Unique assembly of carbonylpyridinium and chromene reveals mitochondrial thiol starvation under ferroptosis and novel ferroptosis inducer

Abstract

To reveal the delicate function of mitochondrial, precise detection tools in spatiotemporal manner remains highly desirable. However, current probes with positive charge warheads for targeting mitochondria diffuse out of the...

Fluorescent probes for ferroptosis bioimaging: advances, challenges, and prospects

“…To solve this, the Yin group constructed a novel probe CM-Mit using the chromene skeleton and carbonylpyridinium structure. 48 Employing a thiol-chromene ''click'' nucleophilic reaction endows the CM-Mit with a high signal to noise ratio, and the formation of o-quinone methide after identifying the target facilitates labelling mitochondrial proteins, improving mitochondrial targeting accuracy. Note that carbonylpyridinium not only served as a mitochondrial-targeting group but is also believed to speed up the recognition process due to its excellent departure ability (Fig.…”

Recent advances in small-molecule fluorescent probes for studying ferroptosis

“…10). 129 In this probe, chromene was selected as the reaction site for thiols, and carbonylpyridinium cation not only enabled the probe to localize in mitochondria, but also promote the recognition reaction between the probe and thiols. Moreover, the o -quinone methide generated after the reaction could label the proteins in the mitochondria, which further facilitated the probe with high mitochondrial targeting ability.…”

Mitochondrial Targeting and Imaging with Small Organic Conjugated Fluorophores: A Review

“…This observation could be in fact attributed to known large uncertainties in the relative determination of this photophysical parameter and not to arise from structural contributions [108] . Given the length of the linker, it was demonstrated in 56 and 57 that whilst substitution of quinolinum in 55 for pyridinium ( 56 ) and benzothiazolium ( 57 ) ensured mitochondrial accumulation, it bears little effect on the photophysical properties [109,99] …”

“…[108] Given the length of the linker, it was demonstrated in 56 and 57 that whilst substitution of quinolinum in 55 for pyridinium (56) and benzothiazolium (57) ensured mitochondrial accumulation, it bears little effect on the photophysical properties. [109,99] Selective mitochondrial targeting in coumarin systems has also been facilitated by means of pyrrolidinium cation. Thiomorpholine substitution on position 4 in the case of 58 [111] was observed to result in a significant bathochromic shift in the absorption spectra and diminish in the Stokes shifts when compared to its structural analogue 59 [112] (λ abs/em max = 552/650 and 440/630 nm for 58 and 59, respectively).…”

“…In some cases ( 48 and 49 , Table 2 ), structural modifications result in rigid molecules which as a consequence are characterized by smaller Stokes shifts than those normally observed in coumarins. These probes employ ammonium [99] and chromene [100] mitochondrial targeting units, respectively. In this regard, reported probes exploiting coumarin chemistries for mitochondrial accumulation and imaging are not solely restricted to the use of ubiquitous triphenylphosphonium ( 50 ) [101] and pyridinium delocalized lipophilic cations.…”