"Freedom of design" in chemical compound space: towards rational design of molecules with targeted quantum-mechanical properties.

The rational design of molecules with targeted quantum-mechanical (QM) properties requires an advanced understanding of the structure-property/property-property relationships (SPR/PPR) that exist across chemical compound space (CCS). In this work, we analyze these fundamental relationships in the sector of CCS spanned by small (primarily organic) molecules using the recently developed QM7-X dataset, a systematic, extensive, and tightly converged collection of 42 QM properties corresponding to ≈4.2M equilibrium and non-equilibrium molecular structures containing up to seven heavy/non-hydrogen atoms (including C, N, O, S, and Cl).

Concise synthesis of ()-reticuline and (+)-salutaridine by combining early-stage organic synthesis and late-stage biocatalysis.

Efficient access to the morphinan scaffold remains a major challenge in both synthetic chemistry and biotechnology. Here, a biomimetic chemo-enzymatic strategy to synthesize the natural promorphinan intermediate (+)-salutaridine is demonstrated. By combining early-stage organic synthesis with enzymatic asymmetric key step transformations, the prochiral natural intermediate 1,2-dehydroreticuline was prepared and subsequently stereoselectively reduced by the enzyme 1,2-dehydroreticuline reductase obtaining ()-reticuline in high ee and yield (>99% ee, up to quant.

Anaerobic demethylation of guaiacyl-derived monolignols enabled by a designed artificial cobalamin methyltransferase fusion enzyme.

Lignin-derived aryl methyl ethers ( coniferyl alcohol, ferulic acid) are expected to be a future carbon source for chemistry. The well-known P450 dependent biocatalytic -demethylation of these aryl methyl ethers is prone to side product formation especially for the oxidation sensitive catechol products which get easily oxidized in the presence of O. Alternatively, biocatalytic demethylation using cobalamin dependent enzymes may be used under anaerobic conditions, whereby two proteins, namely a methyltransferase and a carrier protein are required.

Transmembrane Shuttling of Photosynthetically Produced Electrons to Propel Extracellular Biocatalytic Redox Reactions in a Modular Fashion.

Many biocatalytic redox reactions depend on the cofactor NAD(P)H, which may be provided by dedicated recycling systems. Exploiting light and water for NADPH-regeneration as it is performed, e.g.

Photoconductivity of PbS/perovskite quantum dots in gold nanogaps.

We demonstrate that the photoconductance of colloidal PbS/MAPbI quantum dots in nanoscale gold electrode gaps shows a consistent power law dependence of the photocurrent on the light intensity with an exponent slightly below 0.7. The gap sizes are between 25 and 800 nm and by scanning photocurrent microscopy we evidence the strong localization and high reproducibility of photocurrent generation.

Structure-Based Demystification of Radical Catalysis by a Coenzyme B Dependent Enzyme-Crystallographic Study of Glutamate Mutase with Cofactor Homologues.

Catalysis by radical enzymes dependent on coenzyme B (AdoCbl) relies on the reactive primary 5'-deoxy-5'adenosyl radical, which originates from reversible Co-C bond homolysis of AdoCbl. This bond homolysis is accelerated roughly 10-fold upon binding the enzyme substrate. The structural basis for this activation is still strikingly enigmatic.

Thiols Act as Methyl Traps in the Biocatalytic Demethylation of Guaiacol Derivatives.

Demethylating methyl phenyl ethers is challenging, especially when the products are catechol derivatives prone to follow-up reactions. For biocatalytic demethylation, monooxygenases have previously been described requiring molecular oxygen which may cause oxidative side reactions. Here we show that such compounds can be demethylated anaerobically by using cobalamin-dependent methyltransferases exploiting thiols like ethyl 3-mercaptopropionate as a methyl trap.

PQQ-dependent Dehydrogenase Enables One-pot Bi-enzymatic Enantio-convergent Biocatalytic Amination of Racemic -Allylic Alcohols.

The asymmetric amination of secondary racemic allylic alcohols bears several challenges like the reactivity of the bi-functional substrate/product as well as of the α,β-unsaturated ketone intermediate in an oxidation-reductive amination sequence. Heading for a biocatalytic amination cascade with a minimal number of enzymes, an oxidation step was implemented relying on a single PQQ-dependent dehydrogenase with low enantioselectivity. This enzyme allowed the oxidation of both enantiomers at the expense of iron(III) as oxidant.

Chromoselective Photocatalysis Enables Stereocomplementary Biocatalytic Pathways.

Controlling the selectivity of a chemical reaction with external stimuli is common in thermal processes, but rare in visible-light photocatalysis. Here we show that the redox potential of a carbon nitride photocatalyst (CN-OA-m) can be tuned by changing the irradiation wavelength to generate electron holes with different oxidation potentials. This tuning was the key to realizing photo-chemo-enzymatic cascades that give either the ()- or the ()-enantiomer of phenylethanol.

Regioselectivity of Cobalamin-Dependent Methyltransferase Can Be Tuned by Reaction Conditions and Substrate.

Regioselective reactions represent a significant challenge for organic chemistry. Here the regioselective methylation of a single hydroxy group of 4-substituted catechols was investigated employing the cobalamin-dependent methyltransferase from . Catechols substituted in position four were methylated either in - or -position to the substituent depending whether the substituent was polar or apolar.

Assembly patterns of soil-dwelling lichens after glacier retreat in the European Alps.

Aim: To assess the spatial-temporal dynamics of primary succession following deglaciation in soil-dwelling lichen communities.

Location: European Alps (Austria, Switzerland and Italy).

Methods: Five glacier forelands subjected to relevant glacier retreat during the last century were investigated.

Regioselective Enzymatic β-Carboxylation of -Hydroxy- styrene Derivatives Catalyzed by Phenolic Acid Decarboxylases.

We report on a 'green' method for the utilization of carbon dioxide as C unit for the regioselective synthesis of ()-cinnamic acids regioselective enzymatic carboxylation of -hydroxystyrenes. Phenolic acid decarboxylases from bacterial sources catalyzed the β-carboxylation of -hydroxystyrene derivatives with excellent regio- and (/)-stereoselectivity by exclusively acting at the β-carbon atom of the C=C side chain to furnish the corresponding ()-cinnamic acid derivatives in up to 40% conversion at the expense of bicarbonate as carbon dioxide source. Studies on the substrate scope of this strategy are presented and a catalytic mechanism is proposed based on molecular modelling studies supported by mutagenesis of amino acid residues in the active site.

Identification of an insulin-regulated lysophospholipase with homology to neuropathy target esterase.

Neuropathy target esterase (NTE) is a member of the family of patatin domain-containing proteins and exhibits phospholipase activity in brain and cultured cells. NTE was originally identified as target enzyme for organophosphorus compounds that cause a delayed paralyzing syndrome with degeneration of nerve axons. Here we show that the structurally related murine protein NTE-related esterase (NRE) is a potent lysophospholipase.