Tertiary Alcohols as Radical Precursors for the Introduction of Tertiary Substituents into Heteroarenes

Despite many recent advances in the radical alkylation of electron-deficient heteroarenes since the seminal reports by Minisci and co-workers, methods for the direct incorporation of tertiary alkyl substituents into nitrogen heteroarenes are limited. This report describes the use of tert-alkyl oxalate salts, derived from tertiary alcohols, to introduce tertiary substituents into a variety of heterocyclic substrates. This reaction has reasonably broad scope, proceeds rapidly under mild conditions, and is initiated by either photochemical or thermal activation. Insights into the underlying mechanism of the higher yielding visible-light initiated process were obtained by flash photolysis studies, whereas computational studies provided insight into the reaction scope

Intermolecular oxidative dehydrogenative 3,3 '-coupling of benzo[b]furans and benzo[b]thiophenes promoted by DDQ/H+ : total synthesis of shandougenine B

With an excess of a strong acid, 2,3-dichloro-5,6-dicyano-1,4-quinone (DDQ) is shown to promote metal-free intermolecular oxidative dehydrogenative (ODH) 3,3'-coupling of 2-aryl-benzo[b]furans and 2-aryl-benzo[b]thiophenes up to 92% yield as demonstrated with 9 substrates. Based on the analysis of oxidation potentials and molecular orbitals combined with EPR, NMR and UV-Vis observations, the studied reaction is initiated by a DDQ-substrate charge transfer complex and presumably proceeds via oxidation of the substrate into an electrophilic radical cation that further reacts with another molecule of a neutral substrate. The coupling reactivity can easily be predicted from the oxidation potential of the substrate and the morphology of its frontier molecular orbitals. The intermolecular ODH coupling reaction allowed a concise total synthesis of the natural product shandougenine B.Peer reviewe

Effects of abstinence on brain morphology in alcoholism: A MRI study

Chronic alcohol abuse leads to morphological changes of the brain. We investigated if these volumetric changes are reversible after a period of abstinence. For this reason 41 male and 15 female alcohol patients underwent MRI-scanning after in-patient detoxification (baseline) entering alcoholism treatment programs, and between 6 and 9 months later (follow-up), in a phase of convalescence. Additionally, 29 male and 16 female control subjects were examined. The MRI-scans were delineated and the resulting regions of interest, volumes of lateral ventricles and prefrontal lobes were expressed relatively to total brain volume. Compared to control subjects alcohol patients showed bilaterally decreased prefrontal lobes (11% reduction) and increased lateral ventricles (up to 42% enlargement). The extent of the ventricular increase was depending on patient’s additional psychiatric diagnosis, showing smaller lateral ventricles in patients with additional personality disorder. While at follow-up the size of prefrontal lobes remained unchanged, volumes of the lateral ventricles decreased (5–6% reduction) in alcohol patients with abstinence and improved drinking behavior, especially in patients that underwent only one detoxification. The extent of the ventricular enlargement correlated with the elevation of alcohol related laboratory measures (mean corpuscular volume, gamma-glutamyl transpeptidase). In conclusion this study confirms the hypothesis that alcoholism causes brain damages that are partially reversible. It should be analyzed in further studies with larger sample sizes, if complete brain regeneration is possible maintaining abstinence over a longer period

Tertiary Alcohols as Radical Precursors for the Introduction of Tertiary Substituents into Heteroarenes

Despite many recent advances in the radical alkylation of electron-deficient heteroarenes since the seminal reports by Minisci and co-workers, methods for the direct incorporation of tertiary alkyl substituents into nitrogen heteroarenes are limited. This report describes the use of tert-alkyl oxalate salts, derived from tertiary alcohols, to introduce tertiary substituents into a variety of heterocyclic substrates. This reaction has reasonably broad scope, proceeds rapidly under mild conditions, and is initiated by either photochemical or thermal activation. Insights into the underlying mechanism of the higher yielding visible-light initiated process were obtained by flash photolysis studies, whereas computational studies provided insight into the reaction scope

Mechanism of photocatalytic water oxidation on small TiO2 nanoparticles

We present the first unconstrained nonadiabatic molecular dynamics (NAMD) simulations of photocatalytic water oxidation by small hydrated TiO2 nanoparticles using Tully surface hopping and time-dependent density functional theory. The results indicate that ultrafast electron–proton transfer from physisorbed water to the photohole initiates the photo-oxidation on the S1 potential energy surface. The new mechanism readily explains the observation of mobile hydroxyl radicals in recent experiments. Two key driving forces for the photo-oxidation reaction are identified: localization of the electron–hole pair and stabilization of the photohole by hydrogen bonding interaction. Our findings illustrate the scope of recent advances in NAMD methods and emphasize the importance of explicit simulation of electronic excitations

Mechanism of photocatalytic water oxidation on small TiO2 nanoparticles.

We present the first unconstrained nonadiabatic molecular dynamics (NAMD) simulations of photocatalytic water oxidation by small hydrated TiO2 nanoparticles using Tully surface hopping and time-dependent density functional theory. The results indicate that ultrafast electron-proton transfer from physisorbed water to the photohole initiates the photo-oxidation on the S1 potential energy surface. The new mechanism readily explains the observation of mobile hydroxyl radicals in recent experiments. Two key driving forces for the photo-oxidation reaction are identified: localization of the electron-hole pair and stabilization of the photohole by hydrogen bonding interaction. Our findings illustrate the scope of recent advances in NAMD methods and emphasize the importance of explicit simulation of electronic excitations

Light-activated chemical probing of nucleobase solvent accessibility inside cells.

This corrects the article DOI: 10.1038/nchembio.2548