Modified 6-aza uridines: highly emissive pH-sensitive fluorescent nucleosides.
Optimized facile syntheses and highly desirable spectroscopic properties of two isomorphic fluorescent pyrimidines, comprising a 1,2,4-triazine motif conjugated to a thiophene (1 a) or a furan (1 b), are described. Although structurally related to their 5-modified uridine counterparts, these modified 6-aza-uridines reveal dramatically improved fluorescence properties and a remarkable sensitivity to polarity and pH changes. The thiophene derivative 1 a has an absorption maximum around 335 nm, which upon excitation yields visible emission with a polarity-sensitive maximum and fluorescence quantum yield ranging from 415 nm (Φ=0.8) to 455 nm (Φ=0.2) in dioxane and water, respectively. Nucleoside 1 a also displays susceptibility to acidity. Correlating emission intensity and solution pH yields a pK(a)  value of 6.7-6.9, reasonably close to physiological pH values. The results illustrate that highly sought-after fluorescence features (brightness and responsiveness) are not necessarily the trait of large fluorophores alone, but can be observed with probes that meet stringent isomorphic design criteria.
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA.
Renatus W
RW
Sinkeldam
Patrycja A
PA
Hopkins
Yitzhak
Y
Tor
D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry*; D014529:Uridine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry*
D001372:Aza Compounds; D005456:Fluorescent Dyes; D009705:Nucleosides; D014529:Uridine