Carbon-carbon bond formation between alkylated alkenes and acrylic ester via 2-methoxyalkyl radicals

Methoxymercuration/demercuration reactions of alkenes 10 in $\text{10}$ in the presence of acrylic ester yield products $\text{11}$ in a carbon-carbon bond formation reaction.     

Measurement of endogenous estrogens: analytical challenges and recent advances

Recent developments in the analysis of endogenous estrogens (including both free and conjugated estrogens) are reviewed. Largely due to urging by some cancer researchers, new demands are now being placed on such measurements in terms of sensitivity, throughput, multi-analyte detection and accuracy. Especially high sensitivity is required for detecting estrogens in serum from postmenopausal women, children and men, where concentrations at the low pg/ml level are encountered, and one would prefer to test much less than 1 ml of serum. Aside from throughput, meeting all of these demands may be beyond the reach of immunoassay, the method that has created and continues to dominate this field. Both HPLC and GC versions of mass spectrometry are emerging that have some potential to improve the testing of physiological samples for endogenous estrogens. The following topics are covered in this review: related analyses (e.g. detection of estrogens in environmental samples such as water, where 1-l samples can be collected to provide ng amounts of estrogens); structure and metabolism of estrogens; biological actions (with an emphasis on their role in cancer); immunoassays; HPLC with electrochemical detection; GC-ECD; and various forms of mass spectrometry.     

Phase separation of Lal3 inside single-walled carbon nanotubes.

Simple binary solids can be found to adopt unprecedented structures when confined into nanometre-sized cavities, such as the inner cylindrical bore of single-walled carbon nanotubes (SWNT). In the case of the discussed Lal(x)@SWNT encapsulation composite, the Lal2 "crystal" fragment adopts the structure of bulk Lal3, with one third of the iodine positions unoccupied. A complete characterisation of the encapsulation composite was achieved using an enhanced digital restoration approach of high-resolution transmission electron microscopy (HRTEM) images. The resulting complex exit surface wave provides information about the precise structural data of both filling material and host SWNT, establishing the SWNT's chirality and thus enabling a prediction of the composite's overall electron-transport properties.     

Advances towards Cell-Specific Gene Transfection: A Small-Molecule Approach Allows Order-of-Magnitude Selectivity

A transfection vector that can home in on tumors is reported. Whereas previous vectors that allow moderately cell selective gene transfection used larger systems, this small-molecule approach paved the way for precise structure-activity relationship optimization. For this, biotin, which mediates cell selectivity, was combined with the potent DNA-binding motif tetralysine-guanidinocarbonypyrrol via a hydrophilic linker, thus enabling SAR-based optimization. The new vector mediated biotin receptor (BR)-selective transfection of cell lines with different BR expression levels. Computer-based analyses of microscopy images revealed a preference of one order of magnitude for the BR-positive cell lines over the BR-negative controls.     

UV assisted photo reactive polyether-polyesteramide resin for future applications in 3D printing

Among additive manufacturing, photocuring 3D printing technologies are very relevant because of its high printing speed and high precision. However, the limited performance of photosensitive thermoset polymers is the bottleneck for the application of photocuring 3D printing in some fields, particularly in the biomedical sector. Thus, the development of biodegradable and biocompatible materials is highly desirable and of utmost importance. In this work, a biodegradable and non-cytotoxic thermoset polymer for photocuring 3D printing is reported. It consists of an unsaturated polyesteramide bearing phenylalanine, 2-butene-1,4-diol and fumarate building blocks, which is photocured under UV irradiation using a low molecular weight poly(ethylene glycol) diacrylate as crosslinker. The main characteristics of the new thermoset are: (1) very high volumetric and mechanical integrity stabilities, comparable to that of photocured epoxides; (2) very high degradation temperature; (3) very low water absorption capacity; (4) relatively fast enzymatic degradation, reaching 16.5% after 3 months; and (5) non-cytotoxic response in presence of epithelial cells, even when soluble molecular fragments coming from biodegradation are considered. These properties favor the future utilization of the new polyether-polyesteramide resin in the manufacturing of more sustainable products via 3D printing methods, such as stereolithography, that uses UV sources.     

Mechanistic Insights into RNA Transphosphorylation from Kinetic Isotope Effects and Linear Free Energy Relationships of Model Reactions

Phosphoryl transfer reactions are ubiquitous in biology and the understanding of the mechanisms whereby these reactions are catalyzed by protein and RNA enzymes is central to reveal design principles for new therapeutics. Two of the most powerful experimental probes of chemical mechanism involve the analysis of linear free energy relations (LFERs) and the measurement of kinetic isotope effects (KIEs). These experimental data report directly on differences in bonding between the ground state and the rate‐controlling transition state, which is the most critical point along the reaction free energy pathway. However, interpretation of LFER and KIE data in terms of transition‐state structure and bonding optimally requires the use of theoretical models. In this work, we apply density‐functional calculations to determine KIEs for a series of phosphoryl transfer reactions of direct relevance to the 2′‐O‐transphosphorylation that leads to cleavage of the phosphodiester backbone of RNA. We first examine a well‐studied series of phosphate and phosphorothioate mono‐, di‐ and triesters that are useful as mechanistic probes and for which KIEs have been measured. Close agreement is demonstrated between the calculated and measured KIEs, establishing the reliability of our quantum model calculations. Next, we examine a series of RNA transesterification model reactions with a wide range of leaving groups in order to provide a direct connection between observed Brønsted coefficients and KIEs with the structure and bonding in the transition state. These relations can be used for prediction or to aid in the interpretation of experimental data for similar non‐enzymatic and enzymatic reactions. Finally, we apply these relations to RNA phosphoryl transfer catalyzed by ribonuclease A, and demonstrate the reaction coordinate–KIE correlation is reasonably preserved. A prediction of the secondary deuterium KIE in this reaction is also provided. These results demonstrate the utility of building up knowledge of mechanism through the systematic study of model systems to provide insight into more complex biological systems such as phosphoryl transfer enzymes and ribozymes.