Probing the binding of propranolol enantiomers to alpha1-acid glycoprotein with ligand-detected NMR experiments

Mapping the interactions of a small molecule ligand with a protein can provide information important for biochemical studies and for drug design and development. This information can be determined using the ligand-detected (1)H NMR experiments T(1rho)-NOESY, diffusion, and saturation transfer difference (STD). This work compares the results of these experiments and examines their ability to distinguish the binding epitopes of propranolol enantiomers with alpha 1-acid glycoprotein (AGP). The epitope maps for the propranolol enantiomers are fairly similar, as expected from their similar binding affinities; however, the STD epitope maps provide unique insights into the different orientations of the enantiomers with respect to the AGP binding pocket. Our results suggest that it is best to consider the data provided by several NMR epitope mapping experiments in drawing conclusions about ligand-protein binding interactions.     

Synthesis,characterization and X-ray crystal structures of two non-molecular coordination polymers of manganese(II) and copper(II) with <Emphasis Type="Italic">N</Emphasis>-(2-pyridylmethyl)-<Emphasis Type="SmallCaps">l</Emphasis>-alanine and isothiocyanato ligands

The reduced Schiff base, N-(2-pyridylmethyl)-l-alanine (Pyala), has been prepared and used as a ligand for the synthesis of two new non-centrosymmetrical isothiocyanate mixed-ligand coordination polymers, [MnPyalaSCN] _n and [CuPyalaSCN] _n . Pyala and the metal complexes were characterized by physico-chemical and spectroscopic methods. The single-crystal X-ray structures of the complexes reveal both compounds to be non-molecular coordination polymers which crystallize in the orthorhombic system. The ligand acts as a bridge between two metal centres in both compounds, forming two six-membered rings around each Mn atom and two five-membered rings around each Cu centre. The 1D chains are assembled via N–H?O, N–H?S hydrogen bonds and S–S interactions building 3D helical supramolecular networks in both compounds. Packing of the polymers of both compounds along the b-axis gives chiral channels.     

Accurate mass measurement by matrix‐assisted laser desorption/ionisation time‐of‐flight mass spectrometry. I. Measurement of positive radical ions using porphyrin standard reference materials

A method for the accurate mass measurement of positive radical ions by matrix‐assisted laser desorption/ionisation time‐of‐flight mass spectrometry (MALDI‐TOFMS) is described. Initial use of a conjugated oligomeric calibration material was rejected in favour of a series of meso‐tetraalkyl/tetraalkylaryl‐functionalised porphyrins, from which the two calibrants required for a particular accurate mass measurement were chosen. While all measurements of monoisotopic species were within ±5 ppm, and the method was rigorously validated using chemometrics, mean values of five measurements were used for extra confidence in the generation of potential elemental formulae. Potential difficulties encountered when measuring compounds containing multi‐isotopic elements are discussed, where the monoisotopic peak is no longer the lowest mass peak, and a simple mass‐correction solution can be applied. The method requires no significant expertise to implement, but care and attention is required to obtain valid measurements. The method is operationally simple and will prove useful to the analytical chemistry community. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis, alignment, and magnetic properties of monodisperse nickel nanocubes

This Communication describes the synthesis of highly monodispersed 12 nm nickel nanocubes. The cubic shape was achieved by using trioctylphosphine and hexadecylamine surfactants under a reducing hydrogen atmosphere to favor thermodynamic growth and the stabilization of {100} facets. Varying the metal precursor to trioctylphosphine ratio was found to alter the nanoparticle size and shape from 5 nm spherical nanoparticles to 12 nm nanocubes. High-resolution transmission electron microscopy showed that the nanocubes are protected from further oxidation by a 1 nm NiO shell. Synchrotron-based X-ray diffraction techniques showed the nickel nanocubes order into [100] aligned arrays. Magnetic studies showed the nickel nanocubes have over 4 times enhancement in magnetic saturation compared to spherical superparamagnetic nickel nanoparticles.     

Solvent effects on the steady state photophysics of estrone and 17β-estradiol

Absorption and emission yields for estrone and 17β-estradiol were measured in a variety of room temperature solvents. Molar extinction coefficients were found to not vary as a function of solvent, while fluorescence yields were found to be significantly affected by the polarity and hydrogen-bond accepting ability of the solvent, with the yield for 17β-estradiol being highest in nonpolar, hydrogen-bond donating solvents, and lowest in the nonpolar, hydrogen-bond accepting solvent ethyl acetate. Estrone's emission yield was found to be a factor of ten smaller than 17β-estradiol's. Strong solvent and excitation wavelength dependences were found for the relative amounts of emission between estrone's two emission bands, with increased relative emission occurring in nonpolar aprotic solvents, and under higher excitation energies. These results are interpreted with the aid of vertical excitation energies from time-dependent density functional calculations using both explicit and implicit solvation models.     

