonstrated.     

Self-aspirating atmospheric pressure chemical ionization source for direct sampling of analytes on surfaces and in liquid solutions

A self-aspirating heated nebulizer probe is described and demonstrated for use in the direct analysis of analytes on surfaces and in liquid samples by atmospheric pressure chemical ionization (APCI) mass spectrometry. Functionality and performance of the probe as a self-aspirating APCI source is demonstrated using reserpine and progesterone as test compounds. The utility of the probe to sample analytes directly from surfaces was demonstrated first by scanning development lanes of a reversed-phase thin-layer chromatography plate in which a three-component dye mixture, viz., Fat Red 7B, Solvent Green 3, and Solvent Blue 35, was spotted and the components were separated. Development lanes were scanned by the sampling probe operated under computer control (x, y plane) while full-scan mass spectra were recorded using a quadrupole ion trap mass spectrometer. In addition, the ability to sample the surface of pharmaceutical tablets (viz., Extra Strength Tylenol and Evista tablets) and to detect the active ingredients (acetaminophen and raloxifene, respectively) selectively was demonstrated using tandem mass spectrometry (MS/MS). Finally, the capability to sample analyte solutions from the wells of a 384-well microtiter plate and to perform quantitative analyses using MS/MS detection was illustrated with cotinine standards spiked with cotinine-d3 as an internal standard.     

Biosynthetic studies of marine lipids 10. Double side chain extension in the triply alkylated sponge sterol xestosterol

Xestosterol, a triply alkylated marine sponge sterol, with a symmetrically extended side chain is shown to be efficiently biosynthesized by the sponge Xestospongia testudinaria via a nonstereoselective SAM biomethylation and 1,2-hydrogen shift. De novo biosynthesis via mevalonate, rarely demonstrated in sponges, has also been demonstrated.