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The surface chemistry of Metal-Organic Polyhedra (MOPs) is crucial to their physicochemical properties because it governs how they interact with external substances such as solvents, synthetic organic molecules, metal ions, and even biomolecules. Consequently, the advancement of synthetic methods that facilitate the incorporation of diverse functional groups onto MOP surfaces will significantly broaden the range of properties and potential applications for MOPs. This study describes the use of copper(I)-catalysed, azide-alkyne cycloaddition (CuAAC) click reactions to post-synthetically modify the surface of alkyne-functionalised cuboctahedral MOPs. To this end, a novel Rh(II)-based MOP with 24 available surface alkyne groups was synthesised. Each of the 24 alkyne groups on the surface of the "clickable" Rh-MOP can react with azide-containing molecules at room temperature, without compromising the integrity of the MOP. The wide substrate catalogue and orthogonal nature of CuAAC click chemistry was exploited to densely functionalise MOPs with diverse functional groups, including polymers, carboxylic and phosphonic acids, and even biotin moieties, which retained their recognition capabilities once anchored onto the surface of the MOP.

Homochiral 2-hydroxy-4-butyrolactone derivatives are important structural motifs frequently found in naturally occurring biologically active products, synthetic drugs, biodegradable polymers as well as building blocks and chiral auxiliaries in asymmetric organic synthesis (1). Among the methods described in the literature, the stereoselective reduction of 4-hydroxy-2-oxoacid derivatives to produce 2-hydroxy-4-butyrolactone derivatives remains unexplored. In this communication we report a tandem biocatalytic stereodivergent route for the preparation of these compounds using two stereocomplementary aldolases and oxidoreductases, using simple and achiral starting materials. The strategy comprises (Scheme 1) (i) aldol addition reaction of 2-oxoacids to formaldehyde using both 3-methyl-2-oxobutanoate hydroxymethyltransferase and 2-keto-3-deoxy-L-rhamnonate aldolase and variants thereof, and (ii) subsequent 2-oxogroup reduction of the aldol adduct by both ketopantoate reductase and a delta-1-piperidine-2-carboxylate/delta-1-pyrroline-2-carboxylate reductase with uncovered promiscuous ketoreductase activity. Finally, the formation of the corresponding lactone takes place during the work up and purification steps. Yields, enantiomeric excesses and diasteromeric ratios for a total of 23 structurally diverse 2-hydroxy-3-substituted-4-butyrolactones will be discussed. Moreover, one-pot one-step cascade reactions with the aldolases and reductases operating in tandem will be presented.

NAD(P)H-dependent ¿1-piperideine-2-carboxylate/¿1-pyrroline-2-carboxylate reductase from Pseudomonas syringae pv. tomato (DpkAPsyrin, EC 1.5.1.21) catalyzes the stereoselective reduction of ¿1-piperideine-2-carboxylate and ¿1-pyrroline-2-carboxylate to L-pipecolic acid and L-proline respectively. Furthermore, DpkAPsyrin is also able to catalyze the enantioselective synthesis of N-methyl-L-amino acids from methylamine and various 2-oxo acids [1]. In our research group, we observed that in addition to the imine reductase activity, DpkAPsyrin have a promiscuous ketoreductase activity and, consequently, we consider interesting to exploit its underdeveloped synthetic capabilities for the synthesis of 2-hydroxy-4-arylbut-3-enoic acid (4). These 2-hydroxyacids are intermediates in the synthesis of 2-hydroxy-4-arylbutanoic acid, important building blocks for the production of a variety of angiotensin converting enzyme (ACE) inhibitors (e.g. enalapril, lisinopril, cilapril, and benazepril) [2]. In this communication we reported the preparation of structurally diverse (S)-2-hydroxy-4-arylbut-3-enoic acid (4) (isolated yield: 57%-78% and ee: 87%->99%) from aromatic aldehydes (1) and pyruvate (2) by enzymatic cascade reaction using trans-o-hydroxybenzylidene pyruvate hydratase-aldolase from Pseudomonas putida HBPAPputida) [3] and DpkAPsyrin (Scheme 1). The cascade process was possible because it was found that the ketoreductase preferentially reduced the aldol condensation adducts (3) rather than the pyruvate (2). This allows for high levels of 2-hydroxy-4-arylbut-3-enoic acids (4) conversions ( >95% after 24 h).

Water pollution threatens human and environmental health worldwide. Thus, there is a pressing need for new approaches to water purification. Herein, we report a novel supramolecular strategy based on the use of a metal-organic polyhedron (MOP) as a capture agent to remove nitrogenous organic micropollutants from water, even at very low concentrations (ppm), based exclusively on coordination chemistry at the external surface of the MOP. Specifically, we exploit the exohedral coordination positions of RhII-MOP to coordinatively sequester pollutants bearing N-donor atoms in aqueous solution, and then harness their exposed surface carboxyl groups to control their aqueous solubility through acid/base reactions. We validated this approach for removal of benzotriazole, benzothiazole, isoquinoline, and 1-napthylamine from water.

