Ph.D Thesis

Ph.D StudentSaphier Sigal
SubjectAntibody-Catalyzed Reactions Based on Conformational
DepartmentDepartment of Chemistry
Supervisor PROFESSOR EMERITUS Ehud Keinan


Life on earth depends on the influence that light has on chemistry. Photosynthesis in plants provides the most obvious example in which carbohydrates and oxygen are produced, by the utilization of solar energy. However, when searching for single protein systems one finds that only three examples of photoenzymes are known. The development of new biocatalysts for photochemical reactions is a challenge that can enhance our understanding of basic principles underlying complex systems that utilize light. In addition, catalysis of photochemical reactions offers a unique possibility to study the conformational effects conferred by those catalysts on the reaction pathway.

 Carbonyl compounds that contain g C-H bonds undergo an intramolecular photochemical hydrogen abstraction to produce a 1,4 biradical that can lead to cleavage products (Norrish type II), accompanied by traces of the cyclization products (Yang cyclization). We chose to study the possible effects of antibodies on this reaction. Antibodies were elicited against cis and trans 1,2-diaryl oxetanes. Three antibodies (12B4, 20F10, and 21H9) enhanced the photo-cyclization of a ketone that is structurally related to the oxetane haptens, to produce the corresponding cis-cyclobutanol. The product was obtained with very high enantioselectivity, as established by HPLC with a chiral column. We have studied the characteristics of the reaction with antibody 20F10, including binding constants of the antibody to the cis and trans haptens and to several substrates. In addition, we have studied the reaction parameters, including the dependence on the irradiation wavelength. The results show that this antibody can bind the substrate and force it into a folded conformation that favors formation of the cyclic product over fragmentation. 

Carbonyl compounds lacking g C-H bonds may undergo a b hydrogen abstraction under special stereo-electronic constraints. Two different substrates that lack g hydrogens were synthesized to check this possibility. Preliminary results indicate that these substrates may undergo cyclopropanation in the presence of antibody 20F10, a reaction that does not occur in the absence of the antibody. The two substrates lead to the formation of the same cyclopropanol product.