Publication Date

2018-04-02

Availability

Open access

Embargo Period

2018-04-02

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Chemistry (Arts and Sciences)

Date of Defense

2018-03-21

First Committee Member

James N. Wilson

Second Committee Member

Francisco M. Raymo

Third Committee Member

Marc R. Knecht

Fourth Committee Member

Ryan L. Karkkainen

Abstract

Fluorescence is achieved by emission of electromagnetic radiation in the form of ultraviolet, visible, or infrared photons as a result of an electronic transition from singlet excited state to singlet ground state. Fluorescence spectroscopy is a widely utilized technique for studying the structure and dynamics of matter and living systems. It may come in many forms such as small organic fluorophores taking on a “drug-like” role in biological organisms as well as supramolecular host-guest complexes for applications in drug delivery and cellular imaging. Herein, two research projects at the interface of chemistry and biology will be fully discussed. Although the two ventures have different goals, the overarching theme is confining fluorescent molecules in a tight space, such as a transporter or organic nanoparticle, to enhance the optical properties by restricting motion and limiting solvent accessibility. First, a series of stilbene derivatives were synthesized and investigated as substrates targeting monoamine transporters (MATs). The sensitivity of these fluorescent probes allows binding-induced fluorescence based on their ability to access a twisted intramolecular charge transfer (TICT) state. The photophysical properties of the dyes were studied in solvents differing in polarity and viscosity to model their response and translate this behavior to a binding event. The lack of specificity to the MAT target lead to their use as generic cell membrane stains, comparable to that of a commercially available, widely used dye in biological laboratories. Also, a library of functionalized lignins is reported to demonstrate their utility as nanocontainers for organic dyes in biologically relevant applications. Kraft lignin was modified via SN2 reaction at the phenolic -OH group utilizing a mild base, potassium carbonate, and various alkyl halides, several bearing additional functionalities, with dimethylsulfoxide as solvent. The resulting phenoxy ethers were characterized by 1H- NMR and IR spectroscopy, as well as DLS and SEM to evaluate their morphology and supramolecular organization. Lignin modified with long-chain hydrocarbon tails was found to effectively encapsulate DiD, a cyanine dye, decrease aggregation, enhance optical transitions, and exert a photoprotective effect. The dye-lignin assemblies were also examined as imaging agents, via confocal microscopy, and found to accumulate intracellularly with no leaching of the dye to hydrophobic subcellular components observed. Lignin functionalized with short chain carboxylic acids interacts with ligands directed at the norepinephrine transporter (NET), suggesting applications in sequestration of neuroactive compounds. Lignin nanocontainers can also be employed in other applications such as coatings for cell culture vessels, ion-sensitive cargo release, energy transfer between guest molecules, and specific drug delivery targeting the biotin transport system. This comprehensive list of applications utilizing lignin proves its worth as a nanomaterial in a biomedical setting.

Keywords

fluorescence; fluorescent probes; monoamine transporters; lignin; nanocontainers; cellular imaging

Share

COinS