Recent advances in spirochalcogenurane stereochemistry—A mini review

Allenmark, Stig

doi:10.1002/chir.20510

Cited by 11 publications

(5 citation statements)

References 60 publications

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“…The thioselenurane in product complex 3f9 P 0 formed by following the reaction coordinate is in an unstable conformation 9 0 with the -SMe group trans to the amide. Pseudorotation to 9, the conformation with a trans arrangement of the most electronegative groups (amide and hydroxyl) of the three-center-four-electron bond, 84 should be rapid. 85 The rearranged product complex 3f9 P was 3.6 kcal/mol more stable than 3f9 P 0 and is predicted to be in equilibrium with the reactants (0.1 kcal/mol).…”

Section: ' Theoretical Methodsmentioning

confidence: 99%

Modeling the Mechanism of the Glutathione Peroxidase Mimic Ebselen

Antony

Bayse

2011

Inorg. Chem.

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Ebselen (1), the quintessential mimic of the antioxidant selenoenzyme glutathione peroxidase (GPx), is a potential chemopreventative for various diseases associated with oxidative stress. Density-functional theory (DFT) and solvent-assisted proton exchange (SAPE) are used to model the complex mechanism for scavenging of reactive oxygen species by 1. SAPE is a microsolvation method designed to approximate the role of bulk solvent in chemical processes involving proton transfer. Consistent with experimental studies, SAPE studies predict the reaction of 1 with thiol (RSH) to form a selenenyl sulfide 2 to be preferred under most conditions, with an alternate pathway through a selenoxide 3 possible at high reactive oxygen species (ROS) concentrations ([ROS] ≫ [RSH]). The reduction of 2 to the selenol 4, known to be rate-determining in the protein, has a high SAPE activation barrier due to a strong Se···O interaction which reduces the electrophilicity of the sulfur center of the -SeS- bond of 2. Thiols, such as dithiols and peptide-based thiols, are expected to overcome this barrier through structural features that increase the probability of attack at this sulfur. Thus, in vivo, the GPx-like pathway is the most likely mechanism for 1 under most circumstances, except, perhaps, under extreme oxidative stress where initial oxidation to 3 could compete with formation of 2. Simple thiols, used in various in vitro studies, are predicted by SAPE modeling to proceed through oxidation of 2 to a seleninyl sulfide intermediate. Overall, SAPE modeling provides a realistic interpretation of the redox mechanism of 1 and holds promise for further exploration of complex aqueous-phase reaction mechanisms.

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Section: ' Theoretical Methodsmentioning

confidence: 99%

Modeling the Mechanism of the Glutathione Peroxidase Mimic Ebselen

Antony

Bayse

2011

Inorg. Chem.

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“…Spirodioxyselenuranes such as 2 and 4 are chiral. Stereochemical and chiroptical studies of certain related selenuranes have been reported, while several such compounds have been resolved and their absolute configurations determined . Other derivatives containing camphor moieties were obtained as pure diastereomers .…”

Section: Introductionmentioning

confidence: 99%

NMR and Computational Studies of the Configurational Properties of Spirodioxyselenuranes. Are Dynamic Exchange Processes or Temperature-Dependent Chemical Shifts Involved?

et al. 2012

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Spirodioxyselenurane 4a and several substituted analogs revealed unexpected (1)H NMR behavior. The diastereotopic methylene hydrogens of 4a appeared as an AB quartet at low temperature that coalesced to a singlet upon warming to 267 K, suggesting a dynamic exchange process with a relatively low activation energy. However, DFT computational investigations indicated high activation energies for exchange via inversion through the selenium center and for various pseudorotation processes. Moreover, the NMR behavior was unaffected by the presence of water or acid catalysts, thereby ruling out reversible Se-O or benzylic C-O cleavage as possible stereomutation pathways. Remarkably, when 4a was heated beyond 342 K, the singlet was transformed into a new AB quartet. Further computations indicated that a temperature dependence of the chemical shifts of the diastereotopic protons results in convergence upon heating, followed by crossover and divergence at still higher temperatures. The NMR behavior is therefore not due to dynamic exchange processes, but rather to temperature dependence of the chemical shifts of the diastereotopic hydrogens, which are coincidentally equivalent at intermediate temperatures. These results suggest the general need for caution in ascribing the coalescence of variable-temperature NMR signals of diastereotopic protons to dynamic exchange processes that could instead be due to temperature-dependent chemical shifts and highlight the importance of corroborating postulated exchange processes through additional computations or experiments wherever possible.

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“…The chemistry of spirodioxysulfuranes has been studied extensively due to their interesting structural and stereochemical properties . In addition to the sulfur compounds, some selenium and tellurium analogues have also been studied . The first compound of this kind, spirodioxyselenurane 2 , was synthesized in 1914 by Lesser and Weiss .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Structure, Spirocyclization Mechanism, and Glutathione Peroxidase-like Antioxidant Activity of Stable Spirodiazaselenurane and Spirodiazatellurane

et al. 2010

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The first examples of stable spirodiazaselenurane and spirodiazatellurane were synthesized by oxidative spirocyclization of the corresponding diaryl selenide and telluride and were structurally characterized. X-ray crystal structures of the spirodiazaselenurane and spirodiazatellurane suggest that the structures are distorted trigonal bipyramidal (TBP) with the electronegative nitrogen atoms occupying the apical positions and two carbon atoms and the lone pair of Se/Te occupying the equatorial positions. Interestingly, the spirodiazatellurane underwent spontaneous chiral resolution during crystallization, and the absolute configurations of its enantiomers were confirmed by single-crystal X-ray analyses. A detailed mechanistic study indicates that the cyclization to spirodiazaselenurane and spirodiazatellurane occurs via selenoxide and telluroxide intermediates. The chalcogenoxides cyclize to the corresponding spiro compounds in a stepwise manner via the involvement of hydroxyl chalcogenurane intermediates, and the activation energy for the spirocyclization reaction decreases in the order S > Se > Te. In addition to the synthesis, characterization, and mechanism of cyclization, the glutathione peroxidase (GPx) mimetic activity of the newly synthesized compounds was evaluated. These studies suggest that the tellurium compounds are more effective as GPx mimics than their selenium counterparts due to the fast oxidation of the tellurium center in the presence of peroxide and the involvement of an efficient redox cycle between the telluride and telluroxide intermediate.

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Recent advances in spirochalcogenurane stereochemistry—A mini review

Cited by 11 publications

References 60 publications

Modeling the Mechanism of the Glutathione Peroxidase Mimic Ebselen

Modeling the Mechanism of the Glutathione Peroxidase Mimic Ebselen

NMR and Computational Studies of the Configurational Properties of Spirodioxyselenuranes. Are Dynamic Exchange Processes or Temperature-Dependent Chemical Shifts Involved?

Synthesis, Structure, Spirocyclization Mechanism, and Glutathione Peroxidase-like Antioxidant Activity of Stable Spirodiazaselenurane and Spirodiazatellurane

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