Tuning the pK_a of Fluorescent Rhodamine pH Probes through Substituent Effects

Area of Science:

• Organic Chemistry
• Analytical Chemistry
• Materials Science

Background:

• Rhodamine spirolactams (RSLs) are fluorescent pH probes with a turn-on capability.
• Current RSL design prioritizes biological targeting over pH sensitivity, leaving the structure-pK_a relationship unclear.

Purpose of the Study:

• To investigate the relationship between RSL structure and pK_a values.
• To understand how substituents on the spirolactam nitrogen affect pH sensitivity.

Main Methods:

• Synthesized and characterized 19 aniline-derived RSLs.
• Evaluated pK_a values using the Fujita-Nishioka model for ortho substituent effects.

Main Results:

• RSLs from di-ortho-substituted anilines showed pK_a tunability in the pH 4-6 range.
• Steric and electronic properties of substituents significantly influence RSL pH responsiveness.
• Increasing substituent size and electron-withdrawing character increased pK_a values.

Conclusions:

• Structural modifications of RSLs, particularly ortho substituents, allow for precise tuning of pH sensitivity.
• Developed RSL-doped polymer nanoparticles for ratiometric pH sensing in aqueous media.