Date of Award
Spring 2014
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Chemistry
First Advisor
Steinmetz, Mark G.
Second Advisor
Donaldson, William A.
Third Advisor
Timerghazin, Qadir K.
Abstract
Cage compounds have become an important tool for the study of biological processes. The research focuses on new cage compounds that can unmask functional groups present in biologically important molecules such as proteins, peptides, and oligonucleosides. The project focuses on certain functional groups that are often difficult to release photochemically. These are the thiolate groups present in cysteine residues of proteins and peptides. Thiolate groups are fairly basic leaving groups, unlike the more labile groups such as the carboxylates that are present in proteins and peptides, or the phosphate groups present in nucleosides. The research takes advantage of the ability of zwitterionic intermediates to release basic leaving groups such as the thiolates. The zwitterionic intermediates are generated photochemically by electrocyclic ring closure of aromatic carboxamides that has the chromophore attached to the amide nitrogen. Most importantly, the research utilizes a chromophore that absorbs visible light, so as to minimize the damaging effects that short-wavelength light has on tissue and cells. The research recognizes that triplet energy transfer from triplet excited state of the chromophore to the aromatic ring system attached to carboxamide carbonyl group must be exothermic in order for the electrocyclic ring closure to occur. For a thioxanthone chromophore (ET = 64 kcal mol-1), the aromatic ring system is a naphthothiophene ring system (ET = 62 kcal mol-1). The energy transfer would therefore be exothermic. This cage compound was synthesized with a 3-chloro leaving group. It undergoes photochemical electrocyclic ring closure and chloride expulsion in 50% yield after 1.5 h photolysis. The reaction qualitatively appears to be efficient. In comparison, a 5-benzoylthiophene aromatic ring system with 3-chloro group undergoes the same photoreaction in very low yields over 72 h, even though the triplet energy transfer is exothermic. In this case the photoproduct effectively competes for the incident light with the reactant. The research shows that the naphthothiophene ring system is a viable solution to the triplet energy transfer problem. It also points to a need to improve the solubility of the cage compound by incorporating one or more carboxylate groups into the naphthothiophene ring or the thioxanthone ring.