Chiral Atropisomeric-NHC Catechodithiolate Ruthenium Complexes for Z-Selective Asymmetric Ring-Opening Cross Metathesis of Exo-Norbornenes.

A set of 16 chiral ruthenium complexes containing atropisomerically stable N-Heterocyclic Carbene (NHC) ligands was synthesized from prochiral NHC precursors. After a rapid screening in asymmetric ring-opening-cross metathesis (AROCM), the most effective chiral atrop BIAN-NHC Ru-catalyst (up to 97 : 3 er) was then converted to a Z-selective catechodithiolate complex. The latter proved to be highly efficient in Z-selective AROCM of exo-norbornenes affording valuable trans-cyclopentanes with excellent Z-selectivity (>98 %) and high enantioselectivity (up to 96.5 : 3.5 er).

Chiral oxazolidines acting as transient hydroxyalkyl-functionalized N-heterocyclic carbenes: an efficient route to air stable copper and gold complexes for asymmetric catalysis.

Optically pure oxazolidines were synthesized in nearly quantitative yields from chiral hydroxyalkyl-functionalized imidazolinium salts. Acting as transient chiral diamino N-heterocyclic carbenes (NHCs), these oxazolidines allowed the efficient formation of well-defined copper(i) and gold(i) hydroxyalkyl-NHC complexes, which could be isolated, for the first time, as air stable complexes after silica gel chromatography. Interestingly, X-ray analysis of gold complexes revealed that the hydroxyl-function is not chelated to the metal. Computational studies suggested that both cyclisation to produce oxazolidine and O-H bond elimination to form the transient carbene (prior to coordination) occur through a concerted mechanism. The novel chiral copper-catalysts, as well as oxazolidines alone (copper free), demonstrated excellent performances in asymmetric conjugate addition and allylic alkylation with high regio- and enantio-selectivities (up to 99% ee).

Osteoid Osteoma: Percutaneous CT-guided Cryoablation Is a Safe, Effective, and Durable Treatment Option in Adults.

Background Cryoablation is playing an increasing role in the percutaneous treatment of bone tumors. However, despite its potential advantages over heat-based ablation techniques, the clinical safety and efficacy of cryoablation have not been established for osteoid osteoma treatment. Purpose To evaluate percutaneous CT-guided cryoablation for the treatment of osteoid osteoma in young patients and adults. Materials and Methods This retrospective study reviewed data from 50 consecutive patients who underwent percutaneous CT-guided cryoablation for the treatment of osteoid osteoma between January 2013 and June 2019 in a single institution. In 30 of 50 patients (60%), the procedure was carried out with the patient under local anesthesia and conscious sedation, with the cryoprobe covering the lesion from an extraosseous position, avoiding direct penetration of the nidus. Clinical and radiologic features, procedure-related data, visual analog scale (VAS) pain scores, complications, and overall success rate were evaluated. Statistical analyses were performed by using the nonparametric Friedman test and Wilcoxon signed rank test for repeated measures. Results Fifty patients (median age, 24 years; interquartile range [IQR], 19-38 years; 31 men) underwent CT-guided cryoablation for the treatment of osteoid osteoma, with a 96% (48 of 50 patients) overall clinical success rate. Of the two patients without clinical success, one patient had incomplete pain relief and the other experienced a recurrence of osteoid osteoma at 11 months, which was successfully treated with a second cryoablation procedure. The median VAS pain score was 8 (IQR, 7-8) before the procedure and 0 (IQR, 0-1; P < .001) after the procedure at both primary (6 weeks) and secondary (18-90 months) follow-up. Three of the 50 patients had minor complications (6%); no major complications were reported. Conclusion Osteoid osteoma was safely, effectively, and durably treated with CT-guided percutaneous cryoablation. In the majority of patients, treatment could be performed without general anesthesia, with the cryosphere covering the nidus from an extraosseous position. © RSNA, 2021.

Stereospecific synthesis of chiral P-containing polyaromatics based on 7-membered P-rings.

We present the stereospecific synthesis of helicenoid-based phosphepines (7-membered P-rings) as well as chiral P-containing polycyclic aromatic hydrocarbons. In these systems, an axial to central chirality transfer takes place from the BINAP moiety to the P-atom. The impact of the molecular design on the structure, the (chir)optical (including circularly polarized luminescence) and redox properties are investigated.

Optically Pure C1-Symmetric Cyclic(alkyl)(amino)carbene Ruthenium Complexes for Asymmetric Olefin Metathesis.

