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Teaching statistics and chemometrics using an open source, free and graphical user interface software.
No full textThis report aims to introduce the fundamental features of the JAMOVI software to academics in the chemistry field for use in undergraduate and graduate-level research. It is freeware with a graphical user interface (GUI) and it is written in the R language. The discussion began on descriptive statistics ( mean, median, range, skewness how to check data normality using hypothesis tests (Shapiro-Wilk, Kolmogorov-Smirnov and Anderson-Darling tests). Then, some visual tools for checking data normality were presented (histograms, Q-Q plots, and boxplots). When the data normality was checked, two and more dependent means were compared using parametric tests (t test and ANOVA; Fisher’s). When the data was not normally distributed, nonparametric tests were used (Mann-Whitney and Kruskal-Wallis tests). When the data was paired and normally distributed, two and more than two group means were compared using the paired t-test and RMANOVA, respectively. Their nonparametric versions were also used (Wilcoxon and Friedman tests). Means comparisons were also carried out using boxplots and discriminant plots, which provide a visual interpretation beyond the p-values interpretation. In addition, principal component analysis (PCA) was carried out using JAMOVI\u27s plugin MEDA, which builds scores and loading plots. All tests and plots were done easily using JAMOVI\u27s click-and-go interface
Generation of Protocells by Spontaneous Reaction of Cysteine with Short Chain Thioesters
No full textIt is unknown how the earliest forms of life were compartmentalized. Several models have suggested a role for single-chain lipids such as fatty acids, but the membranes formed are often unstable, particularly when made from shorter alkyl chains (≤C8) that were likely more prevalent on the prebiotic Earth. We show that the amino acid cysteine can spontaneously react with two short-chain (C8) thioesters to form diacyl lipids, generating protocell-like membrane vesicles. The three-component reaction takes place rapidly in water using low concentrations of reactants. Silica can catalyze the formation of protocells through a simple electrostatic mechanism. Several simple aminothiols react to form diacyl lipids, including short peptides. The protocells formed are compatible with functional ribozymes, suggesting that coupling of multiple short-chain precursors may have provided membrane building blocks during the early evolution of cells
Shuttle HAT for mild alkene transfer hydrofunctionalization
No full textHydrogen atom transfer (HAT) from a metal-hydride is a reliable and powerful method for functionalizing unsaturated C–C bonds in organic synthesis. Cobalt hydrides (Co–H) have garnered significant attention in this field, where the weak Co–H bonds are most commonly generated in a catalytic fashion through a mixture of stoichiometric amounts of peroxide oxidant and silane reductant. Here we show that the reverse process of HAT to an alkene, i.e. hydrogen atom abstraction of a C–H adjacent to a radical, can be leveraged to generate catalytically active Co–H species in a new application of shuttle catalysis coined shuttle HAT. This method obviates the need for stoichiometric reductant/oxidant mixtures thereby greatly simplifying the generation of Co–H under exceedingly mild reaction conditions. This approach opens the door for the introduction of functional handles (e.g., iodides) that were previously inaccessible through other catalytic approaches, and paves the way for new reagent design which incorporates this shuttle HAT platform. To demonstrate the generality of this shuttle HAT platform, five different reaction manifolds are shown, including the late-stage C(sp3) iodination of structurally diverse FDA approved drugs
A Fast and Efficient MN-Approach for Reactivity of Natural Product Exploration in Plant Extract: Application to Diterpene Esters from Euphorbia dendroides
No full textNatural products represent a rich source of bioactive compounds covering a large chemical space. Even if challenging, this diversity can be extended by applying chemical modifications. However, these studies require generally multigram amounts of isolated natural products and face frequent testing failures. To overcome this limitation, we propose a rapid and efficient approach that uses molecular networking (MN) to visualize new chemical diversity generated by simple chemical modifications of natural extract. Moreover, the strategy deployed enables the most appropriate reagents to be defined quickly upstream a reaction on a pure compound, in order to maximize chemical diversity. This methodology was applied to the latex extract of Euphorbia dendroides to follow the reactivity towards a series of acids and Lewis acids of three class of diterpene esters identified in this species: jatrophane, terracinolide, and phorbol. Through the molecular networking interpretation, in aim to illustrate our approach, two Lewis acids were selected for chemical modification on previously isolated jatrophane esters. Three rearranged compounds (3−5) were obtained when exposed to BF3.OEt2, showing that the most appropriate reagents can be selected by MN interpretation
The Enantioselective Organocatalytic [1,2]-Rearrangement of Allylic Ammonium Ylides
No full textThe [1,2]-rearrangement of allylic ammonium ylides is traditionally observed as a competitive minor pathway alongside the thermally allowed [2,3]-sigmatropic rearrangement. The challenges associated with developing a catalytic enantioselective variant are amplified as concerted [1,2]-rearrangements are forbidden, with these processes proposed to proceed through homolytic C-N bond fission of the ylide, followed by stereoselective radical-radical recombination. Herein a Lewis basic chiral isothiourea facilitates catalytic [1,2]-rearrangement of prochiral aryl ester ammonium salts to generate unnatural α-amino acid derivatives with unprecedented levels of enantiocontrol (up to 97:3 er) and up to total selectivity over the thermally allowed [2,3]-rearrangement. Key factors in favouring the [1,2]-rearrangement include exploitation of (i) disubstituted terminal allylic substituents, (ii) cyclic N-substituted ammonium salts and (iii) elevated reaction temperatures. Mechanistic studies involving 13C-labelling and crossover reactions, combined with radical trapping experiments and observed changes in product enantioselectivity are consistent with a radical solvent cage effect, with maximum product enantioselectivity observed with promotion of “in-cage” radical-radical recombination. Computational analysis indicates that the distribution between [1,2]- and [2,3]-rearrangement products arises predominantly from C-N bond homolysis of an intermediate ammonium ylide, followed by recombination of the a-amino radical at either the primary or tertiary site of an intermediate allylic radical. Electrostatic interactions involving the bromide counterion and the rearrangement transition states control the facial selectivity of the [1,2]- and [2,3]-rearrangements, while the difficulty of forming a bond in the more sterically hindered tertiary position of the allylic substituent disfavors the formation of the [2,3]-product. These results will impact further investigations and understanding into enantioselective radical-radical reactions
