Hydrogen Tunneling Above Room Temperature Evidenced by Infrared Ion Spectroscopy

While hydrogen tunneling at elevated temperatures has, for instance, often been postulated in biochemical processes, spectroscopic proof is thus far limited to cryogenic conditions, under which thermal reactivity is negligible. We report spectroscopic evidence for H-tunneling in the gas phase at temperatures around 320-350K observed in the isomerization reaction of a hydroxycarbene into an aldehyde. The charge-tagged carbene was generated in situ in a tandem mass spectrometer by decarboxylation of oxo[4-(trimethylammonio)phenyl]acetic acid upon collision induced dissociation. All ion structures involved are characterized by infrared ion spectroscopy and quantum chemical calcula-tions. The charge-tagged phenylhydroxycarbene undergoes 1,2-H-shift to the corresponding aldehyde with an half-life of about 10 s, evidenced by isomer-selective two-color (IR-IR) spectroscopy. In contrast, the deuterated (OD) carbene analogue showed much reduced 1,2-D-shift reactivity with an estimated half-life of at least 200 seconds under the experimental conditions, and provides clear evidence for hydrogen atom tunneling in the H-isotopologue. This is the first spectroscopic confirmation of hydrogen atom tunneling governing 1,2-H-shift reactions at non-cryogenic temperatures, which is of broad significance for a range of (bio)chemical processes, including enzymatic transformations and organocatalysis

The design of organic catalysis for epoxidation by hydrogen peroxide

The potential of various organic species to catalyze epoxidation of ethene by hydrogen peroxide is explored with B3LYP/6-31G* DFT calculations

Breslow intermediates (aminoenols) and their keto tautomers: first gas‐phase characterization by IR ion spectroscopy

Breslow intermediates (BIs) are the crucial nucleophilic amino enol intermediates formed from electrophilic aldehydes in the course of N‐heterocyclic carbene (NHC) catalyzed Umpolung reactions. Both in organocatalytic and enzymatic Umpolung, the question whether the Breslow intermediate exists as the nucleophilic enol, or in the form of its electrophilic keto‐tautomer, is of utmost importance for its reactivity and function. We herein report the preparation of charge‐tagged Breslow intermediates/keto tautomers derived from three different types of NHCs (imidazolidin‐2‐ylidenes, 1,2,4‐triazolin‐5‐ylidenes, thiazolin‐2‐ylidenes) and aldehydes. An ammonium charge‐tag is introduced by either the aldehyde unit or the NHC. ESI‐MS IR‐Ion spectroscopy allowed for the unambiguous conclusion that in the gas‐phase, the imidazolidin‐2‐ylidene derived BI indeed exists as a diamino enol, while both 1,2,4‐triazolin‐5‐ylidenes and thiazolin‐2‐ylidenes give the keto‐tautomer. This result coincides with the tautomeric states observed for the BIs in solution (NMR) and in the crystalline state (XRD), and is in line with our earlier calculations on the energetics of BI keto‐enol equilibria

Hydrogen bonding shuts down tunneling in hydroxycarbenes: a gas-phase study by tandem-mass spectrometry, infrared ion spectroscopy, and theory

Hydroxycarbenes can be generated and structurally characterized in the gas phase by collision-induced decarboxylation of α-keto carboxylic acids, followed by infrared ion spectroscopy. Using this approach, we have shown earlier that quantum-mechanical hydrogen tunneling (QMHT) accounts for the isomerization of a charge-tagged phenylhydroxycarbene to the corresponding aldehyde in the gas phase and above room temperature. Herein, we report the results of our current study on aliphatic trialkylammonio-tagged systems. Quite unexpectedly, the flexible 3-(trimethylammonio)propylhydroxycarbene turned out to be stable-no H-shift to either aldehyde or enol occurred. As supported by density functional theory calculations, this novel QMHT inhibition is due to intramolecular H-bonding of a mildly acidic α-ammonio C-H bonds to the hydroxyl carbene's C-atom (C:···H-C). To further support this hypothesis, (4-quinuclidinyl)hydroxycarbenes were synthesized, whose rigid structure prevents this intramolecular H-bonding. The latter hydroxycarbenes underwent "regular" QMHT to the aldehyde at rates comparable to, e.g., methylhydroxycarbene studied by Schreiner et al. While QMHT has been shown for a number of biological H-shift processes, its inhibition by H-bonding disclosed here may serve for the stabilization of highly reactive intermediates such as carbenes, even as a mechanism for biasing intrinsic selectivity patterns

