Intramolecular AR--O--AR bond formation in calixarenes

The formal dehydration of two vicinal phenol moieties of p-tert-butylcalix[6]arene was achieved in two steps by mild oxidation of the calixarene followed by treatment of the resulting monospirodienone derivative (9c) with an ionic hydrogenation mixture (Et(3)SiH/CF(3)COOH). Reaction of 9c yielded the unsubstituted xanthenocalix[6]arene 11d, while treatment of the monospirodienone derivative of a spherand-type calixarene (13) with Et(3)SiH/CF(3)COOH afforded the dibenzofuran derivative 15. The formation of the latter product indicates that, at least for 13, the rings forming the Ar--O--Ar bond in the product are not those connected by the spiro bond in the starting material. Methylation of the phenolic hydroxyl groups of 11d with methyl p-toluenesulfonate/K(2)CO(3) or dimethyl sulfate/base afforded its dimethyl and tetramethyl ether derivatives. The parent xanthone calix[6]arene derivative 17b was prepared by O-methylation of the phenol groups followed by CrO(3) oxidation of the xanthene methylene group and deprotection of the OH groups. McMurry coupling of calixanthone 17a afforded the dixanthylene 18. Calixarenes 11d and 15 (which possess a xanthene and dibenzofuran group, respectively) were structurally characterized by X-ray crystallography.     

Investigation of the stability of polyelectrolyte multilayer coatings in open-tubular capillary electrochromatography using laser scanning confocal microscopy

A simple polyelectrolyte multilayer (PEM) coating procedure was used for the development of stable modified capillaries. PEM coatings were constructed in fused-silica capillaries using alternating rinses of cationic and anionic polyelectrolytes. The multilayer coatings investigated in this study consisted of two and twenty layer pairs, or bilayers. A bilayer is one layer of a cationic polymer and one layer of an anionic polymer. Poly(diallyldimethylammonium chloride) was used as the cationic polymer, and the polymeric surfactant poly(sodium N-undecanoyl-L-leucylvalinate) was used as the anionic polymer. Previous studies for both chiral and achiral separations have shown that PEM-coated capillaries have excellent reproducibilities, remarkable endurance, and strong stabilities against extreme pH values when used in open-tubular capillary electrochromatography (OT-CEC). In this study, the stability of the coatings was further investigated after exposure to 0.1 M and 1.0 M NaOH. Structural changes of these coatings were monitored using laser scanning confocal microscopy (LSCM) after flushing the capillaries with NaOH. This technique allowed observation of the degradation of the coatings. Observations are discussed in terms of separations using OT-CEC. Electropherograms obtained from the chiral separation of 1,1'-binaphthyl-2,2'-dihydrogenphosphate in OT-CEC showed a decrease in selectivity and an increase in electroosmotic mobility after long exposure to NaOH. The ability to recover the capillaries by exposure to NaOH was also demonstrated. Measurements of electroosmotic mobility and selectivity showed that 2-bilayer and 20-bilayer PEM coatings could be completely removed from the capillary surface after approximately 3.5 and 9.5 h, respectively, of continuous exposure to 1 M NaOH.     

Characterization and application of sodium di(2-ethylhexyl) sulfosuccinate and sodium di(2-ethylhexyl) phosphate surfactants as pseudostationary phases in micellar electrokinetic chromatography

Sodium di(2-ethylhexyl) sulfosuccinate (DOSS) and sodium di(2-ethylhexyl) phosphate (NaDEHP) surfactants, with double alkyl chains and negatively charged headgroups, were characterized using fluorescence quenching, densitometry, and tensiometry techniques to determine their aggregation number, partial specific volume, and critical aggregation concentration. These two surfactants were then applied as pseudostationary phases in micellar electrokinetic chromatography (MEKC) for separations of alkyl phenyl ketones. The aggregation number of NaDEHP was found to be more than two-fold higher than that of DOSS. The partial specific volumes of NaDEHP and DOSS were found to be 0.9003 and 0.8371 mL/g, respectively. The critical aggregation concentrations are 5.12 and 1.80 mM for NaDEHP and DOSS, respectively. The DOSS surfactant provided a wider separation window and had a greater hydrophobic environment than the NaDEHP surfactant under the MEKC experimental conditions studied.     

