Winklergriffin0177

A series of molecular rotors was designed to study and measure the rate accelerating effects of an intramolecular hydrogen bond. The rotors form a weak neutral O-H⋯O[double bond, length as m-dash]C hydrogen bond in the planar transition state (TS) of the bond rotation process. The rotational barrier of the hydrogen bonding rotors was dramatically lower (9.9 kcal mol-1) than control rotors which could not form hydrogen bonds. The magnitude of the stabilization was significantly larger than predicted based on the independently measured strength of a similar O-H⋯O[double bond, length as m-dash]C hydrogen bond (1.5 kcal mol-1). The origins of the large transition state stabilization were studied via experimental substituent effect and computational perturbation analyses. Energy decomposition analysis of the hydrogen bonding interaction revealed a significant reduction in the repulsive component of the hydrogen bonding interaction. The rigid framework of the molecular rotors positions and preorganizes the interacting groups in the transition state. This study demonstrates that with proper design a single hydrogen bond can lead to a TS stabilization that is greater than the intrinsic interaction energy, which has applications in catalyst design and in the study of enzyme mechanisms.Heme as a cofactor has been proposed to bind with β-amyloid peptide (Aβ) and the formed Aβ-heme complex exhibits enhanced peroxidase-like activity. So far, in vitro studies on the interactions between heme, Cu and Aβ have been exclusively performed in dilute solution. However, the intracellular environment is highly crowded with biomolecules. Therefore, exploring how Aβ-heme-Cu complexes behave under molecular crowding conditions is critical for understanding the mechanism of Aβ neurotoxicity in vivo. Herein, we selected PEG-200 as a crowding agent to mimic the crowded cytoplasmic environment for addressing the contributions of crowded physiological environments to the biochemical properties of Aβ-heme, Aβ-Cu and Aβ-heme-Cu complexes. Surprisingly, experimental studies and theoretical calculations revealed that molecular crowding weakened the stabilization of the Aβ-heme complex and decreased its peroxidase activity. Our data attributed this consequence to the decreased binding affinity of heme to Aβ as a result of the alterations in water activity and Aβ conformation. Our findings highlight the significance of hydration effects on the interaction of Aβ-heme and Aβ-Cu and their peroxidase activities. Molecular crowding inside cells may potentially impose a positive effect on Aβ-Cu but a negative effect on the interaction of Aβ with heme. This indicates that Aβ40-Cu but not Aβ40-heme may play more important roles in the oxidative damage in the etiology of AD. Therefore, this work provides a new clue for understanding the oxidative damage occurring in AD.(-)-Lomaiviticin A is a complex C 2-symmetric bacterial metabolite comprising two diazotetrahydrobenzo[b]fluorene (diazofluorene) residues and four 2,6-dideoxy glycosides, α-l-oleandrose and N,N-dimethyl-β-l-pyrrolosamine. The two halves of lomaiviticin A are linked by a single carbon-carbon bond oriented syn with respect to the oleandrose residues. While many advances toward the synthesis of lomaiviticin A have been reported, including synthesis of the aglycon, a route to the bis(cyclohexenone) core bearing any of the carbohydrate residues has not been disclosed. Here we describe a short route to a core structure of lomaiviticin A bearing two α-l-oleandrose residues. The synthetic route features a Stille coupling to form the conjoining carbon-carbon bond of the target and a double reductive transposition to establish the correct stereochemistry at this bond. Two synthetic routes were developed to elaborate the reductive transposition product to the bis(cyclohexenone) target. The more efficient pathway features an interrupted Barton vinyl iodide synthesis followed by oxidative elimination of iodide to efficiently establish the enone functionalities in the target. The bis(cyclohexenone) product may find use in a synthesis of lomaiviticin A itself.Nickel-catalysed aryl amination and etherification are driven with sunlight using a surface-modified carbon nitride to extend the absorption of the photocatalyst into a wide range of the visible region. In contrast to traditional homogeneous photochemical methodologies, the lower cost and higher recyclability of the metal-free photocatalyst, along with the use of readily available sunlight, provides an efficient and sustainable approach to promote nickel-catalysed cross-couplings.Despite the importance of P-chiral organophosphorus compounds in asymmetric catalysis, transition metal-catalyzed methods for accessing P-chiral phosphine derivatives are still limited. Herein, a catalytic enantioselective method for the synthesis of P-stereogenic alkenylphosphinates is developed through asymmetric hydrophosphorylation of alkynes. This process is demonstrated for a wide range of racemic phosphinates and leads to diverse P-stereogenic alkenylphosphinates directly.The construction of enantioenriched azabicyclo[3.3.1]nonan-6-one heterocycles via an enantioselective desymmetrization of allene-linked cyclohexanones, enabled through a dual catalytic system, that provides synchronous activation of the cyclohexanone with a chiral prolinamide and the allene with a copper(i) co-catalyst to deliver the stereodefined bicyclic core, is described. Successful application to oxygen analogues was also achieved, thereby providing a new enantioselective synthetic entry to architecturally complex bicyclic ethereal frameworks. The mechanistic pathway and the origin of enantio- and diastereoselectivities has been uncovered using density functional theory (DFT) calculations.Asymmetrically modified Janus microparticles are presented as autonomous light emitting swimmers. The localized dissolution of hybrid magnesium/polymer objects allows combining chemiluminescence with the spontaneous production of