Assessing The Key Photophysical Properties of Triangulenium Dyes for DNA Binding by Alteration of the Fluorescent Core

Abstract

Four‐stranded G‐quadruplex (G4) DNA is a non‐canonical DNA topology that has been proposed to form in cells and play key roles in how the genome is read and used by the cellular machinery. Previously, a fluorescent triangulenium probe (DAOTA‐M2) was used to visualise G4s in cellulo, thanks to its distinct fluorescence lifetimes when bound to different DNA topologies. Herein, the library of available triangulenium probes is expanded to explore how modifications to the fluorescent core of the molecule affect its photophysical characteristics, interaction with DNA and cellular localisation. The benzo‐bridged and isopropyl‐bridged diazatriangulenium dyes, BDATA‐M2 and CDATA‐M2 respectively, featuring ethyl‐morpholino substituents, were synthesised and characterised. The interactions of these molecules with different DNA topologies were studied to determine their binding affinity, fluorescence enhancement and fluorescence lifetime response. Finally, the cellular uptake and localisation of these optical probes were investigated. Whilst structural modifications to the triangulenium core only slightly alter the binding affinity to DNA, BDATA‐M2 and CDATA‐M2 cannot distinguish between DNA topologies through their fluorescence lifetime. It is argued theoretically and experimentally that this is due to reduced effectiveness of photoinduced electron transfer (PET) quenching. This work presents valuable new evidence into the critical role of PET quenching when using the fluorescence lifetime of triangulenium dyes to discriminate G4 DNA from duplex DNA, highlighting the importance of fine tuning redox and spectral properties when developing new triangulenium‐based G4 probes.

Selective, pH‐Dependent Colorimetric and Fluorimetric Detection of Quadruplex DNA with 4‐Dimethylamino(phenyl)‐Substituted Berberine Derivatives

“…Moreover, this chemosensor and derivatives thereof have the potential to be applied for the fluorimetric detection of pH gradients and extracellular nucleic acids in biofilms, [31] that have been suggested just recently to contain G4‐DNA as functional component [60] . Although numerous fluorescent probes for G4‐DNA are known, [9–19] to the best of our knowledge, no examples have been reported so far with these particular features. Namely, only a few fluorescent probes for G4‐DNA have been reported that operate at lower pH, [61] but these probes do not exhibit the dual‐mode response of compound 3 a .…”

“…For an efficient detection, however, either the emission intensity of the otherwise non‐fluorescent ligand has to increase strongly or the emission energy has to shift distinctly. Thus, several organic fluorophores have been introduced that serve this purpose, for example benzimidazole, [9] benzindole, [10] triazine, [11] coumarin, [12] cyanine, [13] pyridinium, [14,15] quinolinium, [15,16] quinolizinium, [15,17] triangulenium [18] and benzothiazole [19] based dyes. Among the promising compound classes for this application are also DNA‐binding natural products with suitable fluorescence properties, because these compounds usually provide sufficient affinity, and often selectivity, towards DNA, along with the required biocompatibility.…”

“…In this context, quadruplex DNA has been identified as a very important analyte, because of its activity in many biological processes, such as transcription regulation [6,7] or telomerase inhibition [7,8] . As a result, fluorescent probes have been developed and employed widely for the selective detection of G4‐DNA structures [9–19] . Such probes usually consist of a G4‐DNA‐binding molecule whose emission properties change upon association to the target G4‐DNA.…”

Recent Advances in Heterocyclic Nanographenes and Other Polycyclic Heteroaromatic Compounds

“…It displayed emission enhancement upon DNA binding, which was attributed primarily to deaggregation. 57 …”

Utilizing selective chlorination to synthesize new triangulenium dyes

“…In this study we aim at widening the chemical diversity and tuning the optical and redox properties of ADOTA + and DAOTA + dyes by investigating chlorination, specifically targeting positions of the ADOTA + , DAOTA + and DMQA + chromophores not previously investigated. Tuning of the redox properties has become particularly interesting due to the high interest in applications of ADOTA + , DAOTA + and DMQA + in photo induced electron transfer (PET) based sensors [20][21][22][23] , photo catalysts, [7][8][9][24][25] redox agents, 26 and in electroluminescent systems. [27][28] Specifically, we here report the synthesis, and optical and redox properties of 1-chloro-DAOTA + (1), 9,11dichloro-DAOTA + (2) and 5,7-dichloro-ADOTA + (3) (Figure 2).…”