Strategies for the Preparation of Single-Atom Catalysts Using Low-Dimensional Metal-Organic Frameworks.

As single-atom catalysts are important energy materials, their preparation and synthesis methods have become particularly important. The unique structures of low-dimensional metal-organic frameworks and their derivatives provide various strategies for preparing single-atom catalysts. This paper summarizes various strategies for the preparation of single-atom catalysts based on low-dimensional metal-organic frameworks and their derivatives.

Sonodynamic Therapy of NRP2 Monoclonal Antibody-Guided MOFs@COF Targeted Disruption of Mitochondrial and Endoplasmic Reticulum Homeostasis to Induce Autophagy-Dependent Ferroptosis.

The lethality and chemotherapy resistance of pancreatic cancer necessitates the urgent development of innovative strategies to improve patient outcomes. To address this issue, we designed a novel drug delivery system named GDMCN2,which uses iron-based metal organic framework (Fe-MOF) nanocages encased in a covalent organic framework (COF) and modified with the pancreatic cancer-specific antibody, NRP2. After being targeted into tumor cells, GDMCN2 gradually release the sonosensitizer sinoporphyrin sodium (DVDMS) and chemotherapeutic gemcitabine (GEM) and simultaneously generated reactive oxygen species (ROS) under ultrasound (US) irradiation. This system can overcome gemcitabine resistance in pancreatic cancer and reduce its toxicity to non-targeted cells and tissues. In a mechanistic cascade, the release of ROS activates the mitochondrial transition pore (MPTP), leading to the release of Ca2+ and induction of endoplasmic reticulum (ER) stress. Therefore, microtubule-associated protein 1A/1B-light chain 3 (LC3) is activated, promoting lysosomal autophagy. This process also induces autophagy-dependent ferroptosis, aided by the upregulation of Nuclear Receptor Coactivator 4 (NCOA4). This mechanism increases the sensitivity of pancreatic cancer cells to chemotherapeutic drugs and increases mitochondrial and DNA damage. The findings demonstrate the potential of GDMCN2 nanocages as a new avenue for the development of cancer therapeutics.

Metal-Organic Frameworks/Graphdiyne/Copper Foam Composite Membranes for Catalytic Applications.

Graphdiyne (GDY) with a three-dimensional network structure was synthesized on a copper foam (CF) via an in situ Glaser-Hay coupling reaction. A metal-organic framework/GDY composite membrane was designed and synthesized for the first time. CF serves as a template and catalyst for the directed polymerization of GDY membranes. The catalytic activities of HKUST-1/GDY/CF membrane in wet peroxide oxidation of phenol, oxidation of benzyl alcohol, and ring opening of epoxide were studied. The composite membrane has the advantages of appropriateness for continuous operation, simple use process, easy recycling, high catalytic efficiency, etc. It was found that the incorporation of GDY can facilitate electron transfer and effectively improve the catalytic activity of HKUST-1 in membrane catalysis.

Applications of the DIB-BBr3 Protocol in Bromination Reactions.

Non-symmetrical bromoiodanes are useful for bromination reactions, and some protocols were found to be suitable for specific substrates. Herein, we report the use of a DIB/BBr3 protocol for various bromination reactions, including electrophilic bromination of arenes, carbonyl C-H monobromination, bromolactonization, bromocarbocyclization, intermolecular bromoetherification of olefin, and light-triggered C(sp3)-H bromination.

A Mechanochemical, Catalyst-Free Cascade Synthesis of 1,3-Diols and 1,4-Iodoalcohols Using Styrenes and Hypervalent Iodine Reagents.

A mechanochemical and solvent/catalyst-free functionalization of olefins with hypervalent iodine reagents has been developed, enabling the synthesis of 1,3-dioxygenated compounds. Under similar reaction conditions with the addition of molecular iodine, 1,4-iodoalcohols can be synthesized. These valuable products are non-trivial to achieve via standard solution-phase methods. Mechanistic study reveals that the hypervalent iodine reagent might dimerize at solid state with the help of mechanical force. The active monomeric form of hypervalent iodine reagent might trigger the 1,3- and 1,4-difunctionalization reactions in an intermolecular cascade manner.

Hypervalent Chalcogenonium⋠⋠⋠π Bonding Catalysis.

