Unlike ordinary aryl chlorides, the title hererocycles participate readily in Castro-Stephens, Stille, Suzuki, and carbonylation reactions under the catalytic influence of Pd(0).

Fibrolase is an active fibrinolytic agent and possesses potential for use in thrombolytic therapy. Its mode of action had been characterized, both in vitro and in vivo. Possessing three disulfide bonds, native fibrolase is nonglycosylated and binds an intrinsic zinc atom. The zinc is essential for retention of activity and structural integrity. In solution, fibrolase is sensitive to changes in pH and temperature (Pretzer et al., 1991). At neutral to basic pH (pH 5-9), the solubility and stability of fibrolase is nearly constant. Little structural variation can be detected by CD spectroscopy. However, decrease in pH below 5 leads to a pronounced reduction in both the solubility and activity of fibrolase. At pH 3 and below, the solubility of fibrolase returns but the activity does not. This solubility profile is unusual in that the minimal solubility is well removed from the pI (which is 6.7). It is proposed that the behavior of fibrolase with variation in pH can be understood in terms of capacity to bind zinc. At pH 5 to 9, the protein binds zinc and the structure and activity are preserved. Near pH 5, the histidine residues which serve as ligands for the zinc become protonated and zinc binding is lost. Loss of zinc leads to local unfolding of a helical segment of fibrolase, exposing hydrophobic groups which allow the protein to rapidly aggregate. At lower pH values (1-3), the protein again adopts a more globular structure, similar to molten globule states, and the solubility increases. However, without the zinc, fibrolase remains inactive. Changes in pH also affect thermal stability. The Tm for fibrolase moves from 50 degrees C at pH 8 to 43 degrees C at pH 5. Increases in temperature also lead to removal of the zinc ion, again producing a partially denatured protein with a marked tendency to aggregate. In both cases (decrease in pH and increase in temperature), analysis of the CD spectra indicates that the protein has primarily lost alpha-helical secondary structure. A major change in structure can also be observed using NMR spectroscopy. At temperatures below 35 degrees C, the globular structure of fibrolase remains intact, although some increase in chain mobility can be noted with increased temperature. Upon melting, numerous signals collapse as the protein unfolds. Transition temperatures (Tm) as measured by CD and NMR are in good agreement. Similar structural changes can be induced by adding zinc chelators such as EDTA and DTT. This leads to complete loss of activity at EDTA concentrations above 1.0 mM.(ABSTRACT TRUNCATED AT 400 WORDS)

Creating an effective and consistent corporate health, safety, and environment program for a decentralized, international company poses unique challenges. This article describes how, with global company input, Kodak has established a set of twenty-eight corporate HSE performance standards. Worldwide facility compliance with these standards is monitored through Kodak's Corporate HSE Assessment Program and through the Corporate Self-Appraisal Program.

Fibrolase is a metalloprotease with potential use as a fibrinolytic agent. Loss of the intrinsic zinc atom leads to a rapid decrease in enzymatic activity. Circular dichroism measurements indicate that there is a partial unfolding of an α-helical section of the protein concomitant with the loss of zinc. Removal of zinc can be affected by elevated temperatures, acidic pH values, and addition of chelating agents. At low molar concentrations, both ethylenediaminetet-raacetic acid (EDTA) and dithiothreitol (DTT) were found to remove zinc efficiently. Analysis of the sequence of fibrolase identified a segment which possessed a high degree of homology with the metal binding site of other zinc proteases, such as thermolysin and the collagenases. However, the putative zinc binding site in fibrolase lacks the additional glutamate ligand found in thermolysin and subtilisin. This sequence is also predicted to adopt an α-helical conformation. Together, these data indicate that there is a well-defined metal binding site in fibrolase and that metal binding is the most important factor governing the stability of this protein.

Introduction of biotechnology concepts into a pharmaceutics curriculum is essential for students to be properly prepared to meet the future challenges of the pharmaceutical industry. This article provides a description of the approach taken at the University of Kansas to teach pharmaceutical biotechnology at the graduate level within the Department of Pharmaceutical Chemistry. The course was designed to be consistent with the overall educational objectives and philosophy of the Department, which is, to focus on the chemical aspects of pharmaceutics. Therefore, the course is aimed at understanding the basic chemical and structural characteristics which make protein pharmaceuticals unusual and distinct. In addition, the stability and analysis of proteins is emphasized. While some attention is given to the molecular biology, drug delivery, and engineering aspects of biotechnology, it is done to familiarize the students with the areas, so that they can be properly trained to participate in development of proteins into marketable therapeutic agents.

