Multivariate statistical tools applied to the characterization of the proteomic profiles of two human lymphoma cell lines by two-dimensional gel electrophoresis

Mantle cell lymphoma (MCL) cell lines have been difficult to generate, since only few have been described so far and even fewer have been thoroughly characterized. Among them, there is only one cell line, called GRANTA-519, which is well established and universally adopted for most lymphoma studies. We succeeded in establishing a new MCL cell line, called MAVER-1, from a leukemic MCL, and performed a thorough phenotypical, cytogenetical and molecular characterization of the cell line. In the present report, the phenotypic expression of GRANTA-519 and MAVER-1 cell lines has been compared and evaluated by a proteomic approach, exploiting 2-D map analysis. By univariate statistical analysis (Student's t-test, as commonly used in most commercial software packages), most of the protein spots were found to be identical between the two cell lines. Thirty spots were found to be unique for the GRANTA-519, whereas another 11 polypeptides appeared to be expressed only by the MAVER-1 cell line. A number of these spots could be identified by MS. These data were confirmed and expanded by multivariate statistical tools (principal component analysis and soft-independent model of class analogy) that allowed identification of a larger number of differently expressed spots. Multivariate statistical tools have the advantage of reducing the risk of false positives and of identifying spots that are significantly altered in terms of correlated expression rather than absolute expression values. It is thus suggested that, in future work in differential proteomic profiling, both univariate and multivariate statistical tools should be adopted.     

Tris(1,2-dimethyl-3-hydroxy-4(1H)-pyridone)oxotantalum(v): a new water-soluble tantalum complex containing the [Ta=O]3+ core

The synthesis, the characterization and the X-ray crystal structure of a novel tantalum(v) complex tris(1,2-dimethyl-3-hydroxy-4(1H)-pyridone)oxotantalum(v) [TaO(C7H8O2N)3] 1 is reported. Starting from the tantalum pentaethoxide a two-step reaction was carried out observing rigorous anhydrous conditions in methanol in the first step, while the insertion of the oxo group was achieved using water as oxygen donor in the second step. X-Ray diffraction analysis of a crystal of 1 obtained upon evaporation of an aqueous solution shows a seven-coordinate monomeric complex containing the [Ta=O]3+ core in the triclinic space group P1, a = 7.282(3), b = 14.055(5), c = 16.987(6) A, alpha = 65.704(5), beta = 89.155(6), gamma = 75.270(6) degrees, V = 1525(1)A3, Z = 2. Spectroscopic investigation reveals that the complex is highly soluble and stable in water at physiological pH values; as a consequence the complex may represent a potential candidate for the development of new studies on aqueous tantalum(v) chemistry for radiopharmaceutical applications.     

High-Throughput Diversification of Complex Bioactive Molecules by Accelerated Synthesis in Microdroplets

Late-stage diversification of drug molecules is an important strategy in drug discovery that can be facilitated by reaction screening using high-throughput experimentation. Here we present a rapid method for functionalizing bioactive molecules based on accelerated reactions in microdroplets. Reaction mixtures are nebulized at throughputs better than 1 reaction/second and the accelerated reactions occurring in the microdroplets are followed by desorption electrospray ionization mass spectrometry (DESI-MS). Because the accelerated reactions occur on the millisecond timescale, they allow an overall screening throughput of 1 Hz working at the low nanogram scale. Using this approach, an opioid agonist (PZM21) and an antagonist (naloxone) were diversified using three reactions important in medicinal chemistry: sulfur fluoride exchange (SuFEx) click reactions, imine formation reactions, and ene-type click reactions. Some 269 functionalized analogs of naloxone and PZM21 were generated and characterized by tandem mass spectrometry (MS/MS) after screening over 500 reactions.     

Unimer Exchange Is not Necessary for Morphological Transitions in Polymerization-Induced Self-Assembly

Polymerization-induced self-assembly (PISA) has established itself as a powerful and straightforward method to produce polymeric nano-objects of various morphologies in (aqueous) solution. Generally, spheres are formed in the early stages of polymerization that may evolve to higher order morphologies (worms or vesicles), as the solvophobic block grows during polymerization. Hitherto, the mechanisms involved in these morphological transitions during PISA are still not well understood. Combining a systematic study of a representative PISA system with rheological measurements, we demonstrate that—unexpectedly—unimer exchange is not necessary to form higher order morphologies during radical RAFT-mediated PISA. Instead, in the investigated aqueous PISA, the monomer present in the polymerization medium is responsible for the morphological transitions, even though it slows down unimer exchange.     

Thermolytic behaviour of polybutadienyllithium and polystyryllithium in ethylbenzene at high concentrations

The polymerization of butadiene and styrene with lithium and lithium alkyls has been extensively studied. The kinetics and mechanism of the pyrolysis of alkyllithium compounds has also been investigated thoroughly. The mechanism of these elimination reactions is conveniently elucidated by manometric methods, and mechanistic interpretations have been proposed. However, there are less published accounts of the thermal stability of polymer-lithium systems. There is a need to have kinetic data describing the thermal termination of “living” polymers at lithium concentrations approaching those of commercial polymerization systems. This paper will discuss the thermal stabilities of concentrated solutions in ethylbenzene of polystyryllithium and polybutadienyllithium.