New Insights into the Brown Carbon Chromophores and Formation Pathways for Aqueous Reactions of α-Dicarbonyls with Amines and Ammonium.

Aqueous-phase reactions of α-dicarbonyls with ammonium or amines have been identified as important sources of secondary brown carbon (BrC). However, the identities of most chromophores in these reactions and the effects of pH remain largely unknown. In this study, the chemical structures, formation pathways, and optical properties of individual BrC chromophores formed through aqueous reactions of α-dicarbonyls (glyoxal and methylglyoxal) with ammonium, amino acids, or methylamine at different pH's were characterized in detail by liquid chromatography-photodiode array-high resolution tandem mass spectrometry. In total, 180 chromophores are identified, accounting for 29-79% of the light absorption of bulk BrC for different reactions. Thereinto, 155 newly identified chromophores, including 76 imidazoles, 57 pyrroles, 10 pyrazines, 9 pyridines, and 3 imidazole-pyrroles, explain additionally 9-69% of the light absorption, and these chromophores mainly involve four formation pathways, including previously unrecognized reactions of ammonia or methylamine with the methylglyoxal dimer for the formation of pyrroles. The pH in these reactions also shows remarkable effects on the formation and transformation of BrC chromophores; e.g., with the increase of pH from 5.0 to 7.0, the light absorption contributions of imidazoles in identified chromophores decrease from 72% to 65%, while the light absorption contributions of pyrazines increase from 5% to 13% for the methylglyoxal + ammonium reaction; meanwhile, more small nitrogen heterocycles transformed into oligomers (e.g., C9 and C12 pyrroles) via reaction with methylglyoxal. These newly identified chromophores and proposed formation pathways are instructive for future field studies of the formation and transformation of aqueous-phase BrC.

A water-soluble fluorescent pH probe and its application for monitoring lysosomal pH changes in living cells.

Intracellular pH plays a crucial role in many cellular processes, and abnormal intracellular pH has been linked to common diseases such as cancer and Alzheimer's. To address this issue, a water-soluble fluorescent pH probe was designed based on the protonation/deprotonation of the 4-methylpiperazin-1-yl group, using dicyanoisophorone as the fluorophore. In the neutral form of the probe, fluorescence is quenched due to charge transfer from the 4-methylpiperazin-1-yl group to the fluorophore upon excitation. Under acidic conditions, protonation of the 4-methylpiperazin-1-yl group inhibits the photoinduced electron transfer process, leading to an increase in fluorescence intensity. Density-functional theory calculations also verified the fluorescence OFF-ON mechanism. The probe exhibits high selectivity, photostability, fast response to pH changes, and low cytotoxicity to cells. Additionally, the probe selectively accumulates in lysosomes, with a high Pearson coefficient (0.95) using LysoTracker Green DND-26 as a reference. Notably, the probe can monitor lysosomal pH changes in living cells and track pH changes stimulated by chloroquine. We anticipate that the probe has potential for diagnosing pH-related diseases.

A 3,5-dinitropyridin-2yl substituted naphthalimide-based fluorescent probe for the selective detection of biothiols and its application in cell-imaging.

A naphthalimide-based fluorescent probe was developed for the sensitive and selective detection of biothiols. The fluorescence of the probe was quenched by the electron-withdrawing 3,5-dinitropyridin-2-yl group via the photoinduced electron transfer process, and turned on by biothiol-triggered nucleophilic aromatic substitution. The sensing mechanism was confirmed by HPLC analysis and theoretical calculations. The probe shows a satisfactory response time of 30 min with low detection limits (Cys: 0.32 µM; Hcy: 0.88 µM; GSH: 0.46 µM). Furthermore, the probe was successfully utilized to detect endogenous and exogenous biothiols in HeLa cells.

Compatibility of ticagrelor with pharmaceutical excipients studied with thermal and spectroscopic techniques.

The compatibility between ticagrelor and selected excipients (mannitol, calcium phosphate tribasic, sodium carboxymethyl starch, hydroxypropyl cellulose and magnesium stearate) was investigated by differential scanning calorimetry. The compatibility was further corroborated by Raman spectroscopy and isothermal stress testing experiments. These results revealed that ticagrelor has high compatibility with mannitol, calcium phosphate tribasic, sodium carboxymethyl starch, hydroxypropyl cellulose and magnesium stearate.

Base-Promoted Cascade C-C Coupling/N-α-sp3C-H Hydroxylation for the Regiospecific Synthesis of 3-Hydroxyisoindolinones.