Resolvability of infinite designs

In this paper we examine the resolvability of infinite designs. We show that in stark contrast to the finite case, resolvability for infinite designs is fairly commonplace. We prove that every t  -(v,k,Λ)$(v,k,\Lambda )$ design with t finite, v   infinite and k,λ<v$k,\lambda <v$ is resolvable and, in fact, has α   orthogonal resolutions for each α<v$\alpha <v$. We also show that, while a t  -(v,k,Λ)$(v,k,\Lambda )$ design with t and λ finite, v   infinite and k=v$k=v$ may or may not have a resolution, any resolution of such a design must have v parallel classes containing v   blocks and at most λ−1$\lambda -1$ parallel classes containing fewer than v   blocks. Further, a resolution into parallel classes of any specified sizes obeying these conditions is realisable in some design. When k<v$k<v$ and λ=v$\lambda =v$ and when k=v$k=v$ and λ is infinite, we give various examples of resolvable and non-resolvable t  -(v,k,Λ)$(v,k,\Lambda )$ designs.     

Az—a colourful azulene-derived protecting group

Azulen-1-yl-dicarbonyl (Az) is a novel, coloured, protecting group used to mask primary and secondary alcohols. In particular, the use of Az in the construction of carbohydrates, where a number of orthogonal protecting groups are typically required, is of merit. Introduction and removal of the Az-group is performed easily and in near quantitative yields in the presence of other commonly used protecting groups, and the Az-group is compatible with glycosylation reactions using trichloroacetimidate donors. The deep-red colour of the Az-group greatly facilitates the purification of carbohydrate building blocks and the monitoring of coupling reactions. Of particular note is that the Az-group can be selectively introduced on diol systems and removed in the presence of esters, such as acetates.     

Blind estimation of reverberation time in classrooms and hospital wards

This paper investigates blind Reverberation Time (RT) estimation in occupied classrooms and hospital wards. Measurements are usually made while these spaces are unoccupied for logistical reasons. However, occupancy can have a significant impact on the rate of reverberant decay. Recent work has developed a Maximum Likelihood Estimation (MLE) method which utilises only passively recorded speech and music signals, this enables measurements to be made while the room is in use. In this paper the MLE method is applied to recordings made in classrooms during lessons. Classroom occupancy levels differ for each lesson, therefore a model is developed using blind estimates to predict the RT for any occupancy level to within ±0.07 s for the mid-frequency octave bands. The model is also able to predict the effective room and per person absorption area.Ambient sound recordings were also carried out in a number of rooms in two hospitals for a week. Hospital measurements are more challenging as the occurrence of free reverberant decay is rarer than in schools and the acoustic conditions may be non-stationary. However, by gaining recordings over a period of a week, estimates can be gained within ±0.07 s. These estimates are representative of the times when the room contains the highest acoustic absorption. In other words when curtains are drawn, there are many visitors or perhaps a window may be open.     

Use of NMR binding interaction mapping techniques to examine interactions of chiral molecules with molecular micelles

NMR spectroscopy was used to investigate the association of four chiral molecules with the molecular micelle poly(sodium N-undecanoyl-l-leucylvalinate) (poly(SULV)). Adding poly(SULV) to the background electrolyte in electrokinetic chromatography (EKC) allows enantiomeric resolution to be achieved because enantiomers interact differentially with the chiral centers on the micelle headgroups as they both move in the electric field. Pulsed field gradient diffusion experiments were used to measure molecular micelle association constants for enantiomers of each analyte. These association constants were consistent with EKC elution order for the compounds 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BNP), 1,1'-bi-2-naphthol (BOH), and Troger's base. In addition, nuclear Overhauser enhancement spectroscopy, nuclear Overhauser effect difference, and intermolecular cross relaxation diffusion experiments were used to generate binding interaction maps for each chiral analyte. These maps showed that BNP and BOH inserted into the surfactant headgroup's major chiral groove and interacted predominately with the leucine chiral center. (+)-Troger's base was also found to insert into the major chiral groove. However, this compound instead interacted with the valine chiral atom. In diffusion experiments with long diffusion times, the linearized diffusion plots for each analyte-molecular micelle mixture showed curvature characteristic of intermolecular cross relaxation. The magnitude of this effect scaled linearly with the analytes' free energies of binding.