A General Strategy to Develop Intramolecular Spirocyclic Boron Dipyrromethene Fluorophores for Self-Blinking...

Area of Science:

• Organic Chemistry
• Photochemistry
• Biophysical Chemistry

Background:

• Intramolecular spirocyclic fluorophores are crucial for stimuli-responsive probes and super-resolution imaging.
• Existing designs are limited to Rhodamine frameworks, underutilizing the potential of boron dipyrromethene (BODIPY) dyes.
• BODIPY dyes offer superior photostability, brightness, and near-infrared tunability but are rigid, hindering spirocyclization.

Purpose of the Study:

• To develop a general molecular engineering strategy for creating spirocyclic BODIPY dyes.
• To overcome the rigidity limitations of the BODIPY core for intramolecular spirocyclization.
• To establish a new class of high-performance, stimuli-responsive probes based on BODIPY.

Main Methods:

• Introduced 2-(hydroxymethyl)phenyl or 2-carboxyphenyl groups at the meso-position of BODIPY as intramolecular nucleophiles.
• Incorporated electron-withdrawing groups at α/β-positions to modulate core electron density and enhance electrophilicity.
• Utilized single-crystal X-ray diffraction to confirm the spirocyclized structure and mechanism.

Main Results:

• Successfully conferred spirocyclic functionality to BODIPY dyes for the first time.
• Obtained the first single-crystal X-ray structure of a spirocyclized BODIPY, confirming its closed form and blinking mechanism.
• Established a clear pK_a-structure-activity relationship for precise control over the open-closed equilibrium.
• Achieved exceptional brightness (up to ~87,122 M^-1 cm^-1) and enabled self-blinking super-resolution imaging in living cells.

Conclusions:

• Pioneered the extension of intramolecular spirocyclization to the BODIPY scaffold.
• Established a general design strategy for a new class of high-performance, stimuli-responsive BODIPY probes.
• Demonstrated the utility of these novel BODIPY dyes for advanced bioimaging applications under low laser power.