Boëtius Melody E, Hoorens Mark W H, Ošťadnický Martin, Laurent Adèle D, di Donato Mariangela, van Wingaarden Aldo C A, Hilbers Michiel F, Feringa Ben L, Buma Wybren Jan, Medveď Miroslav, Szymanski Wiktor
Department of Radiology, Medical Imaging Center, University Medical Center Groningen Hanzeplein 1 9713GZ Groningen The Netherlands
Center for Systems Chemistry, Stratingh Institute for Chemistry, University of Groningen Nijenborgh 7 Groningen The Netherlands.
Chem Sci. 2024 Jul 26;15(35):14379-89. doi: 10.1039/d4sc01457j.
Visible-light-operated photoswitches are of growing interest in reversibly controlling molecular processes, enabling for example the precise spatiotemporal focusing of drug activity and manipulating the properties of materials. Therefore, many research efforts have been spent on seeking control over the (photo)physical properties of photoswitches, in particular the absorption maxima and the half-life. For photopharmacological applications, photoswitches should ideally be operated by visible light in at least one direction, and feature a metastable isomer with a half-life of 0.1-10 seconds. Here we present our efforts towards the engineering of the half-life of iminothioindoxyl (ITI) photoswitches, a recently discovered class of visible-light-responsive photochromes, whose applicability was hitherto limited by half-lives in the low millisecond range. Through the synthesis and characterization of a library of ITI photoswitches, we discovered variants with a substantially increased thermal stability, reaching half-lives of up to 0.2 seconds. Based on spectroscopic and computational analyses, we demonstrate how different substituent positions on the ITI molecule can be used to tune its photophysical properties independently to fit the desired application. Additionally, the unique reactivity of the ITI derivative that featured a perfluoro-aromatic ring and had the most long-lived metastable state was shown to be useful for labeling of nucleophilic functional groups. The present research thus paves the way for using ITI photoswitches in photopharmacology and chemical biology.
可见光操作的光开关在可逆控制分子过程方面越来越受到关注，例如能够实现药物活性的精确时空聚焦以及操纵材料的性质。因此，人们在寻求对光开关的（光）物理性质进行控制方面投入了大量研究精力，特别是吸收最大值和半衰期。对于光药理学应用而言，理想情况下光开关应能在至少一个方向上由可见光操作，并具有半衰期为0.1至10秒的亚稳态异构体。在此，我们展示了我们在工程化亚胺硫代吲哚酚（ITI）光开关半衰期方面所做的努力，ITI是最近发现的一类可见光响应型光致变色化合物，其适用性迄今受限于低毫秒范围内的半衰期。通过合成和表征一系列ITI光开关，我们发现了热稳定性大幅提高的变体，半衰期可达0.2秒。基于光谱和计算分析，我们展示了如何利用ITI分子上不同的取代基位置独立调节其光物理性质，以适应所需的应用。此外，具有全氟芳环且具有最长寿命亚稳态的ITI衍生物的独特反应性被证明可用于标记亲核官能团。本研究因此为在光药理学和化学生物学中使用ITI光开关铺平了道路。