Productivity of tropical lowland moist forests is often limited by availability and functional allocation of phosphorus (P) that drives competition among tree species and becomes a key factor in determining forestall community diversity. We used non-target 31P-NMR metabolic profiling to study the foliar P-metabolism of trees of a French Guiana rainforest. The objective was to test the hypotheses that P-use is species-specific, and that species diversity relates to species P-use and concentrations of P-containing compounds, including inorganic phosphates, orthophosphate monoesters and diesters, phosphonates and organic polyphosphates. We found that tree species explained the 59% of variance in 31P-NMR metabolite profiling of leaves. A principal component analysis showed that tree species were separated along PC 1 and PC 2 of detected P-containing compounds, which represented a continuum going from high concentrations of metabolites related to non-active P and P-storage, low total P concentrations and high N:P ratios, to high concentrations of P-containing metabolites related to energy and anabolic metabolism, high total P concentrations and low N:P ratios. These results highlight the species-specific use of P and the existence of species-specific P-use niches that are driven by the distinct species-specific position in a continuum in the P-allocation from P-storage compounds to P-containing molecules related to energy and anabolic metabolism.

A new persistent organic free radical has been synthetized with Br atoms occupying the ortho‐ and para‐positions of a trityl core. After the isolation of its two propeller‐like atropisomers, Plus (P) and minus (M), their absolute configurations were assigned by a combination of theoretical and experimental data. Remarkably, no hints of racemization were observed up to 60 °C for more than two hours, due to the higher steric hindrance imposed by the bulky Br atoms. Therefore, when compared to its chlorinated homologue (t1/2=18 s at 60 °C), an outstanding stability against racemization was achieved. A circularly polarized luminescence (CPL) response of both enantiomers was detected. This free radical shows a satisfactory luminescent dissymmetry factor (|glum(592 nm)|≈0.7×10−3) despite its pure organic nature and low luminescence quantum yield (LQY). Improved organic magnetic CPL emitters derived from the reported structure can be envisaged thanks to the wide possibilities that Br atoms at para‐positions offer for further functionalization.

The congested nature of quaternary carbons hinders their preparation, most notably when stereocontrol is required. Here we report a biocatalytic method for the creation of quaternary carbon centers with broad substrate scope, leading to different compound classes bearing this structural feature. The key step comprises the aldol addition of 3,3-disubstituted 2-oxoacids to aldehydes catalyzed by metal dependent 3-methyl-2-oxobutanoate hydroxymethyltransferase from E. coli (KPHMT) and variants thereof. The 3,3,3-trisubstituted 2-oxoacids thus produced were converted into 2-oxolactones and 3-hydroxy acids and directly to ulosonic acid derivatives, all bearing gem-dialkyl, gem-cycloalkyl, and spirocyclic quaternary centers. In addition, some of these reactions use a single enantiomer from racemic nucleophiles to afford stereopure quaternary carbons. The notable substrate tolerance and stereocontrol of these enzymes are indicative of their potential for the synthesis of structurally intricate molecules.

3-Hydroxyisobutyric acid is an important intermediate in the biosynthesis of methacrylic acid. Its biocatalytic synthesis can be performed by aldolase-catalyzed aldol addition of propanal to formaldehyde followed by an enzymatic oxidation of the resulting 3-hydroxy-2-methylpropanal to 3-hydroxyisobutyric acid. In this work, D-fructose-6-phosphate aldolase D6Q variant was investigated as a key step for the biocatalytic preparation of 3-hydroxy-2-methylpropanal, a commercially unavailable precursor of 3-hydroxyisobutyric acid. The kinetic model of this step was developed for the purpose of reactor selection and process optimization. It was found that enzyme operational stability decay is co-dependent on the initial formaldehyde concentration. Thus, the choice of the initial conditions is crucial for a successful process set-up. It was concluded that fed-batch was the best reactor choice for this reaction due to enzyme inhibition by formaldehyde and propanal, and its operational stability decay. At the optimal process conditions, the product concentration, product yield, and volume productivity after 5.5 h were 72 g L−1, 88.5% and 313.7 g L−1 d−1, respectively. Enzymatic oxidation of 3-hydroxy-2-methylpropanal to the corresponding acid was performed as a proof of concept using an aldehyde dehydrogenase in the presence of NAD+, regenerated by water-forming NADH oxidase, and 2.5 g L−1 (24 mM) of 3-hydroxyisobutyric acid was obtained. © 2019 Institution of Chemical Engineers

