Predicting photoluminescence in amines using QSAR modeling methods and the use of DIXELs to determine binding efficacy of cationic polymers to DNA

Abstract

The second part of this thesis focuses on the specifics of gene delivery. Gene therapy is an emerging practice that holds a lot of potential for therapeutic purposes. However, much about the process remains unexplained and wanting to be optimized. What this experiment attempts to determine is the means by which the DNA interacts with its delivery vehicle, in this case a group of cationic polymers. This would allow for the creation of more useful delivery methods that would be optimized for specific strands of DNA. Using Dixels, a program designed to map out electron-based properties of DNA, this experiment attempted to determine how a set of cationic polymers would interact with a strand of DNA for delivery into a cell. The most and least favorable cross-linkers from the provided set were determined from this experiment, as was the fact that the binding to the DNA is most likely done in the major groove.

The process of photoluminescence, or the emission of light due to the relaxation of excited electrons, for the most part is well understood. However, the research presented in this paper is based on photoluminescence that is observed in unconjugated nitrogen-containing compounds, molecules that have no obvious reason for exhibiting this behavior. The purpose of these experiments is to provide an explanation for this phenomenon, despite its improbability. This was attempted using quantitative structure-activity relationship (QSAR) modeling and linear regression models. Despite the fact that no results were produced that explain the cause specifically, it can be concluded that this problem is not one that is electronic alone, and requires a deeper understanding of the interactions and methods that lead to the production of light from these molecules.

The research that is presented in this thesis covers two different projects. One explores the phenomenon of photoluminescence in examples which have no precedent. The other delves into gene delivery, and explaining the specific interactions between the genetic material that is to be delivered, and the vehicle that is delivering it.