Generation and capture of naphthoquinonynes: a new frontier in the development of trypanocidal quinones aryne chemistry.

The regioselective synthesis of functionalized naphthoquinones the formation and capture of naphthoquinonynes has been used to prepare trypanocidal compounds. The target compounds are functionalized on the aromatic ring, leaving the quinoidal ring intact. Using this technique, eighteen functionalized naphthoquinones were succesfull obtained, divided in two main groups: the first scope using -nucleophiles, and the second scope using pyridine -oxides, with yields up to 74%.

Mechanochemically-induced glass formation from two-dimensional hybrid organic-inorganic perovskites.

Hybrid organic-inorganic perovskites (HOIPs) occupy a prominent position in the field of materials chemistry due to their attractive optoelectronic properties. While extensive work has been done on the crystalline materials over the past decades, the newly reported glasses formed from HOIPs open up a new avenue for perovskite research with their unique structures and functionalities. Melt-quenching is the predominant route to glass formation; however, the absence of a stable liquid state prior to thermal decomposition precludes this method for most HOIPs.

Introduction to 'Medicinal Chemistry Small Molecule Probes'.

Gemma Nixon, Khondaker Miraz Rahman and John Spencer introduce the themed collection on 'Medicinal Chemistry Small Molecule Probes'.

Highly selective, reversible water activation by P,N-cooperativity in pyridyl-functionalized phosphinines.

Tetrapyridyl-functionalized phosphinines were prepared and structurally characterized. The donor-functionalized aromatic phosphorus heterocycles react highly selectively and even reversibly with water. Calculations reveal P,N-cooperativity for this process, with the flanking pyridyl groups serving to kinetically enhance the formal oxidative addition process of HO to the low-coordinate phosphorus atom H-bonding.

Rational design of a cyclohexanone dehydrogenase for enhanced α,β-desaturation and substrate specificity.

The selective α,β-desaturation of cyclic carbonyl compounds, which are found in the core of many steroid and bioactive molecules, using green chemistry is highly desirable. To achieve this task, we have for the first time described and solved the structure of a member of the cyclohexanone dehydrogenase class of enzymes. The breadth of substrate specificity was investigated by assaying the cyclohexanone dehydrogenase, from , against several cyclic ketones, lactones and lactams.

Navigating the challenges of lipid nanoparticle formulation: the role of unpegylated lipid surfactants in enhancing drug loading and stability.

Lipid nanoparticles have proved an attractive approach for drug delivery; however, the challenges of optimising formulation stability and increasing drug loading have limited progression. In this work, we investigate the role of unpegylated lipid surfactants (helper lipids) in nanoparticle formation and the effect of blending helper lipids with pegylated lipid surfactants on the formation and stability of lipid-based nanoparticles by nanoprecipitation. Furthermore, blends of unpegylated/pegylated lipid surfactants were examined for ability to accommodate higher drug loading formulations by means of a higher weight percentage (wt%) of drug relative to total mass of formulation components ( drug, surfactants and lipids).

transdermal delivery of H-labelled atovaquone solid drug nanoparticles: a comparison of topical, intradermal injection and microneedle assisted administration.

Inherent barrier properties of the skin impose significant challenges to the transdermal delivery of drugs to systemic circulation. Here, the transdermal permeation and deposition of an anti-malarial prophylactic atovaquone solid drug nanoformulation is radiometrically evaluated following application of a solid microneedle format.

Aptamer modified Zr-based porphyrinic nanoscale metal-organic frameworks for active-targeted chemo-photodynamic therapy of tumors.

Active-targeted nanoplatforms could specifically target tumors compared to normal cells, making them a promising therapeutic agent. The aptamer is a kind of short DNA or RNA sequence that can specifically bind to target molecules, and could be widely used as the active targeting agents of nanoplatforms to achieve active-targeted therapy of tumors. Herein, an aptamer modified nanoplatform DOX@PCN@Apt-M was designed for active-targeted chemo-photodynamic therapy of tumors.

Nanomedicine strategies to improve therapeutic agents for the prevention and treatment of preterm birth and future directions.

The World Health Organisation (WHO) estimates 15 million babies worldwide are born preterm each year, with 1 million infant mortalities and long-term morbidity in survivors. Whilst the past 40 years have provided some understanding in the causes of preterm birth, along with development of a range of therapeutic options, notably prophylactic use of progesterone or uterine contraction suppressants (tocolytics), the number of preterm births continues to rise. Existing therapeutics used to control uterine contractions are restricted in their clinical use due to pharmacological drawbacks such as poor potency, transfer of drugs to the fetus across the placenta and maternal side effects from activity in other maternal systems.

Atom and step economical synthesis of acyclic quaternary centers iridium-catalyzed hydroarylative cross-coupling of 1,1-disubstituted alkenes.

Quaternary benzylic centers are accessed with high atom and step economy by Ir-catalyzed alkene hydroarylation. These studies provide unique examples of the use of non-polarized 1,1-disubstituted alkenes in branch selective Murai-type hydro(hetero)arylations. Detailed mechanistic studies have been undertaken, and these indicate that the first irreversible step is the demanding alkene carbometallation process.

Superprotonic conduction of intrinsically zwitterionic microporous polymers based on easy-to-make squaraine, croconaine and rhodizaine dyes.

