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Seleninic acids and their precursors are well-known oxygen-transfer agents that can catalyze several oxidations with H2O2 as the final oxidant. Until very recently, the Se(iv) "peroxyseleninic" acid species has been considered the only plausible catalytic oxidant. Conversely, in 2020, the involvement of Se(vi) "peroxyselenonic" acid has been proposed for the selenium mediated epoxidation of alkenes. In this work, we theoretically probe different mechanisms of H2O2 activation and of Se(iv) to Se(vi) interconversion. In addition, we investigate through a combined theoretical (DFT) and experimental approach the mechanistic steps leading to the oxidation of aniline to nitrobenzene, when Se(iv) seleninic acid or Se(vi) selenonic acids are used as catalysts and H2O2 as the oxidant. This process encompasses three subsequent organoselenium mediated oxidations by H2O2. These results provide a mechanistic explanation of the advantages and disadvantages of both oxidation states (iv and vi) in the different stages of catalytic oxygen-transfer reactions: hydrogen peroxide activation and actual substrate oxidation. While the Se(vi) "peroxyselenonic" acid is found to be a better oxidant, the privileged role of "peroxyseleninic" acid as the main active species is assessed and its origin is identified in the lower catalyst-distortion that seleninic acid undergoes when activating H2O2. Conversely, the higher catalyst-distortion that characterizes the reaction of selenonic acid with H2O2 supports an inactivating role of Se(iv) to Se(vi) interconversion.
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This study reports a combined approach to assess the antioxidant activity of Zuccagnia-type propolis. Fractions exhibiting the highest antioxidant activities evidenced by DPPH, a ß-carotene bleaching and superoxide radical scavenging activity-non-enzymatic assays, were processed by LC-HRMS/MS to characterize the relevant chemical compounds. A computational protocol based on the DFT calculations was used to rationalize the main outcomes. Among the 28 identified flavonoids, caffeic acids derivatives were in the fraction exhibiting the highest antioxidant activity, with 1-methyl-3-(4'-hydroxyphenyl)-propyl caffeic acid ester and 1-methyl-3-(3',4'-dihydroxyphenyl)-propyl caffeic acid ester as major components. Results clearly showed roles of specific chemical motifs, which can be supported by the computational analysis. This is the first report ascribing the antioxidant ability of Zuccagnia-type propolis to its content in specific caffeic acid derivatives, a potential source of radical scavenging phytochemicals. The proposed protocol can be extended to the study of other plant-products to address the most interesting bioactive compounds.
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Already known molecules which exhibit good electrochemiluminescence (ECL) efficiencies and high photoluminescence quantum yields (PLQY) have been structurally modified in order to increase their performance. The followed strategy is to stiffen the structures to limit the rotational and vibrational freedom degrees and favour radiative decay processes once excited. Molecules under investigation consist of donor-acceptor systems in which the acceptor fraction is a benzonitrile with an imidazole in para position, while the donor fraction consists of four diphenylamine (NPh2) or 3,6-di(tert-butyl)-9H-carbazole (t-BuCz) groups in the remaining positions on the central benzene ring. Therefore, in order to stiffen these systems and restrict the intramolecular rotations (RIR), the imidazole in the para position has been replaced with more extended π-systems, i.e., benzimidazole and phenanthro[9,10-d]imidazole. The restriction of the intramolecular rotation can be clearly observed by 1H NMR analysis. We expected to observe an increase in ECL efficiency and PLQY with the rigidity. Surprisingly, we observed a generally opposite trend: molecules with the smallest imidazole fraction showed the best performance in ECL and higher PLQY. Notably, NPh2 derivatives with benzimidazole and phenanthro[9,10-d]imidazole showed an hypsochromic shift of the emission spectra with concomitant increase of the PLQY as the solvent polarity is increased.
