Design and synthesis of functional cyanine dyes for imaging and therapeutic application

在2020财年，Atanas Kurutos博士在JSPS博士后研究项目“用于成像和治疗应用的功能性花青素染料的设计和合成”下的主要成果包括pH响应染料的结果总结和在染料与颜料杂志上发表。进一步扩展了研究活动，合成了一系列化学结构上带有一个或多个正电荷的近红外聚甲基染料。所有新合成的荧光团的身份都被核磁共振和高分辨率质谱法证实。研究了染料在有机溶剂和水缓冲溶液中的光学特性和光稳定性。在增加染料浓度的水中也研究了自缔合的可能性。采用高效液相色谱法和紫外可见光谱法测定对数P值。根据其化学结构的不同，花菁的对数P值范围很广（~ -2 ~ 8）。染料样品在合作框架中提供给庆应义塾大学的生物学家同事，以研究其细胞毒性和对细胞系的染色能力。结果揭示了一个特定的细胞器标记取决于有机分子的亲脂性，这证明了我们最初的假设和本研究的概念。在完成这项研究的同时，还准备了另外两份科学手稿。

During the FY2020, the main achievements of the JSPS Postdoctoral Fellowship of Dr Atanas Kurutos under the project “Design and synthesis of functional cyanine dyes for imaging and therapeutical applications” cover the summary of the results on the pH responsive dyes and publication in Dyes & Pigments journal. The research activities were further expanded on the synthesis of a series of NIR polymethine dyes bearing one or more positive charges in their chemical structure. The identity of all newly synthesized fluorophores was confirmed by NMR and High-Resolution Mass Spectrometry. The optical characteristics and the photostability of the dyes were studied in both organic solvents and aqueous buffer solutions. The probability of self-association was also studied in water at increasing dye concentrations. The log P values were determined by HPLC and UV-Vis spectroscopic techniques. The cyanines revealed broad range of log P values (~ -2 to 8) depending on their chemical structure. Dye samples were given in collaborative frames to biologist colleagues from Keio University to study their cytotoxicity and staining capabilities to cell lines. The results revealed a specific organelle labeling depending on the lipophilicity of the organic molecules, which proved our initial hypothesis and the concept of this study. The finalization of the research is accompanied by the preparation of another two scientific manuscripts.