Tetracationic Bis-Triarylborane 1,3-Butadiyne as a Combined Fluorimetric and Raman Probe for Simultaneous and Selective Sensing of Various DNA, RNA, and Proteins.

Hashem Amini,Željka Ban,Ivo Crnolatac,Alexandra Friedrich,Sabine Lorenzen,Ivo Piantanida,Florian Rauch,Adriana Kenđel,Matthias Ferger,Snežana Miljanić,Todd B Marder

doi:10.1002/chem.201905328

Abstract

A bis‐triarylborane tetracation (4‐Ar2B‐3,5‐Me2C6H2)‐C≡C−C≡C‐(3,5‐Me2C6H2‐4‐BAr2 [Ar=(2,6‐Me2‐4‐NMe3‐C6H2)+] (24+) shows distinctly different behaviour in its fluorimetric response than that of our recently published bis‐triarylborane 5‐(4‐Ar2B‐3,5‐Me2C6H2)‐2,2′‐(C4H2S)2–5′‐(3,5‐Me2C6H2‐4‐BAr2) (34+). Single‐crystal X‐ray diffraction data on the neutral bis‐triarylborane precursor 2 N confirm its rod‐like dumbbell structure, which is shown to be important for DNA/RNA targeting and also for BSA protein binding. Fluorimetric titrations with DNA/RNA/BSA revealed the very strong affinity of 24+ and indicated the importance of the properties of the linker connecting the two triarylboranes. Using the butadiyne rather than a bithiophene linker resulted in an opposite emission effect (quenching vs. enhancement), and 24+ bound to BSA 100 times stronger than 34+. Moreover, 24+ interacted strongly with ss‐RNA, and circular dichroism (CD) results suggest ss‐RNA chain‐wrapping around the rod‐like bis‐triarylborane dumbbell structure like a thread around a spindle, a very unusual mode of binding of ss‐RNA with small molecules. Furthermore, 24+ yielded strong Raman/SERS signals, allowing DNA or protein detection at ca. 10 nm concentrations. The above observations, combined with low cytotoxicity, efficient human cell uptake and organelle‐selective accumulation make such compounds intriguing novel lead structures for bio‐oriented, dual fluorescence/Raman‐based applications.

Highlights

The use of fluorescent labels to image specific small molecules in live cells is an essential tool in biology, medicinal chemistry, and many other related fields of research
Novel molecule 24+, and studies of its interactions with DNA/RNA/proteins, will address the potential for the development of innovative combined fluorophore-Raman probes for the general purpose of non-covalent probing of DNA/RNA/ proteins, and the impact of the nature of the linker connecting two bis-triarylborane cations on the fluorescent and chirooptic response upon binding to biomacromolecules
Due to the possibility that the compounds studied could interact with proteins, we examined the most naturally abundant protein, bovine serum albumin (BSA), taking into account its versatility of binding sites

Summary

Introduction

Phenyl end-capped polyynes have been employed as alkyne tags for Raman visualization of mobile, small molecules in cells[6] as well as for surface-enhanced Raman spectroscopy (SERS) multiplex cellular imaging,[7] showing very promising applications in supermultiplexed optical imaging and barcoding.[2d] these polyyne-probes relied exclusively on Their Raman response, and were not combined with other sensing techniques. Novel molecule 24+, and studies of its interactions with DNA/RNA/proteins, will address the potential for the development of innovative combined fluorophore-Raman probes for the general purpose of non-covalent probing of DNA/RNA/ proteins, and the impact of the nature of the linker connecting two bis-triarylborane cations on the fluorescent and chirooptic response upon binding to biomacromolecules. Owing to its high sensitivity and ability to produce molecularly specific fingerprint spectra, SERS has been successfully applied for the detection, quantification and biophysical characterization of a variety of biomolecules.[22]

Results and Discussion

Conclusions

Conflict of interest