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The reactivity of Zn2+ tetrahedral complexes with H2O2 was investigated in silico, as a first step in their disruption process. The substrates were chosen to represent the cores of three different zinc finger protein motifs, i. e., a Zn2+ ion coordinated to four cysteines (CCCC), to three cysteines and one histidine (CCCH), and to two cysteines and two histidines (CCHH). The cysteine and histidine ligands were further simplified to methyl thiolate and imidazole, respectively. H2O2 was chosen as an oxidizing agent due to its biological role as a metabolic product and species involved in signaling processes. The mechanism of oxidation of a coordinated cysteinate to sulfenate-κS and the trends for the different substrates were rationalized through activation strain analysis and energy decomposition analysis in the framework of scalar relativistic Density Functional Theory (DFT) calculations at ZORA-M06/TZ2P ae // ZORA-BLYP-D3(BJ)/TZ2P. CCCC is oxidized most easily, an outcome explained considering both electrostatic and orbital interactions. The isomerization to sulfenate-κO was attempted to assess whether this step may affect the ligand dissociation; however, it was found to introduce a kinetic barrier without improving the energetics of the dissociation. Lastly, ligand exchange with free thiolates and selenolates was investigated as a trigger for ligand dissociation, possibly leading to metal ejection; molecular docking simulations also support this hypothesis.
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Notable thermal shifts in diselenides have been documented in 77Se NMR for more than 50 years, but no satisfactory explanation has been found. Here, five hypotheses are considered as possible explanations for the large temperature dependence of the 77Se chemical shifts of diaryl and dialkyl diselenides compared to monoselenides and selenols. Density functional theory calculations are provided to bolster hypotheses and better understand the effects of barrier height and dipole energies. It is proposed that the temperature dependence of diselenide 77Se NMR chemical shifts is due to rotation around the Se-Se bond and sampling of twisted conformers at higher temperatures. The molecular twisting is solvent dependent; here, DMSO-d6 and toluene-d8 were evaluated. No correlation was established between para-substituents on diaryl diselenides and the magnitude of the change in the 77Se NMR shift (Δδ) with temperature.
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The clinical success of [223Ra]RaCl2 (Xofigo®) for the palliative treatment of bone metastases in patients with prostate cancer has highlighted the therapeutic potential of α-particle emission. Expanding the applicability of radium-223 in Targeted Alpha Therapy of non-osseous tumors is followed up with significant interest, as it holds the potential to unveil novel treatment options in the comprehensive management of cancer. Moreover, the use of barium radionuclides, like barium-131 and -135m, is still unfamiliar in nuclear medicine applications, although they can be considered as radium-223 surrogates for imaging purposes. Enabling these applications requires the establishment of chelators able to form stable complexes with radium and barium radionuclides. Until now, only a limited number of ligands have been suggested and these molecules have been primarily inspired by existing structures known for their ability to complex large metal cations. However, a systematic inspection of chelators specifically tailored to Ra2+ and Ba2+ has yet to be conducted. This work delves into a comprehensive investigation of a series of small organic ligands, aiming to unveil the coordination preferences of both radium-223 and barium-131/135m. Electronic binding energies of both metal cations to each ligand were theoretically computed via Density Functional Theory calculations (COSMO-ZORA-PBE-D3/TZ2P), while thermodynamic stability constants were experimentally determined for Ba2+-ligand complexes by potentiometry, NMR and UV-Vis spectroscopies. The outcomes revealed malonate, 2-hydroxypyridine 1-oxide and picolinate as the most favorable building blocks to design multidentate chelators. These findings serve as foundation guidelines, propelling the development of cutting-edge radium-223- and barium-131/135m-based radiopharmaceuticals for Targeted Alpha Therapy and theranostics of cancer.
