Radicals, i.e. molecules with an unpaired electron, are involved as short-lived intermediates in many chemical transformations. While radicals have already played an import role in organic synthesis and macromolecular chemistry for almost a century, recent decades have witnessed a hype in radical chemistry: Photocatalysis, organic electronics, atmospheric chemistry, and enzyme catalysis are just few examples of eminent current research activities. Electron Paramagnetic Resonance (EPR) is the most important method to investigate structure and reactivities of radicals. However, the presently available techniques either allow to detect radicals with high sensitivity (steady-state cw-EPR) or provide high time resolution. We have now developed a method, Ultrawide Single Sideband Phase-Sensitive Detection Time Resolved EPR (U-PSD TREPR), which combines both aspects and allows to detect radicals with an approximately two orders of magnitude higher sensitivity compared to conventional TREPR, without compromising time resolution. This new and universal method can be expected to open a new chapter in radical chemistry.
2. Our solution
Our scientific and technological innovation lies in the development of a novel PSD technique, U-PSD, which utilizes a precisely controlled sequence of laser pulses and magnetic field modulation to generate quadrature-modulated EPR signals. A unique algorithm allows effectively eliminating aliasing image signals and 1/f noise without distorting the desired signal. This innovation enables the accurate retrieval of transient EPR signals, resulting in first-derivative EPR spectra with both high time resolution and exceptional sensitivity.
The prototype demonstrated outstanding performance with a time resolution of 40 ns and a sensitivity of ~1 μM radical. This advancement enables the detection of weak signals of transient radicals in a solution-phase chemical reaction over a wide time range, which was previously not applicable with existing TREPR techniques. This is evident from the comparisons between the two methods. It highlights the unique capabilities of our U-PSD EPR technique.
3. “Seeing the unseen” by U-PSD TREPR
Visualizing the transient radical intermediates directly in reactions is a dream of radical chemists.
Here, we present the first direct observation of all open-shell intermediates in a full photocatalytic cycle using this technique, which provides mechanistic insights into the photocatalytic radical reaction with an unprecedented level of detail. Showcased with a prototypical photocatalytic reaction, we directly observed all radicals and radical ions involved in the photocatalytic addition of a tertiary amine to tert-butyl acrylate. The full picture of the photocatalytic cycle has been vividly illustrated by the fine structures, chemical kinetics, and dynamic spin polarization of all open-shell intermediates directly observed in this prototypical system, thereby offering direct evidence and deeper insights into the reaction mechanism.
It is worth emphasizing that experimental TREPR spectra obtained in photocatalytic systems typically carry valuable information about the origin and fate of radical pairs. As the initial electron transfer (SET) between the excited state of a photocatalyst and a radical precursor can occur either in its excited singlet state or triplet state, and back electron transfers might help regenerating the photocatalyst or suppressing the quantum efficiencies, a distinction between these mechanisms is crucial for comprehending the mechanism and optimizing the efficiency of a photocatalytic reaction, which is, however, a rather challenging task for TA spectroscopies. The CIDEP spectrum obtained through U-PSD TREPR provides us with valuable insights of these processes. This not only deepens our understanding of reaction mechanisms but also contributes to the advancement of new photocatalytic reactions.
4. Potential applications
Radicals play a pivotal role in numerous processes, making our method highly versatile and applicable across diverse scientific disciplines. Beyond the realm of synthetic organic chemistry, our focus will extend to fostering interdisciplinary collaborations that will uncover the method’s potential applications in a variety of scientific fields, such as solar energy science, polymer science, chemical biology, and so on. This will highlight the far-reaching impact of the U-PSD TREPR technique and its capacity to stimulate advancement across numerous scientific disciplines.
In summary, our research endeavors underscore fundamental breakthroughs in time-resolved EPR methodology. We are confident that these initiatives will open a new chapter in free radical chemistry research and related fields.
