Henry B. Wedler

Mechanistic studies of copper(I)-catalyzed 1,3-halogen migration.

An ongoing challenge in modern catalysis is to identify and understand new modes of reactivity promoted by earth-abundant and inexpensive first-row transition metals. Herein, we report a mechanistic study of an unusual copper(I)-catalyzed 1,3-migration of 2-bromostyrenes that reincorporates the bromine activating group into the final product with concomitant borylation of the aryl halide bond. A combination of experimental and computational studies indicated this reaction does not involve any oxidation state changes at copper; rather, migration occurs through a series of formal sigmatropic shifts. Insight provided from these studies will be used to expand the utility of aryl copper species in synthesis and develop new ligands for enantioselective copper-catalyzed halogenation.

Carbocations and the Complex Flavor and Bouquet of Wine: Mechanistic Aspects of Terpene Biosynthesis in Wine Grapes

Computational chemistry approaches for studying the formation of terpenes/terpenoids in wines are presented, using five particular terpenes/terpenoids (1,8-cineole, α-ylangene, botrydial, rotundone, and the wine lactone), volatile compounds (or their precursors) found in wine and/or wine grapes, as representative examples. Through these examples, we show how modern computational quantum chemistry can be employed as an effective tool for assessing the validity of proposed mechanisms for terpene/terpenoid formation.

Visually impaired researchers get their hands on quantum chemistry: application to a computational study on the isomerization of a sterol

In molecular sciences, articles tend to revolve around 2D representations of 3D molecules, and sighted scientists often resort to 3D virtual reality software to study these molecules in detail. Blind and visually impaired (BVI) molecular scientists have access to a series of audio devices that can help them read the text in articles and work with computers. Reading articles published in this journal, though, is nearly impossible for them because they need to generate mental 3D images of molecules, but the article-reading software cannot do that for them. We have previously designed AsteriX, a web server that fully automatically decomposes articles, detects 2D plots of low molecular weight molecules, removes meta data and annotations from these plots, and converts them into 3D atomic coordinates. AsteriX–BVI goes one step further and converts the 3D representation into a 3D printable, haptic-enhanced format that includes Braille annotations. These Braille-annotated physical 3D models allow BVI scientists to generate a complete mental model of the molecule. AsteriX–BVI uses Molden to convert the meta data of quantum chemistry experiments into BVI friendly formats so that the entire line of scientific information that sighted people take for granted—from published articles, via printed results of computational chemistry experiments, to 3D models—is now available to BVI scientists too. The possibilities offered by AsteriX–BVI are illustrated by a project on the isomerization of a sterol, executed by the blind co-author of this article (HBW).

Quantum chemical study of the isomerization of 24-methylenecycloartanol, a potential marker of olive oil refining

AbstractQuantum chemical calculations on the isomerization of 24-methylenecycloartanol are described. An energetically viable mechanism, with a rate-determining protonation step, is proposed. This rearrangement may find applicability in tests for determining if an olive oil has been refined. Graphical AbstractThe results of density functional calculations on the mechanism of a rearrangement of a sterol proposed to occur during olive oil heating are described. These results indicate that this rearrangement can indeed occur at a fast rate under refining conditions, but will not occur at an appreciable rate under conditions for producing extra virgin olive oil.

Oxidopyrylium-Alkene [5 + 2] Cycloaddition Conjugate Addition Cascade (C3) Sequences: Scope, Limitation, and Computational Investigations

Oxidopyrylium-alkene [5 + 2] cycloaddition conjugate addition cascade (C3) sequences are described. Intramolecular cycloadditions involving terminal alkenes, enals, and enones were investigated. Substrates with tethers of varying lengths delivered five- and six-membered carbocycles and heterocycles thus demonstrating the scope and limitation of the cycloaddition-conjugate addition cascade. Several experiments and theoretical calculations provide evidence for the proposed mechanistic pathway.

Blind and Visually Impaired Students Can Perform Computer-Aided Molecular Design with an Assistive Molecular Fabricator

Life science in general and chemistry in particular are inaccessible to blind and visually impaired (BVI) students at the exception of very few individ-uals who have overcome, in a seemingly miraculous way, the hurdles that pave the way to higher education and professional competency. AsteriX-BVI a publicly accessible web server, developed at the Radboud University in the Netherlands already allows BVI scientists to perform a complete series of tasks to automatically manage results of quantum chemical calculations and produce a 3D representation of the optimized structures into a 3D printable, haptic-enhanced format that includes Braille annotations.1

Predicting hydration propensities of biologically relevant α-ketoamides.

Quantum chemical calculations coupled to experiments were used to predict covalent hydration propensities of biologically relevant α-ketoamides. Experimentally determined hydration equilibrium constants for related ketones and aldehydes were compared to computationally determined values to develop a method for predicting hydration equilibrium constants. This method was used on six newly synthesized α-ketoamides to experimentally verify computational predictions. A correlation between calculation and experiment was observed and applied to models of several pertinent APIs. Our results indicate that the keto form is favored for practically all α-ketoamides in biological environs.