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Radio (Elemento) , Radio (Elemento)/química , Radio (Elemento)/uso terapéutico , Humanos , Radioisótopos/química , Complejos de Coordinación/química , Complejos de Coordinación/uso terapéutico , Bario/química , Partículas alfa/uso terapéutico , Quelantes/química , Quelantes/uso terapéutico , Neoplasias/tratamiento farmacológico , Nanomedicina Teranóstica/métodos , Metales Alcalinotérreos/química , Radiofármacos/química , Radiofármacos/uso terapéuticoRESUMEN
In continuation of our previous works on the cytotoxic properties of organopalladium compounds, in this contribution we describe the first systematic study of the anticancer activity of Pd(II)-aryl complexes. To this end, we have prepared and thoroughly characterized a wide range of palladium derivatives bearing different diphosphine, aryl and halide ligands, developing, when necessary, specific synthetic protocols. Most of the synthesized compounds showed remarkable cytotoxicity towards ovarian and breast cancer cell lines, with IC50 values often comparable to or lower than that of cisplatin. The most promising complexes ([PdI(Ph)(dppe)] and [PdI(p-CH3-Ph)(dppe)]), characterized by a diphosphine ligand with a low bite angle, exhibited, in addition to excellent cytotoxicity towards cancer cells, low activity on normal cells (MRC5 human lung fibroblasts). Specific immunofluorescence tests (cytochrome c and H2AX assays), performed to clarify the possible mechanism of action of this class of organopalladium derivatives, seemed to indicate DNA as the primary cellular target, whereas caspase 3/7 assays proved that the complex [PdI(Ph)(dppe)] was able to promote intrinsic apoptotic cell death. A detailed molecular docking analysis confirmed the importance of a diphosphine ligand with a reduced bite angle to ensure a strong DNA-complex interaction. Finally, one of the most promising complexes was tested towards patient-derived organoids, showing promising ex vivo cytotoxicity.
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Antineoplásicos , Complejos de Coordinación , Simulación del Acoplamiento Molecular , Paladio , Fosfinas , Humanos , Paladio/química , Paladio/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Fosfinas/química , Fosfinas/farmacología , Ligandos , Relación Estructura-Actividad , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Estructura MolecularRESUMEN
A series of macrocyclic ligands were considered for the chelation of Pb2+: 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO4S), 1,4,7-tris[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO3S), 1,4,7-tris[2-(methylsulfanyl)ethyl]-10-acetamido-1,4,7,10-tetraazacyclododecane (DO3SAm), 1,7-bis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,10-diacetic acid (DO2A2S), 1,5,9-tris[2-(methylsulfanyl)ethyl]-1,5,9-triazacyclododecane (TACD3S), 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetrazacyclotridecane (TRI4S), and 1,4,8,11-tetrakis[2-(methylsulfanyl)ethyl]-1,4,8,11-tetrazacyclotetradecane (TE4S). The equilibrium, the acid-mediated dissociation kinetics, and the structural properties of the Pb2+ complexes formed by these chelators were examined by UV-Visible and nuclear magnetic resonance (NMR) spectroscopies, combined with potentiometry and density functional theory (DFT) calculations. The obtained results indicated that DO4S, DO3S, DO3SAm, and DO2A2S were able to efficiently chelate Pb2+ and that the most suitable macrocyclic scaffold for Pb2+ is 1,4,7,10-tetrazacyclododecane. NMR spectroscopy gave insights into the solution structures of the Pb2+ complexes, and 1H-207Pb interactions confirmed the involvement of S and/or O donors in the metal coordination sphere. Highly fluxional solution behavior was discovered when Pb2+ was coordinated to symmetric ligands (i.e., DO4S and DO2A2S) while the introduction of structural asymmetry in DO3S and DO3SAm slowed down the intramolecular dynamics. The ligand ability to chelate [203Pb]Pb2+ under highly dilute reaction conditions was explored through radiolabeling experiments. While DO4S and DO3S possessed modest performance, DO3SAm and DO2A2S demonstrated high complexation efficiency under mild reaction conditions (pH = 7, 5 min reaction time). The [203Pb]Pb2+ complexes' integrity in human serum over 24 h was appreciably good for [203Pb][Pb(DO4S)]2+ (80 ± 5%) and excellent for [203Pb][Pb(DO3SAm)]2+ (93 ± 1%) and [203Pb][Pb(DO2A2S)] (94 ± 1%). These results reveal the promise of DO2A2S and DO3SAm as chelators in cutting-edge theranostic [203/212Pb]Pb2+ radiopharmaceuticals.
