Funding from the Analytical and Surface Chemistry Program supports the efforts of Professor Clark Landis of the University of Wisconsin at Madison to study fast chemical reaction kinetics using nuclear magnetic resonance (NMR) spectroscopy. The research merges the information-rich nature of NMR spectroscopy with fast kinetics capabilities by exploring all critical elements of a stopped-flow NMR technique: theory, computational modeling, probe construction and evaluation, and application to chemical reactions. Probe construction activities focus on combining stopped-flow reaction technology with flow NMR capabilities. Both Helmholtz coil and toroid cavity resonators are being developed with the goal of lowering the range of accessible reaction half-lives from ca. 100 seconds to a few milliseconds. Both types of flow probe will be fitted with practical drive systems and the ability to handle air sensitive reagents. Practical realization of stopped-flow NMR capabilities requires understanding of how the spectra are affected by reaction kinetics and various artifacts. Computational procedures for simulation and fitting of experimental data according to any arbitrary kinetic model are being developed, verified, and disseminated. The power of stopped-flow NMR is illustrated by kinetic studies of fast catalytic processes such as metal-catalyzed alkene polymerization.
Because the NMR method can be applied generally, impact of the proposed research spans diverse kinetic processes such as protein folding, catalytic transformations (such as enzymatic, organometallic, or organocatalytic), and other chemical reactions. Products of this research include (1) publications that educate the research community on the capabilities of NMR for studying fast reactions, (2) software methods for simulating NMR spectra of fast reactions, (3) detailed plans and performance evaluations of new NMR probes based on adaptation of flow probes or construction of new toroid cavities, and (4) new classroom materials concerning chemical kinetics and NMR methods. The development of human resources, primarily undergraduate and postdoctoral researchers, results from intimate exposure to an unusually broad array of research issues, ranging from electronics to flow dynamics and chemical catalysis.
Our research addresses a bottleneck in current research capabilities – efficiently obtaining detailed kinetics of fast chemical transformations with an "information-rich" spectroscopic method, nuclear magnetic resonance– through the development of new stopped-flow NMR probes. Intellectual Merit. NMR is arguably the most useful spectroscopic method for monitoring organic, biological, and organometallic materials because the spectra are so rich in easily interpreted information. Although the fundamental theory and capabilities of NMR for monitoring fast chemical reactions were first described a quarter of a century ago, the lack of suitable instrumentation and methods for interpreting spectra of more complex but common reaction scenarios have prevented exploitation. Our research has created the new generation of NMR probe technology through the application of theory, computational modeling, probe construction and evaluation, and validation by application to prototypical fast chemical reactions. Our work resulted in the development and evaluation of practical NMR probes suitable for kinetic studies. We have decreased the range of accessible kinetics from half-lives of approximately 5 seconds to 30 milliseconds. Our first level of development concerns the adaptation of currently available flow probe technology to fast reaction kinetics. This work demonstrated that simple adaptation of existing flow probes to the stopped-flow mode can be practically performed in any Chemistry facility. A second level of development is still ongoing and will result in new probes with mixing times less than 10 milliseconds. Both types of flow probe have been fitted with practical drive systems and the ability to handle air sensitive reagents. Practical realization of stopped-flow NMR capabilities requires understanding of how the spectra are affected by reaction kinetics and various artifacts. Computational procedures for simulation and fitting of experimental data according to any arbitrary kinetic model have been developed, verified, and disseminated. Our probe work has explored the application of a new detectors in stopped-flow environments. Although significant progress was made with toroid coils we have demonstrated that Helmholtz coil technology represents the combination of sensitivitiy and line shape. Importantly, our work has demonstrated the practical application of stopped-flow NMR to difficult, air-sensitive reaction systems such as catalytic alkene polymerization. Fundamental advances in global kinetics analysis, active site counting, and characterization of transient intermediates have resulted. These applications have advanced our opportunities for rapidly gathering fundamental information on the economically important processes. Broader Impacts. Chemical kinetics studies (1) play a central role in practical applications of chemistry such as optimization of industrial processes and reactors and modeling complex chemical networks such as atmospheric chemistry, pharmacokinetics, corrosion, environmental processing of pollutants, and chemical basis of living systems and (2) constitute the prima facie evidence from which reaction mechanisms are derived. Because the NMR method is so general, impact of the proposed research spans such diverse processes as protein folding, catalytic transformations (such as enzymatic, organometallic, and so-called organocatalysts), and synthetic organic reactions.
