Biocatalytic synthesis of ribonucleoside analogues using nucleoside transglycosylase-2.

Ribonucleosides are essential building blocks used extensively in antiviral and oligonucleotide therapeutics. A major challenge in the further development of nucleoside analogues for therapeutic applications is access to scalable and environmentally sustainable synthetic strategies. This study uses the type II nucleoside 2'-deoxyribosyltransferase from (NDT-2) to prepare a suite of ribonucleoside analogues using naturally-occurring uridine and cytidine sugar donors.

Understanding ketone hydrogenation catalysis with anionic iridium(iii) complexes: the crucial role of counterion and solvation.

Catalytic asymmetric hydrogenation of ketones is an important approach to prepare valuable chiral alcohols. Understanding how transition metals promote these reactions is key to the rational design of more active, selective and sustainable catalysts. A highly unusual mechanism for asymmetric hydrogenation of acetophenone catalysed by an anionic Ir hydride system, including a strong counterion dependence on catalyst activity, is explored and rationalised here.

The ubiquitous P(-tol) ligand promotes formation of catalytically-active higher order palladacyclic clusters.

The Herrmann-Beller catalyst, Pd[(C^P)(μ-OAc)], is readily formed by reaction of the cyclic trimer of 'Pd(OAc)' with P(-tol). In the presence of hydroxide, Pd(C^P)(μ-OAc)] converts to [Pd(C^P)(μ -OH)]. Here, we report how this activated Pd precatalyst species, and related species, serve as a conduit for formation of higher order Pd clusters containing multiple cyclopalladated P(-tol) ligands.

Correlated shapeshifting and configurational isomerization.

Herein we demonstrate that the rapid 'shapeshifting' constitutional isomerization of a substituted bullvalene is influenced by the -to- configurational isomerization of a remote carbamate group, giving rise to correlated motion. We find that, while the -configurational isomer of a bulky carbamate favors the -bullvalene constitutional isomer, a noncovalent bonding interaction within the -carbamate tips the equilibrium toward the -bullvalene form. Using DFT modelling and NMR spectroscopy, this long-range interaction is identified as being between the bullvalene core and a pendant phenyl group connected to the carbamate.

A guide to bullvalene stereodynamics.

Here, we analyze the stereodynamic properties of bullvalenes using principal moments of inertia and exit vector plots to draw comparisons with commonly used ring systems in medicinal chemistry. To aid analyses, we first classify (i) the four elementary rearrangement steps available to substituted bullvalenes, which (ii) can be described by applying positional descriptors (α, β, γ, and δ) to the substituents. We also (iii) derive an intuitive equation to calculate the number of isomers for a given bullvalene system.

Towards a 'clicked' PSMA targeting gene delivery bioconjugate-polyplex for prostate cancer.

Prostate cancer is the most common cancer in men in the UK with over 50 000 new cases diagnosed each year and although therapeutic advances in surgery, anti-androgens, radio- and chemotherapy have increased survival rates, there still remains a need for new treatments to combat the most aggressive forms of the disease. Gene therapy offers promise as an alternative approach but is reliant on selective targeting to the cancer cell surface. Herein we describe the novel construction of a prostate specific membrane antigen (PSMA) binding bioconjugate-polyplex, based on a glutamate-urea peptide scaffold using 'click' chemistry, which we demonstrate is capable of targeted delivery of a GFP gene to PSMA overexpressing prostate cancer cells, and therefore may have potential future application as part of a prostate cancer gene delivery therapy.

Sustainable methods for the carboxymethylation and methylation of ursolic acid with dimethyl carbonate under mild and acidic conditions.

Ursolic acid is a triterpene plant extract that exhibits significant potential as an anti-cancer, anti-tumour, and anti-inflammatory agent. Its direct use in the pharmaceutical industry is hampered by poor uptake of ursolic acid in the human body coupled with rapid metabolism causing a decrease in bioactivity. Modification of ursolic acid can overcome such issues, however, use of toxic reagents, unsustainable synthetic routes and poor reaction metrics have limited its potential.

Cross aldol OPAL bioconjugation outcompetes intramolecular hemiaminal cyclisation of proline adjacent N-terminal α-oxo aldehydes at acidic pH.

