Publications by authors named "Kenneth T Stout"
Article Synopsis
- PET radioligands are essential for studying central nervous system drugs, neurodegenerative diseases, and various cancers, but existing radiolabelling methods are limited and slow.
- A new rapid method using metallaphotoredox-catalysis allows for efficient installation of tritium and carbon-11 into pharmaceutical precursors, which is important due to carbon-11's short half-life.
- The technique successfully synthesizes multiple PET radioligands quickly and has potential applications for both preclinical imaging and automated radiotracer production for human clinical use.
A Diels-Alder reaction-based strategy for the synthesis of indoles and related heterocycles is reported. An intramolecular cycloaddition of alkyne-tethered 3-aminopyrones gives 4-substituted indolines in good yield and with complete regioselectivity. Additional substitution is readily tolerated in the transformation, allowing synthesis of complex and non-canonical substitution patterns.
View Article and Find Full Text PDFTracking the structural dynamics of fluorescent protein chromophores holds the key to unlocking the fluorescence mechanisms in real time and enabling rational design principles of these powerful and versatile bioimaging probes. By combining recent chemical biology and ultrafast spectroscopy advances, we prepared the superfolder green fluorescent protein (sfGFP) and its non-canonical amino acid (ncAA) derivatives with a single chlorine, bromine, and nitro substituent at the site to the phenolate oxygen of the embedded chromophore, and characterized them using an integrated toolset of femtosecond transient absorption and tunable femtosecond stimulated Raman spectroscopy (FSRS), aided by quantum calculations of the vibrational normal modes. A dominant vibrational cooling time constant of ~4 and 11 ps is revealed in Cl-GFP and Br-GFP, respectively, facilitating a ~30 and 12% increase of the fluorescent quantum yield vs.
View Article and Find Full Text PDFArticle Synopsis
- Green fluorescent protein (GFP) has transformed bioimaging, but outside its natural environment, the GFP chromophore (HBDI) lacks fluorescence, prompting research into its behavior in solution.
- This study uses femtosecond stimulated Raman spectroscopy (FSRS) and transient absorption (TA) to analyze how energy dissipates during the HBDI chromophore's transition through a conical intersection, revealing key vibrational couplings.
- The findings highlight a delayed coupling onset related to the charge-separated state prior to reaching the TICT state, offering insights into photochemical reactions and laying groundwork for designing efficient molecular systems like nanomachines and fluorescent markers.