As traditional pH meters cannot work well for minute regions (such as subcellular organelles) and in harsh media, molecular pH-sensitive devices for monitoring pH changes in diverse local heterogeneous environments are urgently needed. Here, we report a new dual-modal colorimetric/fluorescence merocyanine-based molecular probe (CPH) for ratiometric sensing of pH. Compared with previously reported pH probes, CPH bearing the benzyl group at the nitrogen position of the indolium group and the phenol, which is used as the acceptor for proton, could respond to pH changes immediately through both the ratiometric fluorescence signal readout and naked-eye colorimetric observation. The sensing process was highly stable and reversible. Most importantly, the suitable pKa value (6.44) allows CPH to presumably accumulate in lysosomes and become a lysosome-target fluorescent probe. By using CPH, the intralysosomal pH fluctuation stimulated by antimalaria drug chloroquine was successfully tracked in live cells through the ratiometric fluorescence images. Additionally, CPH could be immobilized on test papers, which exhibited a rapid and reversible colorimetric response to acid/base vapor through the naked-eye colorimetric analysis. This proof-of-concept study presents the potential application of CPH as a molecular tool for monitoring intralysosomal pH fluctuation in live cells, as well as paves the way for developing the economic, reusable, and fast-response optical pH meters for colorimetric sensing acid/base vapor with direct naked-eye observation.

Based on the 2,2-dipicolylamine (DPA) receptor and naphthalimide fluorophore, three fluorescent probes, RDPA, MDPA and VDPA have been developed for the recognition of mercuric ions. Among them, VDPA, bearing a diglycol group in the imine chain, exhibits good water solubility, and high selectivity towards mercuric ions in PBS water solution. With DPA as the receptor, VDPA showed very high affinity and sensitivity towards Hg2+, and the binding constant and detection limit were calculated to be 2.8 × 1010 M−1 and 5.49 nM, respectively. The MTT assay and living cell imaging experiments suggested that the probe VDPA has potential application for detecting Hg2+ in living cells.

Fluorescence polarization (FP)-based signal is a self-referencing fluorescence signal, and it is less dependent on dye concentration and environmental interferences, which makes FP measurement an attractive alternative sensing technology to fluorescence intensity-based detection. However, most of the fluorescence polarization probes were constructed by introducing fluorescein, rhodamine, and cyanine dyes, which have relatively shorter excited-state lifetimes compared with BODIPY and naphthalimide dyes. Herein, a first naphthalimide based fluorescence polarization probe (BIO) was designed and synthesized for selective and direct detection of cancer cells. The relatively longer excited-state lifetimes and high photostability of naphthalimide makes BIO more sensitive and accuracy in quantitative determination of HeLa cells in homogeneous solution without cell lysis and further separation steps. The detection limit of BIO for HeLa cells was about 85 cells mL–1, the linear range was from 2.5 × 102 cells mL–1 to 1 × 106 cells mL–1 and the response time is no more than 25 min. Moreover, due to the relatively high photostability of naphthalimide, BIO was particularly suitable for live cell imaging under continuous irradiation with confocal microscopy, and the specific interaction of BIO with CD44-overexpressing cell lines was clearly visualized. Importantly, this BIO based sensing platform offers a direct and real-time tool for cancer cell diagnosis when complemented with the use of naphthalimide-based fluorescence polarization probe.Keywords: cancer cells; fluorescence polarization probe; lifetime; live cell imaging; naphthalimide; self-referencing fluorescence sensing technology;

Mercury (Hg2+) is a toxic heavy metal and commonly exists in the ecological environment and polluted biological samples. Small-molecular-weight biological thiols (biothiols, such as GSH and Cys) play an essential role in many biological events. Till now, recently developed approaches for monitoring Hg2+ and biothiols commonly require large and cumbersome instruments, complicated procedures, or an elegant design and synthesis. In this study, we have developed a dynamic light scattering (DLS) based technique for the dual detection of Hg2+ and biothiols. This label free assay based on DNA-mediated gold nanoparticles (DNA–AuNPs) could present an effective toolkit for the determination of Hg2+ (or biothiol) containing samples within 30 min without complicated procedures. To best of our knowledge, this is the first DLS based probe for the dual detection of Hg2+ and biothiols. It exhibited potential for high throughput screening of Hg2+ (or biothiol) containing samples.