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Ciclamas , Plomo , Humanos , Medicina de Precisión , Quelantes/química , LigandosRESUMEN
Silver-111 is an attractive unconventional candidate for targeted cancer therapy as well as for single photon emission computed tomography and can be complemented by silver-103 for positron emission tomography noninvasive diagnostic procedures. However, the shortage of chelating agents capable of forming stable complexes tethered to tumor-seeking vectors has hindered their in vivo application so far. In this study, a comparative investigation of a series of sulfur-containing structural homologues, namely, 1,4,7-tris[2-(methylsulfanyl)ethyl)]-1,4,7-triazacyclononane (NO3S), 1,5,9-tris[2-(methylsulfanyl)ethyl]-1,5,9-triazacyclododecane (TACD3S), 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclotridecane (TRI4S), and 1,4,8,11-tetrakis[2-(methylsulfanyl)ethyl]-1,4,8,11-tetraazacyclotetradecane (TE4S) was conducted to appraise the influence of different polyazamacrocyclic backbones on Ag+ complexation. The performances of these macrocycles were also compared with those of the previously reported Ag+/[111Ag]Ag+-chelator 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO4S). Nuclear magnetic resonance data supported by density functional theory calculations and X-ray crystallographic results gave insights into the coordination environment of these complexes, suggesting that all of the donor atoms are generally involved in the metal coordination. However, the modifications of the macrocycle topology alter the dynamic binding of the pendant arms or the conformation of the ring around the metal center. Combined pH/pAg-potentiometric and spectroscopic experiments revealed that the 12-member N4 backbone of DO4S forms the most stable Ag+ complex while both the enlargement and the shrinkage of the macrocyclic frame dwindle the stability of the complexes. Radiolabeling experiments, conducted with reactor-produced [111Ag]Ag+, evidenced that the thermodynamic stability trend is reflected in the ligand's ability to incorporate the radioactive ion at high molar activity, even in the presence of a competing cation (Pd2+), as well as in the integrity of the corresponding complexes in human serum. As a consequence, DO4S proved to be the most favorable candidate for future in vivo applications.
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Quelantes , Plata , Humanos , Quelantes/química , Plata/química , Medicina de Precisión , Radioisótopos , Espectroscopía de Resonancia MagnéticaRESUMEN
PhSeZnCl, which is also known as Santi's reagent, can catalyze the reduction of hydrogen peroxide by thiols with a GPx-like mechanism. In this work, the first step of this catalytic cycle, i.e., the reduction of H2O2 by PhSeZnCl, is investigated in silico using state-of-the-art density functional theory calculations. Then, the role of the metal is evaluated by replacing Zn with its group 12 siblings (Cd and Hg). The thermodynamic and kinetic factors favoring Zn are elucidated. Furthermore, the role of the halogen is considered by replacing Cl with Br in all three metal compounds, and this turns out to be negligible. Finally, the overall GPx-like mechanism of PhSeZnCl and PhSeZnBr is discussed by evaluating the energetics of the mechanistic path leading to the disulfide product.
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We set up an in silico experiment and designed a chimeric compound integrating molecular features from different efficient ROS (Reactive Oxygen Species) scavengers, with the purpose of investigating potential relationships between molecular structure and antioxidant activity. Furthermore, a selenium centre was inserted due to its known capacity to reduce hydroperoxides, acting as a molecular mimic of glutathione peroxidase; finally, since this organoselenide is a precursor of a N-heterocyclic carbene ligand, its Au(I) carbene complex was designed and examined. A validated protocol based on DFT (Density Functional Theory) was employed to investigate the radical scavenging activity of available sites on the organoselenide precursor ((SMD)-M06-2X/6-311+G(d,p)//M06-2X/6-31G(d)), as well as on the organometallic complex ((SMD)-M06-2X/SDD (Au), 6-311+G(d,p)//ZORA-BLYP-D3(BJ)/TZ2P), considering HAT (Hydrogen Atom Transfer) and RAF (Radical Adduct Formation) regarding five different radicals. The results of this case study suggest that the antioxidant potential of chemical motifs should not be considered as an additive property when designing a chimeric compound, but rather that the relevance of a molecular topology is derived from a chemical motif combined with an opportune chemical space of the molecule. Thus, the direct contributions of single functional groups which are generally thought of as antioxidants per se do not guarantee the efficient radical scavenging potential of a molecular species.
