Analysis and parametric optimization of 1H off-resonance relaxation NMR experiments designed to map polypeptide self-recognition and other noncovalent interactions

The measurement of 1H off-resonance nonselective relaxation rates (R(theta,ns)) has been recently proposed as an effective method to probe peptide self-recognition, opening new perspectives in the understanding of the prefibrillization oligomerization processes in amylodogenesis. However, a full analysis and parametric optimization of the NMR experiments designed to measure R(theta,ns) relaxation rates is still missing. Here we analyze the dependence of the R(theta,ns) rates upon three critical parameters: the tilt angle of the effective field during the spin lock, the static magnetic field, and finally the repetition delay. Our analysis reveals that the tilt angle theta = 35.5 degrees not only minimizes spin-diffusion, but also avoids experimental artifacts such as J-transfer and poor adiabaticity. In addition, we found that when the dominant relaxation mechanism is caused by uncorrelated pairwise 1H dipole-1H dipole interactions the R(35.5 degrees,ns) rate is not significantly affected by static field variations, suggesting a wide applicability of the 1H off-resonance nonselective relaxation experiment. Finally, we show that the self-recognition maps based on the comparative analysis of the R(35.5 degrees,ns) rates can tolerate decreases in the interscan delays without significantly compromising the identification of critical self-association loci. These considerations not only provide a better understanding of the 1H off-resonance nonselective relaxation, but they also serve as guidelines for the optimal setup of this experiment.     

Classification and decomposition of Quantum Markov Semigroups

We show that a QMS on a σ-finite von Neumann algebra can be decomposed as the sum of several ``sub'-semigroups corresponding to transient and recurrent projections. We discuss two applications to physical models.     

Analysis of breakdown process at U50 voltage for plane rod discharges by means of Neural Networks

The influence of many parameters on the electric discharges at U50% can only be correlated by means of an analysis of a large amount of experimental data. The 50% probability of breakdown is considered a random process. We have investigated how to find relevant statistical differences leading to breakdown or withstanding during an impulse voltage test under the same conditions for a plane high voltage electrode and a grounded electrode configuration. An analysis based on Neural Network discrimination has been developed which indicates that measurements do contain some relevant information test at early stages in a reduced time frame.     

A General Acid‐Mediated Hydroaminomethylation of Unactivated Alkenes and Alkynes

In comparison to the extensively studied metal‐catalyzed hydroamination reaction, hydroaminomethylation has received significantly less attention despite its considerable potential to streamline amine synthesis. State‐of‐the‐art protocols for hydroaminomethylation of alkenes rely largely on transition‐metal catalysis, enabling this transformation only under highly designed and controlled conditions. Here we report a broadly applicable, acid‐mediated approach to the hydroaminomethylation of unactivated alkenes and alkynes. This methodology employs cheap, readily available, and bench‐stable reactants and affords the desired amines with excellent functional group tolerance and impeccable regioselectivity. The broad scope of this transformation, as well as mechanistic investigations and in situ domino functionalization reactions are reported.     

Vinyl Cation Stabilization by Silicon Enables a Formal Metal‐Free α‐Arylation of Alkyl Ketones

The ability of silicon to stabilize vinyl cationic species leads to a redox arylation of alkynes whereby the stringent limitations of reactivity and regioselectivity of alkyl‐substituted alkynes are lifted. This allows the synthesis of a range of α‐silyl‐α′‐arylketones under mild conditions in good to excellent yields and with high functional group tolerance, whereby the silicon moiety in the final products can either be removed for a formal acetone monoarylation transform, or capitalized upon for subsequent electrophilic substitutions at either side of the carbonyl group.     

A Novel [OSSO]-Type Chromium(III) Complex as a Versatile Catalyst for Copolymerization of Carbon Dioxide with Epoxides

A new chromium(III) complex, bearing a bis-thioether-diphenolate [OSSO]-type ligand, was found to be an efficient catalyst in the copolymerization of CO₂ and epoxides to achieve poly(propylene carbonate), poly(cyclohexene carbonate), poly(hexene carbonate) and poly(styrene carbonate), as well as poly(propylene carbonate)(cyclohexene carbonate) and poly(propylene carbonate)(hexene carbonate) terpolymers.     

Yttrium-86 Is a Positron Emitting Surrogate of Gadolinium for Noninvasive Quantification of Whole-Body Distribution of Gadolinium-Based Contrast Agents

Gadolinium-based contrast agents (GBCAs) are used to provide diagnostic information in clinical magnetic resonance (MR) examinations. Gadolinium (Gd) has been detected in the brain, bone and skin of patients, months and years following GBCA administration, raising concerns about long term toxicity. Despite increased scrutiny, the concentration, chemical form and fate of the retained gadolinium species remain unknown. Importantly, the whole body biodistribution and organ clearance of GBCAs is poorly understood in humans. Gadolinium lacks suitable isotopes for nuclear imaging. We demonstrate that the yttrium-86 isotope can be used as a gadolinium surrogate. We show that Gd and their analogous Y complexes have similar properties both in solution and in vivo, and that yttrium-86 PET can be used to track the biodistribution of GBCAs over a two-day period.     

Glycosyl‐Substituted Dicarboxylates as Detergents for the Extraction,Overstabilization, and Crystallization of Membrane Proteins

To tackle the problems associated with membrane protein (MP) instability in detergent solutions, we designed a series of glycosyl‐substituted dicarboxylate detergents (DCODs) in which we optimized the polar head to clamp the membrane domain by including, on one side, two carboxyl groups that form salt bridges with basic residues abundant at the membrane–cytoplasm interface of MPs and, on the other side, a sugar to form hydrogen bonds. Upon extraction, the DCODs 8 b , 8 c , and 9 b preserved the ATPase function of BmrA, an ATP‐binding cassette pump, much more efficiently than reference or recently designed detergents. The DCODs 8 a , 8 b , 8 f , 9 a , and 9 b induced thermal shifts of 20 to 29 °C for BmrA and of 13 to 21 °C for the native version of the G‐protein‐coupled adenosine receptor A_2AR. Compounds 8 f and 8 g improved the diffraction resolution of BmrA crystals from 6 to 4 Å. DCODs are therefore considered to be promising and powerful tools for the structural biology of MPs.