An expedient access to the first optically pure ruthenium complexes containing C1-symmetric cyclic (alkyl)(amino)carbene ligands is reported. They demonstrate excellent catalytic performances in asymmetric olefin metathesis with high enantioselectivities (up to 92% ee). Preliminary mechanistic insights provided by density functional theory models highlight the origin of the enantioselectivity.

From Prochiral N-Heterocyclic Carbenes to Optically Pure Metal Complexes: New Opportunities in Asymmetric Catalysis.

Well-defined optically pure transition metal (TM) complexes bearing C1- and C2-symmetric N-heterocyclic carbene (NHC) ligands were prepared from prochiral NHC precursors. As predicted by DFT calculations, our strategy capitalizes on the formation of a metal-carbene bond which induces an axis of chirality. Configurationally stable atropisomers of various NHC-containing TM complexes were isolated by preparative HPLC on a chiral stationary phase in good yields and excellent optical purities (up to 99.5% ee). The carbene transfer from an optically pure Cu complex to a gold or palladium center reveals, for the first time, a full stereoretentivity, supporting the hypothesis of an associative mechanism for the transmetalation. The potential of these new chiral TM complexes was illustrated in asymmetric catalysis with up to 98% ee.

In vitro and in vivo immunomodulatory properties of octyl-ß-D-galactofuranoside during Leishmania donovani infection.

BACKGROUND: The chemotherapeutic arsenal available to treat visceral leishmaniasis is currently limited, in view of many drawbacks such as high cost, toxicity or emerging resistance. New therapeutic strategies are particularly needed to improve the management and the outcome in immunosuppressed patients. The combination of an immunomodulatory drug to a conventional anti-Leishmania treatment is an emerging concept to reverse the immune bias from Th2 to Th1 response to boost healing and prevent relapses. METHODS: Here, immunostimulating and leishmanicidal properties of octyl-ß-D-galactofuranose (Galf) were assessed in human monocyte-derived macrophages (HM) and in a murine model, after challenge with Leishmania donovani promastigotes. We recorded parasite loads and expression of various cytokines and immune effectors in HM and mouse organs (liver, spleen, bone marrow), following treatment with free (Galf) and liposomal (L-Galf) formulations. RESULTS: Both treatments significantly reduced parasite proliferation in HM, as well as liver parasite burden in vivo (Galf, P < 0.05). Consistent with in vitro results, we showed that Galf- and L-Galf-treated mice displayed an enhanced Th1 immune response, particularly in the spleen where pro-inflammatory cytokines TNF-α, IL-1ß and IL-12 were significantly overexpressed compared to control group. The hepatic recruitment of myeloid cells was also favored by L-Galf treatment as evidenced by the five-fold increase of myeloperoxidase (MPO) induction, which was associated with a higher number of MPO-positive cells within granulomas. By contrast, the systemic level of various cytokines such as IL-1ß, IL-6, IL-17A or IL-27 was drastically reduced at the end of treatment. CONCLUSIONS: Overall, these results suggest that Galf could be tested as an adjuvant in combination with current anti-parasitic drugs, to restore an efficient immune response against infection in a model of immunosuppressed mice.

The debut of chiral cyclic (alkyl)(amino)carbenes (CAACs) in enantioselective catalysis.

The popularity of NHCs in transition metal catalysis has prompted the development of chiral versions as electron-rich neutral stereodirecting ancillary ligands for enantioselective transformations. Herein we demonstrate that cyclic (alkyl)(amino)carbene (CAAC) ligands can also engage in asymmetric transformations, thereby expanding the toolbox of available chiral carbenes.

Visible Light Induced Rhodium(I)-Catalyzed C-H Borylation.

An efficient visible light induced rhodium(I)-catalyzed regioselective borylation of aromatic C-H bonds is reported. The photocatalytic system is based on a single NHC-RhI complex capable of both harvesting visible light and enabling the bond breaking/forming at room temperature. The chelating nature of the NHC-carboxylate ligand was critical to ensure the stability of the RhI complex and to provide excellent photocatalytic activities. Experimental mechanistic studies evidenced a photooxidative ortho C-H bond addition upon irradiation with blue LEDs, leading to a cyclometalated RhIII -hydride intermediate.

A kinetic resolution strategy for the synthesis of chiral octahedral NHC-iridium(iii) catalysts.

The transmetalation reaction of a chiral-bidentate NHC-silver complex to racemic [Ir(µ-Cl)(ppy)2]2 operates with kinetic resolution leading to chiral octahedral NHC-iridium(iii) complexes and enantio-enriched bis-cyclometalated iridium(iii) complexes. The iridium(iii) complexes demonstrated efficient catalytic activities in intermolecular [2+2] photocycloaddition reactions and in asymmetric Friedel-Crafts alkylations, respectively.