A base-promoted cascade reaction for the regiospecific synthesis of substituted 3-hydroxyisoindolinones under transition-metal-free conditions is developed. The base-mediated C-C bond coupling and N-α-sp3C-H bond hydroxylation are involved in this procedure, which features high regioselectivity, efficiency, and environmental friendliness. Various substituted 3-hydroxyisoindolinones, including some bioactive molecules, were provided in up to 93% yield for 28 examples.

Selective tracking of lysosomal Cu2+ ions using simultaneous target- and location-activated fluorescent nanoprobes.

Levels of lysosomal copper are tightly regulated in the human body. However, few methods for monitoring dynamic changes in copper pools are available, thus limiting the ability to diagnostically assess the influence of copper accumulation on health status. We herein report the development of a dual target and location-activated rhodamine-spiropyran probe, termed Rhod-SP, activated by the presence of lysosomal Cu(2+). Rhod-SP contains a proton recognition unit of spiropyran, which provides molecular switching capability, and a latent rhodamine fluorophore for signal transduction. Upon activation by lysosomal acidic pH, Rhod-SP binds with Cu(2+) by spiropyran-based proton activation, promoting, in turn, rhodamine ring opening, which shows a "switched on" fluorescence signal. However, to protect Rhod-SP from degradation and interference by the physiological environment, it is engineered on mesoporous silica nanoparticles (MSNs), and the surface of Rhod-SP@MSNs is further anchored with ß-cyclodextrin (ß-CD) to enhance the solubility and bioavailability of Rhod-SP@MSN-CD. Next, to enhance cell specificity, a guiding unit of c(RGDyK) peptide conjugated adamantane (Ad-RGD) as prototypical system, is incorporated on the surface of Rhod-SP@MSN-CD to target integrin αvß3 and αvß5 overexpressed on cancer cells. Fluorescence imaging showed that both Rhod-SP@MSN-CD and Rhod-SP@MSN-CD-RGD were suitable for visualizing exogenous and endogenous Cu(2+) in lysosomes of living cells. This strategy addresses some common challenges of chemical probes in biosensing, such as spatial resolution in cell imaging, the solubility and stability in biological system, and the interference from intracellular species. The newly designed nanoprobe, which allows one to track, on a location-specific basis, and visualize lysosomal Cu(2+), offers a potentially rich opportunity to examine copper physiology in both healthy and diseased states.

A coumarin-based fluorescent probe for recognition of Cu(2+) and fast detection of histidine in hard-to-transfect cells by a sensing ensemble approach.

A coumarin-based fluorescent chemosensor CAQA has been synthesized. It can selectively and sensitively recognize Cu(2+) in aqueous acetonitrile solutions. Using the Cu-containing complex CAQA-Cu(2+) as a sensing ensemble, the device demonstrates highly selective recognition of His/biothiols and was applied in fluorescence imaging of histidine in hard-to-transfect living cells.

Ultrasound, pH, and magnetically responsive crown-ether-coated core/shell nanoparticles as drug encapsulation and release systems.

Core@shell nanoparticles with superparamagnetic iron oxide core, mesoporous silica shell, and crown ether periphery were fabricated toward drug delivery and tumor cell imaging. By the concept of nanovalve based on supramolecular gatekeeper, stimuli-responsive drug delivery nanosystems Fe3O4@SiO2@meso-SiO2@crown ethers were synthesized by (i) modified solvothermal reaction; (ii) sol-gel reaction; and (iii) amide coupling reaction. The successful coupling of the dibenzo-crown ethers onto the mesoporous silica shell was confirmed by thermogravimetric analysis and Infrared spectroscopy. In this system, the "ON/OFF" switching of the gatekeeper supramolecules can be controlled by pH-sensitive intramolecular hydrogen bonding or electrostatic interaction (such as metal chelating). Biological evaluation of the nanoparticles renders them noncytotoxic and can be uptaken by L929 cells. In this work, the antitumor drug (doxorubicin) loading and release profiles which were studied by the UV/visible absorption spectroscopy. The mechanism involves the best-fit binding of crown ethers with cesium or sodium ions at different pH values with ultrasonic wave in phosphate buffered saline (PBS). Magnetic resonance imaging analysis of the particles reveals a high relaxivity, rendering them potentially useful theranostic agents.

Protein recognition via surface molecularly imprinted polymer nanowires.

In this paper, we present a technique for the preparation of polymer nanowires with the protein molecule imprinted and binding sites at surface. These surface imprinting nanowires exhibit highly selective recognition for a variety of template proteins, including albumin, hemoglobin, and cytochrome c. This recognition may be through a multistep adsorption, with the specificity conferred by hydrogen bonding and shape selectivity. Due to the protein imprinted sites are located at, or close to, the surface; these imprinted nanowires have a good site accessibility toward the target protein molecules. Furthermore, the large surface area of the nanowires results in large protein molecule binding capacity of the imprinted nanowires.