Electrophilic Cyanate As a Recognition Motif for Reactive Sulfur Species: Selective Fluorescence Detection of H₂S

Abstract

An ESIPT-based fluorescent dye, 3-hydroxyflavone, is chemically masked with an electrophilic cyanate motif in order to construct a fluorescent probe for cellular sulfur species. This novel probe structure, displays an extremely fast, highly sensitive and selective "turn-on" type fluorescent response toward H 2 S. We have also documented its utility for imaging of H 2 S in the living cells. H ydrogen sulfide (H 2 S), the smallest member among cellular sulfur species, plays critical roles in the functioning of living organisms. The compound is produced in biological systems from various sulfur-containing biomolecules and through a range of particular enzymatic pathways. The assessment of H 2 S levels in the cellular milieu is clearly vital to investigations of cell function and the early diagnosis of some diseases. Understanding the diverse contributions of H 2 S to physiology and pathology therefore first requires the development of efficient methods of visualizing H 2 S production and distribution in living systems. In related research, sustained attention has been paid to the development of molecular tools for probing cellular sulfur species.23−30 Among known analytical tools; fluorescence-based assays are particularly attractive, for they allow the real-time visualization of target species in cellular milieus. During the last several decades, numerous types of fluorescent H 2 S probes have appeared in scientific literature on the topic, most of them involving the use of specific chemical reactions to exploit the reactive and reductive nature of H 2 S. 31−41In general, the construction of any reaction-based H 2 S probe relies on modifying a fluorescent reporter with a reactive masking moiety, which splits away by interacting with H 2 S. To attain high selectivity over other relevant sulfur species, these masking moieties are necessarily highly specific to H 2 S ( Figure 1). 42−48 There are several important issues that have to be taken into account when designing a H 2 S recognition system. At the heart of the matter lies the discrimination of H 2 S over other biological sulfur species such as cysteine and glutathione. Low sensitivity and prolonged response times are other significant stumbling blocks that require attention. Moreover, most masking groups used in probe structures are relatively large

An H2S‐Sensing/CO‐Releasing Flavonol That Operates via Logic Gates

“…Compound 4 displays a three-fold enhanced sensitivity (Figures S9 and S10) for H 2 S over a previously reported H 2 S sensor ( 5 ) based on a flavonol motif (Figure 2). [24] In terms of molecular H 2 S sensors, the 79 nM detection limit of 4 is comparable to several previously reported sensors (Figures S11 and S12). [25–27] …”

“…[24] As shown in Figure 3, the cyanate unit of 4 undergoes cleavage in PBS buffer (pH = 7.4, 10 mM phosphate, 3.0 mM CTAB) at 37 °C to give the free flavonol 2 . The rate of this reaction is enhanced in DMEM F12K cellular media containing fetal bovine serum (10% v:v), with conversion to the free flavonol being complete within ~30 minutes at 37 °C.…”

Ingenious modification of molecular structure effectively regulates excited-state intramolecular proton and charge transfer: a theoretical study based on 3-hydroxyflavone

“…[2][3][4][5] More importantly, avone compounds have a broad range of therapeutic applications such as reducing agents, hydrogen-donating antioxidants, active against cancers, tumors and cardiac problems and having low systemic toxicity. [6][7][8][9][10] These extensive applications are closely related to their intrinsic physical characteristics. A large number of studies regarding excited-state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT) processes have been reported in different systems.…”

Theoretical investigation of excited-state single and double proton transfer mechanisms for 2,5-bis(benzoxazol-2-yl)thiophene-3,4-diol

“…ESIPT represents a complicated phototautomerization process and usually involves the transfer of a hydroxyl/imino proton from a preexisting hydrogen bond to an oxygen or nitrogen acceptor atom in the excited state, resulting in a new isomer dubbed as a proton-transfer tautomer or phototautomer. Owing to the drastic structural alternation, the phototautomer possesses different photophysical properties from that of the original (normal) species, offering great versatility in a variety of applications, such as fluorescent chemosensors, [2][3][4] lasing materials, 5 photostabilizers, [6][7] molecular recognition, [8][9][10] solid state emitters, [11][12][13][14][15] and so forth.…”