Highly fluorescent 2‐Aminopurine derivatives: synthesis, photo‐physical characterization, and preliminary cytotoxicity evaluation

• Published in: European journal of organic chemistry 2023-04, Vol.26 (16), p.n/a
• Main Authors: Gonçalves, Jorge M., Gonçalves, João N. D., Pêra, Ana S., Senhorães, Nádia R., Rodrigues, Ana Rita Oliveira, Oliveira, Rui Pedro Soares de, Coutinho, Paulo J. G., Castanheira, Elisabete M. S., Dias, Alice
• Format: Article
• Language: English
• Subjects: 2-amino-6-cyanopurines; Absorption; Adenine; Ciências Naturais; Ciências Químicas; cytotoxicity; Density functional theory; DFT calculations; Emission spectra; Fluorescence; novel fluorescent nucleobases; Proteger a vida terrestre; Science & Technology; solvatochromism; Synthesis; Toxicity
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202300176

First published: 15 March 2023 New fluorescent nucleobase analogues (FBAs) are emerg-ing as extraordinarily useful tools for DNA labelling tech-nologies. The highly fluorescent adenine analogue 2 aminopurine (2AP) is still the most used within the few hundreds of newly FBAs synthesized, but its excitation in the UV region demands for high energy sources endanger-ing living cells. New and highly fluorescent 2AP deriva-tives, 2-amino-6-cyanopurines, were obtained using novel, simpler, but very efficient synthesis method. All the new compounds exhibit advantageous photophysical properties over 2AP, showing absorption and emission bands ranging the visible region (blue-green region), high fluorescence quantum yields and Stokes’ shifts, especially in non-protic organic solvents. Density Functional Theory calculations (DFT) of electronic and vibrational structure were per-formed, allowing to predict absorption and emission spec-tra in accordance with experimental data. The extensive solvatochromism of compounds gives them important microenvironmental sensitivity to be used as superior fluorescent probes, comparing to 2AP. In addition, these newly synthesized 2-amino-6-cyanopurines exhibit little to no toxicity in assays using yeast cells, making them also valuable candidates for fluorescent studies in living cells. This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of CQUM (UIDB/00686/2020), CBMA (UIDB/04050/2020) and CF-UM-UP (UIDB/04650/2020) units, and National NMR Network (RNRMN) (PINFRA/22161/2016). We also acknowledge Search-ON2: "Revitalization of HPC infrastructure of UMinho" (NORTE 07-0162-FEDER-000086), co-funded by the North Portugal Regional Operational Programme (ON.2 - O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF).