PHOTOCHEMISTRY OF ARYL HALIDES AND ITS APPLICATIONS

在初步调查中，我们发现（i）间氟苯酚和 4-氟色氨酸的衍生物经历了一种新的亲光核反应， 氟基的置换反应，（ii） 4-氯色氨酸和4-氯吲哚经历了同样有趣的， 完全不同的光化学解离产生吲哚基， 和（iii）间氯苯酚根据极性经历任一过程 的溶剂。以前曾报道邻氯苯酚 进行照片-沃尔夫重排，即，环收缩形成 乙烯酮中间体我们建议进行系统的调查， 卤代苯酚、4-卤代吲哚、卤代酪氨酸和 4-卤色氨酸，以实现一个机械的理解， 考虑到这些反应中活性中间体的依赖性， 芳基卤化物的结构和实验条件。以来 卤代酪氨酸和4-卤代色氨酸可以掺入蛋白质中， 通过固相肽合成的常规方法制备肽，和/或 通过分子生物学的方法，而现有的光亲和标记， 不能，所有的蛋白质含有芳香族氨基酸，光化学的 卤代酪氨酸和卤代色氨酸可被开发成新的强效 蛋白质化学中的光亲和标记方法。所以我们也 建议探索这些化合物作为光亲和标记物的用途， 与芝加哥大学的科学家合作， 在其他地方，提出的系统包括胰凝乳蛋白酶，芳基硫酸酯酶，色氨酸 阻遏物，类维生素A结合蛋白和胰岛素：受体相互作用。 随着我们工作的进展，可能会开发更多的系统。 此外，由于蛋白质与其底物之间的共价结合， 或受体可能会导致其生物学特性的深刻改变， 功能，我们的研究可能会导致新的药物和其他设计 生物活性剂。

In a preliminary investigation, we have found that (i) m-fluorophenol and derivatives of 4-fluorotryptophan undergo a novel photonucleophilic displacement reaction of the fluoro group, (ii) derivatives of 4-chlorotryptophan and 4-chloroindoles undergo an equally interesting but entirely different photochemical dissociation to generate indolyl radicals, and (iii) m-chlorophenol undergoes either process depending on the polarity of the solvent. It has been reported previously that o-chlorophenol undergoes a Photo-Wolff Rearrangement, i.e., a ring-contraction to form a ketene intermediate. We propose to carry out a systematic investigation on the photochemistry of halophenols, 4-haloindoles, halotyrosines and 4-halotrytophans in order to achieve a mechanistic understanding with regard to the dependence of the reactive intermediate in these reactions on the structure of the aryl halide and experimental conditions. Since halotyrosines and 4-halotryptophans may be incorporated into proteins and peptides by conventional methods of solid-phase peptide synthesis and/or by methods of molecular biology, while existing photoaffinity labels cannot, and all proteins contain aromatic amino acids, photochemistry of halotyrosines and halotryptophans may be developed into new powerful methods of photoaffinity labelling in protein chemistry. Therefore, we also propose to explore the use of these compounds as photoaffinity labels in collaboration with scientists both at the University of Chicago and elsewhere, systems proposed include chymotrypsin, arylsulfatases, Trp repressor, retinoid binding proteins and insulin:receptor interaction. Additional systems may be developed as our work progresses. Furthermore, since covalent binding between proteins and their substrates or receptors may cause a profound modification of their biological functions, our study may lead to the design of new drugs and other biologically active agents.