Lemniscular [16]Cycloparaphenylene: A Radially Conjugated Figure-Eight Aromatic Molecule.

A cycloparaphenylene-based molecular lemniscate (CPPL) was obtained in a short synthesis involving masked p-phenylene equivalents. The strained figure-eight geometry of CPPL is sustained by the incorporated 9,9'-bicarbazole subunit, which also acts as a stereogenic element. The shape of the distorted [16]cycloparaphenylene nanohoop embedded in CPPL is accurately approximated with a Booth lemniscate. The structure of CPPL, investigated using NMR and Raman spectroscopic methods, revealed strain-dependent features, consistent with the variable curvature of the ring. The electronic and optical properties of CPPL combine features more characteristic of smaller cycloparaphenylenes, such as a reduced optical bandgap and red-shifted fluorescence. CPPL was resolved into enantiomers, which are configurationally stable and provide strong chiroptical responses, including circularly polarized luminescence.

Isolation of Bioactive Compounds from Calicotome villosa Stems.

A phenylethanoid, two steroids, a flavone glucoside and a chalcone have been isolated for the first time from the stems of Calicotome villosa together with a previously isolated flavone glucoside. Their structures were determined by spectroscopic analyses (NMR, HRMS) as basalethanoïd B (1), ß-sitosterol and stigmasterol (2), chrysine-7-O-ß-d-glucopyranoside (3), chrysine 7-((6''-O-acetyl)-O-ß-d-glucopyranoside) (4) and calythropsin (5). The crude extracts and the isolated compounds (except 4), were evaluated for their antioxidant, antimicrobial (against two Gram-positive bacterial strains: Staphylococcus aureus, Bacillus cereus, four Gram-negative bacterial strains: Staphylococcus epidermidis, Klebsiella pneumonia, Acinetobacter baumanii, and three yeasts: Candida albicans, Candida tropicalis, and Candida glabrata), hemolytic, antidiabetic, anti-inflammatory and cytotoxic activity. The crude extracts showed good ability to scavenge the free radical DPPH. Methanol stem extract followed by the dichloromethane stem extract showed moderate antimicrobial potency; furthermore, at 1 mg/mL the methanol extract showed an inhibition of C. albicans growth comparable to nystatin. Dichloromethane, methanol, and aqueous extracts inhibited 98%, 90%, and 80% of HeLa cell proliferation at 2 mg/mL respectively. Weak hypoglycemic and hemolytic effects were exhibited by the crude extracts. Among all the tested compounds, compound 3 showed remarkable hypoglycemic potential (93% at 0.1 mg/mL) followed by compound 5 (90% at 0.3 mg/mL). Compound 5 was the most effective in the DPPH. scavenging assay (100% at 0.1 mg/mL) and cytotoxic assay on HeLa cells (99% and 90% after 24 and 48 h of treatment at 0.1 mg/mL, respectively). No anti-inflammatory effects were displayed by any of the crude extracts or the isolated compounds at any of the tested concentrations.

Fine and Clean Photothermally Controlled NIR Drug Delivery from Biocompatible Nickel-bis(dithiolene)-Containing Liposomes.

This work demonstrates that metal-bis(dithiolene) complexes can be efficiently incorporated inside organic nanocarriers and, that under near-infrared (NIR) irradiation, their high photothermal activity can be finely used to release encapsulated drugs on demand. In contrast to gold nanoparticles and other organic NIR dyes, nickel-bis(dithiolene) complexes do not produce singlet oxygen under irradiation, a highly desirable characteristic to preserve the chemical integrity and activity of the loaded drug during the NIR-triggered release from the nanocarriers. Finally, cytotoxicity experiments performed on various cell lines have shown that the incorporation of such metal complexes do not increase the toxicity of the final liposomal formulation. These results offer great promise for the development of innovative biocompatible drug nanocargos that are able to safely deliver their content on demand under NIR laser irradiation. Moreover, this work demonstrates that metal-bis(dithiolene) complexes, owing to their versatility of functionalization and metal complexation, are attractive photothermal agents for the development of original NIR-responsive materials for application not only in biotechnology but also in materials science.

Transfer of Asymmetry between Proteinogenic Amino Acids under Harsh Conditions.

