Practical Application, Recent Example

CHAPTER 7 High-Throughput Screening and Drug Discovery 

Notwithstanding its relatively recent introduction, it was anticipated that HTS, in conjunction with combinatorial chemistry, would provide a large positive impact on drug discovery productivity and perhaps even identify potential drug candidates directly from large libraries of compounds. 

Tecfinologies Membrane preparations Fluorescence Cell-based fluorescence 

Lead sources Corporate historical Drug Compound acquisition 

Lombardino, J. G., Lowe, J. A. The role of medicinal chemistry in drug discovery - then and now. Nat. Rev. Drug Discov. 2004, 3, 853-862. 

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Other poly(saccharides) find practical applications. For example, konjac and carrageenan have numerous cosmetic and medical uses. Konjac is used in controlled release applications and as a barrier film to protect wounds. Carrageenans are used in dentifrices, hand lotions, shaving creams, shampoos and controlled release systems.i Poly(saccharides) derived from fungi have been shown to possess anti-tumor properties, and some recent research suggests curdlan sulfate may have antiviral activity, including potential anti-AIDS activity. The topic of biologically active poly(saccharides) has been reviewed recently.2 ... 

Cheap methanol may be used as a carbon source to replace carbohydrate in the microbial production of chemicals. For example, polyhydroxybutyrate (PHB), a biodegradable thermoplastic material, can be produced by microbial fermentation. However, its hi cost restricts large-scale application. The cost of the substrate is an important contributing factor to the overall cost of production. The use of methanol to produce PHB, if successfully developed without sacrificing the molecular weight, would significantly improve process economics and increase its practical application. Recent studies have shown promising results [58, 84, 85]. 

Recently, macrocyclic chiral compounds of crown ether or cyclamen type have been attracting wide interest. These compounds contain numerous heteroatoms in their molecules (mainly oxygen, sulfur, and nitrogen) and can find practical applications, for example, as chiral selectors [69,70] and chiral NMR discriminating agents [71]. Asymmetric substitution of two carbon atoms in the ring of crown ether or cyclamen can lead to many different optically active compounds useful in various branches of supramolecular chemistry. Such substitution can be accomplished with appropriate starting compounds that are optically active, for example, amino acids and polyhydroxy alcohols. 

The study of acid-base interaction is an important branch of interfacial science. These interactions are widely exploited in several practical applications such as adhesion and adsorption processes. Most of the current studies in this area are based on calorimetric studies or wetting measurements or peel test measurements. While these studies have been instrumental in the understanding of these interfacial interactions, to a certain extent the interpretation of the results of these studies has been largely empirical. The recent advances in the theory and experiments of contact mechanics could be potentially employed to better understand and measure the molecular level acid-base interactions. One of the following two experimental procedures could be utilized (1) Polymers with different levels of acidic and basic chemical constitution can be coated on to elastomeric caps, as described in Section 4.2.1, and the adhesion between these layers can be measured using the JKR technique and Eqs. 11 or 30 as appropriate. For example, poly(p-amino styrene) and poly(p-hydroxy carbonyl styrene) can be coated on to PDMS-ox, and be used as acidic and basic surfaces, respectively, to study the acid-base interactions. (2) Another approach is to graft acidic or basic macromers onto a weakly crosslinked polyisoprene or polybutadiene elastomeric networks, and use these elastomeric networks in the JKR studies as described in Section 4.2.1. 

It is of special interest for many applications to consider adsorption of fiuids in matrices in the framework of models which include electrostatic forces. These systems are relevant, for example, to colloidal chemistry. On the other hand, electrodes made of specially treated carbon particles and impregnated by electrolyte solutions are very promising devices for practical applications. Only a few attempts have been undertaken to solve models with electrostatic forces, those have been restricted, moreover, to ionic fiuids with Coulomb interactions. We would hke to mention in advance that it is clear, at present, how to obtain the structural properties of ionic fiuids adsorbed in disordered charged matrices. Other systems with higher-order multipole interactions have not been studied so far. Thermodynamics of these systems, and, in particular, peculiarities of phase transitions, is the issue which is practically unsolved, in spite of its great importance. This part of our chapter is based on recent works from our laboratory [37,38]. 

In recent years, the rate of information available on the use of ion-exchange resins as reaction catalysts has increased, and the practical application of ion-exchanger catalysis in the field of chemistry has been widely developed. Ion-exchangers are already used in more than twenty types of different chemical reactions. Some of the significant examples of the applications of ion-exchange catalysis are in hydration [1,2], dehydration [3,4], esterification [5,6], alkylation [7], condensation [8-11], and polymerization, and isomerization reactions [12-14]. Cationic resins in form, also used as catalysts in the hydrolysis reactions, and the literature on hydrolysis itself is quite extensive [15-28], Several types of ion exchange catalysts have been used in the hydrolysis of different compounds. Some of these are given in Table 1. 

The material discussed in our paper, not being comprehensive, is focused mostly on the application of these methodologies in practical synthesis. It provides a general overview of the synthetic methodologies for such important compounds and is illustrated by selected and recent examples from the original literature. 

Bunz et al. pointed out that it would be of interest to develop materials that combine the stability, electron affinity, and high emissive quantum yield of PPEs with the excellent hole injection capabilities of poly(p-phenylene vinylene)s (PPVs) [48]. In line with this notion,recent synthetic activities have focused on the engineering of the band gap, conduction band, and valence band of PAEs with the objective to render these materials more useful for practical applications that exploit their electrically (semi)conducting nature. Examples of materials that emerged from these efforts are discussed in detail in other portions of this volume (in particular the chapters by Bunz, Klemm, and Yamamoto). They include, among others, poly(heteroarylene ethynylenes) such... 

A final caveat that must be applied to phase diagrams determined using DFT calculations (or any other method) is that not all physically interesting phenomena occur at equilibrium. In situations where chemical reactions occur in an open system, as is the case in practical applications of catalysis, it is possible to have systems that are at steady state but are not at thermodynamic equilibrium. To perform any detailed analysis of this kind of situation, information must be collected on the rates of the microscopic processes that control the system. The Further Reading section gives a recent example of combining DFT calculations and kinetic Monte Carlo calculations to tackle this issue. 

A recent development in nuclear medicine that illustrates how advances in basic research are transformed into practical applications is positron emission tomography or PET. PET creates a three-dimensional image of a body part using positron emitting isotopes. Positrons, positively charged electrons, are a form of antimatter. Antimatter consists of particles that have the same mass as ordinary matter, but differ in charge or some other property. For example, antipro-... 

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