Enantiospecific Analysis of Carboxylic Acids Using Cinchona Alkaloid Dimers as Chiral Solvating Agents.

Cinchona alkaloid derivatives as Brønsted base catalysts have attracted considerable attention in the field of asymmetric catalysis. However, their potential application as chiral solvating agents has not been described. In this research, we investigated the use of the Cinchona alkaloid dimer, namely, (DHQ)2PHAL, as a chiral solvating agent for discerning various mandelic acid derivatives through 1H NMR spectroscopy. The addition of catalytic amounts of DMAP facilitated this process. Our experimental results demonstrate that dimeric (DHQ)2PHAL exhibits remarkable chiral discrimination properties regarding the diagnostic split protons of 1H NMR signals (including 24 examples, up to 0.321 ppm). Furthermore, it serves as an excellent chiral discriminating agent and provides good resolution for racemic chiral phosphoric acid as determined by 31P NMR spectroscopy. The quality of enantiodifferentiation has also been evaluated by means of the parameter "resolution (Rs)". Significantly, this class of CSAs based on (alkaloid)2linker systems with an azaaromatic linker can be directly employed, which is commercially available in an enantiopure form at very low cost and exhibits promising potential in determining the enantiopurity of α-hydroxy acids by chemoselective and biocatalytic reactions.

Polyarylisocyanides Derived from an Alkyne-Pd(II) Catalyst as Robust Alignment Media with Excellent Enantiodiscimination.

The development of chiral alignment media for measuring anisotropic NMR parameters provides an opportunity to determine the absolute configuration of chiral molecules without the need for derivatization. However, chiral alignment media with a high and robust enantiodiscriminating property for a wide range of chiral molecules are still scarce. In this study, we synthesized cholesterol-end-functionalized helical polyisocyanides from a chiral monomer using a cholesterol-based alkyne-Pd(II) initiator. These stereoregular polyisocyanides form stable and weak anisotropic lyotropic liquid crystals (LLCs) in dichloromethane systems, exhibiting highly optical activities in both single left- and right-handed helices. The preparation process of the media was straightforward, and the aligning property of the LLCs could be controlled by adjusting the concentration and temperature. Using the chiral polyisocyanides, we extracted the residual dipolar coupling for an enantiomeric pair of isopinocampheol (IPC), as well as a number of pharmaceutical molecules, demonstrating excellent enantiodiscriminating properties for a broad range of chiral compounds.

A palladium-catalyzed sequential Heck coupling/C-C bond activation approach to oxindoles with all-carbon-quaternary centers.

Catalytic construction of oxindoles bearing all-carbon-quaternary centers attracts wide attention from the synthetic chemistry community. Herein, we report a palladium-catalyzed sequential Heck coupling/C-C bond activation of aryl halide-tethered alkenes with benzocyclobutenols affording a series of oxindole-derived compounds in good to excellent yields, as well as the preliminary enantioselectivity results.

Self-Assembly of Helical Polymers and Oligomers to Create Liquid Crystalline Alignment for Anisotropic NMR Parameters.

The measurement of anisotropic residual dipolar couplings (RDCs) parameters for the structure elucidation of organic molecules relies on suitable alignment media. Employment of self-assembled liquid crystalline systems to create anisotropic alignment can be an effective way to realize aligned samples and acquire RDCs. This Mini-review highlights the recent advances on amino acid-based helical polymers and supramolecular oligomers forming rigid, rod-like structures that aggregate into ordered liquid crystalline phases, including amino acid-based helical polyisocyanides, polyacetylenes, polypeptides, and oligopeptides assembled alignment media. The methodology for the determination of anisotropic liquid crystals is briefly discussed, and a summary of recent research progress in the enantiodifferentiation of helical polymers aligned media is followed. In addition, the self-assembled mechanism of oligopeptides and their RDCs structural analysis are also described.

