Gd(III)-Catalyzed Regio-, Diastereo-, and Enantioselective [4 + 2] Photocycloaddition of Naphthalene Derivatives.

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, the CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed asymmetric dearomatization reaction of naphthalene with a chiral PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This reaction features application of a chiral Gd/PyBox complex, which regulates the reactivity and selectivity simultaneously, in excited-state catalysis. A wide range of functional groups is compatible with this protocol, giving the highly enantioenriched bridged polycycles in excellent yields (up to 96%) and selectivity (up to >20:1 chemoselectivity, >20:1 dr, >99% ee). The synthetic utility is demonstrated by a 2 mmol scale reaction, removal of directing group, and diversifications of products. Preliminary mechanistic experiments are performed to elucidate the reaction mechanism.

Silver(I) Complexes with Mefenamic Acid and Nitrogen Heterocyclic Ligands: Synthesis, Characterization, and Biological Evaluation.

Four Ag(I) complexes with mefenamato and nitrogen heterocyclic ligands, [Ag(2-apy)(mef)]2 (1), [Ag(3-apy)(mef)] (2), [Ag2(tmpyz)(mef)2] (3), and {[Ag(4,4'-bipy)(mef)]2(CH3CN)1.5(H2O)2}n (4), (mef = mefenamato, 2-apy = 2-aminopyridine, 3-apy = 3-aminopyridine, tmpyz = 2,3,5,6-tetramethylpyrazine, 4,4'-bipy = 4,4'-bipyridine), were synthesized and characterized. The interactions of these complexes with BSA were investigated by fluorescence spectroscopy, which indicated that these complexes quench the fluorescence of BSA by a static mechanism. The fluorescence data also indicated that the complexes showed good affinity for BSA, and one binding site on BSA was suitable for the complexes. The in vitro cytotoxicity of the four complexes against human cancer cell lines (MCF-7, HepG-2, A549, and MDA-MB-468) and one normal cell line (HTR-8) was evaluated by the MTT assay. Complex 1 displayed high cytotoxic activity against A549 cells. Further studies revealed that complex 1 could enhance the intracellular levels of ROS (reactive oxygen species) in A549 cells, cause cell cycle arrest in the G0/G1 phase, and induce apoptosis in A549 cells in a dose-dependent manner.

Sulfur in Waste-Free Sustainable Synthesis: Advancing Carbon-Carbon Coupling Techniques.

This review explores the pivotal role of sulfur in advancing sustainable carbon-carbon (C-C) coupling reactions. The unique electronic properties of sulfur, as a soft Lewis base with significant mesomeric effect make it an excellent candidate for initiating radical transformations, directing C-H-activation, and facilitating cycloaddition and C-S bond dissociation reactions. These attributes are crucial for developing waste-free methodologies in green chemistry. Our mini-review is focused on existing sulfur-directed C-C coupling techniques, emphasizing their sustainability and comparing state-of-the-art methods with traditional approaches. The review highlights the importance of this research in addressing current challenges in organic synthesis and catalysis. The innovative use of sulfur in photocatalytic, electrochemical and metal-catalyzed processes not only exemplifies significant advancements in the field but also opens new avenues for environmentally friendly chemical processes. By focusing on atom economy and waste minimization, the analysis provides broad appeal and potential for future developments in sustainable organic chemistry.

Enantioselective Synthesis of Cyclobutane Derivatives via Cascade Asymmetric Allylic Etherification/[2 + 2] Photocycloaddition.

Chiral cyclobutane presents as a popular motif in natural products and biologically active molecules, and its derivatives have been extensively used as key synthons in organic synthesis. Herein, we report an efficient synthetic method toward enantioenriched cyclobutane derivatives. The reaction proceeds in a cascade fashion involving Ir-catalyzed asymmetric allylic etherification and visible-light induced [2 + 2] cycloaddition. Readily available branched allyl acetates and cinnamyl alcohols are directly used as the substrates under mild reaction conditions, providing a broad range of chiral cyclobutanes in good yields with excellent diastereo- and enantioselectivities (up to 12:1 dr, >99% ee). It is worth noting that all substrates and catalysts were simultaneously added without any separated step in this approach. The gram-scale reaction and diverse transformations of product further enhance the potential utility of this method.

Visible-light induced dearomatization reactions.

Dearomatization reactions provide rapid access to structurally complex three-dimensional molecules from simple aromatic compounds. Plenty of reports have demonstrated their utilities in the synthesis of natural products, medicinal chemistry, and materials science in the last decades. Recently, visible-light mediated photocatalysis has emerged as a powerful tool to promote many kinds of transformations. The dearomatization reactions induced by visible-light have also made significant progress during the past several years. This review provides an overview of visible-light induced dearomatization reactions classified based on the manner in which aromaticity is disrupted.

