Photochemical Methods for Peptide Macrocyclisation

Photochemical reactions have been the subject of renewed interest over the last two decades, leading to the development of many new, diverse and powerful chemical transformations. More recently, these developments have been expanded to enable the photochemical macrocyclisation of peptides and small proteins. These constructs benefit from increased stability, structural rigidity and biological potency over their linear counterparts, providing opportunities for improved therapeutic agents. In this review, an overview of both the established and emerging methods for photochemical peptide macrocyclisation is presented, highlighting both the limitations and opportunities for further innovation in the field.     

Probing anion-pi interactions in 1-D Co(II), Ni(II), and Cd(II) coordination polymers containing flexible pyrazine ligands

Two flexible thioether-containing heterocyclic ligands bis(2-pyrazylmethyl)sulfide (L1) and 2-benzylsulfanylmethylpyrazine (L2) have arene rings with differing pi-acidities which were used to probe anion-pi binding in five 1-D coordination polymers formed from the metal salts Co(ClO4)2, Ni(NO3)2, and Cd(NO3)2. In {[Co(L1)(MeCN)2](ClO4)2}infinity (1), {[Ni(L1)(NO3)2]}infinity (2), and {[Cd2(L1)(MeCN)(H2O)(NO3)4].H2O}infinity (3.H2O), the symmetrical ligand L1 was bound facially to the metal center and was bridged through a pyrazine donor to an adjacent metal forming a polymer chain. The folding of L1 formed U-shaped pi-pockets in 1 and 3.H2O which encapsulated free and bound anions, respectively. The anions interacted with the pi-acidic centers in a variety of different binding modes including anion-pi-anion and pi-anion-pi sandwiching. A wider pi-pocket was formed in 2 which also contained anion-pi interactions. The polymer chains in 2 were interdigitated through a rare type of complementary T-shaped N(pyrazine)...pi interaction. In {[Co(L2)(H2O)3](ClO4)2.H2O}infinity (4.H2O) and {[Cd(L2)(H2O)(NO3)2]}infinity (5), the unsymmetrical ligand L2 chelated the metal center and bridged through a pyrazine donor to an adjacent metal forming a polymer chain. The ligand arrangement resulted in the anions in both structures being involved in only anion-pi-anion sandwich interactions. In 4.H2O, the noncoordinated ClO4- anions interacted with only one chain while in 5 the coordinated NO3- anions acted as anion-pi supramolecular synthons between chains. Comparison between the polymers formed with ligands L1 and L2 showed that only the more pi-acidic ring was involved in the anion-pi interactions.     

Collisional damping interface for an electrospray ionization time-of-flight mass spectrometer

A new interface between atmosphere and high vacuum has been developed for orthogonal injection of electrosprayed ions into a time-of-flight mass spectrometer. A small rf quadrupole operating at 100 mtorr (1.33 × 10^?4 bar) is its key element. Ions enter the quadrupole with velocities acquired in the free expansion/declustering process. As they pass through the quadrupole their motion is constrained by the rf field. Meanwhile, they lose energy by collisions with the gas molecules. The time delays of ions passing through the quadrupole have been measured in order to determine the average velocities of the ions and the factors determining this value. In addition, a simple computational model based on a Monte Carlo approach has been developed to simulate the ion motion; it shows a considerable decrease in both transverse and axial ion velocity components. As the result of collisional damping the interface provides a dramatic improvement in the overall quality of the ion beam transported into the mass spectrometer. Both resolution and sensitivity of the time-of-flight instrument are improved and mass-to-charge ratio discrimination is greatly reduced.     

Laser-generated ultrasound in single-crystal Mindlin-type plates: theory and experiment

A Mindlin-type plate theory, appropriate for laser-line irradiation of a single-crystal plate with cubic symmetry, is developed to predict the temporal displacement profile in the far-field of the laser source. The [100] crystal axis coincides with the plate normal and the [010] crystal axis is inclined at an angle to the laser-line source. A formal solution for the out-of-plane displacements is obtained using Laplace and Fourier transforms. Both thermoelastic and non-thermal photostrictive source mechanisms are considered. For the particular problem of photostrictive generation, the spatial and temporal dependence are recovered using a hybrid analytical and numerical inversion scheme. Experimental data for a single crystal silicon plate, obtained via pulse laser generation and interferometric detection, is compared with theory.     

