Synthetic cannabinoid receptor agonists are monoamine oxidase-A selective inhibitors.

Synthetic cannabinoid receptor agonists (SCRAs) are one of the fastest growing classes of recreational drugs. Despite their growth in use, their vast chemical diversity and rapidly changing landscape of structures make understanding their effects challenging. In particular, the side effects for SCRA use are extremely diverse, but notably include severe outcomes such as cardiac arrest.

Photochemical Fingerprinting Is a Sensitive Probe for the Detection of Synthetic Cannabinoid Receptor Agonists; toward Robust Point-of-Care Detection.

With synthetic cannabinoid receptor agonist (SCRA) use still prevalent across Europe and structurally advanced generations emerging, it is imperative that drug detection methods advance in parallel. SCRAs are a chemically diverse and evolving group, which makes rapid detection challenging. We have previously shown that fluorescence spectral fingerprinting (FSF) has the potential to provide rapid assessment of SCRA presence directly from street material with minimal processing and in saliva.

Harnessing Plasticity in an Amine-Borane as a Piezoelectric and Pyroelectric Flexible Film.

We demonstrate that trimethylamine borane can exhibit desirable piezoelectric and pyroelectric properties. The material was shown to be able operate as a flexible film for both thermal sensing, thermal energy conversion and mechanical sensing with high open circuit voltages (>10 V). A piezoelectric coefficient of d ≈10-16 pC N , and pyroelectric coefficient of p≈25.

Atomic dispensers for thermoplasmonic control of alkali vapor pressure in quantum optical applications.

Alkali metal vapors enable access to single electron systems, suitable for demonstrating fundamental light-matter interactions and promising for quantum logic operations, storage and sensing. However, progress is hampered by the need for robust and repeatable control over the atomic vapor density and over the associated optical depth. Until now, a moderate improvement of the optical depth was attainable through bulk heating or laser desorption - both time-consuming techniques.

Exposing the Interplay Between Enzyme Turnover, Protein Dynamics, and the Membrane Environment in Monoamine Oxidase B.

There is an increasing realization that structure-based drug design may show improved success by understanding the ensemble of conformations accessible to an enzyme and how the environment affects this ensemble. Human monoamine oxidase B (MAO-B) catalyzes the oxidation of amines and is inhibited for the treatment of both Parkinson's disease and depression. Despite its clinical importance, its catalytic mechanism remains unclear, and routes to drugging this target would be valuable.

Online monitoring of a photocatalytic reaction by real-time high resolution FlowNMR spectroscopy.

We demonstrate how FlowNMR spectroscopy can readily be applied to investigate photochemical reactions that require sustained input of light and air to yield mechanistic insight under realistic conditions. The Eosin Y mediated photo-oxidation of N-allylbenzylamine is shown to produce imines as primary reaction products from which undesired aldehydes form after longer reaction times. Facile variation of reaction conditions during the reaction in flow allows for probe experiments that give information about the mode of action of the photocatalyst.

Magnetic coupling in a hybrid Mn(ii) acetylene dicarboxylate.

The design of ligands that mediate through-bond long range super-exchange in metal-organic hybrid materials would expand chemical space beyond the commonly observed short range, low temperature magnetic ordering. Here we examine acetylene dicarboxylate as a potential ligand that could install long range magnetic ordering due to its spatially continuous frontier orbitals. Using a known Mn(ii)-containing coordination polymer we compute and measure the electronic structure and magnetic ordering.

Modelling flavoenzymatic charge transfer events: development of catalytic indole deuteration strategies.

The formation and chemistry of flavin-indole charge transfer (CT) complexes has been studied using a model cationic flavin. The ability to form a CT complex is sensitive to indole structure as gauged by spectroscopic, kinetics and crystallographic studies. Single crystals of sufficient quality of a flavin-indole CT complex, suitable for X-ray diffraction, have been grown, allowing solid-state structural analysis.

Facile kinetic induction of a dihydropyridide to pyrrolide ring contraction.

Reactions between magnesium 1,4-dihydropyridide or 1,2-dihydro-iso-quinolide derivatives and carbodiimides, RN[double bond, length as m-dash]C[double bond, length as m-dash]NR, generally result in Mg-N insertion and formation of guanidinate complexes. More sterically perturbed systems with N-aryl carbodiimide substitution, however, follow a divergent course of reaction initiating heterocyclic ring contraction and pyrrolide formation under unprecedentedly mild conditions.

Catalytic Amine Oxidation under Ambient Aerobic Conditions: Mimicry of Monoamine Oxidase B.

The flavoenzyme monoamine oxidase (MAO) regulates mammalian behavioral patterns by modulating neurotransmitters such as adrenaline and serotonin. The mechanistic basis which underpins this enzyme is far from agreed upon. Reported herein is that the combination of a synthetic flavin and alloxan generates a catalyst system which facilitates biomimetic amine oxidation.

Modular design of SPIRO-OMeTAD analogues as hole transport materials in solar cells.

We predict the ionisation potentials of the hole-conducting material SPIRO-OMeTAD and twelve methoxy isomers and polymethoxy derivatives. Based on electronic and economic factors, we identify the optimal compounds for application as p-type hole-selective contacts in hybrid halide perovskite solar cells.

Preparation of stereoregular isotactic poly(mandelic acid) through organocatalytic ring-opening polymerization of a cyclic O-carboxyanhydride.

Poly(mandelic acid) (PMA) is an aryl analogue of poly(lactic acid) (PLA) and a biodegradable analogue of polystyrene. The preparation of stereoregular PMA was realized using a pyridine/mandelic acid adduct (Py⋅MA) as an organocatalyst for the ring-opening polymerization (ROP) of the cyclic O-carboxyanhydride (manOCA). Polymers with a narrow polydispersity index and excellent molecular-weight control were prepared at ambient temperature.

