Centre for Systems Chemistry, Stratingh Institute for Chemistry, Faculty for Science and Engineering, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
Department of Radiology, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Angew Chem Int Ed Engl. 2022 Jul 4;61(27):e202201308. doi: 10.1002/anie.202201308. Epub 2022 Mar 10.
Photolabile Protecting Groups (PPGs) are molecular tools used, for example, in photopharmacology for the activation of drugs with light, enabling spatiotemporal control over their potency. Yet, red-shifting of PPG activation wavelengths into the NIR range, which penetrates the deepest in tissue, has often yielded inefficient or insoluble molecules, hindering the use of PPGs in the clinic. To solve this problem, we report herein a novel concept in PPG design, by transforming clinically-applied NIR-dyes with suitable molecular orbital configurations into new NIR-PPGs using computational approaches. Using this method, we demonstrate how Cy7, a class of NIR dyes possessing ideal properties (NIR-absorption, high molecular absorptivity, excellent aqueous solubility) can be successfully converted into Cy7-PPG. We report a facile synthesis towards Cy7-PPG from accessible precursors and confirm its excellent properties as the most redshifted oxygen-independent NIR-PPG to date (λ =746 nm).
光不稳定保护基团 (PPG) 是一种分子工具，例如在光药理学中用于用光激活药物，从而实现对其效力的时空控制。然而，将 PPG 激活波长红移到近红外 (NIR) 范围（在组织中穿透最深）通常会产生效率低下或不溶性分子，从而阻碍了 PPG 在临床上的应用。为了解决这个问题，我们在此报告了一种新的 PPG 设计概念，通过使用计算方法将具有合适分子轨道构型的临床应用的近红外染料转化为新型近红外 PPG。使用这种方法，我们展示了如何将 Cy7（一类具有理想性质（近红外吸收、高分子吸光度、出色的水溶性）的近红外染料）成功转化为 Cy7-PPG。我们报告了一种从易得前体制备 Cy7-PPG 的简便合成方法，并证实了它作为迄今为止最红移的氧独立性近红外 PPG 的优异性质（λ =746 nm）。