The heating above 400 °C of serine, cysteine, selenocysteine and threonine leads to a complete decomposition of the amino acids and to the formation in low yields of alanine for the three formers and of 2-aminobutyric acid for the latter. At higher temperature, this amino acid is observed only when sublimable α-alkyl-α-amino acids are present, and with an enantiomeric excess dependent on several parameters. Enantiopure or enantioenriched Ser, Cys, Sel or Thr is not able to transmit its enantiomeric excess to the amino acid formed during its decomposition. The presence during the sublimation-decomposition of enantioenriched valine or isoleucine leads to the enantioenrichment of all sublimable amino acids independently of the presence of many decomposition products coming from the unstable derivative. All these studies give information on a potentially prebiotic key-reaction of abiotic transformations between α-amino acids and their evolution to homochirality.

Asymmetric Sequential Cu-Catalyzed 1,6/1,4-Conjugate Additions of Hard Nucleophiles to Cyclic Dienones: Determination of Absolute Configurations and Origins of Enantioselectivity.

The first stereocontrolled Cu-catalyzed sequential 1,6/1,4-asymmetric conjugate addition (ACA) of C-metalated hard nucleophiles to cyclic dienones is reported. The use of DiPPAM (diphenylphosphinoazomethinylate) followed by a phosphoramidite as the stereoinducing ligands facilitated both high ee values for the 1,6-ACA and high de values for the 1,4-ACA reaction components, which thus gave enantioenriched 1,3-dialkylated moieties. The absolute configurations were determined by using vibrational circular dichroism (VCD) and optical rotatory dispersion (ORD) spectroscopy, in combination with DFT calculations and X-ray analysis. Interestingly, DFT calculations for the mechanism of enantioselective 1,6-addition by using an unprecedented Cu-Zn bimetallic catalytic system confirmed this attribution. Lastly, exploring intramolecular cyclization avenues for enantioenriched 1,3-dialkylated products provided access to the challenging drimane skeleton.

Readily Accessible Unsymmetrical Unsaturated 2,6-Diisopropylphenyl N-Heterocyclic Carbene Ligands. Applications in Enantioselective Catalysis.

A new multicomponent procedure was applied to the synthesis of (a)chiral bulky unsymmetrical unsaturated 2,6-diisopropylphenyl N-heterocyclic carbene (NHC) precursors with excellent selectivity (up to 95%) and good yields. This approach offers access to new chiral NHC ligands, which have found successful applications in both copper-catalyzed asymmetric allylic alkylation and copper-catalyzed asymmetric borylation.

Data on characterization of nano- and micro-structures resulting from glycine betaine surfactant/kappa-carrageenan interactions by Laser Scanning Confocal Microscopy and Transmission Electron Microscopy.

This article contains data on the Laser Scanning Confocal Microscopy (LSCM) and Transmission Electron Microscopy (TEM) images related to multi-scaled self-assemblies resulting from 'green' cationic glycine betaine surfactant/anionic kappa-carrageenan interactions. These data gave clear evidence of the evolution of the micron-, nano-sized structures obtained at two surfactant/polymer molar ratios (3.5 and 0.8) and after the dilution of the aqueous dispersions with factors of 5 and 10 times. This data article is related to the research article entitled, "Monitoring the architecture of anionic ĸ-carrageenan/cationic glycine betaine amide surfactant assemblies by dilution: A multiscale approach" (Gaillard et al., 2017) [1].

Interactions and hybrid complex formation of anionic algal polysaccharides with a cationic glycine betaine-derived surfactant.

The interaction between anionic algal polysaccharides ((κ)-, (ι)-, (λ)-carrageenans, alginate and ulvan) and a cationic glycine betaine (GB) amide surfactant possessing a C18:1 alkyl chain has been studied using isothermal titration calorimetry (ITC), zeta-potential measurements, dynamic light scattering (DLS), transmission electron microscopy (TEM), atomic force microscopy (AFM), and surface tension measurements. It was observed that this cationic surfactant derived from renewable raw materials induced cooperative binding with the anionic polymers at critical aggregation concentration (CAC) and the CAC values are significantly lower than the corresponding critical micelle concentration (CMC) for the surfactant. The CMC of cationic GB surfactant was obtained at higher surfactant concentration in polysaccharide solution than in pure water. More interestingly, the presence of original polysaccharide/surfactant hybrid complexes formed above the CMC value was evidenced from (κ)-carrageenan by microscopy (TEM and AFM). Preliminary investigations of the structure of these complexes revealed the existence of surfactant nanoparticles surrounded with polysaccharide matrix, probably resulting from electrostatic attraction. In addition, ITC measurements clearly showed that the interactions of the κ-carrageenan was stronger than for other polysaccharides ((ι)-, (λ)-carrageenans, alginate and ulvan). These results may have important impact on the use of the GB amide surfactant in formulations based on algal polysaccharides for several applications such as in food, cosmetics, and detergency fields.