Modified 6-aza uridines: highly emissive pH-sensitive fluorescent nucleosides

Area of Science:

• Organic Chemistry
• Photophysics
• Biophysical Chemistry

Background:

• Pyrimidine derivatives are crucial in medicinal chemistry and molecular probes.
• Existing fluorescent probes often require large structures and can lack sensitivity to microenvironmental changes.
• Isomorphic design principles offer a pathway to developing small, highly functional fluorescent molecules.

Purpose of the Study:

• To synthesize and characterize novel isomorphic fluorescent pyrimidines.
• To investigate the spectroscopic properties, including fluorescence quantum yield and emission maxima.
• To evaluate the sensitivity of these compounds to changes in polarity and pH.

Main Methods:

• Facile synthesis of two isomorphic pyrimidine derivatives containing 1,2,4-triazine conjugated to thiophene (1a) or furan (1b).
• Spectroscopic analysis including UV-Vis absorption and fluorescence emission measurements in various solvents.
• Determination of fluorescence quantum yields and pKa values through pH-dependent emission studies.

Main Results:

• The synthesized thiophene derivative (1a) exhibits absorption around 335 nm and visible emission sensitive to polarity.
• Fluorescence quantum yields range from 0.8 in dioxane to 0.2 in water, with emission maxima shifting from 415 nm to 455 nm.
• Compound 1a demonstrates pH sensitivity with a pKa of 6.7-6.9, close to physiological pH.

Conclusions:

• Novel isomorphic pyrimidines possess excellent fluorescence properties, including high brightness and responsiveness.
• These findings challenge the notion that large fluorophores are solely responsible for desirable fluorescence characteristics.
• The study highlights the potential of isomorphic design in creating sensitive and efficient small-molecule fluorescent probes.