1H-NMR Studies of the Inclusion Complexes between α-Cyclodextrin and Adamantane Derivatives Using Both Exchangeable Hydroxy Protons and Non-Exchangeable Aliphatic Protons

The inclusion complexes between -cyclodextrin (-CD) and adamantane, 1-adamantanol, 1-(hydroxymethyl)-adamantane, 2-adamantanol, and 1,3-adamantanediol in aqueous solution have been studied by ¹H-NMR spectroscopy using both non-exchangeable and exchangeable protons. The complexation-induced ¹H-NMR shifts (CIS) and NOEs of non-exchangeable protons, as well as the CIS, NOEs, temperature coefficients, and linewidth of signals from exchangeable hydroxy protons have been determined. The stoichiometry of the adamantane/-CD complex could not be determined due to the low solubility of adamantane. However, for 0.11 equivalent of adamantane added, two sets of separate ¹H signals for the free and bound -CD were observed. The signal from O(3)H in the complexed form appeared narrow and upfield shifted with a low-temperature coefficient indicating reduced hydration inside the hydrophobic cavity of -CD. Both 1-adamantanol, and 1-(hydroxymethyl)-adamantane formed 1:1 inclusion complexes with -CD and only one set of NMR signals was observed. The CIS and NOEs suggested that both complexes had similar structures. The O(2)H signal of -CD was broadened at low temperature and became narrower as the temperature raised. The broadening increased with higher concentration of guest suggesting interaction between O(2)H of -CD and the guest molecules. The stoichiometry of the -CD/2-adamantanol complex could not be determined with certainty, but the NMR data suggested equilibrium between 2:1 and 1:1 complex. As with adamantane, a sharp and upfield shifted O(3)H signal with a very low-temperature coefficient was observed. No inclusion complex was formed between 1,3-adamantanediol and -CD. This study showed how the hydroxy protons of -CD could be used to obtain complementary information on the geometry and stability of inclusion complexes of -CD.     

Using chemometrics for navigating in the large data sets of genomics, proteomics, and metabonomics (gpm)

This article describes the applicability of multivariate projection techniques, such as principal-component analysis (PCA) and partial least-squares (PLS) projections to latent structures, to the large-volume high-density data structures obtained within genomics, proteomics, and metabonomics. PCA and PLS, and their extensions, derive their usefulness from their ability to analyze data with many, noisy, collinear, and even incomplete variables in both X and Y. Three examples are used as illustrations: the first example is a genomics data set and involves modeling of microarray data of cell cycle-regulated genes in the microorganism Saccharomyces cerevisiae. The second example contains NMR-metabonomics data, measured on urine samples of male rats treated with either of the drugs chloroquine or amiodarone. The third and last data set describes sequence-function classification studies in a set of G-protein-coupled receptors using hierarchical PCA.     

Azetidinic amino acids: stereocontrolled synthesis and pharmacological characterization as ligands for glutamate receptors and transporters

A set of ten azetidinic amino acids, that can be envisioned as C-4 alkyl substituted analogues of trans-2-carboxyazetidine-3-acetic acid (t-CAA) and/or conformationally constrained analogues of (R)- or (S)-glutamic acid (Glu) have been synthesized in a diastereo- and enantiomerically pure form from beta-amino alcohols through a straightforward five step sequence. The key step of this synthesis is an original anionic 4-exo-tet ring closure that forms the azetidine ring upon an intramolecular Michael addition. This reaction was proven to be reversible and to lead to a thermodynamic distribution of two diastereoisomers that were easily separated and converted in two steps into azetidinic amino acids. Azetidines 35-44 were characterized in binding studies on native ionotropic Glu receptors and in functional assays at cloned metabotropic receptors mGluR1, 2 and 4, representing group I, II and III mGlu receptors, respectively. Furthermore, azetidine analogues 35, 36, and 40 were also characterized as potential ligands at the glutamate transporter subtypes EAAT1-3 in the FLIPR Membrane Potential (FMP) assay. The (2R)-azetidines 35, 37, 39, 41 and 43 were inactive in iGlu, mGlu and EAAT assays, whereas a marked change in the pharmacological profile at the iGlu receptors was observed when a methyl group was introduced in the C-4 position, compound 36 versus t-CAA. At EAAT1-3, compound 35 was inactive, whereas azetidines 36 and 40 were both identified as inhibitors and showed selectivity for the EAAT2 subtype.     

Dimers of dipyrrometheneboron difluoride (BODIPY) with light spectroscopic applications in chemistry and biology.

A ground-state dimer (denoted D(I)) exhibiting a strong absorption maximum at 477 nm (epsilon = 97 000 M(-1)cm(-1)) can form between adjacent BODIPY groups attached to mutant forms of the protein, plasminogen activator inhibitor type 1 (PAI-1). No fluorescence from excited D(I) was detected. A locally high concentration of BODIPY groups was also achieved by doping lipid phases (micelles, vesicles) with BODIPY-labeled lipids. In addition to an absorption band located at about 480 nm, a new weak absorption band is also observed at ca. 570 nm. Both bands are ascribed to the formation of BODIPY dimers of different conformation (D(I) and D(II)). Contrary to D(I) in PAI-1, the D(II) aggregates absorbing at 570 nm are emitting light observed as a broad band centered at about 630 nm. The integrated absorption band of D(I) is about twice that of the monomer, which is compatible with exciton coupling within a dimer. The F?rster radius of electronic energy transfer between a BODIPY excited monomer and the ground-state dimer (D(I)()) is 57 +/- 2 A. A simple model of exciton coupling suggests that in D(I) two BODIPY groups are stacked on top of each other in a sandwich-like configuration with parallel electronic transition dipoles. For D(II) the model suggests that the S(0) --> S(1) transition dipoles are colinear. An explanation for the previously reported (J. Am. Chem. Soc. 1994, 116, 7801) exceptional light spectroscopic properties of BODIPY is also presented. These are ascribed to the extraordinary electric properties of the BODIPY chromophore. First, changes of the permanent electric dipole moment (Delta(mu) approximately -0.05 D) and polarizability (-26 x 10(-40) C m(2) V(-1)) between the ground and the first excited states are small. Second, the S(0) <--> S(1) electronic transition dipole moments are perpendicular to Delta(mu).     

Some results connected with Brennan's conjecture

This material is based upon work supported by the National Science Foundation under grant No. DMS-9207071. The US Government has certain rights in this material.     

Metallurgical behaviour of iron in brass studied using Mössbauer spectroscopy

The behaviour of small amounts of Fe in brass is investigated using Mössbauer spectroscopy. Different samples, made from the same ingot material, but run through different annealing temperatures and duration times and then quenched to room temperature, have different amount of γ-Fe. The present work shows that a suitable heat treatment can increase the amount of these precipitations and, that a heat treatment at 650°C is the optimal one for having the highest amount of this phase.     

Identification of Tmem10/Opalin as a novel marker for oligodendrocytes using gene expression profiling

Background  

During the development of the central nervous system, oligodendrocytes generate large amounts of myelin, a multilayered insulating membrane that ensheathes axons, thereby allowing the fast conduction of the action potential and maintaining axonal integrity. Differentiation of oligodendrocytes to myelin-forming cells requires the downregulation of RhoA GTPase activity.