1,721,051 research outputs found
Editorial: Special Issue on "Advanced Strategies for Catalyst Design"
Full text linkThe word catalyst comes from the Greek κατα’λυσις, which means dissolution and was introduced in 1836 by the Swedish Berzelius [...
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
Antioxidant Potential of Anthocyanidins: A Healthy Computational Activity for High School and Undergraduate Students
Full text linkMolecules 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
Selenium-catalyzed reduction of hydroperoxides in chemistry and biology
Full text linkAmong 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
The Role of Selenium in Glutathione Peroxidase: Insights from Molecular Modeling
Full text linkBickelhaupt, F.M. [Promotor]Orian, L. [Promotor
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
Organodiselenides: Organic catalysis and drug design learning from glutathione peroxidase
No full textOrganodiselenides are an important class of compounds characterized by the presence of two adjacent covalently bonded selenium nuclei. Among them, diaryldiselenides and their parent compound diphenyl diselenide attract continuing interest in chemistry as well as in close disciplines like medicinal chemistry, pharmacology and biochemistry. A search in SCOPUS database has revealed that in the last three years 105 papers have been published on the archetypal diphenyl diselenide and its use in organic catalysis and drug tests. The reactivity of the Se-Se bond and the redox properties of selenium make diselenides efficient catalysts for numerous organic reactions, such as Bayer- Villiger oxidations of aldehydes/ketones, epoxidations of alkenes, oxidations of alcohols and nitrogen containing compounds. In addition, organodiselenides might find application as mimics of glutathione peroxidase (GPx), a family of enzymes, which, besides performing other functions, regulate the peroxide tone in the cells and control the oxidative stress level. In this review, the essential synthetic and reactivity aspects of organoselenides are collected and rationalized using the results of accurate computational studies, which have been carried out mainly in the last two decades. The results obtained in silico provide a clear explanation of the anti-oxidant activity of organodiselenides and more in general of their ability to reduce hydroperoxides. At the same time, they are useful to gain insight into some aspects of the enzymatic activity of the GPx, inspiring novel elements for rational catalyst and drug design
Essentials for combined experimental and computational77se nmr of organoselenium catalysts and bioinspired antioxidants
No full textThe importance of selenium in biology, in organic catalysis, and green chemistry is well established. Selenoproteins, among which are ubiquitous glutathione peroxidases (GPx), play a key role in mitigating oxidative stress by reducing H2O2 and hydroperoxides using glutathione as a co-factor. Organoselenides, particularly diphenyl diselenide, in the presence of H2O2, are efficient and often green oxygen transfer agents in important organic reactions, such as Baeyer-Villiger oxidations of ketones/aldehydes, the conversion of alkenes into epoxides, and the oxidations of alcohols and ni-trogen-containing compounds. NMR spectroscopy can facilitate the investigation of the properties of this element in a biological environment and the characterization of the peculiar species of its chem-istry. In this short review, a brief overview of the experimental and computational77Se NMR-based techniques is outlined, with a particular focus on their applications to the study of biologically rele-vant organoselenium compounds and bio-mimetic systems. Experimental protocols, together with computational methods used in different contexts, are presented and their potential as efficient investigation tools is critically discussed. It emerges that while the77Se NMR measurement is a consoli-dated technique, no standard computational protocol is available to compute the shielding constant of the chalcogen nucleus with accuracy and the optimal approach combines molecular dynamics in solution and quantum chemistry calculations to take into account the conformational freedom
In silico acetylene 2+2+2 cycloadditions catalyzed by rh/cr indenyl fragments
Full text linkMetal-catalyzed alkyne [2+2+2] cycloadditions provide a variety of substantial aromatic compounds of interest in the chemical and pharmaceutical industries. Herein, the mechanistic aspects of the acetylene [2+2+2] cycloaddition mediated by bimetallic half-sandwich catalysts [Cr(CO)3IndRh] (Ind = (C9H7)−, indenyl anion) are investigated. A detailed exploration of the potential energy surfaces (PESs) was carried out to identify the intermediates and transition states, using a relativistic density functional theory (DFT) approach. For comparison, monometallic parent systems, i.e., CpRh (Cp = (C5H5)−, cyclopentadienyl anion) and IndRh, were included in the analysis. The active center is the rhodium nucleus, where the [2+2+2] cycloaddition occurs. The coordination of the Cr(CO)3 group, which may be in syn or anti conformation, affects the energetics of the catalytic cycle as well as the mechanism. The reaction and activation energies and the turnover frequency (TOF) of the catalytic cycles are rationalized, and, in agreement with the experimental findings, our computational analysis reveals that the presence of the second metal favors the catalysis
Modelling of Ca2+-promoted structural effects in wild type and post-translationally modified Connexin26
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