Recent Progress of Spectroscopic Probes for Peroxynitrite and Their Potential Medical Diagnostic Applications.

Peroxynitrite (ONOO-) is a crucial reactive oxygen species that plays a vital role in cellular signal transduction and homeostatic regulation. Determining and visualizing peroxynitrite accurately in biological systems is important for understanding its roles in physiological and pathological activity. Among the various detection methods, fluorescent probe-based spectroscopic detection offers real-time and minimally invasive detection, high sensitivity and selectivity, and easy structural and property modification. This review categorizes fluorescent probes by their fluorophore structures, highlighting their chemical structures, recognition mechanisms, and response behaviors in detail. We hope that this review could help trigger novel ideas for potential medical diagnostic applications of peroxynitrite-related molecular diseases.

Synthesis of Heptamethine Cyanines from Furfural Derivatives.

Despite the widespread theranostic utilization of cyanine dyes (Cy7), their synthetic method is still limited with pyridine or cyclohexanone derivatives as starting materials. Herein, we report the synthesis of Cy7 from furfural derivatives. First, a one-pot reaction strategy is developed to solve the unstable problem of the Stenhouse salts. Second, a stepwise condensation strategy is exploited to regioselectively synthesize asymmetrical Cy7. The methodology possesses advantages, such as easy handling, high yield, wide substrate scopes, and good functional group tolerance.

A rhodamine derivative probe for highly selective detection of Cu(II).

BACKGROUND: Abnormal Cu(II) ions levels may affect many biological functions, and it is of great importance to detect Cu(II) ions in organisms. METHODS: Herein, we report a near-infrared (NIR) fluorescent probe EtRh-N-NH2 for the detection of Cu(II). In the probe structure, a rhodamine core was used, and a hydrazine group was employed as the responsive site. Results & Conlusions: EtRh-N-NH2 displayed sensitive, specific and fast response upon Cu(II) with excellent linear relationship between the concentration and fluorescence emission intensity in 0-1 µM range. The releasing EtRh-COOH exhibited 762 nm of emission wavelength with a 75 nm of Stokes shift.

Glutathione-responsive disassembly of disulfide dicyanine for tumor imaging with reduction in background signal intensity.

Near-infrared (NIR) fluorescence imaging has been proved as an effective modality in identifying the tumor border and distinguishing the tumor cells from healthy tissue during the oncological surgery. Developing NIR fluorescent probes with high tumor to background (T/B) signal is essential for the complete debulking of the tumor, which will prolong the survival rate of tumor patients. However, the nonspecific binding and "always-on" properties of the conventional fluorescent probes leads to high background signals and poor specificity. Method: To address this problem, glutathione (GSH)-responsive, two disulfide-bonded dicyanine dyes (ss-diCy5 and ss-diNH800CW) were synthesized. As synthesized dyes are quenched under normal physiological conditions, however, once reached to the tumor site, these dyes are capable of emitting strong fluorescence signals primarily because of the cleavage of the disulfide bond in the tumor microenvironment with high GSH concentration. Besides, the GSH-responsive behavior of these dyes was monitored using the UV-vis and fluorescence spectroscopy. The diagnostic accuracy of the aforementioned dyes was also tested both in tumor cells and 4T1-bearing mice. Results: The fluorescence signal intensity of disulfide dicyanine dyes was quenched up to 89% compared to the mono cyanine dyes, thus providing a very low fluorescence background. However, when the disulfide dicyanine dye reaches the tumor site, the dicyanine is cleaved by GSH into two mono-dyes with high fluorescence strength, thus producing strong fluorescent signals upon excitation. The fluorescent signal of the dicyanine was enhanced by up to 27-fold after interacting with the GSH solution. In vivo xenografts tumor studies further revealed that the fluorescence signals of aforementioned dyes can be quickly recovered in the solid tumor. Conclusion: In summary, the disulfide dicyanines dyes can provide a promising platform for specific tumor-activatable fluorescence imaging with improved T/B value.

Near-Infrared Cyanine-Loaded Liposome-like Nanocapsules of Camptothecin-Floxuridine Conjugate for Enhanced Chemophotothermal Combination Cancer Therapy.

A dual-in-dual synergistic strategy was proposed based on the self-assembly of combinatorial nanocapsules (NCs) from Janus camptothecin-floxuridine (CF) conjugate and the near-infrared absorber of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR) by introducing PEGylated phospholipid of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycerol)-2000] to increase the blood circulation time of NCs. Due to the use of amphiphilic CF and DiR themselves to form liposome-like nanocapsules, the obtained CF-DiR NCs owned a significantly high loading content, a stable co-delivery drug combinations, a no premature release, and an excellent photothermal conversion efficiency. The in vivo fluorescence imaging indicated that CF-DiR NCs could achieve a high tumor accumulation after an intravenous injection. The dual drugs of camptothecin and floxuridine could be coordinately released due to the hydrolysis of the ester bond by the esterase in tumor. The in vivo experiments showed that more cytotoxicity of the CF-DiR NCs-mediated chemo- and photothermal dual therapy to tumor cells could be clearly observed than the chemotherapy or photothermal therapy alone due to the synergistic effect, leading to no recurrence in the entire treatment. All of the results highlighted that CF-DiR NCs were highly effective theranostic agents that could be used for imaging-guided cancer chemophotothermal therapy to conquer an intrinsic resistance to chemotherapeutics.

In situ-generated iodonium ylides as safe carbene precursors for the chemoselective intramolecular Buchner reaction.

A chemoselective intramolecular Buchner reaction employing iodonium ylides as safe carbene precursors has been developed. Iodonium ylides are generated in situ from N-benzyl-2-cyanoacetamides and PhI(OAc)2 in the presence of base and undergo intramolecular Buchner reaction under catalysis from Cu(OAc)2·H2O, affording fused cyclohepta-1,3,5-triene derivatives in up to 85% yield. The N,N-dibenzyl-2-cyanoacetamides with two different benzyl groups undergo intramolecular Buchner reaction on their electron-rich benzyl groups selectively. The reaction is not sensitive to air and moisture and uses a safe alternative version of the corresponding diazo starting materials. The overall transformation involving the carbene pathway has been verified.

Cascade nitrosation and addition-elimination of nitroacetanilides for the highly efficient synthesis of 1,4,2,5-dioxadiazine derivatives.

A domino nitrosation and addition-elimination of nitroacetanilides with NaNO2 and H2SO4 has been developed to synthesize a variety of 1,4,2,5-dioxadiazine-3,6-dicarboxamides in excellent yields. The substrate scope can be extended to aryl nitromethyl ketones. A cascade reaction mechanism is proposed and the conjugated aryl moiety is considered to help stabilize the aci-nitroso species, the key intermediates in the cascade reaction. The methodology is practical and efficient because it avoids the purification of the intermediates. The nitroacetanilides were prepared from nitroacetic acid and various anilines employing DCC-DMAP as coupling reagents, and this protocol also possesses advantages like easy handling and high yields.