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Antioxidantes , Selenio , Antioxidantes/farmacología , Antioxidantes/química , Selenio/química , Ligandos , Especies Reactivas de OxígenoRESUMEN
Sulfoxides and selenoxides oxidize thiols to disulfides while being reduced back to sulfides and selenides. While the reduction mechanism of sulfoxides to sulfides has been thoroughly explored experimentally as well as computationally, less attention has been devoted to the heavier selenoxides. In this work, we explore the reductive mechanism of dimethyl selenoxide, as an archetypal selenoxide and, for the sake of comparison, the reductive mechanism of dimethyl sulfoxide to gain insight into the role of the chalcogen on the reaction substrate. Particular attention is devoted to the key role of sulfurane and selenurane intermediates. Moreover, the capacity of these system to oxidize selenols rather than thiols, leading to the formation of selenyl sulfide bridges, is explored in silico. Notably, this analysis provides molecular insight into the role of selenocysteine in methionine sulfoxide reductase selenoenzyme. The activation strain model of chemical reactivity is employed in the studied reactions as an intuitive tool to bridge the computationally predicted effect of the chalcogen on the chalcogenoxide as well as on the chalcogenol.
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Calcógenos , Sulfóxidos , Sulfóxidos/química , Compuestos de Sulfhidrilo/química , Sulfuros , Oxidación-ReducciónRESUMEN
The SARS-CoV-2 pandemic has prompted global efforts to develop therapeutics. The main protease of SARS-CoV-2 (Mpro) and the papain-like protease (PLpro) are essential for viral replication and are key targets for therapeutic development. In this work, we investigate the mechanisms of SARS-CoV-2 inhibition by diphenyl diselenide (PhSe)2 which is an archetypal model of diselenides and a renowned potential therapeutic agent. The in vitro inhibitory concentration of (PhSe)2 against SARS-CoV-2 in Vero E6 cells falls in the low micromolar range. Molecular dynamics (MD) simulations and density functional theory (DFT) calculations [level of theory: SMD-B3LYP-D3(BJ)/6-311G(d,p), cc-pVTZ] are used to inspect non-covalent inhibition modes of both proteases via π-stacking and the mechanism of covalent (PhSe)2 + Mpro product formation involving the catalytic residue C145, respectively. The in vitro CC50 (24.61 µM) and EC50 (2.39 µM) data indicate that (PhSe)2 is a good inhibitor of the SARS-CoV-2 virus replication in a cell culture model. The in silico findings indicate potential mechanisms of proteases' inhibition by (PhSe)2; in particular, the results of the covalent inhibition here discussed for Mpro, whose thermodynamics is approximatively isoergonic, prompt further investigation in the design of antiviral organodiselenides.
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COVID-19 , SARS-CoV-2 , Humanos , Papaína , Péptido Hidrolasas , Cisteína Endopeptidasas/química , Proteínas no Estructurales Virales/química , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/química , Antivirales/farmacología , Antivirales/química , Simulación del Acoplamiento MolecularRESUMEN
The reactive oxygen species (ROS) scavenging capacities of ginkgolides and bilobalide, which are the peculiar constituents of the extract of Ginkgo biloba, are investigated in silico (level of theory: (SMD)-M06-2X/6-311+G(d,p)//M06-2X/6-31G(d)). Unlike other popular antioxidant natural substances, the carbon backbones of these compounds are entirely aliphatic and exclusively single C-C bonds are present. The selectivity for alkoxyl radicals via hydrogen-atom transfer (HAT) is assessed; importantly, the scavenging of peroxyl radicals is also possible from a peculiar site, here labeled C10 both for ginkgolides and bilobalide. The energetics are described in detail, and the analysis discloses that the studied compounds are powerful scavengers, with thermodynamic and kinetic properties similar to those of Trolox and melatonin, and that, in addition, they display selectivity for peroxyl radicals. These are all chemical-reactivity features contributing to the therapeutic action of the extract of G. biloba.
