Enantioselective Rhodium-Catalyzed Pauson–Khand Reactions of 1,6-Chloroenynes with 1,1-Disubstituted Olefins

An enantioselective rhodium(I)-catalyzed Pauson–Khand reaction (PKR) using 1,6-chloroenynes that contain challenging 1,1-disubstituted olefins is described. In contrast to the previous studies with these types of substrates, which are only suitable for a single type of tether and alkyne substituent, the new approach results in a more expansive substrate scope, including carbon and heteroatom tethers with polar and non-polar substituents on the alkene. DFT calculations provide critical insight into the role of the halide, which pre-polarizes the alkyne to lower the barrier for metallacycle formation and provides the proper steric profile to promote a favorable enantiodetermining interaction between substrate and chiral diphosphine ligand. Hence, the chloroalkyne enables the efficient and enantioselective PKR with 1,6-enynes that contain challenging 1,1-disubstituted olefins, thereby representing a new paradigm for enantioselective reactions involving 1,6-enynes.     

Achieving Control in Micro-/Nanomotor Mobility

Unprecedented opportunities exist for the generation of advanced nanotechnologies based on synthetic micro/nanomotors (MNMs), such as active transport of medical agents or the removal of pollutants. In this regard, great efforts have been dedicated toward controlling MNM motion (e.g., speed, directionality). This was generally performed by precise engineering and optimizing of the motors′ chassis, engine, powering mode (i.e., chemical or physical), and mechanism of motion. Recently, new insights have emerged to control motors mobility, mainly by the inclusion of different modes that drive propulsion. With high degree of synchronization, these modes work providing the required level of control. In this Minireview, we discuss the diverse factors that impact motion; these include MNM morphology, modes of mobility, and how control over motion was achieved. Moreover, we highlight the main limitations that need to be overcome so that such motion control can be translated into real applications.     

The Self-Association of the KRAS4b Protein is Altered by Lipid-Bilayer Composition and Electrostatics

KRAS is a peripheral membrane protein that regulates multiple signaling pathways, and is mutated in ≈30 % of cancers. Transient self-association of KRAS is essential for activation of the downstream effector RAF and oncogenicity. The presence of anionic phosphatidylserine (PS) lipids in the membrane was shown to promote KRAS self-assembly, however, the structural mechanisms remain elusive. Here, we employed nanodisc bilayers of defined lipid compositions, and probed the impact of PS concentration on KRAS self-association. Paramagnetic NMR experiments demonstrated the existence of two transient dimer conformations involving alternate electrostatic contacts between R135 and either D153 or E168 on the “α4/5-α4/5” interface, and revealed that lipid composition and salt modulate their dynamic equilibrium. These dimer interfaces were validated by charge-reversal mutants. This plasticity demonstrates how the dynamic KRAS dimerization interface responds to the environment, and likely extends to the assembly of other signaling complexes on the membrane.     

Thermally Responsive Selenide-containing Materials Based on Transalkylation of Selenonium Salts

Covalent adaptable networks (CANs) possess unique properties as a result of their internal dynamic bonds, such as self-healing and reprocessing abilities. In this study, we report a thermally responsive C−Se dynamic covalent chemistry (DCC) that relies on the transalkylation exchange between selenonium salts and selenides, which undergo a fast transalkylation reaction in the absence of any catalyst. Additionally, we demonstrate the presence of a dissociative mechanism in the absence of selenide groups. After incorporation of this DCC into selenide-containing polymer materials, it was observed that the cross-linked networks display varying dynamic exchange rates when using different alkylation reagents, suggesting that the reprocessing capacity of selenide-containing materials can be regulated. Also, by incorporating selenonium salts into polymer materials, we observed that the materials exhibited good healing ability at elevated temperatures as well as excellent solvent resistance at ambient temperature. This novel dynamic covalent chemistry thus provides a straightforward method for the healing and reprocessing of selenide-containing materials.     

Light-Driven Catalyst-Free Access to Phthalazines: Entry to Antiviral Model Drugs by Merging Domino Reactions**

We report the development of a metal-free four-step one-pot synthetic strategy to access high-value functionalized phthalazines using o-methyl benzophenones as starting compounds. Combining a light-mediated enolization of o-methyl benzophenones/Diels-Alder reaction domino process with a subsequent deprotection/aromatization domino reaction in one-pot leads to sustainable and efficient organic synthesis. The tangible advantages, i. e., absence of catalysts or additives, utilization of commercially available and/or easily accessible substrates, mild reaction conditions, simplicity, and single work-up procedure, make this combined process highly appealing for the direct construction of various 1-aryl-phthalazines. Importantly, in vitro bioactivity evaluation of these newly prepared heterocyclic compounds demonstrated a strong antiviral efficacy against major human pathogens like HCMV and SARS-CoV-2.     

Functional Dithienopyrazines: Structure-Property Relationships**

Dithienopyrazines are only scarcely used as building blocks in organic electronic materials. Here, we report efficient preparation and investigation of syn- and anti-dithienopyrazines, which were functionalized with triaraylamine units to provide different series of donor-acceptor-donor-type materials. The characterization of the optoelectronic properties resulted in valuable structure-property relationships and allowed for the elucidation of the influence of structural effects such as core structure (syn vs anti), type of substituents (directly arylated vs ethynylated aryl), and substitution pattern (α,α’- vs β,β’- vs fourfold substitution). Finally, first application of a dithienopyrazine derivative as model for hole-transport materials tailored for organic electronic devices has been realized.     

Azodicarboxylate-Mediated Peptide Cyclisation: Application to Disulfide Bond Formation in Solution and Solid Phase

Cyclic peptides are important molecules, playing key roles in protein architecture, as chemical probes, and increasingly as crucial structural elements of clinically-useful therapeutics. Herein we report methodology using azodicarboxylates as efficient reagents for the facile synthesis of cyclic peptides through a disulfide bridge. The utility of this approach in both solution and solid-phase, and compatibility with common amino acid side chain functionalities is demonstrated, resulting in cyclic peptides in good yield and purity. This approach has significant potential application for synthesis of molecules of biological or therapeutic significance.     

ChemInform Abstract: Explaining Stability of Transition Metal Carbides — and Why TcC Does Not Exist.

The formation of transition metal (M) carbides M_xC_y and trends of their stability are systematically investigated using the USPEX code within the DFT.