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foundation of chemistry is the knowledge of molecular structure. Knowing how and at what distances atoms of different elements are bonded together in a 3-D architecture is central to the understanding of chemical reactivity and properties. Structural chemistry is an intrinsic part of our systemization of chemical knowledge. Just think of conducting your work as an analytical chemist without any image in your mind of the structure of the molecule whose concentration in a sample you are trying to determine. The gold standard of chemical structure determination has been—and remains—X-ray crystallography. Measuring atomic coordinates by the spatial scattering of X-rays is so heavily practiced, especially by chemists who fashion new structures, as to be an almost routine analytical step. But crystal structures have known foibles. The very forces that cause crystallization include interactions between molecular dipoles and the sharing of proton sites in hydrogen bonds; these can subtly alter molecular structure. So can the forces of solvation. X-ray crystal structures are also static pictures. Some chemists dream of measuring changes in structure in real time, during chemical reactions in solution or the gas phase. For example, reducing ferricyanide to ferrocyanide involves changes in the Fe–N bond lengths, which are known from crystal structures. The reorganization energy involved in changing the bond lengths strongly influences the kinetic rate of the electron-transfer reaction. Suppose that this bond-length change could be observed in real time. Such a capability, if made accessible to numerous laboratories and extended generally to many chemical reactions, would provoke a revolution in chemistry. This dream requires the determination of structure or structurally related properties on very short timescales—such as that of changing solvent coordinates, in the above example. This is a much harder task than we are currently capable of, but progress has been made. The most powerful general tool is NMR spectrometry, which, when implemented as a spin echo experiment, can produce structurally specific reaction dynamics on submicrosecond timescales. On slower time-
© 2005 AMERICAN CHEMICAL SOCIETY
scales, atomic force microscopy is able to probe bending and stretching of single (macro)molecules, and small-angle X-ray scattering can report on alterations in polymer fiber crystallinity that occur during stretching. Really fast (femtosecond) timescale changes have been resolved by electron tomography based on high-resolution transmission electron microscopy, but in these cases the dimension scales are relatively coarse, such as pores and cracks in nanoscale objects. Given the enormous significance of (faster) real-time structural information, new productive directions deserve attention. Two recent reports (Science 2005, 309, 1338–1343; Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 11,185–11,190) described extensions of NMR spin echo ideas to vibrational echoes, in which the measurement timescale is subpicosecond and structurally sensitive. These measurements are built upon technological improvements in ultrashort pulsed IR lasers. They involve producing a phased vibrational excitation of a structurally sensitive bond in the molecular population, followed by pulse probing of the dephasing to determine the timescale in which that bond becomes part of a different molecular arrangement as a result of a reaction. The results demonstrated that formation and dissociation of complexes between phenol and benzene, and between methanol and acetonitrile, occur on timescales of a few picoseconds. This finding pushes the meaning of “real-time” structurally specific measurements to timescales far below NMR capabilities. The reported chemical-exchange 2-D IR experiments are complex—but so was NMR in its birthing years. Assuming no unbreakable technological barriers exist to improving the spectroscopy equipment, we can hope for gradual improvements in the accessibility and generality of the application. Many time-dependent structural questions await maturation of this and even more profound, as yet undiscovered, measurement advances.
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