SYNTHESIS OF PHTHALOCYANINES FOR TUMOR PHOTOTHERAPY

描述：（申请人描述）酞菁类光敏剂在光动力疗法（PDT）中很有前途，这是一种适用于癌症治疗的疗法。特别是，硅酞菁pc4在项目2和项目3以及本拨款下的核心D中所做的工作，以及其他人为NCI药物决策网络所做的合同工作中都显示出了很高的效果。这导致了目前的应用。其中一部分工作的目标是培养出适合于结构测定的pc4晶体，然后用它来测定pc4的单晶x射线结构。第二部分工作的目标是设计、合成和表征高效或易于排泄的新型光敏剂。所制光敏剂分为四类。这些是：可排泄的pc4类似物，磷脂酞菁光敏剂，阳离子芳香胺酞菁光敏剂，以及pc4和pc12类似物。所有的光敏剂都含有酞菁或类酞菁大环。第三部分研究的目标是获得有关新型光敏剂将光能转化为可引发光损伤的化学反应物质的能量的效率的基本信息。为了实现这一目标，将对这些化合物和一些先前制备的化合物进行一系列的光物理和光化学研究。这些研究将主要集中在单个结构特征逐步改变的各种光敏剂系列的成员上，因为了解结构的变化是否明显影响化合物的光性是很重要的。

DESCRIPTION: (Applicant's Description) Phthalocyanines have much promise as photosensitizers for photodynamic therapy (PDT), a therapy applicable to cancer treatment. In particular, the silicon phthalocyanine Pc 4 has been shown to be highly effective both by work done in Projects 2 and 3 and Core D under the present grant, and by contract work done by others for the Drug Decision Network of NCI. This leads to the present application. The goal of one part of the work is to grow a crystal of Pc 4 which is suitable for structure determination and then to use it to determine the single-crystal X-ray structure of Pc 4. The goal of the second part of the work is to design, synthesize and characterize new photosensitizers for PDT that are highly effective or can be easily excreted. The photosensitizers to be made belong to four categories. These are: excretable Pc 4 analogues, phospholipid phthalocyanine photosensitizers, cationic aromatic amine phthalocyanine photosensitizers, and further Pc 4 and Pc 12 analogues. All of the photosensitizers contain phthalocyanine or phthalocyanine-like macrocycles. The goal of the third part of the research is to obtain basic information on the efficiency with which the new photosensitizers transduce photoenergy into the energy of chemically reactive species that can initiate photodamage. To achieve this objective, a series of photophysical and photochemical studies will be done on these compounds and on some the previously made ones. These studies will be focused mainly on members of various series of photosensitizers in which a single structural feature is changed stepwise, since it will be important to know if the changes in structure appreciably influence the photoproperties of the compounds.