Helical Polyisocyanopeptides as Lyotropic Liquid Crystals for Measuring Residual Dipolar Couplings.

Residual dipolar couplings (RDC) emerged to be an important structural parameter for organic and biomolecules. Herein, a new helical polyisocyanopeptide (l,l-PIAF-OBn) that forms lyotropic liquid crystals (LLC) in CDCl3 is proposed as a novel weakly orienting medium for acquiring residual dipolar couplings (RDCs) of organic molecules. We demonstrate its application for the structural elucidation of strychnine and triptolide.

Dinuclear zinc complex catalyzed asymmetric methylation and alkynylation of aromatic aldehydes.

A general AzePhenol dinuclear zinc catalytic system has been successfully developed and introduced into the asymmetric addition of dimethylzinc and alkynylzinc to aromatic aldehydes. In this system, an azetidine derived chiral ligand has proven to be an effective enantioselective promoter. Under the optimal reaction conditions, a series of chiral 1-hydroxyethyl (up to 99% ee) and secondary propargylic alcohols (up to 96% ee) were generated with good yields and enantioselectivities. Additionally, this novel catalytic system showed good functional group compatibility. Remarkably, the substituent's electronic nature alone is not sufficient to allow for exclusive enantioselectivity, an additional substituent's location also had an effect. We proposed that the formation of a stable and structural rigid transition state by the chelation of ortho substituted benzaldehydes to the zinc atom was responsible for the observed higher enantioselectivity. The possible catalytic cycles of both transformations accounting for the stereoselectivity were described accordingly.

An Alignment Medium for Measuring Residual Dipolar Couplings in Pure DMSO: Liquid Crystals from Graphene Oxide Grafted with Polymer Brushes.

Residual dipolar couplings (RDCs) have attracted attention in light of their great impact on the structural elucidation of organic molecules. However, the effectiveness of RDC measurements is limited by the shortage of alignment media compatible with widely used organic solvents, such as DMSO. Herein, we present the first liquid crystal (LC) based alignment medium that is compatible with pure DMSO, thus enabling RDC measurements of polar and intermediate polarity molecules. The liquid crystals were obtained by grafting polymer brushes onto graphene oxide (GO) using free radical polymerization. The resulting new medium offers several advantages, such as absence of background signals, narrow line shapes, and tunable alignment. Importantly, this medium is compatible with π-conjugated molecules. Moreover, sonication-induced fragmentation can reduce the size of GO sheets. The resulting anisotropic medium has moderate alignment strength, which is a prerequisite for an accurate RDC measurement.

Design and Synthesis of Dipeptidomimetic Isocyanonaphthalene as Enhanced-Fluorescent Chemodosimeter for Sensing Mercury Ion and Living Cells.

A novel valine-based isocyanonaphthalene (NpI) was designed and synthesized by using an easy method and enabled the selective fluorescence detection of Hg2+. The chemodosimeter can display an immediate turn-on fluorescence response (500-fold) towards target metal ions upon the Hg2+-mediated conversion of isocyano to amino within NpI. Based on this specific reaction, the fluorescence-enhancement probe revealed a high sensitivity toward Hg2+ over other common metal ions and exhibited excellent aqueous solubility, good antijamming capability, high sensitivity (detection limit: 14.2 nM), and real-time detection. The response mechanism of NpI was supported by NMR spectroscopy, MS analysis and DFT theoretical calculation using various techniques. Moreover, a dipeptidomimetic NpI probe was successfully applied to visualize intracellular Hg2+ in living cells and monitor Hg2+ in real water samples with good recoveries and small relative standard deviations.

Necrostatin-1 decreases necroptosis and inflammatory markers after intraventricular hemorrhage in mice.