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Acid Sphingomyelinase (ASM) is a human phosphodiesterase that catalyzes the metabolism of sphingomyelin (SM) to ceramide and phosphocholine. ASM is involved in the plasma membrane cell repair and is associated with the lysosomal inner lipid membrane by nonbonding interactions. The disruption of those interaction would result in ASM release into the lysosomal lumen and consequent degradation of its structure. Furthermore, SARS-CoV-2 infection has been linked with ASM activation and with a ceramide domain formation in the outer leaflet of the plasma membrane that is thought to be crucial for the viral particles recognition by the host cells. In this study, we have explored in silico the behavior of fluoxetine and related drugs as potential inhibitors of ASM. Theoretically, these drugs would be able to overpass lysosomal membrane and reach the interactions that sustain ASM structure, breaking them and inhibiting the ASM. The analyses of docking data indicated that fluoxetine allocated mainly in the N-terminal saposin domain via nonbonding interactions, mostly of hydrophobic nature. Similar results were obtained for venlafaxine, citalopram, atomoxetine, nisoxetine and fluoxetine's main metabolite norfluoxetine. In conclusion, it was observed that the saposin allocation may be a good indicative of the drugs inhibition mechanism, once this domain is responsible for the binding of ASM to lysosomal membrane and some of those drugs have previously been reported to inhibit the phosphodiesterase by releasing its structure in the lysosomal lumen. Our MD data also provides some insight about natural ligand C18 sphingomyelin conformations on saposin.Communicated by Ramaswamy H. Sarma.
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COVID-19 , Esfingomielina Fosfodiesterasa , Humanos , Esfingomielina Fosfodiesterasa/metabolismo , Fluoxetina/farmacología , SARS-CoV-2/metabolismo , Esfingomielinas , Saposinas , Antidepresivos/farmacología , Ceramidas/metabolismoRESUMEN
The papain-like protease (PLpro) from SARS-CoV-2 is an important target for the development of antivirals against COVID-19. The safe drug disulfiram (DSF) presents antiviral activity inhibiting PLpro in vitro, and it is under clinical trial studies, indicating to be a promising anti-COVID-19 drug. In this work, we aimed to understand the mechanism of PLpro inhibition by DSF and verify if DSF metabolites and derivatives could be potential inhibitors too. Molecular docking, DFT, and ADMET techniques were applied. The carbamoylation of the active site cysteine residue by DSF metabolite (DETC-MeSO) is kinetically and thermodynamically favorable (ΔG = 3.15 and ΔG = - 12.10 kcal mol-1, respectively). Our results strongly suggest that the sulfoxide metabolites from DSF are promising covalent inhibitors of PLpro and should be tested in in vitro and in vivo assays to confirm their antiviral action.
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Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Antivirales/química , Antivirales/farmacología , Ensayos Clínicos como Asunto , Química Computacional , Cisteína , Disulfiram/metabolismo , Disulfiram/farmacología , Humanos , Simulación del Acoplamiento Molecular , Papaína , Péptido Hidrolasas , Inhibidores de Proteasas/química , SulfóxidosRESUMEN
The SARS-CoV-2 proteases Mpro and PLpro are important targets for the development of antivirals against COVID-19. The functional group 1,2,4-thiadiazole has been indicated to inhibit cysteinyl proteases, such as papain and cathepsins. Of note, the 1,2,4-thiadiazole moiety is found in a new class of cephalosporin FDA-approved antibiotics: ceftaroline fosamil, ceftobiprole, and ceftobiprole medocaril. Here we investigated the interaction of these new antibiotics and their main metabolites with the SARS-CoV-2 proteases by molecular docking, molecular dynamics (MD), and density functional theory (DFT) calculations. Our results indicated the PLpro enzyme as a better in silico target for the new antibacterial cephalosporins. The results with ceftaroline fosamil and the dephosphorylate metabolite compounds should be tested as potential inhibitor of PLpro, Mpro, and SARS-CoV-2 replication in vitro. In addition, the data here reported can help in the design of new potential drugs against COVID-19 by exploiting the S atom reactivity in the 1,2,4-thiadiazole moiety. Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-022-02036-5.
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The selenoxide elimination is a well-known reaction in organochalcogen chemistry, with wide synthetic, biological, and toxicological implications. In this work, we apply benchmarked density functional theory (DFT) calculations to investigate different aspects of the title reaction in three (bio)chemically relevant models, spanning minimal systems of theoretical interests as well as biological or synthetic organochalcogenides. The activation strain analysis (ASA) methodology is employed along a suitable reaction coordinate to obtain insight into the role of the chalcogen and of the oxidation state, to pinpoint the factors that tune the elimination reactivity of the investigated systems. Lastly, we computationally validate the hypothesis that telluroxides eliminate more slowly than selenoxides because of a detrimental hydration process that leads to unreactive hydrates.
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Oxidación-ReducciónRESUMEN
Health is a fundamental human right and is a global goal to which extensive research effort is devoted in all fields [...].