Total Synthesis of Cryptophycins and Their 16-(3-Phenylacryloyl) Derivatives

Cryptophycin A, a cyclic depsipeptide isolated from the blue-green alga (cyanobacterium) Nostocsp.GSV 224, has shown excellent activity against solid tumors implanted in mice. The benzylic epoxide, which was shown to be very important for biological activity, is also fairly unstable under both acidic and alkaline conditions. The high doses needed to observe in vivo activity might be a result of this instability. In order to solve this problem while preserving the electrophilic character of the benzylic position, enones 1 and 2 have been proposed as promising analogs of the natural product, and a convergent total synthesis of these compounds is described. In addition, the same strategy was used to prepare Cryptophycins A, B, C, and D.     

A Xanthan-Gum-Stabilized PEG-Conjugated Nanocurcumin Complex: Telescoping Synthesis for Enhanced Permeation Potential

We report a facile room temperature telescoping synthesis of a nanocurcumin complex with 17.5-fold permeation enhancement as determined by comparative in vitro permeation study with raw curcumin. The permeation results were further validated with in silico drug absorption prediction using ADMET predictors.     

Comparison of evaluation procedures used by European external quality assessment scheme organizers for haemoglobin concentration and leukocyte concentration

This study aimed to assess currently used evaluation procedures for haemoglobin concentration and leukocyte concentration in European external quality assessment schemes (EQAS). Participating EQAS organizers were asked to complete a questionnaire gathering information on the statistical procedures used to assess the performance of participants, and to analyse an Excel file with 262 results for haemoglobin concentration and leukocyte concentration. Responses were received from the New York State Proficiency Testing programme in the US and from 11 European EQAS: Belgium, Croatia, Finland, France, Germany, Hungary, Russia, Slovenia, Spain (two organizers), and Switzerland. Five of the 11 European EQAS use fixed limits based upon experience, biological variation, state of the art, or professional consensus. The other EQAS use variable limits based upon statistical analysis of the performance attained. With the exception of the German, Hungarian, and Slovenian schemes, all European EQAS use consensus target values. The percentage of unsatisfactory results obtained by the European EQAS organizers for the given set of data varied between 0.4 and 15.6% for haemoglobin concentration and between 0 and 19.8% for leukocyte concentration.     

Role of the mass asymmetry of reaction on the geometry of vanishing flow

We study the transverse flow throughout the mass asymmetry range as a function of the impact parameter, keeping the total mass of the system fixed. We find that the geometry of vanishing flow (GVF) i.e. the impact parameter at which flow vanishes and its mass dependence is quite sensitive to the mass asymmetry of the reaction. With increase in the mass asymmetry, the value of GVF decreases, while its mass dependence increases. Our results indicate the sizable role of mass asymmetry on GVF as on balance energy.     

An efficient contemporary multicomponent synthesis for the facile access to coumarin-fused new thiazolyl chromeno[4,3-b]quinolones in aqueous micellar medium

Coumarin-fused polycyclic chromenoquinolone derivatives were synthesized in CTAB/water system with high yields. This protocol is competent, feasible, and sequential one-pot multicomponent path for the building of titled products. In this projected route solvents, catalysts and surfactants are optimized, and the excellent results were achieved by CTAB in water. CTAB/water has efficiently catalyzed the synthesis of new thiazolyl chromenoquinolone heterocycles and avoids the use of hazardous conventional organic solvents. The synthesized compounds were confirmed by IR, mass, ¹H NMR spectral, and elemental analysis. This report represents the first case in which surfactant CTAB has been explored in the synthesis of fused chromenoquinolones in water. A probable reaction mechanism has been established to know the role of CTAB.     

Identifying the related compounds using electrospray ionization tandem mass spectrometry: bromotyrosine alkaloids from marine sponge Psammaplysilla purpurea

We have investigated extracts of marine sponge Psammaplysilla purpurea during three collections from Mandapam (Tamil Nadu, India) and Okha (Gujarat, India) and indentified two new bromotyrosine alkaloids, purpurealidin I (7) and J (8) using electrospray ionization tandem mass spectrometry (ESI-MS/MS). This sponge has tremendous chemical diversity of bromotyrosine alkaloids. Here we have used the proteomics approach in identifying related bromotyrosine alkaloids based on the predicated mass fragmentation pattern. The focus is on the examination of detailed product ion spectra of six known compounds that allowed identification of new compounds based on its mass fragmentation pattern. The isotopic pattern of the peaks for protonated molecules indicated the number of bromine atoms present in the molecule. During MS/MS studies, the most prominent product ion peak is for the presence of side chain propane with either free NH(2) or NHMe or Nme(2). The cleavage at C-C bond between oxime-amide carbonyl and amide-phenoxy moiety also gave characteristic product ions. The ESI-MS spectra for all three collections show that the bromotyrosine metabolites vary during different season and also geographical location. Although, some common metabolites were observed during the three collections. Thus, ESI-MS/MS is a method of choice in identifying the related compounds.     

Structure-based design of supercharged, highly thermoresistant antibodies

Mutation of surface residues to charged amino acids increases resistance to aggregation and can enable reversible unfolding. We have developed a protocol using the Rosetta computational design package that "supercharges" proteins while considering the energetic implications of each mutation. Using?a homology model, a single-chain variable fragment antibody was designed that has a markedly enhanced resistance to thermal inactivation and displays an unanticipated ≈30-fold improvement in affinity. Such supercharged antibodies should prove useful for assays in resource-limited settings and for developing reagents with improved shelf lives.     

Cu–ZnO nanocrystallites by aqueous thermolysis method

ZnO and different atomic percentages of Cu-doped ZnO nanocrystallites have been prepared by aqueous thermolysis method using Glycine as a fuel and encapsulating agent. Mechanism and formation of intermediate products have been given for the first time. All the findings given are for samples annealed at 800?°C. XRD of nanocrystalline ZnO and Cu?CZnO has been indexed to hexagonal wurtzite structure. Influence of temperature on thermal properties of gel precursor and Cu-doped ZnO nanoparticles have been investigated using thermogravimetric and differential thermal analysis. Accordingly, samples have been annealed at different temperatures. Infrared studies revealed formation of Cu?CZnO nanoparticles and removal of organic matter at higher temperature.     

Review of AdS/CFT Integrability, Chapter I.3: Long-Range Spin Chains

In this contribution, we review long-range integrable spin chains that originate from the recently discovered integrability in the planar AdS/CFT correspondence. We also briefly summarise the theory of generic integrable perturbatively long-range spin chains.