Chain Sliding versus β-Sheet Formation upon Shearing Single α-Helical Coiled Coils

Coiled coils (CCs) are key building blocks of biogenic materials and determine their mechanical response to large deformations. Of particular interest is the observation that CC-based materials display a force-induced transition from α-helices to mechanically stronger β-sheets (αβT). Steered molecular dynamics simulations predict that this αβT requires a minimum, pulling speed-dependent CC length. Here, de novo designed CCs with a length between four to seven heptads are utilized to probe if the transition found in natural CCs can be mimicked with synthetic sequences. Using single-molecule force spectroscopy and molecular dynamics simulations, these CCs are mechanically loaded in shear geometry and their rupture forces and structural responses to the applied load are determined. Simulations at the highest pulling speed (0.01 nm ns⁻¹) show the appearance of β-sheet structures for the five- and six-heptad CCs and a concomitant increase in mechanical strength. The αβT is less probable at a lower pulling speed of 0.001 nm ns⁻¹ and is not observed in force spectroscopy experiments. For CCs loaded in shear geometry, the formation of β-sheets competes with interchain sliding. β-sheet formation is only possible in higher-order CC assemblies or in tensile-loading geometries where chain sliding and dissociation are prohibited.     

Preparative Scale Applications of C−H Activation in Medicinal Chemistry

C−H activation is an attractive methodology to increase molecular complexity without requiring substrate prefunctionalization. In contrast to well-established cross-coupling methods, C−H activation is less explored on large scales and its use in the production of pharmaceuticals faces substantial hurdles. However, the inherent advantages, such as shorter synthetic routes and simpler starting materials, motivate medicinal chemists and process chemists to overcome these challenges, and exploit C−H activation steps for the synthesis of pharmaceutically relevant compounds. In this review, we will cover examples of drugs/drug candidates where C−H activation has been implemented on a preparative synthetic scale (range between 355 mg and 130 kg). The optimization processes will be described, and each example will be examined in terms of its advantages and disadvantages, providing the reader with an in-depth understanding of the challenges and potential of C−H activation methodologies in the production of pharmaceuticals.     

The first report on a convenient synthesis of novel reactive amphiphilic polysaccharides

New amphiphiles with reactive tosylate groups and ionic sulfuric acid half esters based on the rod-like polysaccharide cellulose were designed via homogeneous tosylation followed by sulfation with the SO₃-pyridine complex in N,N-dimethylacetamide. At appropriate degrees of functionalization the polymers are soluble both in water and dimethyl sulfoxide, and they are promising starting materials for self-organizing systems.