Novel methods to construct small molecule-protein bioconjugates are integral to the development of new biomedicines for a variety of diseases. C-C linked bioconjugates are increasingly desirable in this application due to their stability and can be accessed through cross aldol bioconjugation of reactive α-oxo aldehyde handles easily introduced at the N-terminus of proteins by periodate oxidation. We previously developed an organocatalyst-mediated protein aldol ligation (OPAL) for chemical modification of these reactive aldehydes, but the efficiency of this method was limited when a proline residue was directly adjacent to the N-terminus due to intramolecular hemiaminal formation.

Biomolecular infrared spectroscopy: making time for dynamics.

Time resolved infrared spectroscopy of biological molecules has provided a wealth of information relating to structural dynamics, conformational changes, solvation and intermolecular interactions. Challenges still exist however arising from the wide range of timescales over which biological processes occur, stretching from picoseconds to minutes or hours. Experimental methods are often limited by vibrational lifetimes of probe groups, which are typically on the order of picoseconds, while measuring an evolving system continuously over some 18 orders of magnitude in time presents a raft of technological hurdles.

Enhanced microwave assisted pyrolysis of waste rice straw through lipid extraction with supercritical carbon dioxide.

A combination of supercritical carbon dioxide (scCO) extraction and microwave-assisted pyrolysis (MAP) have been investigated for the valorisation of waste rice straw. ScCO extraction of rice straw led to a 0.7% dry weight yield of lipophilic molecules, at elevated temperatures of 65 °C and pressures of 400 bar.

Reverse thiophosphorylase activity of a glycoside phosphorylase in the synthesis of an unnatural Manβ1,4GlcNAc library.

β-Mannosides are ubiquitous in nature, with diverse roles in many biological processes. Notably, Manβ1,4GlcNAc a constituent of the core -glycan in eukaryotes was recently identified as an immune activator, highlighting its potential for use in immunotherapy. Despite their biological significance, the synthesis of β-mannosidic linkages remains one of the major challenges in glycoscience.

Exploration of piperidine 3D fragment chemical space: synthesis and 3D shape analysis of fragments derived from 20 regio- and diastereoisomers of methyl substituted pipecolinates.

Fragment-based drug discovery is now widely adopted for lead generation in the pharmaceutical industry. However, fragment screening collections are often predominantly populated with flat, 2D molecules. Herein, we report the synthesis of piperidine-based 3D fragment building blocks - 20 regio- and diastereoisomers of methyl substituted pipecolinates using simple and general synthetic methods.

Reclaimed and Up-Cycled Cathodes for Lithium-Ion Batteries.

As electric vehicles become more widely used, there is a higher demand for lithium-ion batteries (LIBs) and hence a greater incentive to find better ways to recycle these at their end-of-life (EOL). This work focuses on the process of reclamation and re-use of cathode material from LIBs. Black mass containing mixed LiMnO and NiCoAlO from a Nissan Leaf pouch cell are recovered via two different recycling routes, shredding or disassembly.

Metasurface-enhanced mid-infrared spectroscopy in the liquid phase.

Vibrational spectroscopy is an important tool in chemical and biological analysis. A key issue when applying vibrational spectroscopy to dilute liquid samples is the inherently low sensitivity caused by short interaction lengths and small extinction coefficients, combined with low target molecule concentrations. Here, we introduce a novel type of surface-enhanced infrared absorption spectroscopy based on the resonance of a dielectric metasurface.

A comprehensive understanding of carbon-carbon bond formation by alkyne migratory insertion into manganacycles.

Migratory insertion (MI) is one of the most important processes underpinning the transition metal-catalysed formation of C-C and C-X bonds. In this work, a comprehensive model of MI is presented, based on the direct observation of the states involved in the coupling of alkynes with cyclometallated ligands, augmented with insight from computational chemistry. Time-resolved spectroscopy demonstrates that photolysis of complexes [Mn(C^N)(CO)] (C^N = cyclometalated ligand) results in ultra-fast dissociation of a CO ligand.

Antibiotic-functionalized gold nanoparticles for the detection of active β-lactamases.

Antimicrobial resistance (AMR) continues to threaten the effective treatment and prevention of bacterial infections. The spread of resistant infections is accelerated by the lack of fast and cost-effective tests for the detection of AMR at the point-of-care. We aimed to address this challenge by developing a diagnostic tool to detect one of the major forms of AMR, the β-lactamase enzymes.

