Advanced Topics

As indicated in Chapter 1, this book has been designed to be an introduction to fluorine NMR and to serve as a practical handbook for use by organic chemists involved in the synthesis of fluorinated organic compounds, with an emphasis on characterization of lightly fluorinated organic compounds. It is meant to serve as a primary source of fluorine, proton, carbon, and to a more limited extent phosphorous and nitrogen 

one would be remiss if one did not at least mention the various analytical and diagnostic NMR techniques that have come into prominent use over the last decade, particularly with respect to their applications to drug discovery. Because of the sensitivity of its chemical shift to local environment, 19F NMR has increasingly been used as a probe in the study of structure and dynamics of small molecules, proteins, and other biological systems.32-36 

19F NMR-based screening has become widely used as a powerful and reliable tool in the identification of potential drug candidates.40-42 

The use of fluorine labeled ligands or substrates allows one, via 19F NMR, to detect weak intermolecular interactions. One such technique (FAXS - Fluorine chemical shift Anisotropy and exchange for Screening) utilizes a fluorine-containing spy molecule to monitor changes in the transverse relaxation rate of the 19F resonance in the presence of a series of test compounds.43 

The use of two-dimensional (2D) NMR techniques has become almost routine for a detailed analysis of complex organic molecules containing carbon and hydrogen. In contrast, 2D 19F NMR methods are not nearly so commonly used in the analysis of fluorine-containing molecules. The reasons for this are generally a combination of instrumental requirements combined with intrinsic differences between fluorine and proton NMR, in particular the wide range of 19F chemical shifts, which to an extent negates the need for 2D, but also can create problems, for example, with respect to uniform excitation of the entire 19F bandwidth. 

Yet another topic involves the extension of the synthesis methods to processes with multiple solutes. Here, the impact of concentration on the slope of phase equilibrium Eq. (11.4) may become a factor for highly nonideal solutions at high concentrations. The analysis techniques presented herein can be extended when the slopes of the equilibrium curves can be approximated as constant, independent of mixture composition. Also, the analyses are simplified when the minimum external MSA for the principal solute is capable of removing the other solutes as well (El-Halwagi and Manousiouthakis, 1989). 

Finally, it is possible to synthesize HENs and MENs simultaneously, for example, in the design of heat-integrated distillation networks (Bagajewicz and Manousiouthakis, 1992 Bagajewicz et al., 1998). 

Bagajewicz, M.J., and V. Manousiouthakis, Mass/Heat-Exchange Network Representation of Distillation Networks, AIChE J., 38(11), 1769(1992). 

El-Halwagi, M.M., Pollution Prevention Through Process Integration Systematic Design Tools, Academic Press, San Diego (1997). 

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At one time, computational chemistry techniques were used only by experts extremely experienced in using tools that were for the most part difficult to understand and apply. Today, advances in software have produced programs that are easily used by any chemist. Along with new software comes new literature on the subject. There are now books that describe the fundamental principles of computational chemistry at almost any level of detail. A number of books also exist that explain how to apply computational chemistry techniques to simple calculations appropriate for student assignments. There are, in addition, many detailed research papers on advanced topics that are intended to be read only by professional theorists. 

This book was designed to aid in research, rather than as a primary text on the subject. However, students may find some sections helpful. Advanced undergraduate students and graduate students will find the basic topics and applications useful. Beginners are advised to first become familiar with the use of computational chemistry software before delving into the advanced topics section. It may even be best to come back to this book when problems arise during computations. Some of the information in the advanced topics section is not expected to be needed until postgraduate work. 

The development of the probabilistic design approach, as already touched on, includes elements of probability theory and statistics. The introductory statistical methods discussed in Appendix I provide a useful background for some of the more advanced topics covered next. Wherever possible, the application of the statistical methods is done so through the use of realistic examples, and in some cases with the aid of computer software. 

The latest research results are deliberately not included. That is, this book is a fundamental teaching text, not a monograph on contemporary composite materials and structures topics. Thus, topics are chosen for their importance to the basic philosophy which includes simplicity of presentation and absorbability by newcomers to composite materials and structures. More advanced topics as well as the nuances of covered topics can be addressed after this book is digested. 

The intended audience of the second volume entitled Chemical Thermodynamics Advanced Applications is the advanced student or research scientist. We have used it, independently of the first volume, as the text for an advanced topics graduate level course in chemical thermodynamics. It can also serve as an introduction to thermodynamic studies involving more specialized disciplines, including geology, chemical separations, and biochemistry, for the research scientist in or outside of those disciplines. We hope it will be especially helpful for non-thermodynamicists who might be unfamiliar with the power and utility of thermodynamics in diverse applications. Given the more advanced nature of the material covered here, problems are only provided at the end of the chapters in this volume. Taken together, the two volumes make an excellent reference source for chemical thermodynamics. 

This chapter will present more advanced topics than those of the first chapter in terms of determining the structure of solids. Consequently, you will gain some knowledge of how one goes about determining the structure of a solid, even if you never have to do it. 

Readers interested in such advanced topics are referred to a number of texts that describe these more complex pharmacokinetic models in detail [1-5] and to the website http //www.boomer.org/pkin/. 

Hirtzel, C. s. Rajagopalam, R. "Colloidal Phenomena Advanced Topics," Noyes Pubs., New Jersey, 1985, pp 88 97. 

Liebman, J. F., Greenberg, A., and Williams, R. E. (1988). Advances in Boron and the Boranes. VCH Publishers, New York. A collection of advanced topics on all phases of boron chemistry. 

There are numerous major textbooks covering various aspects of GC. For more detail and advanced topics related to GC, the reader is referred to these. 

ADVANCED TOPICS SITE SELECTIVE SPECTROSCOPY AND EXCITED STATE ABSORPTION... 

In this section, we will describe two advanced topics that are directly related to the spectroscopy of trivalent rare earth ions. 

ADVANCED TOPIC THE APPLICATION TO OPTICAL TRANSITIONS OP KRAMERS IONS... 

We will not treat in ary detail in this chapter the more advanced topic of scattering of X-rays by distorted crystals. Appropriate theory will be introduced in later chapters as required. In this section we will merely give qualitative descriptions of the effects of various imperfections and qnote some results. 

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