Necrostatin-1, an inhibitor of necroptosis, can effectively inhibit necrotic apoptosis in neurological diseases, which results in the inhibition of inflammation, endoplasmic reticulum stress, and reactive oxygen species production and substantial improvement of neurological function. However, the effects of necrostatin-1 on intraventricular hemorrhage (IVH) remain unknown. In this study, we established a mouse model of IVH by injecting autologous blood into the lateral ventricle of the brain. We also injected necrostatin-1 into the lateral ventricle one hour prior to IVH induction. We found that necrostatin-1 effectively reduced the expression levels of the necroptosis markers receptor-interacting protein kinase (RIP)1, RIP3, mixed lineage kinase domain-like protein (MLKL), phosphorylated (p)-RIP3, and p-MLKL and the levels of interleukin-1ß , interleukin-6, and tumor necrosis factor-α in the surrounding areas of the lateral ventricle. However, necrostatin-1 did not reduce ependymal ciliary injury or brain water content. These findings suggest that necrostatin-1 can prevent local inflammation and microglial activation induced by IVH but does not greatly improve prognosis.

Azaheterocyclic diphenylmethanol chiral solvating agents for the NMR chiral discrimination of alpha-substituted carboxylic acids.

A series of small-membered heterocycle probes, so-called azaheterocycle-containing diphenylmethanol chiral solvating agents (CSAs), have been developed for NMR enantiodiscrimination. These chiral sensors were readily synthesized were inexpensive and efficiently used for the chiral analysis of alpha-substituted carboxylic acids. The sensing method was operationally simple and the processing was straightforward. Notably, we propose (S)-aziridinyl diphenylmethanol as a promising CSA, which has excellent chiral discriminating properties and offers multiple detectable possibilities pertaining to the 1H NMR signals of diagnostic split protons (including 25 examples, up to 0.194 ppm, 77.6 Hz). Its ability to detect the molecular recognition of fluorinated carboxylic acids were further investigated, with a good level of discrimination via the 19F NMR spectroscopic analysis. In addition, an accurate enantiomeric excess (ee) analysis of the p-methoxyl-mandelic acid with different optical compositions have been calculated based on the integration of well-separated proton signals.

Formulation, Characterization And Evaluation Of Curcumin- Loaded PLGA- TPGS Nanoparticles For Liver Cancer Treatment.

BACKGROUND: Liver cancer is a major health problem facing mankind. Currently, the focus of research is to improve the treatment of liver cancer using a variety of treatment options such as providing chemotherapy drugs through nanocarriers. PURPOSE: The aim of this study was to prepare a curcumin-loaded (PLGA/TPGS) NPs delivery system by the emulsification-solvent evaporation method in order to achieve synergistic antitumor activity against liver cancer. METHODS: Curcumin-loaded (PLGA/TPGS) NPs were prepared by the emulsification and solvent evaporation method. The physical and chemical characteristics of NPs such as size, morphology, and release profiles were discussed. In vitro and in vivo studies were carried out to evaluate its anti-tumor activity in target cells. RESULTS: Curcumin-loaded (PLGA/TPGS) NPs could be successfully internalized by HepG2 cells and play a synergistic role in inhibiting the growth of hepatocellular carcinoma cells. They exhibited high target organ accumulation, superior antitumor efficiency, and lower toxicity in vivo. CONCLUSION: The present study indicates that the curcumin-loaded (PLGA/TPGS) NPs provide a promising platform for the treatment of liver cancer.

Residual Dipolar Couplings in Structure Determination of Natural Products.

The determination of natural products stereochemistry remains a formidable task. Residual dipolar couplings (RDCs) induced by anisotropic media are a powerful tool for determination of the stereochemistry of organic molecule in solution. This review will provide a short introduction on RDCs-based methodology for the structural elucidation of natural products. Special attention is given to the current availability of alignment media in organic solvents. The applications of RDCs for structural analysis of some examples of natural products were discussed and summarized. This review provides a short introduction on RDCs-based methodology for the structural elucidation of natural products. Special attention is given to the current availability of alignment media in organic solvents. The applications of RDCs for structural analysis of some examples of natural products were discussed and summarized.