Sun Wenwen, Qi Yuanfeng, Wang Le, Tan Yunpeng, Zhang Xiao, Wang Junfeng, Li Yingbo
College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, China.
College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, China.
Spectrochim Acta A Mol Biomol Spectrosc. 2025 Feb 15;327:125318. doi: 10.1016/j.saa.2024.125318. Epub 2024 Oct 22.
Boronic acid analogs are crucial in modern organic chemistry and drug development, serving as versatile reagents and intermediates with significant therapeutic applications. This area has gained increased interest with the recent development of the drug 4-boron-L-phenylalanine (L-BPA) for boron neutron capture therapy (BNCT). Fluorescent probe technology offers an essential pathway for imaging drugs in vitro and in vivo, providing high sensitivity with great spatial and temporal resolution for both disease diagnosis and drug development. In this paper, we designed and investigated three fluorescent probes-W-1-NN, W-2-NS and W-3-NO-for sensing 4-boron-L-phenylalanine (L-BPA). Among these, only W-1-NN reacts with L-BPA, resulting in a spectral blue-shift change. This probe can "ratiometrically" and specifically detect L-BPA among various metals, with a limit of detection (LOD) of 7.11 μM. Mechanistic studies revealed that the addition of L-BPA disrupts the inherent ESIPT mechanism of W-1-NN in protonic solutions, resulting in the appearance of a new peak at 372 nm. Additionally, theoretical computational studies have also demonstrated that the complexation of W-1-NN with L-BPA triggers a change in the resonance structure, resulting in a larger energy gap and causing a blue shift in the spectrum. Furthermore, W-1-NN has been successfully applied to the detection of L-BPA in human urine. Therefore, the template probe with N/O as the target and the introduction of N atoms can specifically detect L-BPA. This template probe lays the foundation for the detection of L-BPA, and provides great possibilities for the future realization of the template probe to be connected with different fluorophores to make it emit at long wavelengths to reach the target of the near-infrared.
硼酸类似物在现代有机化学和药物开发中至关重要，作为通用试剂和中间体具有重要的治疗应用。随着用于硼中子俘获疗法（BNCT）的药物4-硼-L-苯丙氨酸（L-BPA）的最新开发，该领域受到了越来越多的关注。荧光探针技术为体外和体内药物成像提供了一条重要途径，为疾病诊断和药物开发提供了高灵敏度以及出色的空间和时间分辨率。在本文中，我们设计并研究了三种用于检测4-硼-L-苯丙氨酸（L-BPA）的荧光探针——W-1-NN、W-2-NS和W-3-NO。其中，只有W-1-NN与L-BPA发生反应，导致光谱蓝移变化。该探针能够在多种金属中“比率式”且特异性地检测L-BPA，检测限（LOD）为7.11 μM。机理研究表明，加入L-BPA会破坏W-1-NN在质子溶液中的固有激发态质子转移（ESIPT）机制，导致在372 nm处出现一个新峰。此外，理论计算研究还表明，W-1-NN与L-BPA的络合引发了共振结构的变化，导致能隙增大，从而使光谱发生蓝移。此外，W-1-NN已成功应用于人体尿液中L-BPA的检测。因此，以N/O为靶点并引入N原子的模板探针能够特异性地检测L-BPA。该模板探针为L-BPA的检测奠定了基础，并为未来实现模板探针与不同荧光团连接以使其在长波长下发射从而达到近红外目标提供了极大的可能性。
