Researchers from the Universities of Groningen and Amsterdam in the Netherlands, in collaboration with Italy’s European Laboratory for Non-Linear Spectroscopy, have made significant advancements in photoclick chemistry. By implementing strategic molecular substitution, they have greatly improved the reactivity of the widely-used PQ-ERA reaction, resulting in higher quantum yields and reaction rates.
Their findings were recently published in the journal Chemical Science, the flagship publication of the Royal Society of Chemistry, and the paper was recognized as a HOT Article and Pick of the Week. The research was a joint effort between scientists at the University of Amsterdam, including Michiel Hilbers and Wybren Jan Buma of the Molecular Photonics group, and researchers from the University of Groningen, led by Wiktor Szymanski and Nobel laureate Ben Feringa.
Photoclick chemistry is a specialized form of click chemistry, which was awarded the Nobel Prize in Chemistry in 2022, that utilizes light activation to facilitate efficient chemical reactions and produce desired products. This method offers precise spatial and temporal control over the reaction and has a wide range of applications, including 3D printing, protein labeling, and bioimaging.
One particular photoclick reaction of interest is the PQ-ERA reaction, which involves the light-induced photocycloaddition of 9,10-phenanthrenequinone (PQ) with electron-rich alkenes (ERA). This reaction has garnered attention due to its favorable kinetics and compatibility with biological systems. However, the conventional PQ compounds used in this reaction have limited reactivity, resulting in lower overall efficiency.
To address this limitation, the international research team developed a simple strategy to enhance the reactivity of the PQ triplet state in the PQ-ERA reaction. They achieved this by introducing a thiophene substitution at the 3-position of the PQ scaffold. Through nanosecond time-resolved spectroscopic studies and quantum chemical studies conducted in the Amsterdam Molecular Photonics group, along with femtosecond time-resolved spectroscopic studies carried out in Florence, the researchers gained a fundamental understanding of this specific photoclick chemistry.
The investigations revealed that the thiophene substitution significantly increased the population of the reactive triplet state (3ππ*) during excitation of 3-thiophene PQs. This resulted in a remarkable photoreaction quantum yield, with values reaching up to 98%, as well as high second-order rate constants (k2 up to 1974 M−1 s−1) and notable oxygen tolerance within the PQ-ERA reaction system.
These advancements in photoclick chemistry pave the way for further improvements in the PQ-ERA reaction, offering promising prospects for fast and efficient photoclick transformations. The researchers hope that their work will contribute to the development of more efficient and versatile chemical reactions in various fields of science and technology.
The study, titled “Establishing PQ-ERA photoclick reactions with unprecedented efficiency by engineering the nature of the phenanthraquinone triplet state,” was authored by Youxin Fu, Georgios Alachouzos, Nadja A. Simeth, Mariangela Di Donato, Michiel F. Hilbers, Wybren Jan Buma, Wiktor Szymanski, and Ben L. Feringa. It was published on June 21, 2023, in Chemical Science.