Off-campus UMass Amherst users: To download campus access dissertations, please use the following link to log into our proxy server with your UMass Amherst user name and password.

Non-UMass Amherst users: Please talk to your librarian about requesting this dissertation through interlibrary loan.

Dissertations that have an embargo placed on them will not be available to anyone until the embargo expires.

Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Chemistry

Year Degree Awarded

2018

Month Degree Awarded

February

First Advisor

Sankaran Thayumanavan

Second Advisor

Elizabeth R. Young

Third Advisor

Min Chen

Fourth Advisor

Anthony D. Dinsmore

Subject Categories

Biochemistry, Biophysics, and Structural Biology | Materials Chemistry | Organic Chemistry | Polymer Chemistry

Abstract

In photodynamic therapy, several critical standards are required of photosensitizers including high singlet oxygen quantum yield, biocompatibility in dark, and long term photochemical stability. In addition, current PDT systems lack active targeting strategies to tumor cells, and instead mainly rely on the natural distribution of PS in the body following injection and application of near-infrared light treatment in the tumor region. This thesis describes a series of BODIPY-based molecules that were designed, synthesized and studied as photosensitizers with high singlet oxygen generation capacity through utilizing the heavy atom effect. Additionally, aqueous solubility and active targeting capability were introduced by photosensitizer conjugation to hyaluronic acid, a biocompatible natural polymer that binds CD44+ receptors on cancer cells such as HeLa. A small degree of BODIPY substitution on the nontoxic hyaluronic acid polymer backbone allowed overall viability of the PS in dark, but controlled cytotoxicity was observed upon application of near-infrared LED light. Cytotoxicity studies also established the cell selective cytotoxicity of the hyaluronic acid-BODIPY conjugates, verifying their candidacy for photodynamic applications.

In the field of molecular amplification, self-immolative materials have been widely used for various biological applications including drug delivery, biomarker detection, imaging, and sensing. Traditionally, the chemical design of self-immolative polymer or dendrimer backbones include reporters or prodrugs in their monomeric structure. In such systems, the extend of stimuli-induced amplified signal and release of reporters or prodrugs is directly rely on the degree of polymerization or dendrimer generation. Here, we discuss the design, synthesis, and study of an oligomeric self-immolative polymeric system that produces a morphological signal output as a macroscopic response to a molecular-level stimulus through signal amplification. For this aim, we developed a gel that undergoes a gel-sol transition upon application of light to demonstrate this amplification behavior. In this system, stimuli triggers modification in chemical structure of self-immolative polymer that presence in catalytic amount in the gel, which leads to macroscopic morphological transition. Since this macroscopic morphological change driven by catalytic polymer, the extend of amplified signal in this system is not directly dependent on the degree of polymerization. Successful demonstration of such a system will help achieve rapid and reliable signal amplification.

Organic photovoltaics are an attractive alternate technology to traditional inorganic photovoltaics due to their relatively low weight and feasibility of processing into flexible large panels. Polymer-based organic photovoltaics have been investigated for their efficient charge carrier generation, owing to their low band gap through extensive conjugation. Simultaneously, small molecule based organic photovoltaics have also been developed due to their advantages over polymer-based organic photovoltaics, including facile purification with well-defined monodisperse structural properties, as well as tunable frontier orbital energy alignment. One of the strategies to improve organic photovoltaics performance is developing active materials with a great light-harvesting property for optimal complementarity to the solar energy spectrum. BODIPY molecules are appropriate candidates due to their favorable features as a light-harvesting material, including high extinction coefficients, high photochemical stability, and a relatively easy preparation process. In addition, their frontier energy levels are finely tunable through incorporating with various core structures of different electronegativities. However, their strong absorption profile of simple BODIPY is narrow and limited to visible range (~500 nm). To expand upon the previously reported benefits of BODIPY molecules, we discuss broadening of light absorption profile towards near-infrared through alpha-conjugation extension of BODIPY molecules. Utilizing BODIPY that absorbs into the near-infrared region with high absorption coefficients would allow efficient absorbance of the incident light even in thin films, contributing to enhanced organic photovoltaic performances.

`

Share

COinS