A proof-of-concept study of hypervalent chalcogenonium⋅⋅⋅π bonding catalysis was performed. A new catalytic strategy using 1,2-oxaselenolium salts as chalcogen bond donors and alkenes as chalcogen bond acceptors is described. The feasibility of this concept is demonstrated by the use of trisubstituted selenonium salts in the metal-free catalytic hydrofunctionalization and polymerization of alkenes via unconventional seleniranium ion-like intermediates. The results indicate that counter anions have a significant effect on the catalysis based on hypervalent chalcogenonium⋅⋅⋅π bonding interactions.

Amphiphilic Indoles as Efficient Phase-Transfer Catalysts for Bromination in Water.

Brominated compounds are important, but they are usually prepared in organic solvents. Here, efficient amphiphilic indole-based phase-transfer organocatalysts were developed for environmentally benign bromination reactions in water. As test reactions, hydroxybromination of olefins and aromatic bromination could be conducted in a greener and more sustainable manner compared with methods using organic solvents, producing the corresponding bromides in good yields. Some pure products could be obtained without column chromatography.

Lewis Base Catalyzed Dioxygenation of Olefins with Hypervalent Iodine Reagents.

1,2-Diols are extremely useful building blocks in organic synthesis. Hypervalent iodine reagents are useful for the vicinal dihydroxylation of olefins to give 1,2-diols under metal-free conditions, but strongly acidic promoters are often required. Herein, we report a catalytic vicinal dioxygenation of olefins with hypervalent iodine reagents using Lewis bases as catalysts. The conditions are mild and compatible with various functional groups.

Zwitterion-Catalyzed Deacylative Dihalogenation of ß-Oxo Amides.

α,α-Dihalo-N-arylacetamides are commonly used as intermediates in various organic reactions. In the study described here, a catalytic synthesis of α,α-dihalo-N-arylacetamides from ß-oxo amides was developed using zwitterionic catalysts and N-halosuccinimides as the halogen sources. The corresponding α,α-dihalo-N-arylacetamides were obtained in good to excellent yields, and no aromatic halogenated side products were detected. The reaction conditions were mild, and no strong base or acid was required.

Boron tribromide as a reagent for anti-Markovnikov addition of HBr to cyclopropanes.

Although radical formation from a trialkylborane is well documented, the analogous reaction mode is unknown for trihaloboranes. We have discovered the generation of bromine radicals from boron tribromide and simple proton sources, such as water or tert-butanol, under open-flask conditions. Cyclopropanes bearing a variety of substituents were hydro- and deuterio-brominated to furnish anti-Markovnikov products in a highly regioselective fashion. NMR mechanistic studies and DFT calculations point to a radical pathway instead of the conventional ionic mechanism expected for BBr3.

Lipophilic Indole-Catalyzed Intermolecular Bromoesterification of Olefins in Nonpolar Media.

An environmentally benign and highly versatile catalytic protocol has been successfully applied in the intermolecular bromoesterification between various olefins and carboxylic acids. The use of a highly lipophilic indole catalyst and 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) as the bromine source allows the reaction to proceed in heptane via a solid-liquid phase transfer mechanism, affording the corresponding bromoester products in good-to-excellent yields.

Applications of Selenonium Cations as Lewis Acids in Organocatalytic Reactions.

The use of trisubstituted selenonium salts as organic Lewis acids in electrophilic halogenation and aldol-type reactions has been developed. The substrate scope is broad. The reaction conditions are mild and compatible with various functionalities. This study opens a new avenue for the development of nonmetallic Lewis acid catalysis.

Lewis Base-Promoted Ring-Opening 1,3-Dioxygenation of Unactivated Cyclopropanes Using a Hypervalent Iodine Reagent.

A facile and effective system has been developed for the regio- and chemoselective ring-opening/electrophilic functionalization of cyclopropanes through C-C bond activation by [bis(trifluoroacetoxy)iodo]benzene with the aid of the Lewis basic promoter p-toluenesulfonamide. The p-toluenesulfonamide-promoted system works well for a wide range of cyclopropanes, resulting in the formation of 1,3-diol products in good yields and regioselectivity.

Lewis Base Catalyzed Stereo- and Regioselective Bromocyclization.

Oxygen- and nitrogen-containing heterocyclic compounds are widely recognized as key components in many natural products and biologically relevant molecules, but often the problem comes down to methodologies in synthesizing them. Halocyclization of olefinic substrates is a promising strategy in the construction of O- and N-heterocyclic compounds, which further signifies the development of their asymmetric variants. Over the past years, our group has been devoted to this particular area of asymmetric electrophilic halocyclization with chalcogen-containing molecules as catalysts. In this account, the main focus is on the development of our novel chiral catalysts and applications derived from the reaction products.

