Abstract
The synthesis of novel fluorescent N(9)-alkylated 2-amino-6-triazolylpurine and 7-deazapurine derivatives is described. A new C(2)-regioselectivity in the nucleophilic aromatic substitution reactions of 9-alkylated-2,6-diazidopurines and 7-deazapurines with secondary amines has been disclosed. The obtained intermediates, 9-alkylated-2-amino-6-azido-(7-deaza)purines, were transformed into the title compounds by CuAAC reaction. The designed compounds belong to the push–pull systems and possess promising fluorescence properties with quantum yields in the range from 28% to 60% in acetonitrile solution. Due to electron-withdrawing properties of purine and 7-deazapurine heterocycles, which were additionally extended by triazole moieties, the compounds with electron-donating groups showed intramolecular charge transfer character (ICT/TICT) of the excited states which was proved by solvatochromic dynamics and supported by DFT calculations. In the 7-deazapurine series this led to increased fluorescence quantum yield (74%) in THF solution. The compounds exhibit low cytotoxicity and as such are useful for the cell labelling studies in the future.
Highlights
Purine [1,2,3,4,5,6,7] and 7-deazapurine (IUPAC name: pyrrolo[2,3d]pyrimidine) [8,9,10,11] derivatives have been progressively studied for decades due to their wide range of biological activities and photophysical properties
In the 7-deazapurine series this led to increased fluorescence quantum yield (74%) in THF solution
We have reported here for the first time that 9-alkyl2,6-diazidopurines exhibit C(2)-selectivity in nucleophilic aromatic substitution reactions with amines
Summary
Purine [1,2,3,4,5,6,7] and 7-deazapurine (IUPAC name: pyrrolo[2,3d]pyrimidine) [8,9,10,11] derivatives have been progressively studied for decades due to their wide range of biological activities and photophysical properties. Fluorescent purine nucleoside analogs were recognized as valuable fluorescent probes for DNA and RNA research [17] This paved a way for development of various adenosine and guanosine analogs which in many cases contained an additional substituent at C(8) like compounds A and B (Figure 1) [18,19]. The latter attachment does not significantly affect the natural Watson–Crick base-pairing abilities of the modified compounds. Useful levels of fluorescence were reported for purine nucleos(t)ides bearing azole-type substituents at C(2) or C(6) (e.g., 6-thiazol2-yl derivative C [23] and 2-(1,2,3-triazol)-1-yladenosines D [24,25] (Figure 1)
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