342 research outputs found
Editorial: Special Issue on "Advanced Strategies for Catalyst Design"
No full textThe word catalyst comes from the Greek κατα’λυσις, which means dissolution and was introduced in 1836 by the Swedish Berzelius [...
The Role of Selenium in Glutathione Peroxidase: Insights from Molecular Modeling
No full textBickelhaupt, F.M. [Promotor]Orian, L. [Promotor
Selenium-catalyzed reduction of hydroperoxides in chemistry and biology
No full textAmong the chalcogens, selenium is the key element for catalyzed H2O2 reduction. In organic synthesis, catalytic amounts of organo mono-and di-selenides are largely used in different classes of oxidations, in which H2O2 alone is poorly efficient. Biological hydroperoxide metabolism is dominated by peroxidases and thioredoxin reductases, which balance hydroperoxide challenge and contribute to redox regulation. When their selenocysteine is replaced by cysteine, the cellular antioxidant defense system is impaired. Finally, classes of organoselenides have been synthesized with the aim of mimicking the biological strategy of glutathione peroxidases, but their therapeutic application has so far been limited. Moreover, their therapeutic use may be doubted, because H2O2 is not only toxic but also serves as an important messenger. Therefore, over-optimization of H2O2 reduction may lead to unexpected disturbances of metabolic regulation. Common to all these systems is the nucleophilic attack of selenium to one oxygen of the peroxide bond promoting its dis-ruption. In this contribution, we revisit selected examples from chemistry and biology, and, by using results from accurate quantum mechanical modelling, we provide an accurate unified picture of selenium’s capacity of reducing hydroperoxides. There is clear evidence that the selenoenzymes remain superior in terms of catalytic efficiency
Concerted proton electron transfer or hydrogen atom transfer? an unequivocal strategy to discriminate these mechanisms in model systems
No full textConcerted proton electron transfer (CPET) and hydrogen atom transfer (HAT) are two important mechanisms in many fields of chemistry, which are characterized by the transfer of one proton and one electron. The distinction between these mechanisms may be challenging in several reactions; thus, different computational methods have been developed for this purpose. In this work, we present a computational strategy to distinguish the two mechanisms, rationalizing the factors controlling the reactivity in four different model reactions. Fist, the transition state SOMO (singly occupied molecular orbital) is visualized, presenting all the limits and ambiguities of this analysis. Then, the electron flow along the reaction path is evaluated through the intrinsic bond orbitals (IBOs); this analysis allows to describe correctly the mechanism of each reaction in agreement with previous studies. Furthermore, some structural modifications are applied to the transition state of each system and the energetic differences are rationalized in the framework of the activation strain analysis to understand the geometrical and electronic factors governing the reactivity and the selection of CPET or HAT mechanism. Lastly, the effect of the donor-acceptor distance is evaluated. It emerges that a combined computational analysis is crucial to understand not only the distinction between the two mechanisms, but also the molecular reasons why one mechanism is operative in a specific reaction
Computer and chemistry: facilitating the learning process of the infrared spectra of water and carbon dioxide.
No full textA computational laboratory is proposed for secondary school students to facilitate the learning process of the Infrared (IR) spectra of water and carbon dioxide. In the context of the greenhouse effect, which is the macroscopic phenomenon related to the rate of cooling of our planet in response of being warmed by the sun, students can learn its molecular origin with the support of computer through the simulation of the vibrational spectra of water and carbon dioxide. Input files as well as data are provided so that the laboratory can be proposed even when computational facilities are not available. In particular, the role of computer in chemistry teaching and learning is established because molecular models let the students visualize the subnanometric world which remains elusive in daily experience
Antioxidant Potential of Anthocyanidins: A Healthy Computational Activity for High School and Undergraduate Students
No full textMolecules and Computer: Chemistry Calculations in Class (MC4) is a computational laboratory intended for final-year high school or undergraduate students. The topic is the antioxidant potential of anthocyanidins, which is chemically related to their radical scavenging action via the mechanism of hydrogen atom transfer (HAT). This laboratory combines (bio)chemical and nutraceutical concepts with organic chemical reactions involving radical species. It allows students to apply important physicochemical (thermodynamic) concepts, such as Gibbs free energy of reaction and solvation. Finally, the procedure can easily be tailored to the resources at hand as well as the knowledge of the students. In fact, when computing facilities are not available, the whole set of molecular structures and energy data are provided as well as a simple datasheet required for their analysis. Alternatively, the whole protocol and useful scripts are provided so that students can generate their own results by experiencing the approach to computational chemistry
The glutathione peroxidase family: Discoveries and mechanism
No full textThe discoveries leading to our present understanding of the glutathione peroxidases (GPxs) are recalled. The cytosolic GPx, now GPx1, was first described by Mills in 1957 and claimed to depend on selenium by Rotruck et al., in 1972. With the determination of a stoichiometry of one selenium per subunit, GPx1 was established as the first selenoenzyme of vertebrates. In the meantime, the GPxs have grown up to a huge family of enzymes that prevent free radical formation from hydroperoxides and, thus, are antioxidant enzymes, but they are also involved in regulatory processes or synthetic functions. The kinetic mechanism of the selenium-containing GPxs is unusual in neither showing a defined KM nor any substrate saturation. More recently, the reaction mechanism has been investigated by the density functional theory and nuclear magnetic resonance of model compounds mimicking the reaction cycle. The resulting concept sees a selenolate oxidized to a selenenic acid. This very fast reaction results from a concerted dual attack on the hydroperoxide bond, a nucleophilic one by the selenolate and an electrophilic one by a proton that is unstably bound in the reaction center. Postulated intermediates have been identified either in the native enzymes or in model compounds
A dual attack on the peroxide bond. The common principle of peroxidatic cysteine or selenocysteine residues
No full textThe (seleno)cysteine residues in some protein families react with hydroperoxides with rate constants far beyond
those of fully dissociated low molecular weight thiol or selenol compounds. In case of the glutathione peroxidases,
we could demonstrate that high rate constants are achieved by a proton transfer from the chalcogenol to
a residue of the active site [Orian et al. Free Radic. Biol. Med. 87 (2015)]. We extended this study to three more
protein families (OxyR, GAPDH and Prx). According to DFT calculations, a proton transfer from the active site
chalcogenol to a residue within the active site is a prerequisite for both, creating a chalcogenolate that attacks
one oxygen of the hydroperoxide substrate and combining the delocalized proton with the remaining OH or OR,
respectively, to create an ideal leaving group. The “parking postions” of the delocalized proton differ between the
protein families. It is the ring nitrogen of tryptophan in GPx, a histidine in GAPDH and OxyR and a threonine in
Prx. The basic principle, however, is common to all four families of proteins. We, thus, conclude that the principle
outlined in this investigation offers a convincing explanation for how a cysteine residue can become peroxidatic
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