Date Awarded
2024
Document Type
Thesis
Degree Name
Master of Science (M.Sc.)
Department
Chemistry
Advisor
Christopher Abelt
Committee Member
Lisa Landino
Committee Member
Isaiah Speight
Abstract
We report the succinct total synthesis of 1,5-Acrylodan, a novel solvatochromic fluorophore for the study of microenvironmental polarity in biological and biochemical systems. The reaction sequence proceeds via an aryllithium-directed nucleophilic addition, catalytic Kulinkovich cyclopropanation, and copper-catalyzed oxidative ring-opening to generate the critical acryloyl moiety. The identity of the carbonyl is set in a late-stage procedure; the functionalizable 5-bromo-1-dimethylaminonaphthalene intermediate can be isolated. All organic/catalytic reagents and naphthalic precursors are inexpensive and commercially available. The fluorescence characteristics of the unbound 1,5-Ac are reported, demonstrating strong fluorescence quenching in polar protic solvents. A mild conjugate addition procedure can be employed to afford fluorophore-labelled Human Serum Albumin, an important biomolecular system; the labelling procedure is both site-selective and singular. The 1,5-Ac-HSA complex can be applied to the study of environmental solvation as a function of molecular unfolding patterns; the fluorescence characteristics of the native-state and chemically denatured 1,5-Ac-HSA complex are reported and employed for the determination of denaturation dynamics.
DOI
https://dx.doi.org/10.21220/s2-y7sg-aq15
Rights
© The Author
Recommended Citation
Morrin, Jake Thomas, "Total Synthesis Of 1,5-Acrylodan As A Novel Fluorescent Probe For The Study Of Chemical Denaturation Dynamics In Human Serum Albumin" (2024). Dissertations, Theses, and Masters Projects. William & Mary. Paper 1727787910.
https://dx.doi.org/10.21220/s2-y7sg-aq15
