Boronic acid-based bipyridinium salts as tunable receptors for monosaccharides and alpha-hydroxycarboxylates

Several novel diboronic acid-substituted bipyridinium salts were prepared and, using a fluorescent reporter dye, were tested for their ability to selectively bind various monosaccharides and alpha-hydroxycarboxylates in an aqueous medium. The fluorescence sensing mechanism relies on the formation of a ground-state charge-transfer complex between the dye and bipyridinium. An X-ray crystal structure of this complex is described herein. Glucose selectivity over fructose and galactose was achieved by designing the bipyridinium-based receptors to be capable of attaining a 1:1 receptor/substrate stoichiometry via cooperative diboronic acid binding.     

Evaluation of parameters critical to observing proteins inside living Escherichia coli by in-cell NMR spectroscopy

Our recently developed in-cell NMR procedure now enables one to observe protein conformations inside living cells. Optimization of the technique demonstrates that distinguishing the signals produced by a single protein species depends critically on protein overexpression levels and the correlation time in the cytoplasm. Less relevant is the selective incorporation of (15)N. Poorly expressed proteins, insoluble proteins, and proteins that cannot tumble freely due to associations within the cell cannot yet be observed. We show in-cell NMR spectra of bacterial NmerA and human calmodulin and discuss limitations of the technique as well as prospects for future applications.     

Calculation of Siegert eigenvalues for molecular systems: results for He(21,3S)+ H

The variational calculation of Siegert eigenvalues has previously been shown to provide reliable positions and widths for atomic resonances. This approach is herein extended to molecular problems, and the first such calculations for a molecular autoionizing system, He(2^1,3S)+H→ He+H⁺+e^?, are reported.     

Luminescence characteristics of several classes of drugs affecting the central nervous system

The excitation, fluorescence and phosphorescence characteristics of 29 compounds of psychopharmacological interest have been studied in ethanol at 77 k. Phosphorescence lifetimes are reported and the low-temperature luminescence spectra discussed. Luminescence characteristics of several important 1,4-benzodiazepines in acidic, basic and neutral solution are reported.     

Effects of molecular structure and environment on the photodimerization of substituted anthracenes

Photochemical and photophysical studies of a number of 9-substituted anthracene sandwich pairs in their corresponding photodimer crystal matrices have been carried out. Corresponding studies have also been made in methylcyclohexane matrices at 6 K. Photodimerization of the 9-methyl, 9-chloro and 9-cyano derivatives in the photodimer matrices occurs at 6 K with unit quantum yield. The presence of excimer fluorescence from sandwich pairs indicates the lack of a perfect topochemical orientation while activation processes, leading to photodimerization, involve molecular re-orientation from more stable ground state configurations which are achieved within the constraints imposed by the solvent or crystalline cage.     

Path-integral virial estimator for reaction-rate calculation based on the quantum instanton approximation

The quantum instanton approximation is a type of quantum transition-state theory that calculates the chemical reaction rate using the reactive flux correlation function and its low-order derivatives at time zero. Here we present several path-integral estimators for the latter quantities, which characterize the initial decay profile of the flux correlation function. As with the internal energy or heat-capacity calculation, different estimators yield different variances (and therefore different convergence properties) in a Monte Carlo calculation. Here we obtain a virial (-type) estimator by using a coordinate scaling procedure rather than integration by parts, which allows more computational benefits. We also consider two different methods for treating the flux operator, i.e., local-path and global-path approaches, in which the latter achieves a smaller variance at the cost of using second-order potential derivatives. Numerical tests are performed for a one-dimensional Eckart barrier and a model proton transfer reaction in a polar solvent, which illustrates the reduced variance of the virial estimator over the corresponding thermodynamic estimator.     

Caged Thiophosphotyrosine Peptides

No Abstract     

Selectivities in 1,2,3-triazolide displacements of halides and additions to alkynes

4,5-Dicarbomethoxy-1,2,3-triazolide or 4-phenyl-1,2,3-triazolide displace chloride from ethyl chloroacetate or β-chloropropionate to give both 1-N and 2-N alkylated products. Our highest 2-N to 1-N selectivity was ca 5/1 and was found with the base triethylamine in DMF. The same triazolides and others add to alkynes, e.g. ethyl propiolate, methyl acetylenedicarboxylate, phenylpropiolaldehyde, ethyl phenylpropiolate, etc, to give Michael adducts at the 2-N position exclusively. Here the usual preference holds, i.e., the anti adduct is favored, but anti to syn isomerization usually sets in. On the basis of the available data for nucleophilic substitutions and additions, a limited directioselectivity pattern emerges for H-1,2,3-triazoles (T) and their anions (T^?): neutral T almost invariably leads with 1-N; T^t-- usually adds to unsaturates at 2-N; unsubstituted, 4-substituted and 4,5-disubstituted T^? attack organic halides at both 1-N and 2-N. Compared to phenyl, 2-triazolyl exerts a greater deshielding effect on proton chemical shifts; these and other patterns in the PMR spectra of the Michael adducts are discussed. CNDO calculations indicate that the 1-H is more stable than the 2-H-1,2,3-triazole and that in both neutral triazole and in triazolide, the 1-nitrogen position should lead nucleophilic attacks-this directioselectivity prediction is only partly (and probably fortuitously) correct.     

Identification of mutant firefly luciferases that efficiently utilize aminoluciferins

Firefly luciferase-catalyzed light emission from D-luciferin is widely used as a reporter of gene expression and enzymatic activity both in vitro and in vivo. Despite the power of bioluminescence for imaging and drug discovery, light emission from firefly luciferase is fundamentally limited by the physical properties of the D-luciferin substrate. We and others have synthesized aminoluciferin analogs that exhibit light emission at longer wavelengths than D-luciferin and have increased affinity for luciferase. However, although these substrates can emit an intense initial burst of light that approaches that of D-luciferin, this is followed by much lower levels of sustained light output. Here we describe the creation of mutant luciferases that yield improved sustained light emission with aminoluciferins in both lysed and live mammalian cells, allowing the use of aminoluciferins for cell-based bioluminescence experiments.