Remodelling of the natural product fumagillol employing a reaction discovery approach

In the search for new biologically active molecules, diversity-oriented synthetic strategies break through the limitation of traditional library synthesis by sampling new chemical space. Many natural products can be regarded as intriguing starting points for diversity-oriented synthesis, wherein stereochemically rich core structures may be reorganized into chemotypes that are distinctly different from the parent structure. Ideally, to be suited to library applications, such transformations should be general and involve few steps. With this objective in mind, the highly oxygenated natural product fumagillol has been successfully remodelled in several ways using a reaction-discovery-based approach. In reactions with amines, excellent regiocontrol in a bis-epoxide opening/cyclization sequence can be obtained by size-dependent interaction of an appropriate catalyst with the parent molecule, forming either perhydroisoindole or perhydroisoquinoline products. Perhydroisoindoles can be further remodelled by cascade processes to afford either morpholinone or bridged 4,1-benzoxazepine-containing structures.P50 GM067041 - NIGMS NIH HHS; P50 GM067041-07 - NIGMS NIH HHS; P50 GM067041-08 - NIGMS NIH HHS; P50 GM067041-09 - NIGMS NIH HH

Ionization potentials in the limit of large atomic number

By extrapolating the energies of non-relativistic atoms and their ions with up to 3000 electrons within Kohn-Sham density functional theory, we find that the ionization potential remains finite and increases across a row, even as $Z\rightarrow\infty$. The local density approximation becomes chemically accurate (and possibly exact) in some cases. Extended Thomas-Fermi theory matches the shell-average of both the ionization potential and density change. Exact results are given in the limit of weak electron-electron repulsion.Comment: 4 pages, 5 figure

The Role of Alpha-Band Brain Oscillations as a Sensory Suppression Mechanism during Selective Attention

Evidence has amassed from both animal intracranial recordings and human electrophysiology that neural oscillatory mechanisms play a critical role in a number of cognitive functions such as learning, memory, feature binding and sensory gating. The wide availability of high-density electrical and magnetic recordings (64–256 channels) over the past two decades has allowed for renewed efforts in the characterization and localization of these rhythms. A variety of cognitive effects that are associated with specific brain oscillations have been reported, which range in spectral, temporal, and spatial characteristics depending on the context. Our laboratory has focused on investigating the role of alpha-band oscillatory activity (8–14 Hz) as a potential attentional suppression mechanism, and this particular oscillatory attention mechanism will be the focus of the current review. We discuss findings in the context of intersensory selective attention as well as intrasensory spatial and feature-based attention in the visual, auditory, and tactile domains. The weight of evidence suggests that alpha-band oscillations can be actively invoked within cortical regions across multiple sensory systems, particularly when these regions are involved in processing irrelevant or distracting information. That is, a central role for alpha seems to be as an attentional suppression mechanism when objects or features need to be specifically ignored or selected against

Orbital-free Bond Breaking via Machine Learning

Machine learning is used to approximate the kinetic energy of one dimensional diatomics as a functional of the electron density. The functional can accurately dissociate a diatomic, and can be systematically improved with training. Highly accurate self-consistent densities and molecular forces are found, indicating the possibility for ab-initio molecular dynamics simulations

Gallium(III)-Promoted Halocyclizations of 1,6-Diynes

Adrian Landreth was an REU student, summer 2014Cyclization of 1,6-diynes promoted by stoichiometric Ga(III) halides produces vinyl halides in good to excellent yields. Under acidic conditions, initially formed iodocyclization products undergo in situ Friedel-Crafts cyclizations, giving access to iodo-indenopyridines. The application of the vinyl halides in cross-coupling reactions has been explored, and mechanistic aspects of the cyclization are discussed.HIGMS CMLD Initiative (P50 GM067041) NSF REU - Adrian Landreth support (CHE 1156666) NSF - NMR purchase (CHE 0619339) NSF - HRMS purchase (CHE0443618

Genome-wide profiling of human cap-independent translation-enhancing elements.

We report an in vitro selection strategy to identify RNA sequences that mediate cap-independent initiation of translation. This method entails mRNA display of trillions of genomic fragments, selection for initiation of translation and high-throughput deep sequencing. We identified >12,000 translation-enhancing elements (TEEs) in the human genome, generated a high-resolution map of human TEE-bearing regions (TBRs), and validated the function of a subset of sequences in vitro and in cultured cells