Novel anionic copolymerized surfactants of mixed achiral and chiral surfactants as pseudostationary phases for micellar electrokinetic chromatography

One disadvantage of amino acid-based chiral selectors for micellar electrokinetic chromatography (MEKC) is that either they have very low solubility or are insoluble at acidic pHs. In order to increase solubilities at lower pHs, we have synthesized a highly water-soluble achiral surfactant and copolymerized it with an amino acid-based chiral surfactant. These two surfactants were polymerized either separately or at various molar rations of binary solutions, yielding pure molecular or copolymerized surfactant (CoPS), respectively. All surfactants were characterized by use of several analytical techniques prior to using them as novel pseudostationary phases in MEKC. The chromatographic performance of the CoPS in MEKC was tested with chiral and achiral analytes. The highly soluble sulfate head group significantly increased the solubility of amino acid-based CoPS over a wide range of pH. Three chiral binaphthyl derivatives were tested and each surfactant system was found to have different selectivity.     

On-line delta(18)O measurement of organic and inorganic substances

A method for the automated sample conversion and on-line oxygen isotope ratio (delta(18)O) determination for organic and inorganic substances is presented. The samples are pyrolytically decomposed at 1400 degrees C in the presence of nickelized graphite. With the system presented organic as well as inorganic samples such as nitrates, sulphates and phosphates of 50-100 &mgr;g O can be analyzed for their delta(18)O values with a standard deviation usually better than 0.5 per thousand. Additionally, carbon isotope ratios of organic substances and nitrogen isotope ratios of inorganic nitrogenous compounds are available in the same sample run. Data for international and some inter-laboratory reference materials are presented to show the accuracy and reliability of the method. The effect of some additives on the CO yield was checked for substances which do not pyrolyze completely. Copyright 1999 John Wiley & Sons, Ltd.     

Fluorinated Rings: Conformation and Application

The introduction of fluorine atoms into molecules and materials across many fields of academic and industrial research is now commonplace, owing to their unique properties. A particularly interesting feature is the impact of fluorine substitution on the relative orientation of a C−F bond when incorporated into organic molecules. In this Review, we will be discussing the conformational behavior of fluorinated aliphatic carbo- and heterocyclic systems. The conformational preference of each system is associated with various interactions introduced by fluorine substitution such as charge-dipole, dipole-dipole, and hyperconjugative interactions. The contribution of each interaction on the stabilization of the fluorinated alicyclic system, which manifests itself in low conformations, will be discussed in detail. The novelty of this feature will be demonstrated by presenting the most recent applications.     

Stereochemistry of a spherand-type calixarene

The stereochemistry of the spherand-type calixarene 2a is analyzed in terms of the configuration of the three 2,2'-dihydroxybiphenyl subunits (R or S) and the disposition of the methylene groups (crown or twist). X-ray crystallography indicates that the neutral 2a and its mono- or dianion (in form of the salts 2a(-) x C(5)H(5)NH(+) and 2a(2)(-) x 2Et(3)NH(+)) exist essentially in the same conformation (RRS/SSR-twist). This asymmetric RRS/SSR-twist form is the lowest energy conformer according to molecular mechanics calculations. Low-temperature (1)H NMR data indicate the presence of a major conformer of C(1) symmetry, in agreement with a RRS/SSR-twist form. The lowest energy topomerization pathway mutually exchanges two pairs of methylene protons and is ascribed to an enantiomerization process involving rotation around an Ar-Ar bond.     

Understanding how the herpes thymidine kinase orchestrates optimal sugar and nucleobase conformations to accommodate its substrate at the active site: a chemical approach

The herpes virus thymidine kinase (HSV-tk) is a critical enzyme for the activation of anti-HSV nucleosides. However, a successful therapeutic outcome depends not only on the activity of this enzyme but also on the ability of the compound(s) to interact effectively with cellular kinases and with the target viral or cellular DNA polymerases. Herein, we describe the synthesis and study of two nucleoside analogues built on a conformationally locked bicyclo[3.1.0]hexane template designed to investigate the conformational preferences of HSV-tk for the 2'-deoxyribose ring. Intimately associated with the conformation of the 2'-deoxyribose ring is the value of the C-N torsion angle chi, which positions the nucleobase into two different domains (syn or anti). The often-conflicting sugar and nucleobase conformational parameters were studied using North and South methanocarbadeoxythymidine analogues (6 and 7), which forced HSV-tk to make a clear choice in the conformation of the substrate. The results provide new insights into the mechanism of action of this enzyme, which cannot be gleaned from a static X-ray crystal structure.