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: 6239924
• 负责人: Derrick C. Tabor
• 金额: $ 2.37万
• 依托单位: JOHNSON C. SMITH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-02-01 至 1998-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6239924
• 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.

合成了一系列新型阳离子染料，并对其进行了表征， 作为潜在的光化学治疗剂， （人神经胶质瘤U251 MG和正常皮肤成纤维细胞HSKI细胞培养物）和 开发了体内（恶性大鼠RT 2神经胶质瘤）癌症模型和方法 权力。 一个完整的表征结构，光谱， 这些化合物的物理性质将进行， 可以鉴定结构/生物活性关系。 这是一个 我们研究的长期目标是制备生物活性化合物 其吸收可见光谱的各个区域中的光， 其作用具有高度选择性， 行动方式。 因此，我们的研究将导致化合物， 具有双模态功能的能力，或者可以通过 共价连接到已知具有不同功能的化合物上。 我们的研究将开发路线，脒染料含有一个或多个 乙炔基或炔基。 （C=C）和一个或多个乙烯基或烯基， (CH=CH），遵循Mee的开创性工作。 我们建议扩大 使炔胺与2-取代的苯并噻唑鎓反应的Mee法 盐包括二炔胺和三炔胺与2- 取代的苯并噻唑鎓亲电试剂和原甲酸三乙酯。 我们将合成一系列新颖的染料， 取决于亲电试剂的性质， 乙炔基（炔）和乙烯基（烯）。 这些物质的最大吸收 预计染料也会系统地变化，从 大约513 nm至900 nm，假设每个乙炔基将 最大吸收波长为60 nm。 最大吸收900 对于由2当量的 三炔胺与1当量原甲酸三乙酯。 我们提出 最终将我们的研究扩展到制备苯并恶唑， 苯并硒唑染料。 我们将充分表征这些化合物使用 紫外-可见 NIR（近红外）、IR和1H和13 C 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 在吸收光谱中， 共轭链系统地增加，并探索 这些染料自缔合的倾向。 核磁共振研究可以让我们 为这些染料分配立体化学和区域化学，其中许多染料 可以作为非对映体存在。