The effect of temperature and pH on the activity and conformation of the thrombolytic protein fibrolase was examined. Fibrolase maintained proteolytic activity over 10 days at room temperature (∼22°C). At 37°C, greater than 50% of the proteolytic activity was lost within 2 days and no activity remained after 10 days. Circular dichroism (CD) spectra at elevated temperatures showed that alphahelical structure was lost in a cooperative transition (Tm of 50°C at pH 8). Structural changes were detected by NMR prior to unfolding which were not observable by CD, and the Tm determined by NMR was 46°C at pD 8. The effect of pH on the proteolytic activity and structure of fibrolase was examined over the pH range from 1 to 10. Activity was maintained at neutral to alkaline pH values from pH 6.5 to pH 10.0 but decreased substantially in acidic media. While CD spectra indicated little variation in secondary structure over the pH range 5 to 9, significant differences were noted at pH 2 to 3. The melting temperature of fibrolase decreased to 43°C at pH 5. Protein concentrations determined over the pH range 1 to 10 showed an apparent solubility minimum at pH 5.0, which did not correspond to the isoelectric point of 6.5. Explanations for these observations are proposed.

Chemical reactions potentially useful for converting intractable allotropes of germania (aged hexagonal and tetragonal forms) into reactive products are investigated. The effectiveness of reactions in aqueous solutions under basic, basic‐reductive, acidic‐oxidative, and acidic‐reductive conditions is reported in terms of germania solubilization. Solubility versus time of reaction at elevated temperatures is reported for the most effective medium, 2.5M NaOH. For six flux media, fusion reactions and respective temperatures are reported with the percentage of germania solubilized from the fused melt. Additionally, the crystalline germania materials are characterized by infrared and differential thermal analyses. Chemical procedures compatible with batch or continuous processing methods are discussed.

Ammonia-nitrogen feedstock streams, free of oxygen containing impurities, are essential reagents for fabricating low oxygen contaminated nitride films. An analytical method is described for determining part per billion levels of oxygen containing impurities, which are converted to nitric oxide (NO) through reaction with microwave discharge produced active nitrogen. Quantitative determinations are then based on detecting the resulting chemiluminescence of NO at characteristic wavelengths. This metastable transfer spectrometric method (MTES) provides direct measurements of oxygen impurities over the 14 to 500 ppb region and has dynamic range extending to 200 ppm. The method, unparalleled in its measurement sensitivity for oxygen impurities in flowing nitrogen gas streams, is calibrated with an NBS standard and applied to the determination of the purification efficiency of an on-line resin system for removal of O2, CO and NO from ammonia-nitrogen mixtures. Gaseous streams, doped deliberately in the 0.2 to 100 ppm level with either O2, CO or NO following purification were found to contain less than 10 ppb of the residual impurity. A commercially available 1% ammonia in nitrogen semiconductor grade reagent (99.999%) is shown by MTES to be contaminated with 470 ppb of oxygen impurities.

Banks have traditionally been hostile to the marketing concept. Whilst this is being eroded, banks do not seem to have firmly embraced marketing information systems, according to an interview survey undertaken, although some steps are being made. With their major investments in technology it is crucial that banks take the opportunities to develop a comprehensive marketing information system.

In this article the authors present the results of recent research into the much neglected, but increasingly important, area of marketing information systems in banking. Interviews were conducted with most of the major UK banks, the results of which, combined with literature review, give insight into the penetration of marketing information systems in retail banking, and suggest ways forward for banks in their implementation of marketing information systems.

AbstractEine Reihe chemischer und physikalischer Untersuchungen werden beschrieben: UV‐Spektrum von Pyridin‐1‐nitroimid (Ia) in neutraler und protonierter Fonn; Protonierung (pK‐Werte) der Verbindungen (Ia) und (Ib) (R: 2‐Me) sowie von Vergleichsverbindungen; Reaktionen von (Ia) mit PCl3 bzw. AC2 O zu Pyridin; Fehlversuche zur Alkylierung, Nitrierung, Bromierung und Mercurierung von (Ia); basenkatalysierter H‐/D‐Austausch der Verbindungen (Ia‐d); bei H‐/D‐Austausch mit NaOD bei (Ia) eintretende Ringöffnung zu Glutaconaldehyd‐Derivaten; Massenspektren von (Ia‐d).

Triäthylendiamin (I) läßt sich durch Umsetzung mit nacheinander Hydroxylamin‐O‐ sulfonsäure, KJ und AgNO 3 über das entsprechende Jodid in das Nitrat (II) überführen, das beim Behandeln mit Trifluoracetanhydrid in Trifluoressigsäure (oder mit Nitroniumtetrafluoroborat in Acetonitril) das N‐Nitroimid (III) gibt.

AbstractDas Aminotriazol (I) setzt sich mit Äthylnitrat in Gegenwart von Na‐äthoxid zu dem (als Monohydrat kristallisierenden) Na‐Salz (II) um, das beim Behandeln mit konz. Salzsäure das Nitroimid (IIIa), mit Benzylchlorid (IIIb) und mit Methyltosylat (IIIc) gibt.

The title amines have been converted into the corresponding N-nitroimides by nitration of their N-amino-derivatives in acetic or trifluoroacetic acid–anhydride mixtures or by treatment with nitronium tetrafluoroborate.