Fluorescence switching of imidazo[1,5-a]pyridinium ions: pH-sensors with dual emission pathways

Imidazo[1,5-a]pyridinium ions are identified as highly emissive and water-soluble fluorophores accessed by an efficient three-component coupling reaction. Synthetic modifications of groups conjugated to the polyheterocyclic core are shown to profoundly impact the emission properties of these molecules. Notably, two structural isomers of functionalized imidazo[1,5-a]pyridinium ions were found to exhibit distinct de-excitation pathways, which are responsible for either a fluorescence turn-on or ratiometric response to pH change.     

HDXFinder: automated analysis and data reporting of deuterium/hydrogen exchange mass spectrometry

Hydrogen/deuterium exchange in combination with mass spectrometry (H/D MS) is a sensitive technique for detection of changes in protein conformation and dynamics. However, wide application of H/D MS has been hindered, in part, by the lack of computational tools necessary for efficient analysis of the large data sets associated with this technique. We report a novel web-based application for automatic analysis of H/D MS experimental data. This application relies on the high resolution of mass spectrometers to extract all isotopic envelopes before correlating these envelopes with individual peptides. Although a fully automatic analysis is possible, a variety of graphical tools are included to aid in the verification of correlations and rankings of the isotopic peptide envelopes. As a demonstration, the rate constants for H/D exchange of peptides from rabbit muscle pyruvate kinase are mapped onto the structure of this protein.     

Left–right and dynamic correlation

Within density functional theory, it is natural to separate the correlation energy into two parts: left–right correlation and dynamic correlation. Left–right correlation arises from the exchange part of functionals, and dynamic correlation arises from the correlation part of functionals. We examine the nature of these correlation energies as molecules are distorted. We observe that such a natural separation is not possible using the methods of quantum chemistry. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002     

Characterization of a new tailoring domain in polyketide biogenesis: the amine transferase domain of MycA in the mycosubtilin gene cluster

We report the expression and characterization of a truncated form of MycA from the Mycosubtilin gene cluster from Bacillus subtilis. The MycA fragment contains a new amino transferase (AMT) tailoring domain, allowing the first detailed study of a PLP-dependent enzyme operating in cis within the PKS and NRPS biosynthetic paradigm. As the AMT domain acts on covalently bound beta-ketothioesters, and is therefore a single-turnover system, electrospray ionization-Fourier transform mass spectrometry (ESI-FTMS) was used to observe the amine-transfer reaction both for amine donor substrate specificity and to regiospecifically determine enzyme-bound intermediates. We confirm the function of the AMT domain, dissect the mechanistic steps of amine transfer, identify the preferred amine source, and localize the beta-ketothioester substrate during amine transfer.     

Compact holomorphic mappings on Banach spaces and the approximation property

Let $\text{H}$(E) be the space of complex valued holomorphic functions on a complex Banach space E. The approximation property for $\text{H}$(E), endowed with various natural locally convex topologies, is studied. For example, $\text{H}$(E) with the compact-open topology has the approximation property if and only if E has the approximation property. In order to characterize when $\text{H}$(E) has the approximation property for topologies other than the compact-open, the notion of a compact holomorphic map between Banach spaces in introduced and studied.     

Criteria for the absence of quantum fluctuations after spontaneous symmetry breaking

The lowest-energy state of a macroscopic system in which symmetry is spontaneously broken, is a very stable wavepacket centered around a spontaneously chosen, classical direction in symmetry space. However, for a Heisenberg ferromagnet the quantum groundstate is exactly the classical groundstate, there are no quantum fluctuations. This coincides with seven exceptional properties of the ferromagnet, including spontaneous time-reversal symmetry breaking, a reduced number of Nambu–Goldstone modes and the absence of a thin spectrum (Anderson tower of states). Recent discoveries of other non-relativistic systems with fewer Nambu–Goldstone modes suggest these specialties apply there as well. I establish precise criteria for the absence of quantum fluctuations and all the other features. In particular, it is not sufficient that the order parameter operator commutes with the Hamiltonian. It leads to a measurably larger coherence time of superpositions in small but macroscopic systems.     

Graphene growth on h-BN by molecular beam epitaxy

The growth of single layer graphene nanometer size domains by solid carbon source molecular beam epitaxy on hexagonal boron nitride (h-BN) flakes is demonstrated. Formation of single-layer graphene is clearly apparent in Raman spectra which display sharp optical phonon bands. Atomic-force microscope images and Raman maps reveal that the graphene grown depends on the surface morphology of the h-BN substrates. The growth is governed by the high mobility of the carbon atoms on the h-BN surface, in a manner that is consistent with van der Waals epitaxy. The successful growth of graphene layers depends on the substrate temperature, but is independent of the incident flux of carbon atoms.     

Novel structural templates for estrogen-receptor ligands and prospects for combinatorial synthesis of estrogens

BACKGROUND: The development of estrogen pharmaceutical agents with appropriate tissue-selectivity profiles has not yet benefited substantially from the application of combinatorial synthetic approaches to the preparation of structural classes that are known to be ligands for the estrogen receptor (ER). We have developed an estrogen pharmacophore that consists of a simple heterocyclic core scaffold, amenable to construction by combinatorial methods, onto which are appended 3-4 peripheral substituents that embody substructural motifs commonly found in nonsteroidal estrogens. The issue addressed here is whether these heterocyclic core structures can be used to prepare ligands with good affinity for the ER. RESULTS: We prepared representative members of various azole core structures. Although members of the imidazole, thiazole or isoxazole classes generally have weak binding for the ER, several members of the pyrazole class show good binding affinity. The high-affinity pyrazoles bear close conformational relationship to the nonsteroidal ligand raloxifene, and they can be fitted into the ligand-binding pocket of the ER-raloxifene X-ray structure. CONCLUSIONS: Compounds such as these pyrazoles, which are novel ER ligands, are well suited for combinatorial synthesis using solid-phase methods.