About discovery

We tend to think about discovery and innovation in linear terms, but the process is completely nonlinear. There are all kinds of nonlinearities—for example, the technology transfer process of the feedback that is built into the culture of an institution, who gets rewarded for what behavior, and whether there is economic benefit to the individual participants in that process. The nonlinearity of innovation makes it interesting and difficult to manage while trying to enhance the efficiency of the process. 

Another distinction about discovery bioanalysis is that ease of methods development is often more important than the net speed at which samples can be processed. This statement is again a manifestation of the high number of NCEs that are encountered in discovery. Consequently, enormous growth has occurred with on-line methods that combine sample preparation and analysis in a single injection format. Although several formats exist, the common link to all on-line methods is that they invoke column-switching techniques. The popularity of these methods can be traced, in part, to the ability to adjust extraction/analysis conditions on-the-fly and leads to extremely facile method development. In the section that follows, off-line and on-line methods are considered separately. Coverage of these subtopics can also be found in a number of review articles [4—7,44,45]. 

What was true in the past about discovery, however, will undoubtedly continue into the future. That truth is, a great many compounds must be synthesized to find one that is safe, efficacious, and useful. In 1967, for instance, almost 176,000 compounds were tested by pharmaceutical laboratories. Of those, only 1,375 were active enough and sufficiently safe to warrant testing in humans. For each compound reaching the market, 7,000 were screened and underwent preliminary testing (3). 

However, the discovery in 1962 by Voronel and coworkers [H] that the constant-volume heat capacity of argon showed a weak divergence at the critical point, had a major impact on uniting fluid criticality widi that of other systems. They thought the divergence was logaritlnnic, but it is not quite that weak, satisfying equation (A2.5.21) with an exponent a now known to be about 0.11. The equation applies both above and... 

The lead discovery process is depicted in Figure 10.4-4 and shows how the different methods are interconnected. A lead structure can be discovered by serendipity. In rational drug design all information available about a target serves to direct... 

Manganese minerals are widely distributed oxides, silicates, and carbonates are the most common. The discovery of large quantities of manganese nodules on the floor of the oceans may become a source of manganese. These nodules contain about 24% manganese together with many other elements in lesser abundance. 

The cost of dysprosium metal has dropped in recent years since the development of ion-exchange and solvent extraction techniques, and the discovery of large ore bodies. The metal costs about 300/kg in purities of 99+%. 

This book is mainly about my life in search of new chemistry. Because some of my work centered around the discovery of extremely strong superacids, which are sometimes also called magic acids, I chose the title A Life of... 

In the early days following the discovery of chirality it was thought that only molecules of the type CWXYZ, multiply substituted methanes, were important in this respect and it was said that a molecule with an asymmetric carbon atom forms enantiomers. Nowadays, this definition is totally inadequate, for two reasons. The first is that the existence of enantiomers is not confined to molecules with a central carbon atom (it is not even confined to organic molecules), and the second is that, knowing what we do about the various possible elements of symmetry, the phrase asymmetric carbon atom has no real meaning. 

High Pressure in the Chemical Industry. The use of high pressure in industry may be traced to early efforts to Hquefy the so-called permanent gases using a combination of pressure and low temperature. At about the same time the chemical industry was becoming involved in high pressure processes. The discovery of mauveine in 1856 led to the development of the synthetic dye industry which was well estabUshed, particularly in Germany, by the end of the century. Some of the intermediate compounds required for the production of dyes were produced, in autoclaves, at pressures of 5-8 MPa (725-1160 psi). 

Cyclodienes. These are polychlorinated cycHc hydrocarbons with endomethylene-bridged stmctures, prepared by the Diels-Alder diene reaction. The development of these insecticides resulted from the discovery in 1945 of chlordane, the chlorinated adduct of hexachlorocyclopentadiene and cyclopentadiene (qv). The addition of two Cl atoms across the double bond of the ftve-membered ring forms the two isomers of chlordane [12789-03-6] or l,2,4,5,6,7,8,8-octachloro-2,3,3t ,4,7,7t -hexahydro-4,7-methano-lJT-indene, QL-trans (mp 106.5°C) and pt-tis (32) (mp 104.5°C). The p-isomerhas signiftcantiy greater insecticidal activity. Technical chlordane is an amber Hquid (bp 175°C/267 Pa, vp 1.3 mPa at 25°C) which is soluble in water to about 9 fig/L. It has rat LD qS of 335, 430 (oral) and 840, 690 (dermal) mg/kg. Technical chlordane contains about 60% of the isomers and 10—20% of heptachlor. It has been used extensively as a soil insecticide for termite control and as a household insecticide. 

Reverse Osmosis. This was the first membrane-based separation process to be commercialized on a significant scale. The breakthrough discovery that made reverse osmosis (qv) possible was the development of the Loeb-Sourirajan asymmetric cellulose acetate membrane. This membrane made desalination by reverse osmosis practical within a few years commercial plants were installed. The total worldwide market for reverse osmosis membrane modules is about 200 million /yr, spHt approximately between 25% hoUow-ftber and 75% spiral-wound modules. The general trend of the industry is toward spiral-wound modules for this appHcation, and the market share of the hoUow-ftber products is gradually falling (72). 

The First Reactor. When word about the discovery of fission in Germany reached the United States, researchers thereafter found that (/) the principal uranium isotope involved was uranium-235 (2) slow neutrons were very effective in causing fission (J) several fast neutrons were released and (4) a large energy release occurred. The possibiUty of an atom bomb of enormous destmctive power was visualized. 

For well over 100 years after its discovery and initial preparation, oxygen was made either chemically or by the electrolysis of water. Early in the twentieth century, Linde and Claude introduced processes for the Hquefaction and distillation of air that have since grown into a mature and highly competitive industry. In 1991, over 13.4 X 10 (4.7 x 10 ft ) of oxygen was produced in the United States. About 70 X 10 (24.7 x 10 ft ) was... 

Some hquid defoamers are preemulsified relatives of paste defoamers. In addition to the fatty components mentioned above, kerosene [8008-20-6] or an organic cosolvent such as 2-propanol have been used to enhance stabiUty of the oil—water emulsion and the solubiUty of the defoamer s active ingredients. These cosolvents are used less frequently as concerns increase about volatile organic emissions (VOCs) from the paper machine. Additionally, the use of ultrapure mineral oil in defoamers has become commonplace. Concern about the creation of 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and 2,3,7,8-tetrachlorodibenzofuran (TCDF) in the pulping process has led to the discovery of unchlorinated precursor molecules, especially in recycled mineral oil and other organic cosolvents used in defoamer formulations (28). In 1995 the mineral oil that is used is essentially free of dibenzodioxin and dibenzofuran. In addition, owing to both the concern about these oils and the fluctuating cost of raw materials, the trend in paper machine defoamers is toward water-based defoamers (29). 

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