Insights into the Main Protease of SARS-CoV-2: Thermodynamic Analysis, Structural Characterization, and the Impact of Inhibitors
No full textThe main protease of SARS-CoV-2 (Mpro) is an essential enzyme for coronaviral maturation and is the target of Paxlovid, which is currently the standard-of-care treatment for COVID-19. There remains a need to identify new inhibitors of Mpro as viral resistance to Paxlovid emerges. Here, we report the use of native mass spectrometry coupled with 193-nm ultraviolet photodissociation (UVPD) to structurally characterize Mpro and its interactions with potential covalent inhibitors. Melting temperatures and the overall energy landscape were obtained using variable temperature nano-electrospray ionization (vT-nESI), thus providing quantitative evaluation of inhibitor binding on the stability of Mpro. The melting temperature was determined to be approximately 30°C for the dimer and 36°C for the monomer, suggesting an initial thermal dissociation pathway before subsequent unfolding of the monomer species. Thermodynamic parameters extracted from Van’t Hoff plots revealed that the dimeric complexes containing each inhibitor showed enhanced stability through increased melting temperatures as well as overall lower average charge states, giving insight into the basis for potential inhibition mechanisms
Can we achieve atmospheric chemical environments in the laboratory? An integrated model-measurement approach to chamber SOA studies
No full textSecondary organic aerosol (SOA), atmospheric particulate matter formed from low-volatility products of volatile organic compound (VOC) oxidation, impacts both air quality and climate. Current 3D models, however, cannot reproduce the observed variability in atmospheric organic aerosol. Because many SOA model descriptions are derived from environmental chamber experiments, our ability to represent atmospheric conditions in chambers directly impacts our ability to assess the air quality and climate impacts of SOA. Here, we develop a new approach that leverages global modeling and detailed mechanisms to design chamber experiments that mimic the atmospheric chemistry of organic peroxy radicals (RO2), a key intermediate in VOC oxidation. Drawing on decades of laboratory experiments, we develop a framework for quantitatively describing RO2 chemistry and show that no previous experimental approaches to studying SOA formation have accessed the relevant atmospheric RO2 fate distribution. We show proof-of-concept experiments that demonstrate how SOA experiments can access a range of atmospheric chemical environments and propose several directions for future studies
BIOMX-DB: A web application for the BIOFACQUIM natural product database
No full textNatural product databases (NPDBs) are an integral part of chemoinformatics and computer-aided drug design. Despite their pivotal role, a distinct scarcity of projects in Latin America, particularly in Mexico, provides accessible tools of this nature. Herein, we introduce BIOMX-DB, an open and freely accessible web-based database designed to address this gap. BIOMX-DB enhances the features of the existing Mexican natural product database, BIOFACQUIM, by incorporating advanced search, filtering, and download capabilities. The user-friendly interface of BIOMX-DB aims to provide an intuitive experience for researchers. For seamless access, BIOMX-DB is freely available at www.biomx-db.co
Divergent Total Syntheses of Pyrroloiminoquinone Alkaloids Ena-bled by the Development of a Larock/Buchwald–Hartwig Annula-tion/Cyclization
No full textABSTRACT: Pyrroloiminoquinone alkaloids are a large class of natural products that display a wide range of biologi-cal activities. Synthetic approaches to these natural products typically rely on a common late-stage C10-oxygenated pyrroloiminoquinone intermediate, but these strategies often lead to lengthy synthetic sequences that are not ame-nable to divergent syntheses. We devised an alternative approach aimed at the early introduction of the C10 nitro-gen, which we hypothesized would enable late-stage diversification. This strategy hinged upon a Larock/Buchwald–Hartwig annulation/cyclization to quickly access the core of these alkaloids. We report the development of this cas-cade process, which was facilitated by a dual ligand system in addition to selective functionalization of the key inter-mediate, to provide the shortest total syntheses to date of makaluvamines A, C, and D and isobatzelline B, and the first total synthesis of makaluvamine N
Enantio- and Z-Selective d-Hydroarylation of Aryldienes via Rh-Catalyzed Conjugate Addition
No full textMetal-catalyzed enantioselective conjugate arylations of electron-poor alkenes are highly selective processes for C(sp2)–C(sp3) bond formation. d-Selective hydroarylations of electron-poor dienes are less well developed and reactions that deliver high enantioselectivity while giving single alkene isomer products are elusive. Here we report the Rh-catalyzed d-arylation of aryldienes that gives nearly exclusive Z-1,4-addition products (generally with >95:5 positional and geometrical selectivity). This remote functionalization provides access to chiral diarylated butenes from readily available precursors poised for further functionalization, including in the synthesis of bioactive molecules. Mechanistic studies suggest that protonolysis of a Rh-allyl intermediate generated by diene insertion into a Rh-aryl is the rate determining step and occurs by an inner-sphere proton transfer pathway