Selenium-Substituted Monomethine Cyanine Dyes as Selective G-Quadruplex Spectroscopic Probes with Theranostic Potential

Abstract

The binding interactions of six ligands, neutral and monocationic asymmetric monomethine cyanine dyes comprising benzoselenazolyl moiety with duplex DNA and RNA and G-quadruplex structures were evaluated using fluorescence, UV/Vis (thermal melting) and circular dichroism (CD) spectroscopy. The main objective was to assess the impact of different substituents (methyl vs. sulfopropyl vs. thiopropyl/thioethyl) on the nitrogen atom of the benzothiazolyl chromophore on various nucleic acid structures. The monomethine cyanine dyes with methyl substituents showed a 100-fold selectivity for G-quadruplex versus duplex DNA. Study results indicate that cyanines bind with G-quadruplex via end π-π stacking interactions and possible additional interactions with nucleobases/phosphate backbone of grooves or loop bases. Cyanine with thioethyl substituent distinguishes duplex DNA and RNA and G-quadruplex structures by distinctly varying ICD signals. Furthermore, cell viability assay reveals the submicromolar activity of cyanines with methyl substituents against all tested human cancer cell lines. Confocal microscopy analysis shows preferential accumulation of cyanines with sulfopropyl and thioethyl substituents in mitochondria and indicates localization of cyanines with methyl in nucleus, particularly nucleolus. This confirms the potential of examined cyanines as theranostic agents, possessing both fluorescent properties and cell viability inhibitory effect.

Fluorescent Probes for Biomacromolecules Based on Monomethine Cyanine Dyes

“…This method has been successfully applied to the synthesis of both symmetrical and unsymmetrical MCDs (Figure 3): This method was used in a recent work [8] for the synthesis of symmetrical MCDs with various terminal heterocyclic groups and substituents at nitrogen atoms. It is also widely used for the synthesis of unsymmetrical MCDs with different heterocyclic residues [9][10][11][12]. The thioalkyl method was applied in the synthesis of a number of MCDs derived from SYBR green II [13].…”

“…The interaction of new unsymmetrical MCD 20-26 (Figure 14), containing a benzoselenazole fragment, with dsDNA/RNA was studied in [11,12]. It has been shown that the dyes interact with dsDNA with significant fluorescent growth; the dyes containing a methyl group at the nitrogen atom in the benzothiazole core (dyes 20 and 21) were found to be more suitable as fluorescent markers (up to a 63-fold increase in the fluorescence intensity in the presence of dsDNA).…”

“…For ligand-biopolymer interaction, CD spectroscopy provides valuable information about the structure of the complex and the location of the ligands. Binding with DNA and RNA induces the appearance of a CD signal of initially achiral dye molecules, and various The interaction of new unsymmetrical MCD 20-26 (Figure 14), containing a benzoselenazole fragment, with dsDNA/RNA was studied in [11,12]. It has been shown that the dyes interact with dsDNA with significant fluorescent growth; the dyes containing a methyl group at the nitrogen atom in the benzothiazole core (dyes 20 and 21) were found to be more suitable as fluorescent markers (up to a 63-fold increase in the fluorescence intensity in the presence of dsDNA).…”

Photonics of Some Monomethine Cyanine Dyes in Solutions and in Complexes with Biomolecules

“…A wide range of biological and biomedical systems currently being studied with the use of spectral fluorescent probes stimulates a permanent emergence of research aimed at developing new efficient and selective dye probes for the detection and staining of biomolecules in such systems (see, e.g., [ 16 , 17 , 18 ]). There are a large number of works by different research groups devoted to the synthesis and spectral fluorescent study of various MCDs (symmetrical and unsymmetrical) in order to develop probes for nucleic acids [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. There are also some works directed to the study of primary photophysical and photochemical processes in MCD molecules, both free and noncovalently bound to nucleic acids [ 35 , 36 , 37 , 38 , 39 , 40 ] (see also the review [ 41 ]).…”

“…2023, 24, x FOR PEER REVIEW 2 of 27 molecules in such systems (see, e.g., [16][17][18]). There are a large number of works by different research groups devoted to the synthesis and spectral fluorescent study of various MCDs (symmetrical and unsymmetrical) in order to develop probes for nucleic acids [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. There are also some works directed to the study of primary photophysical and photochemical processes in MCD molecules, both free and noncovalently bound to nucleic acids [35][36][37][38][39][40] (see also the review [41]).…”