The basis for unprecedented noncovalent bonding between anions and the aryl centroid of electron-deficient aromatic rings has been demonstrated by an ab initio study of the interaction between 1,3,5-triazine and the fluoride, chloride, and azide ion at the MP2 level of theory. Minima are also located corresponding to C[bond]H...X(-) hydrogen bonding, reactive complexes for nucleophilic attack on the triazine ring, and pi-stacking interactions (with azide). Trifluoro-1,3,5-triazine also participates in aryl centroid complexation and forms nucleophilic reactive complexes with anions. This novel mode of bonding suggests the development of new cyclophane-type receptors for the recognition of anions.

Ever since Pasteur noticed that tartrate crystals exist in two non-superimposable forms that are mirror images of one another--as are left and right hands--the phenomenon of chirality has intrigued scientists. On the molecular level, chirality often has a profound impact on recognition and interaction events and is thus important to biochemistry and pharmacology. In chemical synthesis, much effort has been directed towards developing asymmetric synthesis strategies that yield product molecules with a significant excess of either the left-handed or right-handed enantiomer. This is usually achieved by making use of chiral auxiliaries or catalysts that influence the course of a reaction, with the enantiomeric excess (ee) of the product linearly related to the ee of the auxiliary or catalyst used. In recent years, however, an increasing number of asymmetric reactions have been documented where this relationship is nonlinear, an effect that can lead to asymmetric amplification. Theoretical models have long suggested that autocatalytic processes can result in kinetically controlled asymmetric amplification, a prediction that has now been verified experimentally and rationalized mechanistically for an autocatalytic alkylation reaction. Here we show an alternative mechanism that gives rise to asymmetric amplification based on the equilibrium solid-liquid phase behaviour of amino acids in solution. This amplification mechanism is robust and can operate in aqueous systems, making it an appealing proposition for explaining one of the most tantalizing examples of asymmetric amplification-the development of high enantiomeric excess in biomolecules from a presumably racemic prebiotic world.

The uric acid/xanthine H+ symporter, UapA, is a high-affinity purine transporter from the filamentous fungus Aspergillus nidulans. Here we present the crystal structure of a genetically stabilized version of UapA (UapA-G411VΔ1–11) in complex with xanthine. UapA is formed from two domains, a core domain and a gate domain, similar to the previously solved uracil transporter UraA, which belongs to the same family. The structure shows UapA in an inward-facing conformation with xanthine bound to residues in the core domain. Unlike UraA, which was observed to be a monomer, UapA forms a dimer in the crystals with dimer interactions formed exclusively through the gate domain. Analysis of dominant negative mutants is consistent with dimerization playing a key role in transport. We postulate that UapA uses an elevator transport mechanism likely to be shared with other structurally homologous transporters including anion exchangers and prestin.

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A coherent mechanistic rationalization of the role of water in aldol reactions employing aromatic aldehydes shows that the intrinsic kinetic effect of water within the catalytic cycle is a suppression of reaction rate. The presence of water suppresses formation of key intermediates within the cycle as well as reversibly and irreversibly formed spectator species such as oxazolidinones and oxapyrrolizidines, respectively. The net effect on the observed productivity of the reaction will depend on the balance between these two effects. This work highlights the complex role that water plays both on and off the catalytic cycle and the need to separate these effects to achieve mechanistic understanding.

International audienceThe ten year old Houk–List model for rationalising the origin of stereoselectivity in the organocatalysed intermolecular aldol addition is revisited, using a variety of computational techniques that have been introduced or improved since the original study. Even for such a relatively small system, the role of dispersion interactions is shown to be crucial, along with the use of basis sets where the superposition errors are low. An NCI (non-covalent interactions) analysis of the transition states is able to identify the noncovalent interactions that influence the selectivity of the reaction, confirming the role of the electrostatic NCH d+ /O dÀ interactions. Simple visual inspection of the NCI surfaces is shown to be a useful tool for the design of alternative reactants. Alternative mechanisms, such as proton-relays involving a water molecule or the Hajos–Parrish alternative, are shown to be higher in energy and for which computed kinetic isotope effects are incompatible with experiment. The Amsterdam manifesto, which espouses the principle that scientific data should be citable, is followed here by using interactive data tables assembled via calls to the data DOI (digital-object-identifiers) for calculations held on a digital data repository and themselves assigned a DOI

Against the flow? What factors dictate the relative merits of microflow reactors versus batch‐reaction flasks for homogeneous catalytic reactions? The optimal reaction protocol must be decided on a case‐by‐case basis. Flask reactors equipped with in situ detection devices provide a concise and information‐rich means of obtaining the intrinsic kinetic information required to make this decision.

ABSTRACT:Solvents crucially alter the rates and selectivity of liquid-phase organic reactions, often hindering the development of new synthetic routes or, if chosen wisely, facilitating routes by improving rates and selectivities. To address this challenge, a systematic methodology is proposed that quickly identifies improved reaction solvents by combining quantum mechanical computations of the reaction rate constant in a few solvents with a computer-aided molecular design (CAMD) procedure. The approach allows the identification of a high-performance solvent within a very large set of possible molecules. The validity of our CAMD approach is demonstrated through application to a classical nucleophilic-substitution reaction for the study of solvent effects, the Menschutkin reaction. The results are successfully validated via in-situ kinetic experiments. A space of 1341 solvents is explored in silico, but requiring quantum mechanical calculations of the rate constant in only 9 solvents, and uncovering a solvent that increases the rate constant by 40%.What is the best solvent for a given chemical reaction? Given that the rate and selectivity of chemical reactions can vary by several orders of magnitude in different solvents, 1,2 this question has important ramifications for the exploration of novel reaction routes and the development of industrial processes. 3,4 When investigating new liquid-phase reactions, it is essential to find a solvent that promotes the desired reaction without excessive catalyst deactivation, side-product formation, or solubility limitations. Indeed, a poor solvent choice can result in a missed opportunity to investigate novel chemistry or catalysts. At the process-development level, the problem of solvent choice is 2 compounded by the numerous safety, environmental and process constraints that must be satisfied.Yet, few tools exist to support this decision, especially when it affects reaction kinetics, and researchers are often left to choose on the basis of qualitative chemical knowledge and/or extensive and costly experimental investigations.Advances in the understanding of liquid-phase reactions remain a topic of intense academic interest 5 and practical relevance, as illustrated by identification of the development of solvent selection techniques as a key priority area by the ACS Green Chemistry roundtable. 6 A very promising avenue of research in this direction is the development of Computer-Aided Molecular Design (CAMD) techniques. CAMD offers systematic methodologies, typically in the form of algorithms, to identify chemical species/molecular structures that perform a chosen function best (e.g., maximize the rate of a given reaction). The resulting molecular designs can be used to guide experiments in an otherwise huge space of possibilities. CAMD techniques have been widely applied in the context of solvent design for separations, and have had a significant impact on academic and industrial practice. 7 In a batch extractive distillation for fine chemicals processing, for example, ...