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

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.

Bis(phenylethynyl)arene Linkers in Tetracationic Bis‐triarylborane Chromophores Control Fluorimetric and Raman Sensing of Various DNAs and RNAs

“…These CD results along with the strong binding affinities of 3 , 4 and 6 to dsDNA/RNA (Table 3) and the observed thermal stabilization effects (Table 2), support binding within the minor groove of dsDNA and the major groove of dsRNA, respectively. This is in accordance with our earlier studies on this novel class of DNA/RNA sensors [88, 89] …”

“…The three compounds with longer linkers ( 3 – 5 ) all strongly stabilized the dsDNA/RNA even at rather low ratios of compound to polynucleotide (in the following, this ratio is generally given as: r [compound]/[polynucleotide] ; Figures S27–S35), with anthracene analogue 5 causing the strongest stabilization (Table 2). Our previously reported bithiophene compound 1 [88] and buta‐1,3‐diyne compound 2 [89] stabilized DNA and RNA to a similar extent (Δ T m =7–10 °C). Intriguingly, the short anthracene compound 6 had a very weak effect on the thermal stability of DNA/RNA (Figures S36 and S37).…”

“…Single crystals suitable for X‐ray diffraction analysis for the trimethylsilyl‐protected precursor to compound A were obtained. The solid‐state molecular structure of C [89] is reported in Table S1 and Figure S13 in the Supporting Information, and the geometry of C does not exhibit a significant deviation from those of the triarylborane groups in 3N and 4N .…”

“…However, emission maxima were strongly dependent on the type of bio‐macromolecule (DNA/RNA vs. protein), which allowed us to suggest a protein‐like binding site for 1 in the cell. In contrast, the emission of buta‐1,3‐diyne analogue 2 (Figure 2) was strongly quenched by DNA, RNA and protein [89] . Thus, it was indicated that the linker connecting the two triarylborane moieties in tetracationic bis‐triarylboranes has a profound impact on its fluorescence response when sensing bio‐macromolecules.…”

Phenylpyridyl‐Fused Boroles: A Unique Coordination Mode and Weak B−N Coordination‐Induced Dual Fluorescence

“…Triarylboranes are of current interest due to their potential applications in various fields, such as non‐linear optics, [1] live cell imaging, [2a–d] DNA/RNA/protein binding, [2e,f] anion sensors, [3] frustrated Lewis pairs (FLPs), [4] etc., [5] with their properties resulting from the vacant p z orbital on the 3‐coordinate boron atom. This vacant p z orbital can be attacked by nucleophiles, thus 3‐coordinate boranes have been widely used as Lewis acids.…”