Design of “Click” Fluorescent Labeled 2′-deoxyuridines via C5-[4-(2-Propynyl(methyl)amino)]phenyl Acetylene as a Universal Linker: Synthesis, Photophysical Properties, and Interaction with BSA

Abstract

Microenvironment-sensitive fluorescent nucleosides present attractive advantages over single-emitting dyes for sensing inter-biomolecular interactions involving DNA. Herein, we report the rational design and synthesis of triazolyl push-pull fluorophore-labeled uridines via the intermediacy of C5-[4-(2-propynyl(methyl)amino)]phenyl acetylene as a universal linker. The synthesized nucleosides showed interesting solvatochromic characteristic and/or intramolecular charge transfer (ICT) features. A few of them also exhibited dual-emitting characteristics evidencing our designing concept. The HOMO-LUMO distribution showed that the emissive states of these nucleosides were characterized with more significant electron redistribution between the C5-[4-(2-propynyl(methyl)amino)]phenyl triazolyl donor moiety and the aromatic chromophores linked to it, leading to modulated emission property. The solvent polarity sensitivity of these nucleosides was also tested. The synthesized triazolyl benzonitrile (10C), naphthyl (10E), and pyrenyl (10G) nucleosides were found to exhibit interesting ICT and dual (LE/ICT) emission properties. The dual-emitting pyrenyl nucleoside maintained a good ratiometric response in the BSA protein microenvironment, enabling the switch-on ratiometric sensing of BSA as the only protein biomolecule. Thus, it is expected that the new fluorescent nucleoside analogues would be useful in designing DNA probes for nucleic acid analysis or studying DNA-protein interactions via a drastic change in fluorescence response due to a change in micropolarity.

Extension of furopyrimidine nucleosides with 5-alkynyl substituent: Synthesis, high fluorescence, and antiviral effect in the absence of free ribose hydroxyl groups

“…The iodine attached to the furopyrimidine core quenched the emission of fluorescence almost completely for iodonucleoside 4 (Φ = 0.04), in line with identified halogen effect. 58 Overall, the quantum yields of alkynyl furopyrimidines are competitive with those of recently reported alkynyl fluorescent nucleosides, 59 , 60 and are even comparable with values for nucleosides labeled with auxiliary chromophores. 61 …”

Glycoconjugates Based on Supramolecular Tröger’s Base Scaffold: Synthesis, Photophysics, Docking, and BSA Association Study

“…In fact, the H-bonds have an important role in the complex stabilization, as already reported in the literature. 54,55 The interaction of the Tröger’s base in I B 52,56 and II A 51,57,58 subdomains could induce conformational changes in BSA. As a result, the tryptophan fluorescence quenching can be affected.…”

Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction

“…Nucleoside analogs are molecules of high pharmacological interest for the treatment of various conditions, especially cancer and viral diseases [1][2][3][4][5]. The substitution at C-5 of the uracil nucleobase provides a common framework for materials with potent biological properties [6][7][8][9][10]. Modification on this site of the nucleobase usually does not interfere with Watson-Crick base pairing.…”