Novel pyrido[2,3-d]pyrimidines for bioimaging: Effect of water content on enhanced fluorescence and the mechanism of aggregation-induced blue-shifted emission

IF 4.3 2区化学 Q1 SPECTROSCOPY

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy Pub Date : 2025-07-21 DOI:10.1016/j.saa.2025.126729

Patrycja Rawicka , Mateusz Korzec , Mateusz Dulski , Jacek Mularski , Patryk Rurka , Maria Książek , Anna Mrozek-Wilczkiewicz , Katarzyna Malarz

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引用次数: 0

Abstract

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/H₂O 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.

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用于生物成像的新型吡啶[2,3-d]嘧啶：水含量对荧光增强的影响及聚集诱导蓝移发射的机制

含有吡啶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引起了人们的极大兴趣。然而，它们代表了细胞成像中一个未开发的领域。本文开发了一类基于吡啶[2,3-d]嘧啶支架的聚集诱导发射（AIE）荧光团。我们合成了一个小系列的衍生物，评估了它们在各种溶剂中的光谱特性，考虑了荧光量子产率、荧光寿命和它们的衰变成分。重要的是，物理化学参数也在MeOH/H2O环境下进行了评估，表明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，由于水含量的增加，其荧光增强，保留了显著的斯托克斯位移。荧光形成的分子机制的深入表征与聚集诱导的蓝移发射效应（AIBSE）有关。TD-DFT计算表明，ET06存在不同的空间构象态，分别为单分子态和聚集态。讨论了分子在基态和激发态的构象和能量变化对含水介质中荧光发射的影响。最后，生物学研究表明，ET06对癌症和正常细胞的细胞毒性可以忽略不计。高荧光强度的细胞和可能的亲和力和倾向积聚在线粒体和溶酶体也证实。这些发现对吡啶[2,3-d]嘧啶的分子行为和性质提供了有价值的见解，促进了设计用于生物成像的新型荧光探针的前景。

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来源期刊

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 物理-光谱学

CiteScore

8.40

自引率

11.40%

发文量

1364

审稿时长

40 days

期刊介绍： Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy (SAA) is an interdisciplinary journal which spans from basic to applied aspects of optical spectroscopy in chemistry, medicine, biology, and materials science. The journal publishes original scientific papers that feature high-quality spectroscopic data and analysis. From the broad range of optical spectroscopies, the emphasis is on electronic, vibrational or rotational spectra of molecules, rather than on spectroscopy based on magnetic moments. Criteria for publication in SAA are novelty, uniqueness, and outstanding quality. Routine applications of spectroscopic techniques and computational methods are not appropriate. Topics of particular interest of Spectrochimica Acta Part A include, but are not limited to: Spectroscopy and dynamics of bioanalytical, biomedical, environmental, and atmospheric sciences, Novel experimental techniques or instrumentation for molecular spectroscopy, Novel theoretical and computational methods, Novel applications in photochemistry and photobiology, Novel interpretational approaches as well as advances in data analysis based on electronic or vibrational spectroscopy.