H2 bubbles, and thus generating directed motion. These light-emitting microswimmers are synthesized by using a straightforward methodology based on bipolar electromilling, followed by indirect bipolar electrodeposition of an electrophoretic paint. An optimization of the experimental parameters enables in the first step the formation of well-defined isotropic or anisotropic Mg microparticles. Subsequently, they are asymmetrically modified by wireless deposition of an anodic paint. The degree of asymmetry of the resulting Janus particles can be fine-tuned, leading to a controlled directional motion due to anisotropic gas formation. find more This autonomous motion is coupled with the emission of bright orange light when Ru(bpy)3 2+ and S2O8 2- are present in the solution as chemiluminescent reagents. The light emission is based on an original process of interfacial redox-induced chemiluminescence, thus allowing an easy visualization of the swimmer trajectories.Breast cancer recurrence is the greatest contributor to patient death. As the immune system has a long-term immune memory effect, immunotherapy has great potential for preventing cancer recurrence. However, cancer immunotherapy is often limited due to T cell activation being blocked by insufficient tumor immunogenicity and the complex immunosuppressive tumor microenvironment. Here we show a tumor acidity activatable and Ca2+-assisted immuno-nanoagent to synergistically promote T cell activation and enhance cancer immunotherapy. When the immuno-nanoagent reaches the acidic tumor microenvironment, the CaCO3 matrix disintegrates to release immune stimulants (CpG ODNs and IDOi) and Ca2+. CpG ODNs are responsible for triggering dendritic cell maturation to increase the immunogenicity for activation of T cells. And IDOi can inhibit the oxidative catabolism of tryptophan to kynurenine for preventing T-cell anergy and apoptosis. Due to the complexity of the immunosuppressive microenvironment, it is difficult to restore T cell activation by inhibiting only one pathway. Fortunately, the released Ca2+ can promote the activation and proliferation of T cells with the support of the immune stimulants. In vivo experiments demonstrate that our Ca2+-assisted immuno-nanoagent can significantly suppress tumor progression and protect mice from tumor rechallenge due to the long-term memory effect. This immunotherapeutic strategy may provide more possibilities for clinical applications such as treating cancer and preventing relapse.The construction of double carbohelicenes is highly fascinating yet challenging work. Disclosed herein is a streamlined and simplified synthetic route to double carbohelicenes starting from nitroarenes through sequential nitro-activated ortho-C-H arylation, denitrative alkenylation and intramolecular cyclodehydrogenation. In this synthetic strategy, the nitro group plays a dual role namely as a leaving group for the denitrative alkenylation and as an activating group for ortho-C-H arylation, which is distinct from those of aryl halides in a conventional coupling reaction. In this work, the palladium-catalyzed Heck-type alkenylation of nitroarenes has been presented, in which the conventionally inert Ar-NO2 bond is cleaved. This work provides a novel synthetic strategy for polycyclic aromatic hydrocarbons (PAHs).DNA molecular machines are DNA self-assemblies that perform quasi-mechanical movement at the micro-nano scale, and have attracted increasing attention in the fields of biosensing, drug delivery and biocomputing. Herein, we report the concept and operation of an interparticle relatively motional DNA walker. The walker is composed of walking particles (WPs) and track particles (TPs). The WPs and TPs are obtained by respective functionalization of locked walking strands containing DNAzyme sequences and fluorophore-labelled track strands containing substrate sequences onto gold nanoparticles (AuNPs). Triggered by the target that specifically unlocks the walking strand, the liberated walking strands cooperatively hybridize with the track strands. The track strand gets cleaved by the DNAzyme, accompanied by the fluorophore release. The adjacent walking strand on the WP subsequently hybridizes to the next track strand, inducing the relative motion of the WP around the TP. After walking along the surface of one TP, the WP can continue to interact with another TP. As a result of the improved moving freedom and area, the interparticle motional mode induces high continuity and achieves large signal accumulation. Taking Zika virus RNA fragments (ZIKV-RNA) as a model target, the DNA walker shows a high sensitivity with a detection limit of 118 pM, and can reliably detect the target in biological fluids due to the stability of its components. The constructed DNA walker provides a new type of free and robust motion mode between particles and holds potential in clinical diagnosis.All key chemical transformations in biology are catalysed by linear oligomers. Catalytic properties could be programmed into synthetic oligomers in the same way as they are programmed into proteins, and an example of the discovery of emergent catalytic properties in a synthetic oligomer is reported. Dynamic combinatorial chemistry experiments designed to study the templating of a recognition-encoded oligomer by the complementary sequence have uncovered an unexpected imine polymerase activity. Libraries of equilibrating imines were formed by coupling diamine linkers with monomer building blocks composed of dialdehydes functionalised with either a trifluoromethyl phenol (D) or phosphine oxide (A) H-bond recognition unit. However, addition of the AAA trimer to a mixture of the phenol dialdehyde and the diamine linker did not template the formation of the DDD oligo-imine. Instead, AAA was found to be a catalyst, leading to rapid formation of long oligomers of D. AAA catalysed a number of different imine formation reactions, but a complementary phenol recognition group on the aldehyde reaction partner is an essential requirement.