•A highly selective and ratiometric fluorescent probe for detecting periodate was synthesized.•A first ratiometric approach for simultaneously monitoring changes of periodate was developed.•Live-cell fluorescence imaging of periodate with target fluorescent probe PDS-2 was developed.•PDS-2 can be used for studying effect of periodate on live cells and other biological samples.•PDS-2 based test papers were prepared and used for monitoring periodate in water.Periodate is widely used in organic and bioorganic chemistry, and also related to food and environmental safety. To best of our knowledge, there is no efficient tools reported for simultaneously quantifying periodate with high accuracy and discriminating periodate from other forms of iodine. We have synthesized, characterized and applied a first ratiometric fluorescent probe (PDS-2) for simultaneous monitoring of changes of periodate based on the excited-state intramolecular proton transfer mechanism. This PDS-2 based fluorescent technique may enable for a better understanding of periodate related biological and chemical processes. Also, it is an efficient tool for public health, food safety and environmental protection.

•A naphthalimide-based fluorescent probe CP has been synthesized with facile steps, which can selectively and sensitively recognize Cu2+ in water solution (100% H2O).•The Cu-containing complex CP@Cu can serve as a turn-on fluorescent probe demonstrating particular detection of histidine with low LOD, which exhibits remarkable fluorescence enhancement for dozens of times upon His added.•Such metal complex can be applied in the recognition of histidine rich proteins and the intracellular imaging of histidine.A naphthalimide-based fluorescent probe CP has been synthesized with simple steps. It can selectively and sensitively recognize copper ions (Cu2+) in HEPES buffer (50 mM, pH 7.2). The fluorescence intensity of CP is linearly proportional to the concentration of Cu2+ ranging from 0–8.3 μM (correlation coefficient R2=0.9808). The resulted complex CP@Cu can serve as a turn-on fluorescent probe for the detection of histidine and histidine rich proteins in broad pH application range. Upon the addition of histidine, the fluorescence intensity of CP@Cu exhibits a linear correlation with the concentration of histidine ranging from 0–200 μM (correlation coefficient R2=0.9912). Moreover, CP@Cu has potential for imaging histidine in vitro experiments and has promise in real sample applications with great validity.

Based on the 2,2-dipicolylamine (DPA) receptor and naphthalimide fluorophore, three fluorescent probes, RDPA, MDPA and VDPA have been developed for the recognition of mercuric ions. Among them, VDPA, bearing a diglycol group in the imine chain, exhibits good water solubility, and high selectivity towards mercuric ions in PBS water solution. With DPA as the receptor, VDPA showed very high affinity and sensitivity towards Hg2+, and the binding constant and detection limit were calculated to be 2.8 × 1010 M−1 and 5.49 nM, respectively. The MTT assay and living cell imaging experiments suggested that the probe VDPA has potential application for detecting Hg2+ in living cells.

Mercury (Hg2+) is a toxic heavy metal and commonly exists in the ecological environment and polluted biological samples. Small-molecular-weight biological thiols (biothiols, such as GSH and Cys) play an essential role in many biological events. Till now, recently developed approaches for monitoring Hg2+ and biothiols commonly require large and cumbersome instruments, complicated procedures, or an elegant design and synthesis. In this study, we have developed a dynamic light scattering (DLS) based technique for the dual detection of Hg2+ and biothiols. This label free assay based on DNA-mediated gold nanoparticles (DNA–AuNPs) could present an effective toolkit for the determination of Hg2+ (or biothiol) containing samples within 30 min without complicated procedures. To best of our knowledge, this is the first DLS based probe for the dual detection of Hg2+ and biothiols. It exhibited potential for high throughput screening of Hg2+ (or biothiol) containing samples.