Decarboxylative ipso Amination of Activated Benzoic Acids

In the presence of a bimetallic Pd/Cu system with 1,10‐phenanthroline as the ligand and either air or N‐methylmorpholine N‐oxide as the oxidant, electron‐deficient benzoic acids undergo oxidative decarboxylative coupling with unprotected amines. This operationally simple aniline synthesis is widely applicable with respect to the amine and gives good yields, even on multigram scale. The orthogonality of this reaction to other Pd‐catalyzed cross‐couplings allows the concise synthesis of multisubstituted arenes by sequential C?C, C?Cl, and C?N functionalizations. Mechanistic investigations suggest the intermediacy of a hypervalent Pd species.     

Ethynylphosphonamidates for the Rapid and Cysteine‐Selective Generation of Efficacious Antibody–Drug Conjugates

Requirements for novel bioconjugation reactions for the synthesis of antibody–drug conjugates (ADCs) are exceptionally high, since conjugation selectivity as well as the stability and hydrophobicity of linkers and payloads drastically influence the performance and safety profile of the final product. We report Cys‐selective ethynylphosphonamidates as new reagents for the rapid generation of efficacious ADCs from native non‐engineered monoclonal antibodies through a simple one‐pot reduction and alkylation. Ethynylphosphonamidates can be easily substituted with hydrophilic residues, giving rise to electrophilic labeling reagents with tunable solubility properties. We demonstrate that ethynylphosphonamidate‐linked ADCs have excellent properties for next‐generation antibody therapeutics in terms of serum stability and in vivo antitumor activity.     

A Crystallographic Charge Density Study of the Partial Covalent Nature of Strong N⋅⋅⋅Br Halogen Bonds

The covalent nature of strong N?Br???N halogen bonds in a cocrystal ( 2 ) of N‐bromosuccinimide ( NBS ) with 3,5‐dimethylpyridine ( lut ) was determined from X‐ray charge density studies and compared to a weak N?Br???O halogen bond in pure crystalline NBS ( 1 ) and a covalent bond in bis(3‐methylpyridine)bromonium cation (in its perchlorate salt ( 3 ). In 2 , the donor N?Br bond is elongated by 0.0954 Å, while the Br???acceptor distance of 2.3194(4) is 1.08 Å shorter than the sum of the van der Waals radii. A maximum electron density of 0.38 e Å^?3 along the Br???N halogen bond indicates a considerable covalent contribution to the total interaction. This value is intermediate to 0.067 e Å^?3 for the Br???O contact in 1 , and approximately 0.7 e Å^?3 in both N?Br bonds of the bromonium cation in 3 . A calculation of the natural bond order charges of the contact atoms, and the σ*(N1?Br) population of NBS as a function of distance between NBS and lut , have shown that charge transfer becomes significant at a Br???N distance below about 3 Å.     

Dielectric relaxation spectroscopy of aqueous micellar electrolyte solutions: A novel application to infer Dukhin number and zeta potential of a micelle

The complex permittivities of aqueous SDS solutions, with and without the addition of sodium chloride (NaCl), are measured in the frequency range from 200 MHz to 14 GHz. The SDS concentrations are chosen such that the SDS molecules aggregate to micelles. In this frequency range, the measured spectra allow for the identification of two different relaxation processes. That is, the relaxation of the water molecules at frequencies above 1 GHz and the micellar relaxation at frequencies lower than 1 GHz. It is found that the addition of NaCl to the system mostly affects the micellar relaxation process. In detail, the time constant as well as the amplitude of the relaxation decrease by adding NaCl. These effects are attributed to the change in the solution conductivity that changes the properties of the micelle's electrical double layer. We also extract the Dukhin number of the micelles as a function of surfactant and electrolyte content from the measurements. The Dukhin number is a dimensionless group that describes the influence of the surface conductivity on a phenomena. A regression between Dukhin numbers and free sodium ions is found so that all data collapses on a single curve independent of the surfactant concentration. The surface conductivity is a manifestation of the electrical double layer and we use the Bikerman equation to infer the zeta potential of the micelles. Comparison to literature data shows very good agreement and proves that dielectric relaxation spectroscopy can be engaged to infer the zeta potential of micelles. Abbreviations: CMC critical micelle concentration, DRS dielectric relaxation spectroscopy, EDL electrical double layer     

Mechanochemistry and thermochemistry are different: stress-induced strengthening of chemical bonds

Most chemical reactions require activation which is conventionally supplied by heat. In stark contrast, mechanical activation by applied external forces opens intriguing novel possibilities. Here, the first direct comparison of mechanical versus thermal activation of bond breaking is provided. Studying both thiolate-copper interfaces and junctions provides evidence for vastly different reaction pathways and product classes. This is understood in terms of directional mechanical manipulation of coordination numbers and system fluctuations in the process of mechanical activation.     

Energy harvesting through arterial wall deformation: A FEM approach to fluid–structure interactions and magneto-hydrodynamics

Engineers are confronted with the energy demand of active medical implants in patients with increasing life expectancy. Scavenging energy from the patient’s body is envisioned as an alternative to conventional power sources. Joining in this effort towards human-powered implants, we propose an innovative concept that combines the deformation of an artery resulting from the arterial pressure pulse with a transduction mechanism based on magneto-hydrodynamics. To overcome certain limitations of a preliminary analytical study on this topic, we demonstrate here a more accurate model of our generator by implementing a three-dimensional multiphysics finite element method (FEM) simulation combining solid mechanics, fluid mechanics, electric and magnetic fields as well as the corresponding couplings. This simulation is used to optimize the generator with respect to several design parameters. A first validation is obtained by comparing the results of the FEM simulation with those of the analytical approach adopted in our previous study. With an expected overall conversion efficiency of 20% and an average output power of 30 μW, our generator outperforms previous devices based on arterial wall deformation by more than two orders of magnitude. Most importantly, our generator provides sufficient power to supply a cardiac pacemaker.