Unclicking the Click: Metal‐Assisted Mechanochemical Cycloreversion of Triazoles Is Possible

Krupička, Martin; Dopieralski, Przemysław; Marx, Dominik

doi:10.1002/ange.201612507

Cited by 3 publications

(2 citation statements)

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“…How these problems are overcome, particularly in view of whether the prFMN-dependent catalysis in these enzymes is similar to the Fdc branch, awaits a more detailed analysis of additional members of the UbiD family. Finally, our data suggests mechanochemical reversion of 1,3-dipolar cycloaddition reactions is feasible, providing further support to the possibility of developing mechanoresponsive materials through reversible click-chemistry [8][9][10][11] . Our data show Nature is able to harness and control 1,3dipolar cycloaddition chemistry by combination of a unique cofactor with strict mechanochemical control.…”

Section: Discussionsupporting

confidence: 60%

“…Diels-Alder reactions have also recently been found to be catalysed by dedicated enzymes 6 , but these are not reported to be reversible. Similarly, 1,3-dipolar cycloaddition reactions such as biocompatible 'click'chemistry are not considered reversible 7 , although the possibility of force-induced cycloreversion is a recent and controversial topic [8][9][10][11] . In the case of the fungal ferulic acid decarboxylase (Fdc) UbiD-enzyme 12 , 1,3-dipolar cycloaddition between prFMN iminium and the cinnamic acid substrate (Fig 1) is proposed to lead to an initial pyrrolidine cycloadduct (Int1) that supports decarboxylation concomitant with ring opening, resulting in formation of a distinct prFMN-alkene adduct (Int2).…”

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confidence: 99%

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Enzymatic control of cycloadduct conformation ensures reversible 1,3-dipolar cycloaddition in a prFMN-dependent decarboxylase

et al. 2019

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The UbiD enzyme plays an important role in bacterial ubiquinone (coenzyme Q) biosynthesis. It belongs to a family of reversible decarboxylases that interconvert propenoic or aromatic acids with the corresponding alkenes or aromatic compounds using a prenylated flavin (prFMN) cofactor. This cofactor is suggested to support (de)carboxylation through a reversible 1,3-dipolar cycloaddition process. Here we report an atomic-level description of the reaction of the UbiD related ferulic acid decarboxylase with substituted propenoic and propiolic acids (data ranging from 1.01 to 1.39 Å). The enzyme is only able to couple (de)carboxylation of cinnamic acid-type compounds to reversible 1,3-dipolar cycloaddition, while formation of dead-end prFMN cycloadducts occurs with distinct propenoic and propiolic acids. The active site imposes considerable strain on covalent intermediates formed with cinnamic and phenylpropiolic acids. Strain reduction through mutagenesis negatively affects catalytic rates with cinnamic acid, indicating a direct link between enzyme-induced strain and catalysis that is supported by computational studies.Many enzymes make use of covalent catalysis to achieve substantial rate enhancements, often by recruiting cofactors such as PLP 1 , TPP 2 and flavins 3 . To ensure high turnover, these enzymes are inherently required to ensure both rapid and reversible cofactor-ligand adduct formation. In the case of the UbiD enzyme family, reversible decarboxylation has been suggested to occur via a 1,3-dipolar cycloaddition process between the substrate and the UbiD-cofactor, prenylated FMN (prFMN) 4 , enabled by the azomethine ylide character of the Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

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Section: Discussionsupporting

confidence: 60%

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Enzymatic control of cycloadduct conformation ensures reversible 1,3-dipolar cycloaddition in a prFMN-dependent decarboxylase

et al. 2019

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Mechanochemistry in [6]Cycloparaphenylene: A Combined Raman Spectroscopy and Density Functional Theory Study

Qiu

Peña-Álvarez

Baonza³

et al. 2018

ChemPhysChem

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Raman spectroscopy under high pressures up to 10 GPa and density functional computations up to 30 GPa are combined to obtain insights into the behavior of a prototypical nanohoop conjugated molecule, [6]cycloparaphenylene ([6]CPP). Upon increasing pressure, the nanohoop undergoes deformations, first reversible ovalization and then at even higher pressures aggregates are formed. This irreversible aggregation is caused by the formation of new intermolecular σ-bonds. Frequencies and derivatives of the Raman frequency shifts as a function of pressure are well reproduced by the computations. The frequency behavior is tied to changes in aromatic/quinonoid character of the nanohoop. The modeling at moderate high pressures reveals the deformation of the [6]CPP molecules into oval-like and peanut-like shapes. Surprisingly the pressure derivatives of the observed Raman mode shifts undergo a sudden change around a pressure value that is common to all Raman modes, indicating an underlying geometrical change extended over the whole molecule that is interpreted by the computational modeling. Simulations predict that under even larger deformations caused by higher pressures, oligomerization reactions would be triggered. Our simulations demonstrate that these transformations would occur regardless of the solvent, however pressures at which they happen are influenced by solvent molecules encapsulated in the interior of the [6]CPP.

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The Mechanism of Flex‐Activation in Mechanophores Revealed By Quantum Chemistry

et al. 2020

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Flex‐activated mechanophores can be used for small‐molecule release in polymers under tension by rupture of covalent bonds that are orthogonal to the polymer main chain. Using static and dynamic quantum chemical methods, we here juxtapose three different mechanical deformation modes in flex‐activated mechanophores (end‐to‐end stretching, direct pulling of the scissile bonds, bond angle bendings) with the aim of proposing ways to optimize the efficiency of flex‐activation in experiments. It is found that end‐to‐end stretching, which is a traditional approach to activate mechanophores in polymers, does not trigger flex‐activation, whereas direct pulling of the scissile bonds or displacement of adjacent bond angles are efficient methods to achieve this goal. Based on the structural, energetic and electronic effects responsible for these observations, we propose ways of weakening the scissile bonds experimentally to increase the efficiency of flex‐activation.

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Unclicking the Click: Metal‐Assisted Mechanochemical Cycloreversion of Triazoles Is Possible

Cited by 3 publications

References 46 publications

Enzymatic control of cycloadduct conformation ensures reversible 1,3-dipolar cycloaddition in a prFMN-dependent decarboxylase

Enzymatic control of cycloadduct conformation ensures reversible 1,3-dipolar cycloaddition in a prFMN-dependent decarboxylase

Mechanochemistry in [6]Cycloparaphenylene: A Combined Raman Spectroscopy and Density Functional Theory Study

The Mechanism of Flex‐Activation in Mechanophores Revealed By Quantum Chemistry

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