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: 3777766
• 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/3777766
• 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.

一系列新型阳离子染料将被合成、表征和 研究作为体外潜在的光化学疗法 （人神经胶质瘤 U251MG 和正常皮肤成纤维细胞 HSKI 细胞培养物）和 开发体内（恶性大鼠 RT 2 神经胶质瘤）癌症模型和方法 由权力。 结构、光谱和特征的完整表征 这些化合物的物理性质将被进行，以便 可以识别结构/生物活性关系。 它是一个 我们研究的长期目标是制备生物活性化合物 吸收可见光谱各个区域的光，表现出 它们的作用具有高度选择性，并且包含多种 行动方式。 因此，我们的研究将产生以下化合物： 具有双峰功能的能力或者可以通过以下方式实现 与已知功能不同的化合物共价连接。 我们的研究将开发含有一种或多种脒染料的路线 乙炔基或炔基。 (C=C)，和一个或多个乙烯基或烯基， (CH=CH)，继 Mee 的开创性工作之后。 我们建议延长 Mee 法使炔胺与 2-取代苯并噻唑鎓反应 盐包括二炔胺和三炔胺与2-的反应 取代的苯并噻唑鎓亲电子试剂和原甲酸三乙酯。 我们将合成一系列系统不同的新型染料， 取决于亲电子试剂的性质 乙炔基（yne）和乙烯基（ene）基团。 这些物质的吸收最大值 预计染料也会发生系统变化，从 大约 513 nm 至 900 nm，假设每个乙炔基将 最大吸收长度为 60 nm。 此吸收最大值为 900 nm 预计是由 2 当量的反应形成的染料 三炔胺与1当量原甲酸三乙酯。 我们建议 最终扩展我们的研究以制备苯并恶唑和 苯并硒唑染料。 我们将使用以下方法充分表征这些化合物 紫外可见分光光度计。 NIR（近红外）、IR 以及 1H 和 13C NMR 研究。 紫外-可见、近红外 近红外和傅立叶变换红外研究将使我们能够观察和量化变化 吸收光谱中乙炔基和乙烯基的数量 系统地增加共轭链并探索 这些染料的自缔合倾向。 核磁共振研究将使我们能够 为这些染料指定立体化学和区域化学，其中许多 可以作为非对映异构体存在。