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.
