PHOTOCHEMISTRY OF DIAZENIUMDIOLATES--NO RELEASING DRUGS

描述（改编自摘要）：一氧化氮（NO） 参与神经传递控制的生物调节剂，血液 凝血和血压 此外，NO已被证明可以杀死 癌细胞 因此，以前的研究集中在开发 可以有效和选择性地递送NO的药物，例如，对肿瘤细胞 而不会显著影响其他生物调节过程。 二醇二氮烯鎓是一类令人感兴趣的此类药物， 发展 最近使二醇二氮烯鎓更有效的药物的努力， 集中于使用这些化合物的衍生物来递送NO 具体到目标地点。 拟议研究的一个主要目标是 开发二醇二氮烯鎓的光化学前体， 有效的NO释放剂。 由于在其他领域的初步实验 实验室与经典的光保护基团， 令人失望的结果，反应途径将得到澄清，使更多的 可以合理设计高效的光触发NO释放药物。 在 此外，如果diazeniumdiolates是享受常规医疗用途，其基本 必须理解光化学，以便可以 预期和避免 拟议研究的具体目的是实现上述目标， 简要概述了：（1）光化学反应途径 的O-烷基化二醇二氮烯鎓将通过产物分析来阐明 和时间分辨红外（TRIR）光谱的强大工具。 （二） 氧取代氮烯（O-氮烯），建议作为中间体 通过O-烷基化二醇二氮烯鎓盐的光解将有效地产生， 表征了 (3)由于O-氮烯是迄今为止未研究的一类 中间体的反应性将由双方详细检查 实验和计算方法。 (4)最终，新的O-烷基化 用于高效光化学生产二醇二氮烯鎓衍生物的方法 将设计和测试NO。

DESCRIPTION (Adapted from abstract): Nitric oxide (NO) is an important bioregulator that is involved in the control of neurotransmission, blood clotting, and blood pressure. In addition, NO has been shown to kill cancerous tumor cells. Thus, previous research has focused on developing drugs that can deliver NO efficiently and selectively, e.g., to tumor cells without dramatically affecting other bioregulatory processes. Diazeniumdiolates are an interesting class of such drugs presently under development. Recent efforts to make diazeniumdiolates more effective pharmaceuticals have concentrated on using derivatives of such compounds to deliver NO specifically to a targeted site. A major goal of the proposed research is to develop photochemical precursors to diazeniumdiolates that can be used as effective NO-releasing agents. Since initial experiments in other laboratories with classic photoprotecting groups gave unexpected and disappointing results, reaction pathways will be clarified so that more efficient phototriggered NO-releasing drugs can be rationally designed. In addition, if diazeniumdiolates are to enjoy routine medical use, their basic photochemistry must be understood so that phototoxicity issues may be anticipated and avoided The specific aims of the proposed research, which address the above goals, are briefly outlined: (1) Reaction pathways involved in the photochemistry of O-alkylated diazeniumdiolates will be elucidated with product analysis and the powerful tool of time-resolved infrared (TRIR) spectroscopy. (2) Oxygen-substituted nitrenes (O-nitrenes), proposed to be intermediates efficiently produced by photolysis of O-alkylated diazeniumdiolates will be characterized. (3) Since O-nitrenes are a heretofore unstudied class of intermediates their reactivity will be examined in detail by both experimental and computational methods. (4) Ultimately, new O-alkylated diazeniumdiolate derivatives for the efficient photochemical production of NO will be designed and tested.