Examples from the Literature

From the compounds with the highest similarity to the 43 queries, 18 were screened in cellular and cell-free assays for inhibition of the synthesis of 5-LO products. Two were found to be sufficiently active. These two hits were in turn used as queries for a second round of virtual screening on the same in-house compound collection. None of the further 55 analogues screened showed higher potency, but nevertheless the 2 original hits represented novel chemotypes of inhibitors of the 5-LO pathway. 

An identical approach was used by Branca et al. [16] at Merck and led to the identifcationofanovel inhibitor of poly(ADP-ribose) polymerase-1 (PARPl). The 2D descriptors were similar to the CATS all the two-point pharmacophores in each molecule were derived from all possible atom pairs and described in terms of atom types, number of Jt electrons, number of heavy atoms attached, and number of covalent bonds separating the two atoms along the shortest path. Known PARPl inhibitors were collected from patents, publications, and publicly available databases and used to train a support vector machine (SVM) classifier. A SVM constructs the plane that best separates active and inactive compounds in the multidimensional space defined by the molecular descriptors. The results of the SVM were used to classify the compounds in the Merck collection and those predicted to be active were screened. One compound was particularly potent and was chosen as the starting point for a structure-activity relationship (SAR) exploration of this chemical class. Docking studies on the PARPl crystal structure were used to guide the synthetic efforts. 

At Johnson Johnson Pharmaceutical Research and Development (J JPRD) in Europe 2D LEVS is routinely applied in conjunction with in vitrohigh-throughput screening (HTS). Some of the common scenarios are as follows  

1) Preparation of a focused compound library The collection of chemically diverse compounds normally tested in an HTS (a few hundred thousands) can be replaced or complemented with analogues of known ligands, if these are known in-house or are available from public sources. The analogues are identified in the corporate collection by using the known ligands as queries in 2DLBVS. 

Virtual screening used in conjunction with HTS should yield a higher hit rate than the default HTS. The latter can be considered to comprise a random selection, for the most part, of drug-like compounds. 

It is appropriate to add here a few general comments concerning details of mass spectrometric parameters given in published papers. Some of these details that should always be included are unfortunately not always available. For example, it is not uncommon to read that MS/MS detection was used but, while the m/z values of precursor and fragment ions are specified, the effective resolution of both stages of m/z filtering (e.g., the isolation width for the precursor) are not. This is important because, in trace analysis, it is always necessary to find a fit for purpose compromise between selectivity (increases with resolution, i.e., with decreasing peak widths) and response ( sensitivity in the colloquial sense) for which 

It is hoped that the present choice of examples provides a broad view perspective of quantitative mass spectrometry and successfully emphasizes that this is truly an extremely powerful and versatile interdisciplinary technology. Two books relevant to this chapter deal with trace analysis techniques applied to environmental samples (Loconto 2005) and the use of mass spectrometry in drug metabolism studies (Korfmacher 2004). 

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While the stick plot examples already presented show net and multiplet effects as separate phenomena, the two can be observed in the same spectrum or even in the same NMR signal. The following examples from the literature will illustrate real life uses of CIDNP and demonstrate the variety of structural, mechanistic, and spin physics questions which CIDNP can answer. 

The stability phase diagrams contain a wealth of information. Using some selected examples from the literature it is intended to show their range of application in the field of corrosion. 

Many recent examples show the importance of ionic radii and solvation in the conductivity of concentrated solutions. Suffice it to refer to three examples from the literature. 

However this was not always the case. It is possible to demonstrate, on the basis of selected examples from the literature representing the experimental evidence and the authors original interpretation, that the catalytic activity of palladium or its alloys changes sometimes dramatically, when there is a possibility of their being converted into the corresponding hydrides. 

The literature on sucrose loss in manufacture is extensive, but not all studies have been conducted on the principles of sound scientific method. An example from the literature of a study with questionable results is a report by Cecil,62 on the effect of pH on sucrose loss during boiling in the open-pan sulfitation (OPS) process. The OPS process is used in some tropical sugar cane growing areas to produce small amounts of a sugar product known as gur, panela, or piloncillo for local consumption. Juice (massecuite from Kenyan OPS mill diluted to 20... 

The problem of relationship between the activation parameters-the so called isokinetic relationship or compensation law—is of fundamental importance in structural chemistry, organic or inorganic. However, there are few topics in which so many misunderstandings and controversies have arisen as in connection with this problem. A critical review thus seems appropriate at present, in order to help in clarifying ideas and to draw attention to this treatment of kinetic or equilibrium data. The subject has already been reviewed (1-6), but sufficient attention has not been given to the statistical treatment which represents the heaviest problems. In this review, the statistical problems are given the first place. Theoretical corollaries are also dealt with, but no attempt was made to collect all examples from the literature. It is hoped that most of the important... 

