Basis and Limitations of the Reactivity-Selectivity Principle

The reactivity-selectivity principle (RSP), which describes a linear relationship between the decrease in selectivity and increase in reactivity of molecules X_m in their reactions with Y₁ and Y₂, has been much criticized during the last few years. The present paper shows the kind of reactions where the RSP does not hold and reveals how the individual types of reaction can be distinguished by varying the solvent. The dependence of molecule selectivity on temperature produces a further effect. An isoselective relationship (ISR) can be deduced when this dependence is taken into account. This relationship is not concerned with the connection between the temperature-dependent rate and competition constants, but with the connection existing between activation enthalpies and activation entropies, which are temperature-independent over wide ranges. The application of the ISR to different types of reactions makes it possible to characterize and distinguish between short-lived intermediates and underlines the significance of the isoselective temperature (T_is) in interpreting the reaction parameters of linear free energy relationships and in planning syntheses.     

Electron-capture mass spectrometry: recent advances

Electron-capture (EC) is a sensitive and selective ionization technique for mass spectrometry (MS). In the most familiar form of EC, a susceptible analyte (electrophore) is detected after eluting from a gas chromatography (GC) column, where a low attomole detection limit for standards is routine. High-performance liquid chromatography can facilitate sample cleanup prior to detection by GC-EC-MS, but carryover and shifts in retention time for the "invisible" analyte can be difficulties. Solid-phase extraction avoids these difficulties, but the degree of cleanup and recovery can be problems. Alternative electrophoric derivatizing reagents are available to help deal with interferences, and new reagents such as "AMACE1" are emerging. Releasable forms of electrophores can be used as tags for labeling macromolecules, motivated by the desire to multiplex ligand-type assays. The conventional, gas-phase ion source for EC is not well-understood, especially the role of wall reactions. Using an electron monochromator to tune the electron energy adds to the selectivity and information provided by EC-MS. High-resolution and tandem EC-MS measurements are emerging. Electron-capture dissociation is a new technique to sequence small- to medium-sized peptides, having the advantage of providing more extensive sequence information relative to other MS techniques. Particle-beam EC-MS tends to be less sensitive than GC-EC-MS, but not always. Recently it was demonstrated that EC-MS can be accomplished on an ordinary laser desorption time-of-flight mass spectrometer, and also by using atmospheric pressure chemical ionization. Two applications are discussed here in detail: bile acids and oxidized phenylalanine. EC-MS is well-established as a useful technique for trace analysis in special cases, and the scope of its usefulness is broadening (qualitative analysis and detection of more polar and larger molecules), based on advances in both the chemical and instrumental aspects of this technique.     

EP-2104R: a fibrin-specific gadolinium-Based MRI contrast agent for detection of thrombus

Thrombus (blood clot) is implicated in a number of life threatening diseases, e.g., heart attack, stroke, pulmonary embolism. EP-2104R is an MRI contrast agent designed to detect thrombus by binding to the protein fibrin, present in all thrombi. EP-2104R comprises an 11 amino acid peptide derivatized with 2 GdDOTA-like moieties at both the C- and N-terminus of the peptide (4 Gd in total). EP-2104R was synthesized by a mixture of solid phase and solution techniques. The La(III) analogue was characterized by and 1D and 2D NMR spectroscopy and was found to have the expected structure. EP-2104R was found to be significantly more inert to Gd(III) loss than commercial contrast agents. At the most extreme conditions tested (pH 3, 60 degrees C, 96 hrs), less than 10% of Gd was removed from EP-2104R by a challenge with a DTPA based ligand, while the commercial contrast agents equilibrated within minutes to hours. EP-2104R binds equally to two sites on human fibrin (Kd = 1.7 +/- 0.5 microM) and has a similar affinity to mouse, rat, rabbit, pig, and dog fibrin. EP-2104R has excellent specificity for fibrin over fibrinogen (over 100-fold) and for fibrin over serum albumin (over 1000-fold). The relaxivity of EP-2104R bound to fibrin at 37 degrees C and 1.4 T was 71.4 mM(-1) s(-1) per molecule of EP-2104R (17.4 per Gd), about 25 times higher than that of GdDOTA measured under the same conditions. Strong fibrin binding, fibrin selectivity, and high molecular relaxivity enable EP-2104R to detect blood clots in vivo.     

An intra/intermolecular suzuki sequence to benzopyridyloxepines containing geometrically pure exocyclic tetrasubstituted alkenes

A route to enable the preparation of 5-benzylidenyl-benzopyridyloxepine analogues was developed to continue our research in the field of nuclear hormone receptor modulators. The key steps are 1) a syn-stereoselective diboration of a tethered aryl alkyne; 2) an intramolecular Suzuki cross-coupling reaction, which forms in a stereo- and regiocontrolled fashion, the 5-exoalkylidenyl 7-membered ring imbedded within the core of the scaffold and; 3) an intermolecular Suzuki to furnish the final tetra-substituted olefinic benzopyridyloxepines.     

Turning the Ship: The Transformation of DESY, 1993–2009

This article chronicles the most recent history of the Deutsches Elektronen-Synchrotron (DESY) located in Hamburg, Germany, with particular emphasis on how this national laboratory founded for accelerator-based particle physics shifted its research program toward multi-disciplinary photon science. Synchrotron radiation became DESY’s central experimental research program through a series of changes in its organizational, scientific, and infrastructural setup and the science policy context. Furthermore, the turn toward photon science is part of a broader transformation in the late twentieth century in which nuclear and particle physics, once the dominating fields in national and international science budgets, gave way to increasing investment in the materials sciences and life sciences. Synchrotron radiation research took a lead position on the experimental side of these growing fields and became a new form of big science, generously funded by governments and with user communities expanding across both academia and industry.     

Polysulfonylamines. CXX. Bis(tetrahydrothiophene‐S)gold(I) benzene‐1,2‐disulfonimidate

Both ions of the title compound, [Au(C₄H₈S)₂](C₆H₄NO₄S₂), display crystallographic twofold symmetry. The Au atom exhibits linear coordination, with Au—S = 2.2948 (14) Å and S—Au—S = 178.47 (9)°. The crystal packing consists of layers of anions connected by C—H?O hydrogen bonds; the cations occupy cavities in these layers and the ions are linked by Au?N contacts of 3.009 (7) Å. Further C—H?O interactions connect the layers.     

On the Mechanism of Long-Range Electron Transfer through DNA

Hopping between bases of similar redox potentials is the mechanism by which charge transport occurs through DNA. This was shown by rate measurements performed with double strands 1 – 3 . This mechanism explains why hole transfer displays a strong sequence dependence, and postulates that electron transfer in unperturbed DNA should not be dependent on the sequence.     

Electron Transfer through DNA in the Course of Radical-Induced Strand Cleavage

No benefit from base stacking is observed for rates of electron transfer in DNA. This conclusion was drawn from experiments with a new DNA assay in which a radical cationic site, generated by strand cleavage, can be reduced by the guanine bases in the same DNA (the electron transfer is indicated by arrows in the diagram). The distance dependence of this electron transfer step is determined by the chemical yield of the reduction product.