Acceptor Influence on Thiolate Sensing by Hemicyanine Dyes

Abstract

Promoting selective interactions between a nucleophile and electrophilic dye in complex environments is a central goal in nucleophilic chemosensor development. Commonly employed dyes are hemicyanines containing either the N-methylbenzothiazolium (Btz) or the N-methyl-3,3-dimethylindolium (Ind) acceptors. The dyes are related to α,β-unsaturated carbonyls and contain two sites of reactivity (C2 vs C4) with the C2-site directly attached to the quaternary nitrogen possessing greater electrophilicity. We demonstrate the regioselectivity between reactions of sodium thiomethoxide (NaSMe) with two electrophilic hemicyanine dyes bearing Btz (1) or Ind (2) in dipolar aprotic solvent–water mixtures. Adduct complexation was followed by NMR spectroscopy, and structures were optimized in the gas phase to estimate relative adduct stability. The key results include finding a preference for thiolate attachment at the C4-site to generate an enamine adduct with no evidence for attachment at the more electrophilic C2-position. Equilibration between NaSMe and water also affords NaOH that displays a thermodynamic preference for C2-attachment. Dye 1 containing the Btz moiety exhibits greater selectivity for the thiolate addition, with dye 2 being more reactive toward adventitious water to generate OH-adducts. Our data affords diagnostic 1H/13C NMR adduct signals, regioselectivity for various dye/nucleophile combinations, and suggests use of the Btz acceptor for direct thiolate detection.

A Turn‐On Sensor for Highly Sensitive and Selective Detect Heparin in Human Serum Albumin

“…This type of dye is endowed with excellent chemical and photophysical properties due to the efficient ICT process. [27][28][29] 1,8-naphthalimide, as a classical fluorophore, has been developed and applied in different fields as a role of a molecular fluorescence sensor based on its small molecular structure and the excellent properties of rigid plane frame, easy modification and stability. The new compounds can be easily synthesized by Suzuki Miyaura coupling reaction.…”

“…Hemicyanine dyes usually contain a conjugated benzothiolium or indolium group as an electron acceptor and a hydroxyl or amino group as an electron donor to form a donor‐ð‐acceptor (D‐ð‐A) system. This type of dye is endowed with excellent chemical and photophysical properties due to the efficient ICT process [27–29] . 1,8‐naphthalimide, as a classical fluorophore, has been developed and applied in different fields as a role of a molecular fluorescence sensor based on its small molecular structure and the excellent properties of rigid plane frame, easy modification and stability.…”

Temperature Sensing of Thiolate Addition by Phenolate Merocyanine Dyes: Importance of the Quinone Methide Resonance Structure

“…We recently examined the regioselectivity between reactions of NaSMe and two N-donor MCs bearing the Btz (X = S) or Ind (X = C(Me) 2 ) acceptors in dipolar aprotic solvent/water mixtures (Figure 1A). 17 Herein, we demonstrate the donor and temperature influence on reversible thiolate conjugate addition to MCs containing the Btz acceptor in 9:1 N,N-dimethylformamide (DMF)/water (Figure 1B). Our key finding is that the zwitterionic phenolate dye (PhOBtz) displays impressive temperature sensitivity to thiolate addition to afford an optical thermometer solution with the brightly colored phenolate dye favored upon heating and the colorless thiolate adduct favored upon cooling.…”

Hemicyanine‐Based Near‐Infrared Activatable Probes for Imaging and Diagnosis of Diseases

“…Another versatile strategy for HNAP‐based fluorescence detection is to disrupt the π‐conjugated systems by nucleophilic reactions or oxidative cleavage [12] . The rapid expansion of probes targeting nucleophilic reagents including cyanides, sulfides, and reactive oxygen species (ROS) provide examples of this approach.…”

“…Recently, a growing number of studies have investigated the development of hemicyanine‐based NIR activatable probes (HNAPs) in response to various biomarkers [11] . With the characteristic D‐π‐A motif of hemicyanine, the sensing mechanism of HNAP is commonly achieved by adjusting the intramolecular charge transfer (ICT) process between its donor and acceptor [12] . A versatile strategy towards the molecular‐level specificity of HNAPs is to cage the hemicyanine scaffold with a biomarker‐specific moiety which reduces the electron‐donating ability of the donor, causing ICT blocking and quenching of fluorescence signals.…”