In the following example from the literature [39], the correlahon with lipophilicity is studied for 47 compounds in two series which have been designed for dopamine D2 receptor affinity. As seen in Fig. 17.1, there is no clear relahon between D2 activity and lipophilicity (r=0.11). 

In another example from the literature [40], we see a strong correlation between potency and PSA. In this case a series of 53 CCR5 receptor agonists have been... 

These examples from the literature compiled by Babers indicate that resistance to different materials is developing among different species and in several localities. It may become more extensive with organic insecticides because of their more widespread use as well as the greater number of chemicals that will be applied in the field. 

The direct optimization of a single response formulation modelled by either a normal or pseudocomponent equation is accomplished by the incorporation of the component constraints in the Complex algorithm. Multiresponse optimization to achieve a "balanced" set of property values is possible by the combination of response desirability factors and the Complex algorithm. Examples from the literature are analyzed to demonstrate the utility of these techniques. 

In this chapter, I will try to present an introduction to these various techniques with emphasis on EXAFS and X-ray standing waves and their application to the study of electrochemical interfaces. Each technique will be treated from theoretical and experimental points of view, and selected examples from the literature will be employed to illustrate their application to the study of electrochemical interfaces. 

This chapter does not provide a detailed discussion or explanation of the modelling methods that are available to polymer scientists, but instead attempts to outline the methods that are available without going into too much technical detail, and illustrates, through examples from the literature, what can been achieved. References will be given to more detailed technical descriptions of the techniques discussed. 

A related example from the literature is the reaction of [(CO)4Cr(SnPh3)9] with [Me2N=CCl2]+, which yields the carbyne complex (CO)4(SnPh3)CrsCNMe, [17],... 

In this section, we will discuss some examples from the literature, in which the approximation methods derived in this chapter have been used. In several cases, the approximations have been compared with more-accurate path integral simulations to assess their validity. This is not meant as a full review rather, several case studies have been chosen to illustrate the tools we have developed. We will first look at simpler examples and then discuss water models and applications in enzyme kinetics. 

The selectivity in the Heck reaction of allylic alcohol 111 is interesting, and the factors that lead to the observed preference for (3-hydride elimination toward nitrogen in this system are unclear, although a combination of steric effects and stereoelectronic factors (i.e., alignment of C-H and C-Pd bonds, nN a c H interactions) is likely involved. Examination of related examples from the literature (Scheme 4.20) reveals no clear trend. Rawal and Michoud examined substrate 115, which lacks the influence of both the amine and hydroxyl substituents and also seems to favor (3-hydride elimination within the six-membered ring over formation of the exocyclic olefin under standard Heck conditions [18a]. However, under... 

The broadest class of models, phenomenological models, account explicitly for individual phenomena such as swelling, diffusion, and degradation by incorporation of the requisite transport, continuity, and reaction equations. This class of models is useful only if it can be accurately parameterized. As phenomena are added to the model, the number of parameters increases, hopefully improving the model s accuracy, but also requiring additional experiments to determine the additional parameters. These models are also typically characterized by implicit mean-field approximations in most cases, and model equations are usually formulated such that explicit solutions may be obtained. Examples from the literature are briefly outlined below. 

The following examples, from the literature and our own work, demonstrate some of the potential applications for Raman spectroscopy in the pharmaceutical sciences. 

When one of the reacting partners in the Wittig-Horner reaction, either the phosphine oxide or the carbonyl compound, has a double bond, the product is a diene. The Wittig-Horner reaction was utilized by Smith and coworkers in the total synthesis of milbemycin (equation 98)170. They found that when sodium hexamethyldisilazide was employed as a base, the desired E-diene selectivity is high (85%). Some examples from the literature where the Wittig-Horner reaction has been utilized for the construction of E-double bonds present in dienes and polyenes are given in Table 19171. 

As with the prior edition, this work will be of use not only to the dedicated "phosphorus chemist" but also to the practicing chemist who only occasionally is involved with organophosphorus chemistry, using it as an aspect of other synthetic pursuits. To this end, it contains numerous experimental examples from the literature with added notes from the authors own experiences in utilizing these reactions. It is intended to be not only a source of critical and annotated references but also a working guide for the chemist in the laboratory. 

There are several examples from the literature that show that corrosion has seriously (and often quickly) deteriorated sewer networks (EWPCA, 1982 Aldred and Eagles, 1982 ASCE, 1989). Although corrosion is difficult to predict, the number of examples and extent of the problems observed have given a comprehensive knowledge of where and when concrete corrosion may exist. This knowledge can briefly be summarized as follows. 

This chapter is designed to show how coordination chemistry may be studied in the gas phase and give some examples from the literature. The examples will mainly be from the past decade. This chapter will concentrate on ions studied by MS and cannot be comprehensive since the literature is too extensive. The literature involving coordination chemistry of gas-phase ions is very extensive and in many cases the quoted sources were often not aware of, or did not consider, the processes being observed as coordination chemistry. This chapter will concentrate on the reactions of transition metal systems and changes in coordination behavior. There will inevitably be similarities of gas- and condensed-phase behavior, but these instances may only be occasionally highlighted. 