Gold-catalysed cascade rearrangements of ynamide propargyl esters.

The Au(I)-catalysed rearrangement of propargylic esters formed from an ynamide has been studied. The reaction is facile, and when conducted in the presence of a reactive indole nucleophile, leads to a cascade process whereby γ-indolyl α-acyloxyenamides are formed in good yield and excellent E-stereoselectivity.

Point-to-helical chirality transfer for a scalable and resolution-free synthesis of a helicenoidal DMAP organocatalyst.

The synthesis of a second-generation [6]-helicenoidal DMAP organocatalyst is reported. The synthesis is reliant upon a highly diastereoselective Rh-catalysed [2 + 2 + 2] triyne cycloisomerization, using an existing stereocentre to control the sense of forming helicity. Taken together, a scalable (>1 g), resolution-free entry to a helical DMAP with the capacity for subsequent functionalization, has been achieved.

Biomimetic flavin-catalyzed aldehyde oxidation.

The oxidation of alkyl and aryl aldehydes to their corresponding carboxylic acids has been achieved through the action of a biomimetic bridged flavin catalyst. The reaction uses readily available 35% aqueous hydrogen peroxide and is operationally simple. The oxidation is a green and sustainable reaction, obviating chlorinated solvents with minimal byproducts.

Remote stereocontrol in [3,3]-sigmatropic rearrangements: application to the total synthesis of the immunosuppressant mycestericin G.

The Ireland-Claisen [3,3]-sigmatropic rearrangement has been used to access biologically important β,β'-dihydroxy α-amino acids. The rearrangement reported is highly stereoselective and offers excellent levels of remote stereocontrol. This strategy has been used to synthesize the natural immunosuppressant mycestericin G and ent-mycestericin G, allowing for a revision of absolute configuration of this natural product.

Si-free enolate Claisen rearrangements of enamido substrates.

α-Alkyl β-amino esters are available in high diastereoselectivity through a silicon-free Claisen enolate [3,3]-sigmatropic rearrangement of enamide esters. Optimisation studies have probed the crucial role of the initial enolisation and the nature of the enamide N-centre. The demonstration of chirality transfer and the formation of β-proline systems, is also presented.

Design, synthesis, and evaluation of a helicenoidal DMAP Lewis base catalyst.

The design, synthesis, and study of a helical dialkylaminopyridine Lewis base catalyst is reported. Helical DMAP analogue 4 is based upon a helicenoid structure and displays good to excellent levels of selectivity (S ≤ 116) in the kinetic resolution of chiral secondary alcohols. Catalyst 4 displays excellent reactivity with exceptionally low loadings of 0.

Development of the Ireland-Claisen rearrangement of alkoxy- and aryloxy-substituted allyl glycinates.

The Ireland-Claisen rearrangement of 3-alkoxy- and 3-aryloxy-substituted allyl glycinates is presented. This [3,3]-sigmatropic rearrangement route offers direct access to syn β-alkoxy and β-aryloxy α-amino acid systems. In particular, N,N-diboc glycine esters rearrange with excellent diastereoselectivities (dr > 25:1).

Stereoselective synthesis of cyclohexanones via phase transfer catalyzed double addition of nucleophiles to divinyl ketones.

Functionalized cyclohexanones are formed in excellent yield and diastereoselectivity from a phase transfer catalyzed double addition of active methylene pronucleophiles to nonsymmetrical divinyl ketones.

Organocatalytic diimide reduction of enamides in water.

Bridged flavinium organocatalysts have displayed efficacy in the diimide mediated reduction of enamides in aqueous conditions. This represents the first diimide reduction of an electron rich alkene and offers a clean alternative to the use of alkylating agents for N-alkylation.

A practical protocol for the highly E-selective formation of aryl-substituted silylketene acetals.

The E/Z-selectivity in the formation of silylketene acetals derived from phenylacetate esters, mediated by LiHMDS, has been studied by in situ NMR techniques. The formation is seen to be highly E-selective with use of the newly developed protocol. Isolated aryl-substituted silylketene acetals are now attainable with high levels of E-geometrical purity in excellent yield.

Studies toward the photochemical synthesis of functionalized [5]- and [6]carbohelicenes.

An efficient route to nonsymmetrical helical menthyl esters by means of an oxidative photocyclization reaction of dissymmetric bis-stilbenes is reported. The developed route allows the introduction of functionality on rings A, E, or F, and the influence of the substituent pattern on the photochemical reaction has been examined. Diastereoselectivity is observed when a double chiral induction strategy with dimenthyl helicene esters synthesized in a 70:30 ratio of isomers is used.

One-pot o-nitrobenzenesulfonylhydrazide (NBSH) formation-diimide alkene reduction protocol.

A one-pot protocol for the formation of 2-nitrobenzenesulfonylhydrazide (NBSH) from commercial reagents and subsequent alkene reduction is presented. The transformation is operationally simple and generally efficient for effecting diimide alkene reductions. A range of 16 substrates have been reduced, highlighting the unique chemoselectivity of diimide as a reduction system.

Stereoselective double Friedel-Crafts alkylation of indoles with divinyl ketones.

A tandem double Friedel-Crafts reaction of indoles and nonsymmetrical divinyl ketones has been achieved. The tandem reaction forms complex [6-5-7]-tricyclic indoles in excellent yields. The reaction is completely regioselective and offers high levels of syn diastereoselectivity.