SYNTHESIS CHARACTERIZATION AND BIOLOGICAL STUDY OF NOVAL CATIONIC DYES

新型阳离子染料的合成表征及生物学研究

• 批准号: 3734139
• 负责人: DERRICK C TABOR
• 金额: --
• 依托单位: JOHNSON C. SMITH UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3734139
• 关键词: antineoplastics; chemical structure function; chemical substitution; chemical synthesis; cyanine; drug screening /evaluation; dyes; human tissue; infrared spectrometry; laboratory rat; neoplastic cell culture for noncancer research; nuclear magnetic resonance spectroscopy; photochemistry; thiazoles; tissue /cell culture; ultraviolet spectrometry

A novel series of cationic dyes will be synthesized, characterized, and investigated as potential photochemical therapeutics using in vitro (human glioma U251MG and normal skin fibroblasts HSKI cell cultures) and in vivo (malignant rat RT 2 glioma) cancer models and methods developed by Powers. A complete characterization of structural, spectral, and physical properties of these compounds will be conducted so that structure/biological activity relationships may be identified. It is a long range goal of our research to prepare biologically active compounds that absorb light in various regions of the visible spectrum, exhibit a high degree of selectivity in their action, and that contain multiple modes of action. Thus, our research will result in compounds that either possess the ability to function bimodally or that can be made so by covalent attachment to compounds that are known to function differently. Our research will develop routes to amidinium dyes containing one or more ethynyl or yne groups. (C=C), and one or more vinyl or ene groups, (CH=CH), following the pioneering work of Mee. We propose to extend Mee's method of reacting ynenamines with 2-substituted benzothiazolium salts to include the reaction of diynenamines, and triynenamines with 2- substituted benzothiazolium electrophiles, and triethyl orthoformate. We will synthesize a novel series of dyes that vary systematically, depending upon the nature of the electrophile in the number of either ethynyl (yne) and vinyl (ene) groups. The absorption maxima of these dyes are expected to vary systematically as well, starting from approximately 513 nm up to 900 nm, assuming that each ethynyl group will length the absorption maximum by 60 nm. This absorption maximum of 900 nm is expected for the dye formed from the reaction of 2 equivalents of a triynenamine with 1 equivalent of triethyl orthoformate. We propose to ultimately extend our research to prepare benzoxazole and benzoselenazole dyes. We will fully characterize these compounds using UV-Vis. NIR (near infrared), IR and 1H and 13C NMR studies. UV-Vis, NIR and NIR, and FT-IR studies will allow us to observe and quantify changes in the absorption spectra as the number ethynyl and vinyl groups within the conjugation chain are systematically increased and to explore the propensity of these dyes to self associate. NMR studies will allow us to assign stereochemistry and regiochemistry for these dyes many of which can exist as diastereomers.

将合成一系列新型阳离子染料，并对其进行表征和表征。 作为潜在的光化学疗法的体外研究 (人脑胶质瘤U251 MG和正常皮肤成纤维细胞HSKI细胞培养)和 体内(大鼠恶性RT-2胶质瘤)肿瘤模型和方法的建立 被鲍尔斯。对结构、光谱和 这些化合物的物理性质将被进行测试，以便 可以识别结构/生物活性关系。这是一个 我们研究的长期目标是制备具有生物活性的化合物 在可见光光谱的不同区域吸收光，表现为 在其行动中高度选择性，且包含多个 行动模式。因此，我们的研究将导致化合物或 具有双峰起作用的能力或可通过以下方式发挥作用 与已知功能不同的化合物的共价结合。 我们的研究将开发含有一种或多种酰胺染料的路线 乙炔基或乙炔基团。(C=C)以及一个或多於一个乙烯基团或烯基， (CH=CH)，遵循MEE的开创性工作。我们建议延长 苯乙胺与2-取代苯并噻唑反应的MEE法 盐类，包括二亚胺和三亚胺与2-亚胺的反应 取代苯并噻唑类亲电体和原甲酸三乙酯。 我们将合成一系列新的染料，这些染料有系统地变化， 根据亲水性的不同，它们的数量 乙炔(炔)和乙烯(烯)基团。这些物质的吸收极大值 染料预计也会有系统的变化，从 约513 nm至900 nm，假设每个乙炔基团 最大吸收波长为60 nm。这个吸收最大值为900 对于由2个当量的 一种三苯胺，相当于原甲酸三乙酯。我们建议 为了最终扩大我们的研究以制备苯并恶唑和 苯并噻唑类染料。我们将充分描述这些化合物的特征，使用 紫外可见。近红外光谱、红外光谱、~1H和~(13)C核磁共振研究。紫外可见，近红外 近红外光谱和傅立叶变换红外光谱研究将使我们能够观察和量化变化 在吸收光谱中以乙炔和乙烯基的数目表示 系统地增加了共轭链，并探索了 这些染料的自我缔合倾向。核磁共振研究将使我们 指定这些染料的立体化学和区域化学，其中许多 可以以非对映异构体的形式存在。