The values obtained for the proton transfer in these four systems (Table IV) are typically as expected for these rapid processes. Examples from the literature where similar reactions were studied in metal complexes include the [Cr(OH)(OH2)]2+ (62) and [VO(OH2)5]2+ (63) systems. In the proton exchange study of the hexaaqua aluminate(III) system a bimolecular process, similar to that proposed for the systems in this study, for the exchange between the [Al(OH2)6]3+ and [Al(OH2)5(OH)]2+ (64) complexes was postulated. 

In Table 11.6 illustrative examples from the literature are enlisted which give the reader an impression about the different chemistries that can be mastered with these screening techniques. As can be seen, in some cases the individual advantages of a technique might overcome its general drawbacks, or at least render them less important. This strongly depends on the investigated chemistiy, e.g., mass-transfer limitations are in a number of cases not the main problem of liquid/liquid catalytic reactions. 

In cationic polymerisations it is commonly found that the degree of polymerisation (DP) changes abruptly as the concentration of one of the constituents of the reaction mixture is varied. These variations, especially the very sharp DP peaks, have not been explained hitherto in detail. A theory is developed which accounts quantitatively for all forms of DP variation in terms of neutralisation, or formation, or both successively, of chain-breaking agents, as the concentration of the relevant reactant is changed. The theory is illustrated by applying it to six examples from the literature. 

The Table lists the results of applying these modified conditions to a number of biaryl derivatives, including recent examples from the literature. With the exception of entry 6, that employs a non-reactive aromatic chloride, all the cross-couplings result in excellent yields and are indicative of the generality of this procedure. 

It is not our aim to provide here a comprehensive review of solid-state organic chemistry. We intend rather to dwell on the interplay between stereochemical factors and solid-state effects, using examples from the literature as illustrations. Before this elaboration, however, we provide a brief discussion of some relevant aspects of organic crystal structures and their roles in determining reaction course. 

The reactions of dienes and other polyenes can be broadly classified as either addition reactions, coupling (or substitution reactions) or rearrangements (including metathesis reactions). This chapter will present recent examples from the literature of synthetic transformations involving polyenes. Cycloaddition and ring closing metathesis reactions appeared in volume one of this series and therefore will not be covered in this chapter. Citations for more detailed descriptions of the individual reactions discussed in this chapter and for more comprehensive reviews appear in the text. 

The next generalization, number 3 above, has to do with the notion that two simple cations will react with one another less rapidly than a cation and an anion of corresponding size would. Table I presents examples from the literature, where, in every case, a proton reacts with species of different charge types, and there is a steady decrease in the rate of reaction as one proceeds from top to bottom in that table. 

Abstract Flow cytometry is a technique for rapidly examining multiple characteristics of individual cells, by recording fluorescence signals emitted from cell-associated reporter molecules, and measuring cellular light scattering properties. This chapter introduces the principles and practice of flow cytometry, and reviews examples from the literature that highlight applications of this experimental tool in the neurosciences. The chapter concludes with protocols for three basic procedures that illustrate some practical aspects of analytical flow cytometry. 

In this chapter, brief information shall be given on the relationship between SCCO2 properties, its solubiUzation power and its use as reaction medium for homogeneous catalysis. Current research activities from our laboratories [25] together with selected examples from the literature shall be presented, the focus being on making available criteria as to how to conduct those processes in future appUcations. 

A growing number of studies report on the occurrence of PFCs in food. The outcome of these studies has been related to potential dietary intake and exposure levels (mainly by the estimation of the daily intake). Most selected examples from the literature can be seen in Table 2. It is important to remark that PFOS and PFOA tend to bind to certain proteins rather than bioconcentrate in fat, but they have also some potential to bioaccumulate in the food chain. 

A few empirical and theoretical studies to postulate a general set of rules for the fabrication of asymmetric membranes by phase inversion mechanism (in which the polymer solution is coagulated within a nonsolvent bath) have been attempted. Thus, for example, from the literature which described the formation of asymmetric membranes, Klein and Smith (5) compiled working rules in the early 1970s regarding the requirements of a casting solution ... 

Some authentic examples from the literature are provided In excerpts 17E and 17F. 

This modification of the Curtius reaction has been used extensively in many laboratories and has been found to be generally applicable. Some examples from the literature include the stereoselective synthesis of a wide variety of cyclopropylamine derivatives from the corresponding acids,11-13 the stereoselective preparation of some substituted norbornylamines from easily isomerized acids,14 the preparation of some 1-aminocyelobutancearboxylic acids from the corresponding acid esters,18 the preparation of a substituted cyclobutanone from... 

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