Assembly, structure and thermoelectric properties of 1,1'-dialkynylferrocene 'hinges'.

Dialkynylferrocenes exhibit attractive electronic and rotational features that make them ideal candidates for use in molecular electronic applications. However previous works have primarily focussed on single-molecule studies, with limited opportunities to translate these features into devices. In this report, we utilise a variety of techniques to examine both the geometric and electronic structure of a range of 1,1'-dialkynylferrocene molecules, as either single-molecules, or as self-assembled monolayers.

Reductive aminations by imine reductases: from milligrams to tons.

The synthesis of secondary and tertiary amines through the reductive amination of carbonyl compounds is one of the most significant reactions in synthetic chemistry. Asymmetric reductive amination for the formation of chiral amines, which are required for the synthesis of pharmaceuticals and other bioactive molecules, is often achieved through transition metal catalysis, but biocatalytic methods of chiral amine production have also been a focus of interest owing to their selectivity and sustainability. The discovery of asymmetric reductive amination by imine reductase (IRED) and reductive aminase (RedAm) enzymes has served as the starting point for a new industrial approach to the production of chiral amines, leading from laboratory-scale milligram transformations to ton-scale reactions that are now described in the public domain.

Multi-component self-assembled molecular-electronic films: towards new high-performance thermoelectric systems.

The thermoelectric properties of parallel arrays of organic molecules on a surface offer the potential for large-area, flexible, solution processed, energy harvesting thin-films, whose room-temperature transport properties are controlled by quantum interference (QI). Recently, it has been demonstrated that constructive QI (CQI) can be translated from single molecules to self-assembled monolayers (SAMs), boosting both electrical conductivities and Seebeck coefficients. However, these CQI-enhanced systems are limited by rigid coupling of the component molecules to metallic electrodes, preventing the introduction of additional layers which would be advantageous for their further development.

A "one pot" mass spectrometry technique for characterizing solution- and gas-phase photochemical reactions by electrospray mass spectrometry.

The characterization of new photochemical pathways is important to progress the understanding of emerging areas of light-triggered inorganic and organic chemistry. In this context, the development of platforms to perform routine characterization of photochemical reactions remains an important goal for photochemists. Here, we demonstrate a new instrument that can be used to characterise both solution-phase and gas-phase photochemical reactions through electrospray ionisation mass spectrometry (ESI-MS).

Self-assembled gel tubes, filaments and 3D-printing with metal nanoparticle formation and enhanced stem cell growth.

This paper reports simple strategies to fabricate self-assembled artificial tubular and filamentous systems from a low molecular weight gelator (LMWG). In the first strategy, tubular 'core-shell' gel structures based on the dibenzylidenesorbitol-based LMWG DBS-CONHNH were made in combination with the polymer gelator (PG) calcium alginate. In the second approach, gel filaments based on DBS-CONHNH alone were prepared by wet spinning at elevated concentrations using a 'solvent-switch' approach.

Correction: Glycosylated cyclophellitol-derived activity-based probes and inhibitors for cellulases.

[This corrects the article DOI: 10.1039/D0CB00045K.].

Radical-anion coupling through reagent design: hydroxylation of aryl halides.

The design and development of an oxime-based hydroxylation reagent, which can chemoselectively convert aryl halides (X = F, Cl, Br, I) into phenols under operationally simple, transition-metal-free conditions is described. Key to the success of this approach was the identification of a reducing oxime anion which can interact and couple with open-shell aryl radicals. Experimental and computational studies support the proposed radical-nucleophilic substitution chain mechanism.

Double diffusion for the programmable spatiotemporal patterning of multi-domain supramolecular gels.

To achieve spatial resolution of a multi-component gel, a double diffusion approach is used which enables the precise programming of self-assembled patterned domains with well-defined shapes and sizes. The low-molecular-weight gelators (LMWGs) used in this study are pH-responsive DBS-COH and thermally-responsive DBS-CONHNH (both based on 1,3:2,4-dibenzylidenesorbitol, DBS). A DBS-CONHNH gel was initially assembled in a tray, and then loaded at carefully-selected positions with either basified DBS-COH ( DBS-carboxylate) or an acid.