Iridium-Catalyzed Asymmetric Allylic Benzylation with Photogenerated Hydroxy-o-Quinodimethanes.

An iridium-catalyzed asymmetric allylic benzylation of aryl vinyl carbinols under light irradiation is described. 2-Methylbenzophenone derivatives are employed and activated to hydroxy-o-quinodimethanes by an ultraviolet (UV) light. This approach enables asymmetric allylic benzylation with high enantioselectivity (up to 99 % ee) from readily available 2-methylbenzophenones without the utilization of strong bases, and pre-activation or pre-functionalization of the substrates. Moreover, deuterium experiments reveal the generation of nucleophilic benzyl species from 2-methylbenzophenone under UV irradiation.

Intermolecular Dearomatization of Naphthalene Derivatives by Photoredox-Catalyzed 1,2-Hydroalkylation.

An intermolecular hydroalkylative dearomatization of naphthalenes with commercially available α-amino acids is achieved via visible-light photoredox catalysis. With an organic photocatalyst, a series of multi-substituted 1,2-dihydronaphthalenes are obtained in good-to-excellent yields. Intriguingly, by tuning the substituents at the C2 position of naphthalenes, formal dearomative [3+2] cycloadditions occur exclusively via a hydroalkylative dearomatization-cyclization sequence. This overall redox-neutral method features mild reaction conditions, good tolerance of functionalities, and operational simplicity. Diverse downstream elaborations of the products are demonstrated. Preliminary mechanistic studies suggest the involvement of a radical-radical coupling pathway.

Asymmetric Dearomatization of Indole Derivatives with N-Hydroxycarbamates Enabled by Photoredox Catalysis.

Dearomatization of indoles provides efficient synthetic routes for substituted indolines. In most cases, indoles serve as nucleophiles. Reported here is an asymmetric dearomatization reaction of indole derivatives that function as electrophiles. The combination of a photocatalyst and chiral phosphoric acid open to air unlocks the umpolung reactivity of indoles, enabling their dearomatization with N-hydroxycarbamates as nucleophiles. A variety of fused indolines bearing intriguing oxy-amines were constructed in excellent yields with moderate to high enantioselectivities. Mechanistic studies show that the realization of two sequential single-electron transfer oxidations of the indole derivatives is key, generating the configurationally biased carbocation species while providing the source of stereochemical induction. These results not only provide an efficient synthesis of enantioenriched indoline derivatives, but also offer a novel strategy for further designing asymmetric dearomatization reactions.

Visible-Light-Promoted Intermolecular Oxidative Dearomatization of ß-Naphthols with N-Hydroxycarbamates.

An intermolecular oxidative dearomatization of ß-naphthols with N-hydroxycarbamates promoted by visible light was realized by means of photogenerated ß-naphthol radical cation intermediates. With a commercially available organic dye, the naphthalenones bearing a fully substituted stereogenic center were obtained with up to 92 % yield under aerobic conditions (26 examples). In addition, the rearrangement of C-O coupling products to C-N coupling compounds could be achieved merely in the presence of Cs2 CO3 . This transformation simultaneously provides an attractive and synthetically useful approach to access the aminative dearomatization compounds.

Immobilization of unraveled immunoglobulin G using well-oriented ZZ-His protein on functionalized microtiter plate for sensitive immunoassay.

Highly efficient protein immobilization is extremely crucial for solid-phase immunoassays. We present a strategy for oriented immobilization of functionally intact immunoglobulin G (IgG) on a polystyrene microtiter plate via iminodiacetic acid (IDA)-Ni(2+) and ZZ-His protein interaction. We immobilized a ZZ-EAP (Escherichia coli alkaline phosphatase)-His fusion protein, which exhibits Fc binding, His tag, and intrinsic AP activities, and analyzed it against the interaction between rabbit IgG anti-horseradish peroxidase (anti-HRP) and its binding partner HRP to investigate the specificity and efficacy of this method. We compared the IDA-Ni(2+)-(ZZ-His) method with ZZ-EAP random immobilization using sandwich enzyme-linked immunosorbent assay, and the results showed that the former method had an enhanced signal, 10-fold higher sensitivity, and a wider linear range. Thus, the proposed method allows a broad range of oriented immobilized functionally intact IgG antibodies on polystyrene plates using only one type of IDA-Ni(2+) chelate surface because the ZZ protein can bind to the Fc region of various IgGs.

catena-Poly[[bis-[aqua-(1,10-phenanthroline)lead(II)]-bis-(µ3-2-hy-droxy-5-sulfonato-benzoato)] acetic acid monosolvate].

