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Single-Molecule Chemistry
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ver the course of the past year, I had occasion to study some of the beginnings of single-molecule spectroscopy (SMS), which emerged in the 1980s. The importance of this subject—and indeed many, if not most, subsequent SM experiments—lies in the detection and study of the properties of individual molecules. Researchers began to recognize that the electronic absorbance and emission spectra of large groups of molecules (i.e., bulk samples) represent ensemble averages. The averaging conceals the diversity of actual molecular behavior that does exist and thereby denies the chemist a deeper understanding of molecular properties. Imagine observing a dissolved phenol molecule on as small a timescale and as short a distance scale as you would like. In methanolic solution, a diversity of solvation states will exist at any given time—the methanol dipoles interact with the hydroxyl site in a variety of orientations and form a variety of hydrogen bond interactions. The electronic absorbance spectra (and emission spectra from excited states) will differ to some degree across the solvation states. The underlying electronic-state differences would evoke a range of chemical reactivities of the phenol; for example, in proton dissociation, a range variety of dynamic behavior and of microscopic pK values would exist. The preceding experiment has not been achieved (as far as I know), but it illustrates the direction of SMS introduced by Moerner in 1987. He measured the optical absorbance of pentacene dissolved in a terphenyl host crystal at 1.5 K and subsequently, in 1991, measured the corresponding fluorescence emission. Although most pentacene molecules emitted at energies near the average, some emitted at energies different enough to allow their discrete emissions to be measured. Furthermore, their emission energies sometimes changed, abruptly or gradually. The behavior was interpreted as thermal rearrangements in the environment of the pentacene in the host crystal. This beginning has led to widespread interest in SMS and the introduction of new experimental SM tactics that allow measurements at room temperature, in solutions, and on surfaces. The fluorescence emissions of isolated molecules resting on surfaces and of lone molecules in highly dilute and/or confined solution volumes have been widely reported. Fascinating molecular variances have emerged. For example, SM spectroelectrochemistry shows variations in the electrochemi© 2007 AMERICAN CHEMICAL SOCIETY
cal oxidation potentials of individual, adsorbed, conducting polymer molecules. Individual enzymes in confined solution volumes exhibit variations in their reaction rates with substrates. Fluorescence microscopy has revealed a range of DNA bending and turning behavior during alternating-field gel electrophoresis. Surface-enhanced Raman emission of molecules at nanoparticle surfaces can sometimes be so highly enhanced as to illuminate SMs. Emitting molecules often exhibit photoblinking, which means that they alternate between highly emissive and nonemissive states, for a plethora of possible reasons. The advanced state of technology associated with force microscopy has produced other, nonphotonic avenues to SM investigation. In these experiments, the force(s) required to bend, stretch, or twist a molecule are measured by anchoring one end of it and measuring the force required to move the other end with some kind of probe tip or optical tweezers. This can even be done while the captured molecule undergoes a chemical reaction. SM force measurements are mostly applied to biomolecules; they are large and more readily tethered and are typically folded in complex ways. Thus, SM force experiments open an important new window to understanding the energetics and dynamics of the internal bonding events that govern folding processes. This has evoked a high state of excitement in the biophysics and biochemistry communities. A recent issue of Science (May 25, 2007) has a special section on SM, including force measurements. Molecular mechanics has taken on a new meaning! I have by no means exhausted mention of the range of known SM experimental strategies. Publications dealing with SM measurements number in the thousands, and the momentum of this exciting field shows no sign of slackening. The words “single molecule” have great cachet, and the scientific impact, including that on analytical chemistry, has been significant. I close by pointing to Analytical Chemistry’s March 2007 Editorial (p 1765), which reaffirms that this journal’s scope encompasses fundamental and practical applications of how to measure important chemical parameters. Certainly those of single-molecule environments qualify!
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