Mo(Tm(Me))(O)2Cl]: an alternative functional model of sulfite oxidase

The hydrotris(methimazolyl)borate anion (TmMe) has been used to synthesize an alternative functional model ([Mo(TmMe)(O)2Cl]) of the metalloenzyme sulfite oxidase. It has been shown that the complex undergoes oxygen atom transfer chemistry and that it performs the primary function of the enzyme, sulfite oxidation. A method using ion chromatography has been developed to definitively prove that sulfite is oxidized to sulfate. Employment of a soft tripodal ligand has allowed us to tune the redox potentials of our complex so that they are significantly closer to those reported for sulfite oxidase.     

Kinetics of colloidal templating using emulsion drop consolidation

The emulsion templating of ordered colloidal microsphere assemblies by Manoharan et al. involves a consolidation process where dispersed phase fluid is transported from droplets into a continuous phase. Consolidation can be approximated as a diffusion process with moving boundaries. The kinetics of consolidation are investigated here by following droplet shrinkage with time as a prelude to understanding rate effects on assembly structure. Consolidation kinetics are influenced by liquid diffusivity, the number of colloidal particles in a droplet, and the surfactant concentration. While surfactant exhibits little effect well below its critical micelle concentration (CMC) value, it significantly slows consolidation above the CMC. For a specific continuous phase (i.e., silicone oil and fluorinated silicone oil), with proper scalings, the droplet size shrinks with time following a power law independent of droplet diameter, surfactant concentrations, and particle number concentration. The power law exponent varies from 1/2 to 2/3 with different continuous oil phases as a result of concentration and interfacial effects. This study leads to an improved understanding of colloidal microstructure development at interfaces that can be applied in novel materials synthesis and drug delivery areas.     

Mass spectrometric study of N‐glycans from serum of woodchucks with liver cancer

Woodchucks have been a preferred lab animal model of chronic hepatitis B viral infection. The model recapitulates the disease progression of HBV infection to hepatocellular carcinoma (HCC) and has documented similarities in protein glycosylation with human HCC. This study examined N‐glycans in serum of animals with(out) HCC. Oligosaccharides were released enzymatically using PNGaseF from total serum or from serum partially fractionated by extraction. Two different extraction procedures – reversed‐phase high‐performance liquid chromatography (RP‐HPLC) and solid‐phase extraction (SPE) on a cation‐exchange/reversed‐phase STRATA‐XC cartridge – were used with the purpose of confirming glycosylation profiles. Oligosaccharides were analyzed by matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) after derivatization with phenylhydrazine and/or permethylation. Characteristic fragment ions produced under MS/MS conditions allowed discrimination between isomeric structures of oligosaccharides, including those sialylated with two types of acidic residues. The complementary methods allowed structural characterization of oligosaccharides from various N‐glycan classes. Furthermore, to validate results, glycosylation profiles of woodchuck sera were compared to glycans obtained from mouse serum on the same conditions. In summary, we have identified 40 N‐glycan structures in the serum of woodchucks and some types of oligosaccharide structures appeared to increase in HCC samples following protease digest. The study provides improved tools for the characterization of N‐glycans from total serum in the progression of liver disease. Copyright © 2009 John Wiley & Sons, Ltd.     

Surface analysis by means of photoemission and other photon‐stimulated processes

In the decades after World War 11, there was an explosion of fundamental research in solids and practical applications thereof. Although surfaces were not ignored in this work, until recently they were not strongly emphasized. In the last few years there has been a growing emphasis on the study of surfaces and related interfaces. There are several reasons for hs. First, as knowledge regarding the bulk properties of solids became increasingly complete, it became more and more evident how little was known about the surfaces. Thus, the study of surfaces is an exciting new frontier of scientific knowledge. Secondly, the development of devices and processes that depend on surfaces has been increasingly hindered by the lack of knowledge about surfaces, interfaces, and interactions that take place on surfaces. As a result, new techniques for experimental studies of surfaces have recently been developed.^1,2 These show great promise for allowing examination of surfaces and interfaces on a microscopic and even atomic level, and for the gathering of detded information impossible to obtain in the past. Finally, theoretical methods³ are being rapidly developed, which provide increasingly detailed insight into surfaces and interactions on surfaces.