Molecular Trap Research Articles

Rhenium-Based Molecular Trap as an Evanescent Wave Infrared Chemical Sensing Medium for the Selective Determination of Amines in Air.

An evanescent wave infrared chemical sensor was developed to selectively detect volatile amines with heterocyclic or phenyl ring. To achieve this goal, a rhenium-based metallacycle with a "molecular-trap" structure was designed and synthesized as host molecules to selectively trap amines with heterocyclic or phenyl ring through Re-amine and π-π interactions. To explore the trapping properties of the material, a synthesized Re-based molecular trap was treated on an IR sensing element, and wide varieties of volatile organic compounds (VOCs) were examined to establish the selectivity for detection of amines. Based on the observed IR intensities, the Re-based molecular trap favors interaction with amines as evidenced by the variation of absorption bands of the Re molecular trap. With extra π-π interaction force, molecules, such as pyridine and benzylamine, could be detected. After optimization of the parameters for IR sensing, a rapid response in the detection of pyridine was observed, and the linear ranges were generally up to 10 mg/L with a detection limit around 5.7 μg/L. In the presence of other VOCs, the recoveries in detection of pyridine were all close to 100%.

Catching a Disease: A Molecular Trap as a Therapy for Pulmonary Arterial Hypertension.

Catching a Disease: A Molecular Trap as a Therapy for Pulmonary Arterial Hypertension.

Methods of gas purification and effect on the ion composition in an RF atmospheric pressure plasma jet investigated by mass spectrometry

The analysis of the ion chemistry of atmospheric pressure plasmas is essential to evaluate ionic reaction pathways during plasma-surface or plasma-analyte interactions. In this contribution, the ion chemistry of a radio-frequency atmospheric pressure plasma jet (μ-APPJ) operated in helium is investigated by mass spectrometry (MS). It is found, that the ion composition is extremely sensitive to impurities such as N2, O2 and H2O. Without gas purification, protonated water cluster ions of the form H+(H2O) n are dominating downstream the positive ion mass spectrum. However, even after careful feed gas purification to the sub-ppm level using a molecular sieve trap and a liquid nitrogen trap as well as operation of the plasma in a controlled atmosphere, the positive ion mass spectrum is strongly influenced by residual trace gases. The observations support the idea that species with a low ionization energy serve as a major source of electrons in atmospheric pressure helium plasmas. Similarly, the neutral density of atomic nitrogen measured by MS in a He/N2 mixture is varying up to a factor 3, demonstrating the significant influence of impurities on the neutral species chemistry as well.

Microwave-mediated magneto-optical trap for polar molecules**Project supported by the Fundamental Research Funds for the Central Universities of China.

Realizing a molecular magneto-optical trap has been a dream for cold molecular physicists for a long time. However, due to the complex energy levels and the small effective Lande g-factor of the excited states, the traditional magneto-optical trap (MOT) scheme does not work very well for polar molecules. One way to overcome this problem is the switching MOT, which requires very fast switching of both the magnetic field and the laser polarizations. Switching laser polarizations is relatively easy, but fast switching of the magnetic field is experimentally challenging. Here we propose an alternative approach, the microwave-mediated MOT, which requires a slight change of the current experimental setup to solve the problem. We calculate the MOT force and compare it with the traditional MOT and the switching MOT scheme. The results show that we can operate a good MOT with this simple setup.

Building a Molecular Trap for a Serine Protease from Aptamer and Peptide Modules

In drug development, molecular intervention strategies are usually based on interference with a single protein function, such as enzyme activity or receptor binding. However, in many cases, protein drug targets are multifunctional, with several molecular functions contributing to their pathophysiological actions. Aptamers and peptides are interesting synthetic building blocks for the design of multivalent molecules capable of modulating multiple functions of a target protein. Here, we report a molecular trap with the ability to interfere with the activation, catalytic activity, receptor binding, etc. of the serine protease urokinase-type plasminogen activator (uPA) by a rational combination of two RNA aptamers and a peptide with different inhibitory properties. The assembly of these artificial inhibitors into one molecule enhanced the inhibitory activity between 10- and 10,000-fold toward several functions of uPA. The study highlights the potential of multivalent designs and illustrates how they can easily be constructed from aptamers and peptides using nucleic acid engineering, chemical synthesis, and bioconjugation chemistry. By aptamer to aptamer and aptamer to peptide conjugation, we created, to the best of our knowledge, the first trivalent molecule which combines three artificial inhibitors binding to three different sites in a protein target. We hypothesize that by simultaneously preventing all of the functional interactions and activities of the target protein, this approach may represent an alternative to siRNA technology for a functional knockout.