The exchange activities of [Fe] hydrogenase (iron–sulfur-cluster-free hydrogenase) from methanogenic archaea in comparison with the exchange activities of [FeFe] and [NiFe] hydrogenases

[Fe] hydrogenase (iron–sulfur-cluster-free hydrogenase) catalyzes the reversible reduction of methenyltetrahydromethanopterin (methenyl-H4MPT+) with H2 to methylene-H4MPT, a reaction involved in methanogenesis from H2 and CO2 in many methanogenic archaea. The enzyme harbors an iron-containing cofactor, in which a low-spin iron is complexed by a pyridone, two CO and a cysteine sulfur. [Fe] hydrogenase is thus similar to [NiFe] and [FeFe] hydrogenases, in which a low-spin iron carbonyl complex, albeit in a dinuclear metal center, is also involved in H2 activation. Like the [NiFe] and [FeFe] hydrogenases, [Fe] hydrogenase catalyzes an active exchange of H2 with protons of water; however, this activity is dependent on the presence of the hydride-accepting methenyl-H4MPT+. In its absence the exchange activity is only 0.01% of that in its presence. The residual activity has been attributed to the presence of traces of methenyl-H4MPT+ in the enzyme preparations, but it could also reflect a weak binding of H2 to the iron in the absence of methenyl-H4MPT+. To test this we reinvestigated the exchange activity with [Fe] hydrogenase reconstituted from apoprotein heterologously produced in Escherichia coli and highly purified iron-containing cofactor and found that in the absence of added methenyl-H4MPT+ the exchange activity was below the detection limit of the tritium method employed (0.1 nmol min−1 mg−1). The finding reiterates that for H2 activation by [Fe] hydrogenase the presence of the hydride-accepting methenyl-H4MPT+ is essentially required. This differentiates [Fe] hydrogenase from [FeFe] and [NiFe] hydrogenases, which actively catalyze H2/H2O exchange in the absence of exogenous electron acceptors

Asymmetric Organocatalysis in Deep Eutectic Solvents

The recent advances in asymmetric organocatalysis using eutectic mixtures as a reaction medium are revised in this mini‐review. In addition, the first enantioselective transformations using chiral eutectic solvents, which play the role of a green medium and organocatalyst, are described. In this mini‐review we intend to deepen not only in the synthetic aspects of asymmetric organocatalysis in eutectic mixtures, but also in the fundamental issues that seem to be essential for a successful development of this promising, and at the same time challenging, methodology.This work was supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (MICINN, PGC2018-096616-B-I00), the University of Alicante (VIGROB-173 and VIGROB-316FI), and the University of Pisa (PRA_2018_36)

Consequences of conformational flexibility in hydrogen-bond-driven self-assembly processes

We report the synthesis and self-assembly of chiral, conformationally flexible C3-symmetrical trisamides. A strong Cotton effect is observed for the supramolecular polymers in linear alkanes but not in cyclic alkanes. MD simulations suggest 2:1 conformations of the amides within the aggregates in both types of solvents, but a chiral bias in only linear alkanes.JAB, MGI, RPAG, EWM and ARAP would like to thank the Gravity program 024.001.035, NWO TOP-PUNT 718.014.003 for financial support and Anneloes Oude Vrielink for TEM imaging. FDM and ML acknowledge the Swedish e-Research Center (SeRC) for financial support, the Swedish Research Council (Grant No. 621-2014-4646), SNIC (Swedish National Infrastructure for Computing) and Dr Julien Idé for providing the code for exciton coupling calculations

Effect of capping groups at the N- and C-termini on the conformational preference of α,β-peptoids

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