In the title compound, [Pb2(C7H4O6S)2(C12H8N2)2(H2O)2]·CH3COOH, the seven-coordinate Pb(II) atom is chelated by two N atoms of one 1,10-phenanthroline ligand, four O atoms from three 5-sulfosalicylate dianions and one water O atom. Each dianion serves as a bridging ligand, connecting adjacent Pb(II) atoms into a centrosymmetric polymeric chain extending parallel to [001]. There are π-π inter-actions between the aromatic systems of neighbouring dianions, with plane-to-plane distances of 3.371 (2) Å, and between phenanthroline ligands, with a centroid-to-centroid distance of 3.484 (2) Å. O-H⋯O hydrogen bonding additionally stabilizes the crystal packing. The acetic acid mol-ecules are incorporated in the voids of this arrangement. They exhibit half-occupancy due to disorder around a centre of inversion.

Chiral Brønsted Acid-Catalyzed Intramolecular Asymmetric Allylic Alkylation of Indoles with Primary Alcohols.

Herein, chiral Brønsted acid-catalyzed intramolecular asymmetric allylic alkylation of indoles with allylic primary alcohols is described. The allyl alcohols were directly employed as the allylic precursors in this metal-free protocol, without preactivation or any additional activating reagents. This method provides the convenient synthesis of a broad range of functionalized tetrahydrocarbazoles in excellent yields (≤97%) with good enantioselectivity (≤93% ee). The optimal conditions are compatible for gram-scale reaction.

Photoredox-Catalyzed Intermolecular Hydroalkylative Dearomatization of Electron-Deficient Indole Derivatives.

Dearomatization of indole derivatives offers a straightforward approach to access diverse indolines. To date, the corresponding dearomative transformations involving electron-deficient indoles are limited. Herein, we report a one-electron strategy for dearomatization of electron-deficient indoles via a photoredox-catalyzed hydroalkylation employing commercially available glycine derivatives as the hydrofunctionalization reagents. Followed by DBU-mediated lactamization, structurally appealing lactam-fused indolines are obtained in good to excellent yields with exclusive selectivity.

Thermosensitive Chitosan Hydrogels Containing Polymeric Microspheres for Vaginal Drug Delivery.

Thermosensitive hydrogels have increasingly received considerable attention for local drug delivery based on many advantages. However, burst release of drugs is becoming a critical challenge when the hydrogels are employed. Microspheres- (MS-) loaded thermosensitive hydrogels were thus fabricated to address this limitation. Employing an orthogonal design, the spray-dried operations of tenofovir (TFV)/Bletilla striata polysaccharide (BSP)/chitosan (CTS) MS were optimized according to the drug loading (DL). The physicochemical properties of the optimal MS (MS F) were characterized. Depending on the gelation temperature and gelating time, the optimal CTS-sodium alginate- (SA-) α,ß-glycerophosphate (GP) (CTS-SA-GP) hydrogel was obtained. Observed by scanning electron microscope (SEM), TFV/BSP/CTS MS were successfully encapsulated in CTS-SA-GP. In vitro releasing demonstrated that MS F-CTS-SA-GP retained desirable in vitro sustained-release characteristics as a vaginal delivery system. Bioadhesion measurement showed that MS-CTS-SA-GP exhibited the highest mucoadhesive strength. Collectively, MS-CTS-SA-GP holds great promise for topical applications as a sustained-release vaginal drug delivery system.

Site-specific covalent attachment of an engineered Z-domain onto a solid matrix: an efficient platform for 3D IgG immobilization.

Immobilized antibodies with oriented and homogeneous patterns are crucial to solid-phase molecular recognition assay. Antibody binding protein-based immobilization can effectively present the desired antibodies. However, steadily installing the stromatoid protein with site-specific attachment manner onto a matrix surface remains to be elucidated. In this study, we present an optimal protocol to tightly attach an immunoglobulin G (IgG)-binding protein (Z-domain) through covalent incorporation of Cys-tag and maleimide group onto polystyrene surface to guarantee site-specific, oriented, and irreversible attachment, resulting in a highly efficient platform for three-dimensional IgG immobilization. The actual IgG-binding characteristic of immobilized Z-Cys was investigated by employing affinity chromatography and size exclusion chromatography. And the efficacy and potential of this platform was demonstrated by applying it to the analysis of interaction between rabbit anti-HRP IgG and its binding partner HRP. The proposed approach may be an attractive strategy to construct high performance antibody arrays and biosensors given that the antibody is compatible with the Z-domain.