Double Deprotonation of CHCN by an Iron-Aluminium Complex.

Herein we present the first double deprotonation of acetonitrile (CHCN) using two equivalents of a bimetallic iron-aluminium complex. The products of this reaction contain an exceeding simple yet rare [CHCN] dianion moiety that bridges two metal fragments. DFT calculations suggest that the bonding to the metal centres occurs through heavily polarised covalent interactions.

Platinum(II)-Based Optical Probes for Imaging Quadruplex DNA Structures via Phosphorescence Lifetime Imaging Microscopy.

G-quadruplex DNA is a non-canonical structure that forms in guanine-rich regions of the genome. There is increasing evidence showing that G-quadruplexes have important biological functions, and therefore molecular tools to visualise these structures are important. Herein we report on a series of new cyclometallated platinum(II) complexes which, upon binding to G-quadruplex DNA, display an increase in their phosphorescence, acting as switch-on probes.

Squarephaneic Tetraanhydride: A Conjugated Square-Shaped Cyclophane for the Synthesis of Porous Organic Materials.

Aromatic carboxylic anhydrides are ubiquitous building blocks in organic materials chemistry and have received considerable attention in the synthesis of organic semiconductors, pigments, and battery electrode materials. Here we extend the family of aromatic carboxylic anhydrides with a unique new member, a conjugated cyclophane with four anhydride groups. The cyclophane is obtained in a three-step synthesis and can be functionalised efficiently, as shown by the conversion into tetraimides and an octacarboxylate.

Allosteric Hotspots in the Main Protease of SARS-CoV-2.

Inhibiting the main protease of SARS-CoV-2 is of great interest in tackling the COVID-19 pandemic caused by the virus. Most efforts have been centred on inhibiting the binding site of the enzyme. However, considering allosteric sites, distant from the active or orthosteric site, broadens the search space for drug candidates and confers the advantages of allosteric drug targeting.

Prediction of Protein Allosteric Signalling Pathways and Functional Residues Through Paths of Optimised Propensity.

Allostery commonly refers to the mechanism that regulates protein activity through the binding of a molecule at a different, usually distal, site from the orthosteric site. The omnipresence of allosteric regulation in nature and its potential for drug design and screening render the study of allostery invaluable. Nevertheless, challenges remain as few computational methods are available to effectively predict allosteric sites, identify signalling pathways involved in allostery, or to aid with the design of suitable molecules targeting such sites.

Effect of Religious Fasting in Ramadan on Blood Pressure: Results From LORANS (London Ramadan Study) and a Meta-Analysis.

Background Ramadan fasting is practiced by hundreds of millions every year. This ritual practice changes diet and lifestyle dramatically; thus, the effect of Ramadan fasting on blood pressure must be determined. Methods and Results LORANS (London Ramadan Study) is an observational study, systematic review, and meta-analysis.

Synthesis and Transformations of NH-Sulfoximines.

Recent years have seen a marked increase in the occurrence of sulfoximines in the chemical sciences, often presented as valuable motifs for medicinal chemistry. This has been prompted by both pioneering works taking sulfoximine containing compounds into clinical trials and the concurrent development of powerful synthetic methods. This review covers recent developments in the synthesis of sulfoximines concentrating on developments since 2015.

Photochemical Probe Identification of a Small-Molecule Inhibitor Binding Site in Hedgehog Acyltransferase (HHAT).

The mammalian membrane-bound -acyltransferase (MBOAT) superfamily is involved in biological processes including growth, development and appetite sensing. MBOATs are attractive drug targets in cancer and obesity; however, information on the binding site and molecular mechanisms underlying small-molecule inhibition is elusive. This study reports rational development of a photochemical probe to interrogate a novel small-molecule inhibitor binding site in the human MBOAT Hedgehog acyltransferase (HHAT).

Epoxidation of Alkenes by Peracids: From Textbook Mechanisms to a Quantum Mechanically Derived Curly-Arrow Depiction.

Using the intrinsic bond orbital (IBO) analysis based on accurate quantum mechanical calculations of the reaction path for the epoxidation of propene using peroxyacetic acid, we find that the four commonly used curly arrows for representing this reaction mechanism are insufficient and that seven curly arrows are required as a result of changes to σ and π bonding interactions, which are usually neglected in all textbook curly arrow representations. The IBO method provides a convenient quantitative method for deriving curly arrows in a rational manner rather than the normal representations used ubiquitously in teaching organic chemistry.

Autocatalytic Metallization of Fabrics Using Si Ink, for Biosensors, Batteries and Energy Harvesting.

Commercially available metal inks are mainly designed for planar substrates (for example, polyethylene terephthalate foils or ceramics), and they contain hydrophobic polymer binders that fill the pores in fabrics when printed, thus resulting in hydrophobic electrodes. Here, a low-cost binder-free method for the metallization of woven and nonwoven fabrics is presented that preserves the 3D structure and hydrophilicity of the substrate. Metals such as Au, Ag, and Pt are grown autocatalytically, using metal salts, inside the fibrous network of fabrics at room temperature in a two-step process, with a water-based silicon particle ink acting as precursor.

Subthreshold Operation of Organic Electrochemical Transistors for Biosignal Amplification.

With a host of new materials being investigated as active layers in organic electrochemical transistors (OECTs), several advantageous characteristics can be utilized to improve transduction and circuit level performance for biosensing applications. Here, the subthreshold region of operation of one recently reported high performing OECT material, poly(2-(3,3'-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-[2,2'-bithiophen]-5-yl)thieno[3,2-]thiophene), p(g2T-TT) is investigated. The material's high subthreshold slope (SS) is exploited for high voltage gain and low power consumption.

