Highly Fluorescent 2‐Aminopurine Derivatives: Synthesis, Photo‐physical Characterization, and Preliminary Cytotoxicity Evaluation

Abstract

New fluorescent nucleobase analogues (FBAs) are emerging as extraordinarily useful tools for DNA labelling technologies. 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 endangering living cells. New and highly fluorescent 2AP derivatives, 2-amino-6-cyanopurines, were obtained using simpler but efficient synthesis method. All the new compounds exhibit advantageous photophysical proper-ties 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 performed, allowing to predict absorption and emission spectra. In addition, these 2amino-6-cyanopurines exhibit little to no toxicity in assays using yeast cells.

Synthesis of 6,8-diaminopurines via acid-induced cascade cyclization of 5-aminoimidazole precursors and preliminary anticancer evaluation

“…In a recently reported work, 25 the preparation of N -cyanoimidoylcyanides 1 was achieved from 5-amino-4-cyanoformimidoylimidazole by an addition reaction of cyanamide to these precursors followed by elimination of ammonia. In that study, N -cyanoimidoylcyanides 1 were then converted to highly fluorescent 2-amino-6-cyanopurines through an intramolecular cyclization that involves a nucleophilic attack of the 5-amino group on the cyanoimino unit.…”

“…The imidazole precursors 1 , the N -cyanoimidoylcyanides, were prepared according to a recently reported method. 25 Intermediate compounds 2 were not easy to isolate because they are highly soluble in reaction solvents. So, only a few compounds 2 could be fully characterized.…”

2,4,5-Triaminopyrimidines as blue fluorescent probes for cell viability monitoring: synthesis, photophysical properties, and microscopy applications

“…Previously, highly fluorescent 2-amino-6-cyanopurines 2 were synthesized through condensation reactions of imidazole precursors with cyanamide, followed by cyclization of key intermediates 1 (Scheme 1). 23 Aiming to generate new fluorescent analogues, the reactivity of this new purine scaffold was investigated. Attempts to modify the 6-cyano group revealed that purines 2 with 9-aryl substituents undergo ring-opening of the imidazole moiety upon heating in acidic media, which generates new N 4 -substituted 2,4,5-triaminopyrimidines 3 .…”

Screening for Novel Fluorescent Nucleobase Analogues Using Computational and Experimental Methods: 2-Amino-6-chloro-8-vinylpurine (2A6Cl8VP) as a Case Study

“…A, T (U), C, and G are building blocks of nucleic acids and are very weakly fluorescent . In order to probe the structure and dynamics of DNA and RNA sequences and their interaction with other biological molecules, structural nucleobase analogues have been developed with high-emission quantum yields. − These structural analogues are called fluorescent nucleic acid base analogues (FBAs). A summary of recent developments in the field of FBAs can be found in these articles. − Two of the oldest known fluorescent base analogues are 2-aminopurine (2AP) and ethenoadenine (εA), both of which are fluorescent analogues of adenine.…”