Syntheses and photophysical properties of some 5(2)-aryl-2(5)-(4-pyridyl)oxazoles and related oxadiazoles and furans

A number of 5-aryl-2-(4-pyridyl)oxazoles, a 2-aryl-5-(4-pyridyl)oxazole, the related oxadiazole and furan, several 2-(4-pyridyl)cycloalkano[d]oxazoles, and many of their quaternary salts were prepared. No single standard synthesis was effective for preparation of more than a few of the 25 free bases described; methods often unique to a base were employed. Minor variations in structure sometimes produced large differences in absorption and emission wavelengths, as well as in the magnitude of the extinction coefficient. The salts are of interest as laser dyes, scintillation fluors, biological stains, and shifters for luminescent solar concentrators.     

Multinuclear NMR studies and ab initio structure calculations of hindered phencyclone diels‐alder adducts from symmetrical cyclic dienophiles: Cyclohexene,vinylene carbonate,vinylene trithiocarbonate and two N‐aryl maleimides

A series of hindered Diels‐Alder adducts have been prepared from phencyclone, 1 , with various unusual symmetrical cyclic dienophiles, including cyclohexene, 2a ; vinylene carbonate, 2b ; vinylene trithiocarbonate, 2c ; and the N‐aryl maleimides: N‐(4‐dimethylamino‐3,5‐dinitrophenyl)maleimide (“Tuppy's maleimide”), 2d ; and N‐[3,5‐bis(trifluoromethyl)phenyl]maleimide, 2e . The highly hindered adducts, 3a‐e , respectively, were extensively characterized by one‐ and two‐dimensional NMR methods, observing proton, carbon‐13 and fluorine‐19. High resolution COSY45 spectra permitted rigorous proton NMR assignments. The 2D heteronuclear C‐H chemical shift correlation spectra (HETCOR, XHCORR) were obtained for adducts 3a‐d , allowing specific assignments for protonated carbons. Corrections to earlier proton NMR assignments for the vinylene carbonate adduct are given; results of the gated decoupling ¹³C NMR experiment for this adduct supported endo adduct stereochemistry. Relative proton chemical shifts for bridgehead phenyls of adduct 3c appeared anomalous relative to other adducts, suggesting possible special anisotropic interactions (with endocyclic sulfur or other anisotropic groups in the product) due to the unusual calculated orientation of the phenyls. The unsubstituted bridgehead phenyls in all adducts were shown to exhibit slow exchange limit (SEL) ¹H and ¹³C spectra on the NMR timescales at ambient temperatures (7 tesla) showing slow rotations about the C(sp³)‐C(aryl sp²) bonds. The rapid rotation of the N‐aryl rings of the maleimide adducts was indicated by fast exchange limit spectra, suggesting that ortho substitution of the N‐aryl ring may be necessary to slow this rotation to the SEL regime. Ab initio geometry optimizations at the Hartree‐Fock level were carried out for each adduct, with the 6‐31G* basis sets. Appreciable geometry differences were seen in calculated structures, and significant NMR chemical shift differences were experimentally observed, depending on the nature of the groups attached to the (Z)‐HC=CH moiety of the dienophiles.     

Synthesis of some heterocyclic skeletons via organoiron complexes. Crystal and molecular structure of (5a,6,7,8,9,9a-η6-1,4-benzoxathiino[3,2-b]pyridine)(η5-cyclopentadienyl)iron hexafluorophosphate

Synthesis of the heterocyclic skeletons of some biologically active compounds from (η⁶-o-dichlorobenzene)(η⁵-cyclopentadienyrl)iron hexafluorophosphate in a two step procedure is described. Cyclopentadienyliron hexafluorophosphate complexes of 1,4-benzodioxino[2,3-b]pyridine, 1,4-benzoxathiino[3,2-b]pyridine, 10H-pyrido[3,2-b]benzoxazine, benzo[b]naphtho[2,3-e][1,4]dioxin, 4-methylbenzo[b]benzopyran-2-one[7,6-e][1,4]dioxin and benzo[b]anthracen-9,10-diono[1,2-e][1,4]dioxin were isolated and characterized. Upon pyrolytic sublimation of these complexes the free heterocycles were obtained and characterized. (η⁶-1,4-Benzoxathiino[3,2-b]pyridine)(η⁵-cyclopentadienyl)iron hexafluorophosphate crystalizes in the orthothombic system, space group Pbca; the dihedral angle between the planes of outer rings was found to be 176.8 (1).     

The American (USA) perspective six years after implementation of CLIA'88 (Federal) regulations

 On September 1, 1992 all testing sites in the United States were required to comply with the Clinical Laboratory Improvement Amendments of 1988 (CLIA'88). These regulations, based on both total quality management (TQM) and continuous quality improvement (CQI) principles, reshaped the environment for more than 90% of laboratories. CLIA'88 represented a revolutionary change by imposing universal, uniform regulations based on test complexity for all sites examining materials derived from the human body for the purpose of providing information for the diagnosis, prevention, or treatment of disease. CLIA'88 specifies minimum requirements for personnel, quality control, and proficiency testing (PT). In addition, laboratories are required to follow manufacturers' directions and comply with other specified good laboratory practices. PT is mandated for most of the frequently run analyses and quality assurance requirements integrate the principles of CQI as well as TQM into the regulatory process. Biannual inspection is integral to CLIA'88, however, laboratories can choose other federally approved ("deemed") professional organizations, such as the Commission on Office Laboratory Accreditation, the College of American Pathologists, or the Joint Commission on Accreditation of Healthcare Organization, having standards that meet or exceed those of CLIA'88. CLIA'88 has still not been finalized. This article discusses the impact and changes since CLIA's implementation in 1992. Received: 5 October 1998 · Accepted: 20 October 1998     

Proton-ionizable crown compounds. 17. Transport studies of alkali metal ions in a H2O-CH2Cl2-H2O liquid membrane system by macrocycles containing two sulfonamide groups derived fromo- andm-phenylene diamine

The transport of alkali metal cations by several macrocycles possessing two sulfonamide groups as a part of an 18-, 20-, or 21-membered macroring has been studied. Some of these compounds were found to be more effective transport agents than the proton-ionizable pyridone- and triazole-containing crown ethers reported previously. The factors affecting transport, such as ring size, source and receiving phase pH, and the nature of the groups attached to the sulfonamide nitrogen atoms were examined. Also, extraction experiments by some of the ligands were performed. The behavior of sulfonamide type crowns in single and competitive transport of the alkali metal cations is explained. The mechanism of transport appears to be complex. Transport of one or two cations per molecule of the disulfonamide carriers occurs. Complexation of these cations appears to occur both within and outside the macrocycle cavity. Our results also suggest that kinetic factors may play a significant role in transport rates and selectivities.Deceased: September 5, 1987.     

Oxaziridinium salts as hydrophobic epoxidation reagents: remarkable hydrophobically-directed selectivity in olefin epoxidation

Selective epoxidation of cinnamates versus crotonate was used to detect hydrophobic binding of the cinnamates in the transition states with hydrophobic oxidizing agents in water solution. With peracids as oxidants, no such effect was seen, in accord with the calculated geometries of epoxidation in which the hydrophobic groups of substrate and oxidant could not stack. However, with oxaziridinium salts carrying fused benzene rings there was significantly high selectivity for the cinnamates in water solution, which could be suppressed with added 2-propanol. The hydrophobically induced selectivity changes were even larger, in free energy terms, than those reported previously for the atom-transfer reactions in hydride reductions. Furthermore, the oxaziridinium ions could be generated with oxone from catalytic amounts of the corresponding iminium salts. These substrate selectivities should also carry over to positional selectivities in polyenes.     

Facile synthesis of 2-bromo-3-fluorobenzonitrile: an application and study of the halodeboronation of aryl boronic acids

A scaleable synthesis of 2-bromo-3-fluorobenzonitrile via the NaOMe-catalyzed bromodeboronation of 2-cyano-6-fluorophenylboronic acid was developed. The generality of this transformation was demonstrated through the halodeboronation of a series of aryl boronic acids. Both aryl bromides and aryl chlorides were formed in good to excellent yields when the corresponding aryl boronic acid was treated with 1,3-dihalo-5,5-dimethylhydantoin and 5 mol % NaOMe.     

