查看更多>>摘要：Putin's invasion of Ukraine is unfortunately just the latest reminder that energy and geopolitics have historically been tightly intertwined1, but whether this relationship continues will be, in large part, down to chemists. If we are clever about it, chemistry - the central science - can be at the core of world energy democratization. Hyperbole? Perhaps. But as you recall Einstein's quip that "everything is energy and that's all there is to it", consider how chemistry can fuel equitable access to energy. As a preamble, it helps here if you hail from a country that has over 900 islands, 94 of which are permanently inhabited.
查看更多>>摘要：Do enzymes offer a special electrostatic environment for catalysing reactions? How is such an environment different from that offered by solvent molecules organized around a reactant? And is the electrostatic environment of enzymes the key to their exceptional catalytic power? These questions, which reside at the intersection of several fields, including catalysis, biochemistry, mechanistic organic chemistry and electrochemistry have puzzled chemists of many stripes for decades, challenging and taunting those who seek to design enzyme mimics. And answering them is difficult, because the inner environment of an enzyme, which features internal fields generated through the combination of charged amino acids and their molecular dipoles, is inaccessible to many of the conventional tools used to measure electrostatic fields. One method by which to study the internal fields within enzymes is vibrational Stark-shift spectroscopy1, which uses probe molecules that have vibrational signatures that are sensitive to electric fields. Thus, one may infer the electric field within a given enzyme by measuring the shift in the vibrational frequency of the probe molecule when compared with the frequency of the probe in a reference environment outside the enzyme.
查看更多>>摘要：The development of mild and efficient strategies for the construction of carbon-heteroatom bonds remains one of the most important goals in organic chemistry, with particular interest in methods for aromatic C-O bond formation. Currently, transition-metal-catalysed Ullmann-type chemistry is one of the most popular methods for the construction of C-O bonds1. The traditional catalytic cycle for the transition-metal-catalysed synthesis of phenols involves three fundamental steps: oxidative addition, ligand metathesis and reductive elimination (Fig. la, left). The oxygen source in these reactions is usually H2O or a protic oxygen-based nucleophile in combination with a base.
查看更多>>摘要：There is a relentless need for the development of novel antibiotics as treating infections with antibiotics places selective pressures on pathogens, inevitably leading to antibiotic resistance1. Screening for compounds that, rather than inhibiting bacterial growth, target bacterial virulence pathways has been suggested as an alternative approach to address infections2. This antivirulence approach disarms bacteria of key proteins and toxins required for establishing infection. Contrary to antibiotics, antivirulence drugs avoid imposing the selective pressures that propagate antibiotic resistance. Therefore, these drugs could prove remarkably valuable in reducing the severity of antibiotic-resistant infections.
查看更多>>摘要：The incorporation of nitrogen atom(s) into pharmaceutical lead compounds can often drastically alter their molecular properties to bring forth the intended physiological effects1. Hence, it is perhaps not surprising that a staggering 60% of all FDA-approved medicines contains at least one nitrogen atom in a cyclic form, collectively referred to as N-heterocycles2. Cross-coupling reactions and Buchwald-Hartwig amination have revolutionized methods for the synthesis of N-heteroaromatics - 'flat' N-heterocycles -via C-C and C-N bond formations. Saturated (or partially saturated) N-heterocycles containing non-planar sp~3-hybridized atoms have recently been suggested to be better pharmaceutical lead scaffolds compared with unsaturated compounds3. However, strategies for the syntheses of molecules with increased saturation have so far largely relied on intramolecular cyclization, which can be difficult to apply when trying to access structural diversity (Fig. 1a).
查看更多>>摘要：Over the past three decades, crystalline porous materials, such as metal-organic frameworks (MOFs) and covalent organic frameworks, have emerged as an exciting research frontier of chemistry and materials science1,2. The resulting intrinsic porosity and high surface area are of interest for a range of applications, including gas adsorption and separation, sensing and catalysis. These structures often have a high prevalence of rigid aromatic components and generally form well-crystallized products with few geometric degrees of freedom. But such structures tend to have rigid internal cavities that may be disadvantageous, as recent findings have shown that adaptable (flexible) pore environments have superior guest-to-framework interactions3.
查看更多>>摘要：The recently described in vivo gene silencing activity of a xeno nucleic acid (XNA)-modified version of the classic 10-23 DNAzyme (X10-23) has created substantial interest1-3. Our data suggest that the core claim of the manuscript-that the observed gene silencing activity is mediated by the RNA endonuclease catalytic activity of the X10-23 DNAzyme (rather than an antisense effect)-should be reconsidered. We have arrived at this opinion both through examination of the data in the Nature Chemistry paper (Wang et al.1), a companion paper in the Journal of the American Chemical Society (Nguyen et al.2) and by comparison with results we have obtained with the X10-23 DNAzyme (kindly provided by the authors) targeting an RNA sequence (residues 202-215) from exon 2 of the oncogene KRAS (reported as exon 1 in ref.'). Further supporting data are provided by examination of the activities of other modified versions of the 10-23 DNAzyme, as well as all-FANA XNAzymes4, also targeting RNA sequences in KRAS exon 2.
查看更多>>摘要：In their recent communication, Taylor and Holliger argue that the gene silencing activity observed for the X10-23 DNAzyme is primarily the result of an antisense mechanism that is promoted by RNase H rather than the intrinsic catalytic activity of the enzyme1. The evidence they offer in support of their criticism derives from RNA cleavage assays performed under cell-free conditions that compare the 10-23 and X10-23 DNAzymes to unpublished FANAzymes (Fzl2B and Fzl66) from their laboratory. Despite several requests, the authors declined to share their unpublished work (cited as ref.4 of their comment), which was needed to evaluate the biochemical properties of their reagents.
Elanna B. StephensonJaime L. KornerKatherine S. Elvira
9页
查看更多>>摘要：Model membranes can be used to elucidate the intricacies of the chemical processes that occur in cell membranes, but the perfectly biomimetic, yet bespoke, model membrane has yet to be built. Droplet interface bilayers are a new type of model membrane able to mimic some features of real cell membranes better than traditional models, such as liposomes and black lipid membranes. In this Perspective, we discuss recent work in the field that is starting to showcase the potential of these model membranes to enable the quantification of membrane processes, such as the behaviour of protein transporters and the prediction of in vivo drug movement, and their use as scaffolds for electrophysiological measurements. We also highlight the challenges that remain to enable droplet interface bilayers to achieve their full potential as artificial cells, and as biological analytical platforms to quantify molecular transport.
查看更多>>摘要：The [n]cycloparaphenylenes ([n]CPPs)-n para-linked phenylenes that form a closed-loop-have attracted substantial attention due to their unique cyclic structure and highly effective para-conjugation leading to a myriad of fascinating electronic and optoelectronic properties. However, their strained topology prevents the π-extension of CPPs to convert them either into armchair nanobelts or planarized CPP macrocycles. Here we successfully tackle this long-standing challenge and present the bottom-up synthesis and characterization of atomically precise in-plane π-extended [12]CPP on Au(111) by low-temperature scanning probe microscopy and spectroscopy combined with density functional theory. The planar π-extended CPP is a nanog-raphene with an all-armchair edge topology. The exclusive para-conjugation at the periphery yields delocalized electronic states and the planarization maximizes the overlap of p orbitals, which both reduce the bandgap compared to conventional CPPs. Calculations predict ring currents and global aromaticity in the doubly charged system. The intriguing planar ring topology and unique electronic properties make planar π-extended CPPs promising quantum materials.
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