Nitrogen heterocycles are structural motifs found in many bioactive natural products and of utmost importance in pharmaceutical drug development. In this work, a stereoselective synthesis of functionalized N-heterocycles was accomplished in two steps, comprising the biocatalytic aldol addition of ethanal and simple aliphatic ketones such as propanone, butanone, 3-pentanone, cyclobutanone, and cyclopentanone to N-Cbz-protected aminoaldehydes using engineered variants of d-fructose-6-phosphate aldolase from Escherichia coli (FSA) or 2-deoxy-d-ribose-5-phosphate aldolase from Thermotoga maritima (DERA Tma ) as catalysts. FSA catalyzed most of the additions of ketones while DERA Tma was restricted to ethanal and propanone. Subsequent treatment with hydrogen in the presence of palladium over charcoal, yielded low-level oxygenated N-heterocyclic derivatives of piperidine, pyrrolidine and N-bicyclic structures bearing fused cyclobutane and cyclopentane rings, with stereoselectivities of 96–98 ee and 97:3 dr in isolated yields ranging from 35 to 79%. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Asymmetric aldol addition of simple aldehydes and ketones to electrophiles is a cornerstone reaction for the synthesis of unusual sugars and chiral building blocks. We investigated D-fructose-6-phosphate aldolase from E. coli (FSA) D6X variants as catalysts for the aldol additions of linear and cyclic non-functionalized aliphatic ketones or ethanal as nucleophiles to non-phosphorylated hydroxyaldehydes. Thus, addition of propanone, cyclobutanone, cyclopentanone or ethanal to 3-hydroxypropanal or (S)- or (R)-3-hydroxybutanal catalyzed by FSA D6H and D6Q variants furnished rare deoxysugars in 8-77% isolated yields with high stereoselectivity (97:3 dr and >95% ee). © 2018 American Chemical Society.

4-Hydroxy-2-ketoacid derivatives are versatile building blocks for the synthesis of amino acids, hydroxy carboxylic acids and chiral aldehydes. Pyruvate aldolases are privileged catalysts for a straightforward access to this class of ketoacid compounds. In this work, a Class II pyruvate aldolase from Escherichia coli K-12, 2-keto-3-deoxy-L-rhamnonate aldolase (YfaU), was evaluated for the synthesis of amino acid derivatives of proline, pipecolic acid, and pyrrolizidine-3-carboxylic acid. The aldol addition of pyruvate to N-protected amino aldehydes was the key enzymatic aldol addition step followed by catalytic intramolecular reductive amination. The corresponding N-Cbz-amino-4-hydroxy-2-ketoacid (Cbz=benzyloxycarbonyl) precursors were obtained in 51%-95% isolated yields and enantioselectivity ratios from 26:74 to 95:5, with chiral -substituted N-Cbz-amino aldehydes. (S)-N-Cbz-amino aldehydes gave aldol adducts with preferentially (R)-configuration at the newly formed stereocenter, whereas the contrary is true for (R)-N-Cbz-amino aldehydes. Addition reactions to achiral amino aldehydes rendered racemic aldol adducts. Molecular models of the pre-reaction ternary complexes YfaU-pyruvate enolate-acceptor aldehyde were constructed to explain the observed stereochemical outcome of the reactions. Catalytic reductive amination of the aldol adducts yielded 4-hydroxy-2-pipecolic acid, and unprecedented C5 substituted 4-hydroxy proline and pyrrolizidine-3-carboxylic acid derivatives.

The synthesis of two novel BDPA-like radicals, a benzyl amino (BAm-BDPA, 7) and a cyano (CN-BDPA, 5) derivative, is reported and their behaviour as polarizing agents for fast dissolution Dynamic Nuclear Polarization (DNP) is evaluated. The radical 7 is a promising candidate for DNP studies since it is soluble in neat [1-13C]pyruvic acid (PA), and therefore the use of an additional glassing agent for sample homogeneity is avoided. In addition, a 60 mM sample of 7 offers optimum 13C NMR signal enhancements using fairly short polarization times (about 1800 s). It is shown that DNP-NMR measurements using 7 can be performed much more efficiently in terms of the signal enhancement per polarization build-up time unit than when using the reference OX63 or BDPA radicals. These enhanced features are translated to a substantial reduction of polarization times that represents an optimum temporary use of the DNP polarizer and allow economized liquid helium consumption.

Polyanionic and electroactive hybrids based on octasilsesquioxanes bearing metallacarborane units are developed. They show remarkable solubility in organic solvents and outstanding thermal stability. The metallacarboranes act as independent units simultaneously undergoing the reversible redox process.