Porous organic polymers (POPs) have been prepared a novel metal free polycondensation between a tritopic indole-based monomer and squaric, croconic and rhodizonic acids. Each of the three POPs exhibited high BET surface areas (331-667 m g) and zwitterionic structures. Impedance measurements revealed that the intrinsic POPs were relatively weak proton conductors, with a positive correlation between the density of oxo-groups and the proton conduction.

Tuning the local chemical environment of ZnSe quantum dots with dithiols towards photocatalytic CO reduction.

Sunlight-driven CO reduction to renewable fuels is a promising strategy towards a closed carbon cycle in a circular economy. For that purpose, colloidal quantum dots (QDs) have emerged as a versatile light absorber platform that offers many possibilities for surface modification strategies. Considerable attention has been focused on tailoring the local chemical environment of the catalytic site for CO reduction with chemical functionalities ranging from amino acids to amines, imidazolium, pyridines, and others.

Force-modulated reductive elimination from platinum(ii) diaryl complexes.

Coupled mechanical forces are known to drive a range of covalent chemical reactions, but the effect of mechanical force applied to a spectator ligand on transition metal reactivity is relatively unexplored. Here we quantify the rate of C(sp)-C(sp) reductive elimination from platinum(ii) diaryl complexes containing macrocyclic bis(phosphine) ligands as a function of mechanical force applied to these ligands. DFT computations reveal complex dependence of mechanochemical kinetics on the structure of the force-transducing ligand.

Selective cleavage of unactivated arene ring C-C bonds by iridium: key roles of benzylic C-H activation and metal-metal cooperativity.

The cleavage of aromatic C-C bonds is central for conversion of fossil fuels into industrial chemicals and designing novel arene functionalisations through ring opening, expansion and contraction. However, the current progress is hampered by both the lack of experimental examples of selective oxidative addition of aromatic C-C bonds and limited understanding of the factors that favour insertion into the C-C rather than the C-H bonds. Here, we describe the comprehensive mechanism of the only reported chemo- and regioselective insertion of a transition metal into a range of substituted arene rings in simple iridium(i) complexes.

Using pyrene to probe the effects of poloxamer stabilisers on internal lipid microenvironments in solid lipid nanoparticles.

Solid lipid nanoparticles (SLNs) have proved to be effective nanocarriers with many advantages over other non-lipid-based systems. The development of new SLN formulations is often hindered through poor drug loading capacity and time-consuming optimisation of lipid/stabiliser combinations. One challenge in the development of new SLN formulations is understanding the complex interactions between amphiphilic stabilisers and hydrophobic lipids; the nature of these interactions can significantly impact SLN properties, including the internal polarity within the nanoparticle core.

Anhydrous nanoprecipitation for the preparation of nanodispersions of tenofovir disoproxil fumarate in oils as candidate long-acting injectable depot formulations.

The facile formation of drug nanoparticles in injectable/ingestible oils, of water-soluble antiretroviral tenofovir disoproxil fumarate, using a novel nanoprecipitation is presented with studies showing drug release into relevant aqueous media.

Identification of different carbenium ion intermediates in zeolites with identical chabazite topology C-C through-bond NMR correlations.

C-C through-bond NMR correlation experiments reveal the stabilization of different carbenium ion intermediates in two zeolites possessing identical CHA topology (H-SAPO-34 and H-SSZ-13) during the methanol to olefins reaction.

Correction: Sustainable inverse-vulcanised sulfur polymers.

[This corrects the article DOI: 10.1039/C8RA04446E.].

Sustainable inverse-vulcanised sulfur polymers.

We demonstrate two renewable crosslinkers that can stabilise sustainable high sulfur content polymers, inverse-vulcanisation. With increasing levels of sulfur produced as a waste byproduct from hydrodesulfurisation of crude oil and gas, the need to find a method to utilise this abundant feedstock is pressing. The resulting sulfur copolymers can be synthesised relatively quickly, using a one-pot solvent free method, producing polymeric materials that are shape-persistent solids at room temperature and compare well to other inverse vulcanised polymers.

Branched copolymer-stabilised nanoemulsions as new candidate oral drug delivery systems.

The delivery of drugs to the bloodstream oral administration may suffer from a number of complications including poor dissolution, first pass metabolism and the active intervention of efflux transporters such as P-glycoproteins; drugs which are efflux substrates may cause considerable problems across many clinical conditions. Here we have employed a branch-polymer stabilised nanoemulsion strategy to create highly robust oil droplets ( peanut oil, castor oil and soybean oil) containing different dissolved antiretroviral drugs used in the daily fight against HIV/AIDS. Although very limited difference in permeation through a Caco-2 gut epithelium model was seen for efavirenz, the permeation of the protease inhibitor lopinavir was considerably higher (approximately 10-fold) when applied to an epithelium monolayer in emulsion form than the control within an aqueous DMSO vehicle.

Visible-Light-Driven Hydrogen Evolution Using Planarized Conjugated Polymer Photocatalysts.

Linear poly(p-phenylene)s are modestly active UV photocatalysts for hydrogen production in the presence of a sacrificial electron donor. Introduction of planarized fluorene, carbazole, dibenzo[b,d]thiophene or dibenzo[b,d]thiophene sulfone units greatly enhances the H evolution rate. The most active dibenzo[b,d]thiophene sulfone co-polymer has a UV photocatalytic activity that rivals TiO, but is much more active under visible light.