Microfluidic routing of aqueous and organic flows at high pressures: fabrication and characterization of integrated polymer microvalve elements

This paper presents the first systematic engineering study of the impact of chemical formulation and surface functionalization on the performace of free-standing microfluidic polymer elements used for high-pressure fluid control in glass microsystems. System design, chemical wet-etch processes, and laser-induced polymerization techniques are described, and parametric studies illustrate the effects of polymer formulation, glass surface modification, and geometric constraints on system performance parameters. In particular, this study shows that highly crosslinked and fluorinated polymers can overcome deficiencies in previously-reported microvalve architectures, particularly limited solvent compatibility. Substrate surface modification is shown effective in reducing the friction of the polymer-glass interface and thereby facilitating valve actuation. A microchip one-way valve constructed using this architecture shows a 2 x 10(8) ratio of forward and backward flow rates at 7 MPa. This valve architecture is integrated on chip with minimal dead volumes (70 pl), and should be applicable to systems (including chromatography and chemical synthesis devices) requiring high pressures and solvents of varying polarity.     

SITE-DIRECTED MUTAGENESIS OF THE LH2 LIGHT-HARVESTING COMPLEX OF Rhodobacter sphaeroides: CHANGING βLys23 TO Gin RESULTS IN A SHIFT IN THE 850 nm ABSORPTION PEAK

The present study describes the construction of a Rhodobacter sphaeroides light-harvesting (LH2) mutant in which the charged residue βSLys23 is changed by site-directed mutagenesis to a Gin residue, and the characterization of the resulting mutant complex by a range of spectroscopic techniques. In the 77 K absorption spectrum of the mutant, the peak equivalent to the 850 nm peak in the wild-type membrane is blue-shifted by approximately 18 nm to 837 nm; except for this blue-shift, the 77 K. fluorescence excitation and emission spectra and the circular dichroism spectrum of the mutant are very similar to the equivalent spectra from the wild-type membranes, suggesting that the mutation βLys23 → Gin probably does not cause any major changes in the conformation or aggregation state of these membranes. Possible causes of the 18 nm blue-shift in the absorption spectrum are discussed.     

Optimization of tetramethoxysilane-derived sol gel entrapment protocol stabilizes highly active chlorophyllase

Entrapment of membrane proteins is a challenging task compared to that involving soluble proteins. Chlorophyllase, a membrane protein, was successfully entrapped in tetramethoxysilane-derived sol-gel. Pre-gel sol typically consists of an aqueous suspension of chlorophyllase, precursors including tetramethoxysilane and/or methytrimethoxysilane, and sodium fluoride as catalyst. To obtain a highly active entrapped enzyme preparation, the effects of various immobilization parameters, including the chemical compositions of pre-gel sol (water/silane ratio, precursor type and proportions, enzyme loading, sodium fluoride concentration), and sol-gel process parameters (aging and drying time and approach) have been investigated. Chlorophyllase demonstrated the highest activity in gel derived from a pre-gel sol with water/silane ratio of 30 and enzyme loading of 0.257 mg_protein/g_gel, and showed moderately lower activity in organically modified sol-gel than that in hydrophilic sol-gel. The effects of water/silane ratio and precursor combinations on the activity of entrapped chlorophyllase were also studied by examining the pore morphology of gel via nitrogen adsorption-desorption. Longer aging time leads to an entrapped chlorophyllase preparation with higher activity. Chlorophyllase preparation demonstrated negligible activity after air-drying for 12 h while lyophilized chlorophyllase preparation demonstrated 8, 4 and 4 times higher activity than air-dried, vacuum-dried and solvent-dried preparations. Chlorophyllase demonstrated 30% higher activity in the improved sol-gel protocol than that from a non-optimized sol-gel protocol developed in a previous study.