Wave Packet Dynamical Calculations for Charge Transport of Organic Semiconductors: Role of Molecular Vibrations and Trap Potentials

We present a theoretical study of relationships between charge transport properties and disorder in rubrene single crystals. We take into account two different types of disorder, namely, intrinsic dynamical disorder due to intermolecular vibrations and extrinsic static disorder. Then we evaluate the transport properties using our wave-packet dynamical approach which gives us a unified theoretical description from hopping to band transport behavior. We show that the mobilities are completely changed from the intrinsic power-law temperature dependence to the thermally activated behavior by introduction of the extrinsic trap potentials.

Developing a passive trap for diffusive atmospheric 14CO2 sampling

14C-CO2 measurement is an unique tool to quantify source-based emissions of CO2 for both the urban and natural environments. Acquiring a sample that temporally integrates the atmospheric 14C-CO2 signature that allows for precise 14C analysis is often necessary, but can require complex sampling devices, which can be difficult to deploy and maintain, especially for multiple locations. Here we describe our progress in developing a diffusive atmospheric CO2 molecular sieve trap, which requires no power to operate. We present results from various cleaning procedures, and rigorously tested for blank and memory effects. Traps were tested in the environment along-side conventional sampling flasks for accuracy. Results show that blank and memory effects can be minimized with thorough cleaning and by avoiding overheating, and that diffusively collected air samples agree well with traditionally canister-sampled air.

Damage-associated molecular pattern-activated neutrophil extracellular trap exacerbates sterile inflammatory liver injury.

Innate immunity plays a crucial role in the response to sterile inflammation such as liver ischemia/reperfusion (I/R) injury. The initiation of liver I/R injury results in the release of damage-associated molecular patterns, which trigger an innate immune and inflammatory cascade through pattern recognition receptors. Neutrophils are recruited to the liver after I/R and contribute to organ damage and innate immune and inflammatory responses. Formation of neutrophil extracellular traps (NETs) has been recently found in response to various stimuli. However, the role of NETs during liver I/R injury remains unknown. We show that NETs form in the sinusoids of ischemic liver lobes in vivo. This was associated with increased NET markers, serum level of myeloperoxidase-DNA complexes, and tissue level of citrullinated-histone H3 compared to control mice. Treatment with peptidyl-arginine-deiminase 4 inhibitor or DNase I significantly protected hepatocytes and reduced inflammation after liver I/R as evidenced by inhibition of NET formation, indicating the pathophysiological role of NETs in liver I/R injury. In vitro, NETs increase hepatocyte death and induce Kupffer cells to release proinflammatory cytokines. Damage-associated molecular patterns, such as High Mobility Group Box 1 and histones, released by injured hepatocytes stimulate NET formation through Toll-like receptor (TLR4)- and TLR9-MyD88 signaling pathways. After neutrophil depletion in mice, the adoptive transfer of TLR4 knockout or TLR9 knockout neutrophils confers significant protection from liver I/R injury with a significant decrease in NET formation. In addition, we found inhibition of NET formation by the peptidyl-arginine-deiminase 4 inhibitor and that DNase I reduces High Mobility Group Box 1 and histone-mediated liver I/R injury. Damage-associated molecular patterns released during liver I/R promote NET formation through the TLR signaling pathway. Development of NETs subsequently exacerbates organ damage and initiates inflammatory responses during liver I/R.