Lewis Basic Sulfide Catalyzed Electrophilic Bromocyclization of Cyclopropylmethyl Amide.

A Lewis basic sulfide catalyzed electrophilic bromocyclization of cyclopropylmethyl amide has been developed. The catalytic protocol is applicable to both 1,1- and 1,2-substituted cyclopropylmethyl amides, giving oxazolines and oxazines in good yields and excellent diastereoselectivity.

Catalytic asymmetric bromoetherification and desymmetrization of olefinic 1,3-diols with C2-symmetric sulfides.

An enantioselective and highly diastereoselective bromoetherification and desymmetrization of olefinic 1,3-diols has been developed using a C2-symmetric cyclic sulfide catalyst. This methodology has been successfully applied to the synthesis of the key intermediate of an orally active antifungal drug posaconazole (Noxafil).

A platinum(II) terpyridine metallogel with an L-valine-modified alkynyl ligand: interplay of Pt⋠⋠⋠Pt, π-π and hydrogen-bonding interactions.

A series of platinum(II) terpyridine complexes with L-valine-modified alkynyl ligands has been synthesized. A complex with an unsubstituted terpyridine and one valine unit on the alkynyl is shown to be capable of gel formation, which is in sharp contrast to the gelation properties of the corresponding organic counterparts. Upon sol-gel transition, a drastic color change from yellow to red is observed, which is indicative of the involvement of Pt⋅⋅⋅Pt interactions. Through the concentration- and temperature-dependent UV/Vis absorption, emission, circular dichroism, and (1) H NMR studies, the contribution of hydrogen bonding, Pt⋅⋅⋅Pt and π-π stacking interactions as driving forces for gelation have been established, and the importance of maintaining a delicate balance between different intermolecular forces has also been illustrated.

NBS-initiated electrophilic phenoxyetherification of olefins.

A one-pot electrophilic phenoxyetherification using an olefin, a cyclic ether, a phenol, and N-bromosuccinimide has been developed. This type of multicomponent reaction (MCR) is useful in the synthesis of building blocks that are potentially applicable to self-assembly complex construction.

Design, synthesis and crystallographic analysis of nitrile-based broad-spectrum peptidomimetic inhibitors for coronavirus 3C-like proteases.

Coronaviral infection is associated with up to 5% of respiratory tract diseases. The 3C-like protease (3CL(pro)) of coronaviruses is required for proteolytic processing of polyproteins and viral replication, and is a promising target for the development of drugs against coronaviral infection. We designed and synthesized four nitrile-based peptidomimetic inhibitors with different N-terminal protective groups and different peptide length, and examined their inhibitory effect on the in-vitro enzymatic activity of 3CL(pro) of severe-acute-respiratory-syndrome-coronavirus. The IC(50) values of the inhibitors were in the range of 4.6-49 µM, demonstrating that the nitrile warhead can effectively inactivate the 3CL(pro) autocleavage process. The best inhibitor, Cbz-AVLQ-CN with an N-terminal carbobenzyloxy group, was ~10x more potent than the other inhibitors tested. Crystal structures of the enzyme-inhibitor complexes showed that the nitrile warhead inhibits 3CL(pro) by forming a covalent bond with the catalytic Cys145 residue, while the AVLQ peptide forms a number of favourable interactions with the S1-S4 substrate-binding pockets. We have further showed that the peptidomimetic inhibitor, Cbz-AVLQ-CN, has broad-spectrum inhibition against 3CL(pro) from human coronavirus strains 229E, NL63, OC43, HKU1, and infectious bronchitis virus, with IC(50) values ranging from 1.3 to 3.7 µM, but no detectable inhibition against caspase-3. In summary, we have shown that the nitrile-based peptidomimetic inhibitors are effective against 3CL(pro), and they inhibit 3CL(pro) from a broad range of coronaviruses. Our results provide further insights into the future design of drugs that could serve as a first line defence against coronaviral infection.

Head-to-tail dimerization and organogelating properties of click peptidomimetics.

Click triazole-based oligopeptides 1-3 were found to self-dimerize (K(dim) ≈ 10-680 M(-1)) in a head-to-tail fashion based on (1)H variable concentration, 2D, and H/D exchange NMR, VPO, CD, FT-IR studies and Gaussian 03 simulations. The dimerization constant K(dim) was shown to increase with increasing number of the amino acid units. Within the same oligomeric series, the K(dim) value is strongly affected by the size of the C-terminal end group. The tripeptides 2 are also excellent organogelators of aromatic solvents.