Ring-Expanded N-Heterocyclic Carbenes for Copper-Mediated Azide-Alkyne Click Cycloaddition Reactions.

A series of well-defined copper(I) complexes bearing ring-expanded N-heterocyclic carbene (NHC) ligands has been applied to the azide-alkyne cycloaddition reaction. The obtained results notably showed that the six-membered NHC ligands outperform well-established five-membered ones. [CuI(Mes-6)] displayed a remarkable catalytic activity while respecting the strict criteria for click reactions.

Direct Reductive Amination of Carbonyl Compounds Catalyzed by a Moisture Tolerant Tin(IV) Lewis Acid.

Despite the ever-broadening applications of main-group 'frustrated Lewis pair' (FLP) chemistry to both new and established reactions, their typical intolerance of water, especially at elevated temperatures (>100 °C), represents a key barrier to their mainstream adoption. Herein we report that FLPs based on the Lewis acid PrSnOTf are moisture tolerant in the presence of moderately strong nitrogenous bases, even under high temperature regimes, allowing them to operate as simple and effective catalysts for the reductive amination of organic carbonyls, including for challenging bulky amine and carbonyl substrate partners.

Divergent Synthesis of Cyclopropane-Containing Lead-Like Compounds, Fragments and Building Blocks through a Cobalt Catalyzed Cyclopropanation of Phenyl Vinyl Sulfide.

Cyclopropanes provide important design elements in medicinal chemistry and are widely present in drug compounds. Here we describe a strategy and extensive synthetic studies for the preparation of a diverse collection of cyclopropane-containing lead-like compounds, fragments and building blocks exploiting a single precursor. The bifunctional cyclopropane ()-ethyl 2-(phenylsulfanyl)-cyclopropane-1-carboxylate was designed to allow derivatization through the ester and sulfide functionalities to topologically varied compounds designed to fit in desirable chemical space for drug discovery.

Copper(I)-Phosphinite Complexes in Click Cycloadditions: Three-Component Reactions and Preparation of 5-Iodotriazoles.

The remarkable activity displayed by copper(I)-phosphinite complexes of general formula [CuBr(L)] in two challenging cycloadditions is reported: a) the one-pot azidonation/cycloaddition of boronic acids, NaN, and terminal alkynes; b) the cycloaddition of azides and iodoalkynes. These air-stable catalysts led to very good results in both cases and the expected triazoles could be isolated in pure form under 'Click-suitable' conditions.

Studies on the synthesis, stability and conformation of 2-sulfonyl-oxetane fragments.

2-(Arylsulfonyl)oxetanes have been prepared as new structural motifs of interest for medicinal chemistry. These are designed to fit within fragment space and be suitable for screening in fragment based drug discovery, as well as being suitable for further elaboration or incorporation into drug-like compounds. The oxetane ring is constructed through an efficient C-C bond forming cyclisation which allows the incorporation of a wide range of aryl-sulfonyl groups.

2-(Aryl-sulfonyl)oxetanes as designer 3-dimensional fragments for fragment screening: synthesis and strategies for functionalisation.

2-Sulfonyl-oxetanes have been prepared, affording non-planar structures with desirable physicochemical properties for fragment based drug discovery. The oxetane motif was formed by an intramolecular C-C bond formation. The fragments were further functionalised via organometallic intermediates at the intact oxetane and aromatic rings.

Electronic effects in oxo transfer reactions catalysed by salan molybdenum(VI) cis-dioxo complexes.

A series of molybdenum(vi) cis-dioxo complexes containing tetradentate salan ligands with different para-substitutions on the phenoxy group have been prepared. These complexes catalyse the oxygen atom transfer reaction between dimethylsulfoxide and triphenylphosphine. During oxo transfer catalysis, the complexes are resistant to formation of catalytically inactive oxo-bridged dimeric Mo(v) complexes.

The mechanism of GroEL/GroES folding/refolding of protein substrates revisited.

The thermodynamics and kinetics of zinc-cytochrome c (ZnCyt c) interactions with Escherichia coli molecular chaperone GroEL (Chaperonin 60; Cpn60) are described. Zinc(II)-porphyrin represents a flexible fluorescent probe for thermodynamic complex formation between GroEL and ZnCyt c, as well as for stopped-flow fluorescence kinetic experiments. Data suggests that GroEL and GroEL/GroES-assisted refolding of unfolded ZnCyt c takes place by a mechanism that is quite close to the Anfinsen Cage hypothesis for molecular chaperone activity.

What Role Can Chemistry Play in Cationic Liposome-Based Gene Therapy Research Today?

Gene therapy research is still in trouble owing to a paucity of acceptable vector systems to deliver nucleic acids to patients for therapy. Viral vectors are efficient but may be too dangerous for routine clinical use. Synthetic non-viral vectors are inherently much safer but are currently not efficient enough to be clinically viable.

[(OC) Cr=BSi(SiMe ) ]: A Terminal Borylene Complex with an Electronically Unsaturated Boron Atom.

An extremely low-field shifted B NMR signal at δ=204.3 and a very short Cr-B distance of 187.8 pm characterize the title compound [(OC) Cr=B-Si(SiMe ) ], which is the first borylene complex in which the boron atom is both coordinatively and electronically unsaturated.