Modulating the Self-Assembly of Amphiphilic X-Shaped Block Copolymers with Cyclodextrins: Structure and Mechanisms

Inclusion complexes between cyclodextrins and polymers-so-called pseudopolyrotaxanes (PPR)-are at the origin of fascinating supramolecular structures, which are finding increasing uses in biomedical and technological fields. Here we explore the impact of both native and a range of modified cyclodextrins (CD) on the self-assembly of X-shaped poly(ethylene oxide)-poly(propylene oxide) block copolymers, so-called Tetronics or poloxamines, by focusing on Tetronic 904 (T904, Mw 6700). The effects are markedly dependent on the type and arrangement of the substituents on the macrocycle. While native CDs drive the formation of a solid PPR, most substituted CDs induce micellar breakup, with dimethylated β-CD (DIMEB) having the strongest impact and randomly substituted CDs a much weaker disruptive effect. Using native α-CD as a "molecular trap", we perform competitive binding experiments-where two types of CDs thread together onto the polymer chains-to establish that DIMEB indeed has the highest propensity to form an inclusion complex with the polymer, while hydroxypropylated CDs do not thread. 1D (1)H NMR and ROESY experiments confirm the formation of a soluble PPR with DIMEB in which the CD binds preferentially to the PO units, thus providing the drive for the observed demicellization. A combination of dynamic light scattering (DLS) and small-angle neutron scattering (SANS) is used to extract detailed structural parameters on the micelles. A binding model is proposed, which exploits the chemical shifts of selected protons from the CD in conjunction with the Hill equation, to prove that the formation of the PPR is a negatively cooperative process, in which threaded DIMEBs hamper the entrance of subsequent macrocycles.

The design and performance of a portable handheld 11CO2 delivery system

We constructed a hand-held device to efficiently trap [11C]CO2 from the cyclotron target, safely transport up to 3.7GBq (100mCi) doses to remote sites and release it without the need for a liquid cryogen. The system consists of a 180W furnace and a miniature molecular sieve trap (80–100mg; 80–100mesh 13×) placed inside a lead pig weighing 11.1kg. The overall [11C]CO2 delivery efficiency of the device is ~82% (> 99% trapping efficiency). Radiation dose rates measured at 30cm from the surface of the pig are <43.5µSv/h (5mR/h) up to 2.59GBq (70mCi).

Photocleavable dimerizer for the rapid reversal of molecular trap antagonists (597.3)

Developing a molecular tool that can rapidly turn on and off an acute antagonist will be immensely helpful to understand the initiation of a cellular program. Herein, we report the development of a photocleavable analog of AP20187, a cell permeable molecule used to dimerize FKBP fusion proteins and initiate biological signaling cascades, gene expression or disrupt protein‐protein interactions. We demonstrate that this reagent in conjugation with a molecular trap permits the ability to rapidly and specifically antagonize a molecular interaction in vitro and follow a biological process due to this acute antagonism (e.g., endosome dispersion). More importantly, photocleavage of the analog permits the unique ability to follow the cell’s return to homeostasis. Herein, we demonstrated the fine temporal control of endosome dispersion and restoration using an LC8 trap. We posit that this photocleavable AP20187 analog can be used in other systems where the dimerization of FKBP has been used to initiate signaling pathways (e.g., kinases). In toto, the combination of a molecular trap and the photocleavable analog opens up new avenues to study signaling events within a single cell in a whole organism.Grant Funding Source: Supported by the generous support of R21NS071166 and also by P30 CA033572 from the NCI

Photocleavable Dimerizer for the Rapid Reversal of Molecular Trap Antagonists

Herein, we report the development of a photocleavable analog of AP20187, a cell-permeable molecule used to dimerize FK506-binding protein (FKBP) fusion proteins and initiate biological signaling cascades and gene expression or disrupt protein-protein interactions. We demonstrate that this reagent permits the unique ability to rapidly and specifically antagonize a molecular interaction in vitro and follow a biological process due to this acute antagonism (e.g. endosome dispersion) and to release the trap upon photocleavage to follow the cell's return to homeostasis. In addition, this photocleavable AP20187 analog can be used in other systems where the dimerization of FKBP has been used to initiate signaling pathways, offering the ability to correlate the duration of a signaling event and a cellular response.

