Aydogan-Sun Yagmur, Egyed Alexandra, Winter Arthur H, Wachtveitl Josef
Institute of Physical and Theoretical Chemistry, Goethe-University Frankfurt, Frankfurt am Main 60438, Germany.
Department of Chemistry, Iowa State University, Ames, Iowa 50010, United States.
J Am Chem Soc. 2025 Aug 6;147(31):28002-28014. doi: 10.1021/jacs.5c07710. Epub 2025 Jul 28.
Photocages enable light-triggered cargo release in biological systems, but their excitation is often restricted to UV/visible wavelengths, where tissue penetration is limited. Two-photon excitation (2PE) offers a solution by allowing near-infrared (NIR) or short-wave infrared (SWIR) activation within biological windows of maximal tissue transparency. While photocaging in the first biological window (650-950 nm) has been demonstrated, applications in the second biological window (1000-1350 nm) remain unexplored. Here, we investigate the two-photon absorption (2PA) properties of 11 BODIPY photocages featuring single-photon absorption spanning 450-750 nm, focusing on 3- and 5-position substitutions to identify key motifs that enhance 2PA in the 900-1500 nm range. We find that strong charge transfer character and increased vibrational freedom can relax symmetry-related selection rules, significantly enhancing 2PA. Cross sections (δ) exceeded 4000 GM at 900 nm for a bis(styryl)-BODIPY with carbazole units and reached 1110 GM at 1240 nm for its monostyryl analog. Two additional B-methylated molecules with improved uncaging quantum yields were synthesized, yielding uncaging action cross sections (δΦ) up to 5.8 GM at 900 nm and around 1 GM at 1300-1400 nm. Notably, these modifications preserve the core photophysical properties of BODIPY, making them ideal for molecular engineering. These findings highlight key design principles for efficient 2P-activatable photoactuators operating in the NIR-II biological window and show that heterolytic C-O bond cleavage can be triggered by two SWIR photons carrying as little as 20 kcal/mol each.
光笼能够在生物系统中实现光触发的货物释放，但其激发通常局限于紫外线/可见光波长，而在这些波长下组织穿透能力有限。双光子激发（2PE）提供了一种解决方案，它允许在组织透明度最高的生物窗口内进行近红外（NIR）或短波红外（SWIR）激活。虽然已经证明了在第一个生物窗口（650 - 950纳米）中的光笼效应，但在第二个生物窗口（1000 - 1350纳米）中的应用仍未得到探索。在这里，我们研究了11种硼二吡咯光笼的双光子吸收（2PA）特性，这些光笼的单光子吸收范围为450 - 750纳米，重点关注3位和5位取代，以确定在900 - 1500纳米范围内增强2PA的关键基序。我们发现，强电荷转移特性和增加的振动自由度可以放宽与对称性相关的选择规则，显著增强2PA。对于带有咔唑单元的双（苯乙烯基）-硼二吡咯，其在900纳米处的截面（δ）超过4000 GM，而其单苯乙烯基类似物在1240纳米处达到1110 GM。合成了另外两种具有改善的解笼量子产率的B - 甲基化分子，在900纳米处产生高达5.8 GM的解笼作用截面（δΦ），在1300 - 1400纳米处约为1 GM。值得注意的是，这些修饰保留了硼二吡咯的核心光物理性质，使其成为分子工程的理想选择。这些发现突出了在近红外-II生物窗口中高效2P可激活光致动器的关键设计原则，并表明异裂C - O键断裂可以由每个携带低至20千卡/摩尔的两个SWIR光子触发。
