Molecular rotor-based fluorophores have been widely used as a fluorogenic tool to detect protein aggregation. However, it remains enigmatic how structural differences could systematically affect the fluorogenic behavior. In this work, we chemically installed π-rich polyene or polymethine structure between rotation moieties of rotor-based fluorophores and investigated how such structural change could affect fluorogenic behavior. Combining the photophysical analysis with modeling, we rationalized that rotor-based fluorophores with extended π bridge (extended rotors) will experience higher rotational energy barrier in the excited state compared to their single-bonded analogs (simple rotors). Consequently, extended rotors are more readily to be kinetically trapped in excited states compared to single rotors. The fluorogenicity differences originated from their distinct rotational energy barrier become much obvious in non-viscous micro-environment, represented by low viscosity solution or soluble misfolded proteins. Using protein aggregation experiments both in-vitro and in live cells, we further demonstrate the feasibility of detecting soluble misfolded proteins by installing π-rich bridge onto previously non-sensitive simple rotors. This work could envision the design of novel molecular rotor-based fluorophores with controlled fluorogenicity. Collectively, such fluorophores could be useful tools to study protein aggregation at different stages.

Development of novel molecular rotor-based fluorophores with controlled fluorogenic property

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.