Roadblocks on the E.Coli Genome: The Workings of a Molecular Mouse Trap at the Single-Molecule Level

During DNA replication in E.coli, replication forks are prevented from moving beyond the termination site by Tus proteins that bind to specific, asymmetric Ter DNA sites. The Tus-induced blockage is known to depend on the fork's direction of approach. It is hypothesized that strand separation on the blocking side triggers the formation of a molecular roadblock by the binding of a base to a high affinity site on the Tus protein. In this study, we use single-molecule multiplexed magnetic tweezers to investigate the origin of the asymmetry of the Tus-Ter block. We use 1kb DNA hairpins that contain a single Ter site in either the permissive or non-permissive orientation. Application of pulling forces >16pN causes mechanical unzipping of the hairpins, thereby mimicking the DNA unwinding that accompanies DNA replication. When wtTus binds to the hairpin with the permissively oriented Ter site, strand separation is transiently blocked; conversely, when wtTus is bound to the non-permissive Ter hairpin, strand separation is fully blocked. Under physiological conditions the non-permissive Tus-Ter lock was ubiquitous, independent of the loading rate, and withstood the largest forces we could apply (>70pN). Interestingly, the probability of lock formation strongly depends on the ionic strength of the solution. Our ability to distinguish simple DNA binding from the locking process and to apply this to a series of Tus mutants allows us to put together a complete picture of the Tus-Ter lock.

Autoresonant-spectrometric determination of the residual gas composition in the ALPHA experiment apparatus

Knowledge of the residual gas composition in the ALPHA experiment apparatus is important in our studies of antihydrogen and nonneutral plasmas. A technique based on autoresonant ion extraction from an electrostatic potential well has been developed that enables the study of the vacuum in our trap. Computer simulations allow an interpretation of our measurements and provide the residual gas composition under operating conditions typical of those used in experiments to produce, trap, and study antihydrogen. The methods developed may also be applicable in a range of atomic and molecular trap experiments where Penning-Malmberg traps are used and where access is limited.

Visible cathodoluminescence of quantum dot films by direct irradiation of electron beam and its materialization as a field emission device

The field emission (FE) device based on quantum dot (QD) films as a cathodoluminescent (CL) material has not emerged yet due to the relatively low quantum efficiency and weak photostability of nanocrystals (NCs). Here we improve film stability and luminescence yields by preparing neat films of well-packed core-multishell QDs using spray coating method and then using low-temperature atomic layer deposition (ALD) to infill the pores of these films with metal oxides to produce inorganic nanocomposites. The ALD coatings to protect oxidation and degradation by electrons prevent internal atomic and molecular diffusion and decrease surface trap densities of QD films. Furthermore, the CL of the core-multishell QD films is 2.4 times higher than before ALD infilling. We fabricate the FE device by combining cathode structure with carbon nanotube (CNT) emitters and anode plates with QD thin film and successfully can get brilliant images of the light-emitting FE device. Our research opens a way for developing new quantum optoelectronics with high-performance.

Measurement of SLAP2 and GISP δ17O and proposed VSMOW‐SLAP normalization for δ17O and 17Oexcess

RATIONALEThe absence of an agreed‐upon δ17O value for the primary reference water SLAP leads to significant discrepancies in the reported values of δ17O and the parameter 17Oexcess. The accuracy of δ17O and 17Oexcess values is significantly improved if the measurements are normalized using a two‐point calibration, following the convention for δ2H and δ18O values.METHODSNew measurements of the δ17O values of SLAP2 and GISP are presented and compared with published data. Water samples were fluorinated with CoF3. Helium carried the O2 product to a 5A (4.2 to 4.4 Å) molecular sieve trap submerged in liquid nitrogen. The O2 sample was introduced into a dual‐inlet ThermoFinnigan MAT 253 isotope ratio mass spectrometer for measurement of m/z 32, 33, and 34. The δ18O and δ17O values were calculated after 90 comparisons with an O2 reference gas.RESULTSWe propose that the accepted δ17O value of SLAP be defined in terms of δ18O = −55.5 ‰ and 17Oexcess = 0, yielding a δ17O value of approximately −29.6968 ‰. Using this definition for SLAP and the recommended normalization procedure, the δ17O value of GISP is −13.16 ± 0.05 ‰ and the 17Oexcess value of GISP is 22 ± 11 per meg. Correcting previous published values of GISP δ17O to both VSMOW and SLAP improves the inter‐laboratory precision by about 10 per meg.CONCLUSIONSThe data generated here and compiled from previous studies provide a substantial volume of evidence to evaluate the various normalization techniques currently used for triple oxygen isotope measurements. We recommend that reported δ17O and 17Oexcess values be normalized to the VSMOW‐SLAP scale, using a definition of SLAP such that its 17Oexcess is exactly zero. Copyright © 2013 John Wiley &amp; Sons, Ltd.

