Elucidating the Structure–Reactivity Correlations of Phenothiazine‐Based Fluorescent Probes toward ClO⁻

Abstract

In this work, with the aim of developing effective molecular probes and investigating the structure-reactivity correlation, a short series of phenothiazine-based fluorescent probes are designed for the detection of ClO with differing electron push-pull groups. Sensing experiment results and single-crystal X-ray analysis with the aid of time-dependent DFT (TD-DFT) calculations reveal that substituting groups with increasing electron-withdrawing ability can increase the dihedral angle of the phenothiazine moiety and reduce the gap energy of the probes, leading to enhanced reactivity toward ClO . Both PT1 and PT2 show two-color switching upon detection of ClO . PT1, with the strong electron-donating group thiophene, shows a fluorescence color switch from salmon to blue. PT2, with a medium electron-donating/accepting group benzothiazole, shows a fluorescence color switch from red to green. However, both PT1 and PT2 show almost no response to ONOO . Through the introduction of strong electron-withdrawing ketone combined with a cyano group, PT3 shows a cyan emission upon detection of ClO and weak red emission upon detection of ONOO . HRMS and H NMR results confirm that PT1 and PT2 have the same sensing mode, in which the divalent sulfur of phenothiazine can be oxidized to sulfoxide by ClO . Upon reaction with ClO , PT3 experiences two-step reactions. It is first oxidized into the sulfone structure by ClO , and then transformed into sulfoxide phenothiazine aldehyde. Upon encountering ONOO , PT3 changes into an aldehyde structure and some nonfluorescent byproducts. Owing to their special selectivity and high sensitivity, PT1 and PT2 are applied to image the endogenous ClO in macrophage cells and zebrafish larvae. This study is expected to provide useful guidelines for probe design for various applications.

Fluorescent phenothiazine-fused boron complexes for ratiometric hypochlorite imaging

“…It is worth noting that phenothiazine (PTZ)-based fluorescent probes usually have the advantages of high selectivity, good sensitivity, and short response time. [27][28][29][30][31][32] However, the emission wavelengths of PTZ itself and its derivatives are commonly too short to meet the in vivo imaging requirement. Thus, immense efforts have been paid to red-shift the emission wavelength to the visible or near-infrared region via a hybridization molecular engineering strategy.…”

“…Thus, immense efforts have been paid to red-shift the emission wavelength to the visible or near-infrared region via a hybridization molecular engineering strategy. 27,29,[31][32][33] For example, Gupta et al reported an OCl − probe HCP with an emission maximum (λ em ) at 615 nm by conjugating PTZ with BODIPY through an ethylene group; 33 27,31,32 It should be noted that these hybridized probes usually display very weak fluorescence due to the intrinsic strong charge transfer (CT) nature. After oxidation of the sulfur atom to sulfoxide by hypochlorite, the charge transfer effect from the PTZ unit to the electron-withdrawing group could be inhibited, resulting in a turn-on fluorescence response.…”

“…Thus, immense efforts have been paid to red-shift the emission wavelength to the visible or near-infrared region via a hybridization molecular engineering strategy. 27,29,31–33 For example, Gupta et al reported an OCl − probe HCP with an emission maximum ( λ em ) at 615 nm by conjugating PTZ with BODIPY through an ethylene group; 33 Hou et al and Zeng et al fused PTZ with coumarin or rhodamine constructed OCl − probes PDC and TJ2 with the λ em at 650 nm and 730 nm, respectively. 27,31,32 It should be noted that these hybridized probes usually display very weak fluorescence due to the intrinsic strong charge transfer (CT) nature.…”

General Strategy to Achieve Color-Tunable Ratiometric Two-Photon Integrated Single Semiconducting Polymer Dot for Imaging Hypochlorous Acid

“…The N and S atoms in PT molecule can endow PT with superior electron-donating ability, while the thioether can be specifically oxidized into the electron-withdrawing unit, sulfoxide structure, by ClO – . This strong contrast in electron-donating/-withdrawing property of PT molecule before and after being oxidized by ClO – can greatly tune the ICT and FRET processes within polymers, and this has been confirmed in the design of small-molecule fluorescent probes. , Consequently, the multicolored all-in-one polymers-derived Pdots-based probes can be achieved through adjusting ICT and FRET processes with the oxidation reaction between PT and ClO – . Combining the above design strategies (Scheme a), the design ideas of desired all-in-one fluorene-based polymers are described step by step from the perspective of fluorescence emission wavelength and signal output mode.…”

Phenothiazine appended thiophene derivative: a trilateral approach to copper ion detection in living cells and aqueous samples

“…19 Thus, in such a context, we successfully synthesized the phenothiazine-thiophene acetonitrile compound PTZ-SCN through a simple Knoevenagel condensation reaction. 20,21 The newly synthesized PTZ-SCN demonstrated sensitivity and selectivity towards Cu 2+ in both simulated physiological conditions (CH 3 CN : HEPES buffer) and within cells. PTZ-SCN and PTZ-SCN-Cu 2+ were examined by various techniques.…”