Rawicka Patrycja, Korzec Mateusz, Dulski Mateusz, Mularski Jacek, Rurka Patryk, Książek Maria, Mrozek-Wilczkiewicz Anna, Malarz Katarzyna
A. Chełkowski Institute of Physics, University of Silesia in Katowice, 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
Institute of Chemistry, University of Silesia in Katowice, 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
Spectrochim Acta A Mol Biomol Spectrosc. 2026 Jan 5;344(Pt 2):126729. doi: 10.1016/j.saa.2025.126729. Epub 2025 Jul 21.
Compounds containing the pyridopyrimidine core have attracted significant interest due to their promising biological properties and potential for medical applications. However, they represent an unexplored area in cellular imaging. Herein, a new class of aggregation-induced emission (AIE) fluorophores based on the pyrido[2,3-d]pyrimidine scaffold has been developed. We synthesized a small series of derivatives, which were evaluated for their spectroscopic properties in various solvents, considering fluorescence quantum yields, fluorescence lifetimes, and their decay components. Importantly, the physicochemical parameters were also evaluated in a MeOH/HO environment, suggesting the possible behavior of the derivatives in the cellular environment. Our analyses revealed the excellent photophysical properties of the ET06 compound, which exhibited enhanced fluorescence as a result of increasing water content, retaining significant Stokes shifts. An in-depth characterization of the molecular mechanism of fluorescence formation was linked to an aggregation-induced blue-shifted emission effect (AIBSE). TD-DFT calculations showed the existence of different spatial conformational states of ET06 in the single molecule state and aggregated states in at sandwich arrangement. Molecular conformational and energy changes in the ground and excited states, which had a significant effect on fluorescence emission in water-containing media, were also discussed. Finally, biological studies revealed negligible cytotoxicity of ET06 against cancer and normal cells. High fluorescence intensity in cells and a possible affinity and tendency to accumulate in mitochondria and lysosomes were also confirmed. These findings provide valuable insights into the molecular behavior and properties of pyrido[2,3-d]pyrimidines, boosting the landscape for designing new fluorescent probes for bioimaging.
含有吡啶并嘧啶核心的化合物因其具有良好的生物学特性和医学应用潜力而备受关注。然而，它们在细胞成像领域仍是一个未被探索的领域。在此，基于吡啶并[2,3-d]嘧啶支架开发了一类新型的聚集诱导发光（AIE）荧光团。我们合成了一小系列衍生物，并在各种溶剂中评估了它们的光谱性质，考虑了荧光量子产率、荧光寿命及其衰减成分。重要的是，还在甲醇/水的环境中评估了物理化学参数，这暗示了衍生物在细胞环境中的可能行为。我们的分析揭示了ET06化合物优异的光物理性质，其由于含水量增加而表现出增强的荧光，并保留了显著的斯托克斯位移。对荧光形成分子机制的深入表征与聚集诱导蓝移发射效应（AIBSE）有关。TD-DFT计算表明ET06在单分子状态和夹心排列的聚集状态下存在不同的空间构象状态。还讨论了基态和激发态的分子构象和能量变化，这些变化对含水介质中的荧光发射有显著影响。最后，生物学研究表明ET06对癌细胞和正常细胞的细胞毒性可忽略不计。还证实了其在细胞中的高荧光强度以及可能在线粒体和溶酶体中积累的亲和力和趋势。这些发现为吡啶并[2,3-d]嘧啶的分子行为和性质提供了有价值的见解，推动了用于生物成像的新型荧光探针的设计前景。
