Azetidines-Containing Fluorescent Purine Analogs: Synthesis and Photophysical Properties

Analogues of N,N-dimethyladenine exploiting both thieno-and isothiazolo-pyrimidine cores were modified with 3-subsituted azetidines to yield visibly emissive and responsive fluorophores. The emission quantum yields, among the highest seen for purine analogues (0.64 and 0.77 in water and dioxane respectively), correlated with the Hammett inductive constants of the substituents on the azetidine ring. Ribosylation of the difluoroazetidino-modified nucleobase yielded an emissive nucleoside that displayed a substantially lower emission quantum yield in water, compared to the precursor nucleobase. Importantly, high emission quantum yield was restored in deuterium oxide, which highlights the potential impact of the sugar moiety on the photophysical features of fluorescent nucleosides, a functionality usually considered non-chromophoric and photophysically benign.

Automated summary

Analogues of N,N-dimethyladenine with thieno- and isothiazolo-pyrimidine cores were modified using 3-substituted azetidines to produce fluorescent fluorophores with high emission quantum yields. The substituents on the azetidine ring correlated with the emission quantum yields. Ribosylation of the modified nucleobase resulted in a lower emission quantum yield in water compared to the precursor nucleobase, but the high emission quantum yield was restored in deuterium oxide, indicating the potential impact of the sugar moiety on the photophysical features of fluorescent nucleosides.