Azobenzenes are versatile photoswitches that can be used to generate elaborate optical tools including photopharmaceuticals. However, the targeted application-guided design of new photoswitches with specific properties remains challenging. We have developed synthetic protocols for derivatives of the dfdc (di-ortho-fluoro-di-ortho-chloro) azobenzene scaffold with chemical alterations in the para-/ortho-positions and performed an in-depth study into their photophysical properties with an emphasis on the n → π* absorption band using NMR, UV-vis and X-ray analysis. The data was used to establish a computational approach that allows to compute realistic UV-vis spectra by combining TD-DFT excited-state calculations from 6000 thermally accessible structures generated through MD simulations of these structurally flexible ortho-substituted azobenzenes. We added 15 new visible light-operated photoswitches to the toolbox for the development of optical devices with relaxation rates across multiple orders of magnitudes and identified several examples with stronger bathochromic shifts than the dfdc azobenzene lead structure. Our combined experimental and computational study forms the foundation for the advanced in silico design and synthesis of new highly red-shifted photoswitches. To showcase the potential of dfdc azobenzenes for the development of chemical tools, we synthesized dfdc-OptoBI-1 and demonstrated its biological activity as a red light-operated activator of TRPC6 channels in HEK293 cells.

中文翻译：

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高度红移偶氮苯基光学工具开发平台

偶氮苯是多功能的光开关，可用于生成包括光药在内的复杂光学工具。然而，具有特定特性的新型光开关的有针对性的应用导向设计仍然具有挑战性。我们开发了 dfdc（二邻氟-二邻氯）偶氮苯支架衍生物的合成方案，在对位/邻位发生化学改变，并使用 NMR、UV-vis 和 X 射线分析对其光物理特性进行了深入研究，重点是 n → π* 吸收带。这些数据用于建立一种计算方法，该方法允许通过结合 TD-DFT 激发态计算来计算真实的紫外-可见光谱，这些结构是通过这些结构柔性邻位取代偶氮苯的 MD 模拟生成的 6000 个热可及结构。我们在工具箱中添加了 15 个新的可见光作光开关，用于开发具有多个数量级弛豫率的光学器件，并确定了几个比 dfdc 偶氮苯铅结构具有更强的深变色偏移的例子。我们的实验和计算研究相结合，为先进的计算机设计和合成新的高度红移光开关奠定了基础。为了展示 dfdc 偶氮苯在化学工具开发中的潜力，我们合成了 dfdc-OptoBI-1 并证明了其在 HEK293 细胞中作为 TRPC6 通道的红光激活剂的生物活性。