The application of theoretical tools for predicting molecular structure, such as ab initio calculations and density functional methods, are discussed in Chapter 6. These tools provide only a first approximation to the molecular structure. There is much room for further development of theoretical molecular structure calculations, but even so such methods have already become a standard part of molecular structure determinations.

The following section presents a variety of instrumental spectroscopic techniques for the determination either of molecular structure or of parameters related to molecular structure. The applicability of each method, its particular advantages as well as its limitations, are presented. It is not an exhaustive list. The spectroscopic methods are discussed in order of increasing excitation energy.

NMR has proven to be invaluable as a tool for structure determination, particularly of new compounds isolated from nature. All synthetic chemists use NMR to see whether they have made the product they want, even if it is a previously unknown molecule. In fact, NMR has really revolutionized the practice of organic synthesis. NMR is typically applied to molecules in solution, so it can be used with noncrystalline materials, for which x-ray crystallography is not possible. It also can be used to learn whether the structure determined in the solid state by x-ray methods is maintained in solution. This is particularly important for proteins, which are flexible enough that they can change shape to some extent when they dissolve. A Nobel Prize in 1991 went to Richard Ernst for inventing new techniques in NMR that are important tools in the study of proteins. Kurt Wüthrich shared a Nobel Prize in 2002 for developing NMR methodology that enables determination of the three-dimensional structures of biological macromolecules in solution.

NMR finds its main application in the analysis of solutions, using ¹H as the most sensitive nucleus; ¹³C, ¹⁹F, and ³¹P nuclei are also used frequently. NMR yields information on chemical functional groups of organic ligands and has revolutionized work in synthesis. Multi-dimensional techniques can be used for finding spatial connections between nuclei and gaining information on molecular dynamics. An important recent advance is NMR on solids, not solutions, with which it is possible to study the structures of polymers, of proteins in membranes, and of chemicals immobilized on solid supports. The application of NMR to imaging the human body, or magnetic resonance imaging (MRI), has revolutionized the practice of medicine.

The major current limitation of NMR is its sensitivity (ca. 10⁻⁴ M in ¹H, ¹³C, ¹⁹F, ³¹P). It is expected that higher sensitivities will be reached in the future as more powerful magnets with improved instrumentation and software become available. The ultimate goal would be to perform NMR analyses of single molecules.

Front Matter (R1-R14)

Executive Summary (1-10)

1 Introduction (11-15)

2 The Structures and Cultures of the Disciplines: The Common Chemical Bond (16-21)

3 Synthesis and Manufacturing: Creating and Exploiting New Substances and New Transformations (22-40)

4 Chemical and Physical Transformations (41-54)

5 Isolating, Identifying, Imaging, and Measuring Substances and Structures (55-70)

6 Chemical Theory and Computer Modeling: From Computational Chemistry to Process Systems Engineering (71-94)

7 The Interface with Biology and Medicine (95-122)

8 Materials by Design (123-147)

9 Atmospheric and Environmental Chemistry (148-159)

10 Energy: Providing for the Future (160-170)

11 National and Personal Security (171-179)

12 How To Achieve These Goals (180-194)

Appendix A: Biographical Sketches of Steering Committee Members (195-201)

Appendix B: Statement of Task (202-202)

Appendix C: Contributors (203-208)

Index (209-224)