The Tomato Prf Complex Is a Molecular Trap for Bacterial Effectors Based on Pto Transphosphorylation

The major virulence strategy of phytopathogenic bacteria is to secrete effector proteins into the host cell to target the immune machinery. AvrPto and AvrPtoB are two such effectors from Pseudomonas syringae, which disable an overlapping range of kinases in Arabidopsis and Tomato. Both effectors target surface-localized receptor-kinases to avoid bacterial recognition. In turn, tomato has evolved an intracellular effector-recognition complex composed of the NB-LRR protein Prf and the Pto kinase. Structural analyses have shown that the most important interaction surface for AvrPto and AvrPtoB is the Pto P+1 loop. AvrPto is an inhibitor of Pto kinase activity, but paradoxically, this kinase activity is a prerequisite for defense activation by AvrPto. Here using biochemical approaches we show that disruption of Pto P+1 loop stimulates phosphorylation in trans, which is possible because the Pto/Prf complex is oligomeric. Both P+1 loop disruption and transphosphorylation are necessary for signalling. Thus, effector perturbation of one kinase molecule in the complex activates another. Hence, the Pto/Prf complex is a sophisticated molecular trap for effectors that target protein kinases, an essential aspect of the pathogen's virulence strategy. The data presented here give a clear view of why bacterial virulence and host recognition mechanisms are so often related and how the slowly evolving host is able to keep pace with the faster-evolving pathogen.

Reusable glucose sensing using carbon nanotube-based self-assembly

Lipid functionalized single walled carbon nanotube-based self assembly forms a super-micellar structure. This assemblage has been exploited to trap glucose oxidase in a molecular cargo for glucose sensing. The advantage of such a molecular trap is that all components of this unique structure (both the trapping shell and the entrapped enzyme) are reusable and rechargeable. The unique feature of this sensing method lies in the solid state functionalization of single walled carbon nanotubes that facilitates liquid state immobilization of the enzyme. The method can be used for soft-immobilization (a new paradigm in enzyme immobilization) of enzymes with better thermostability that is imparted by the strong hydrophobic environment provided through encapsulation by the nanotubes.

On-Chip Alternating Current Electrophoresis in Supported Lipid Bilayer Membranes

By forming lipid bilayers within SU8 patterns, between interdigitated electrodes, we have demonstrated that it is possible to manipulate charged membrane components using low applied voltages over relatively short time scales. Two distinct patterns were studied: a nested "fish trap" which served as a molecular trap, and a diffusion aided Brownian ratchet which operated as a molecular pump. By reducing the size of the structures we have demonstrated that large applied fields (>200 V/cm) can be achieved on-chip, using low applied potentials (<13 V). By using ac fields applied orthogonal to the direction of desired motion, the molecular pumps provide a voltage independent method for moving charged components within lipid membranes over large distances. The reduced scale of the trap structures compared to those previously used in our laboratory has led to over a 10-fold decrease in the operational time require for charge build-up, from 16 h down to 1.5 h. The observed benefits of scaling means that these systems should be suitable for the on-chip separation and manipulation of charged species within supported lipid membranes.

Variable-Temperature Rate Coefficients of Proton-Transfer Equilibrium Reaction C2H4 + H3O+ ⇄ C2H5+ + H2O Measured with a Coaxial Molecular Beam Radio Frequency Ring Electrode Ion Trap

The rate coefficients for the forward and reverse proton-transfer reactions C(2)H(4) + H(3)O(+) ⇄ C(2)H(5)(+) + H(2)O are studied with respect to independent varied neutral molecule and ion temperatures. The measurements are performed using a coaxial molecular beam radio frequency ring electrode ion trap at trap temperatures down to 23 K and beam temperatures up to 450 K. The temperature-dependent rate coefficients suggest that in this temperature window, the reaction proceeds through a statistically equilibrated complex. In order to explain the observed rate coefficients, a new type of reaction temperature was defined in these studies that considered collisional and internal (rotational and vibrational) degrees of freedom of both H(3)O(+) and C(2)H(4). The enthalpy and entropy of the equilibrium reaction deduced from a Van't Hoff plot are ΔH = (5.1 ± 0.5) kJ·mol(-1) and ΔS = (-15.0 ± 0.9) J·mol(-1)·K(-1), respectively.