Asymmetric Cross-Coupling of Aldehydes with Diverse Carbonyl or Iminyl Compounds by Photoredox-Mediated Cobalt Catalysis.

The asymmetric cross-coupling of unsaturated bonds, hampered by their comparable polarity and reactivity, as well as the scarcity of efficient catalytic systems capable of diastereo- and enantiocontrol, presents a significant hurdle in organic synthesis. In this study, we introduce a highly adaptable photochemical cobalt catalysis framework that facilitates chemo- and stereoselective reductive cross-couplings between common aldehydes with a broad array of carbonyl and iminyl compounds, including N-acylhydrazones, aryl ketones, aldehydes, and α-keto esters. Our methodology hinges on a synergistic mechanism driven by photoredox-induced single-electron reduction and subsequent radical-radical coupling, all precisely guided by a chiral cobalt catalyst. Various optically enriched ß-amino alcohols and unsymmetrical 1,2-diol derivatives (80 examples) have been synthesized with good yields (up to 90% yield) and high stereoselectivities (up to >20:1 dr, 99% ee). Of particular note, this approach accomplishes unattainable photochemical asymmetric transformations of aldehydes with disparate carbonyl partners without reliance on any external photosensitizer, thereby further emphasizing its versatility and cost-efficiency.

Photo-Induced C-H Methylation Reactions.

Direct C-H methylation is a highly valuable approach for introducing methyl groups into organic molecules, particularly in pharmaceutical chemistry. Among the various methodologies available, photo-induced methylation stands out as an exceptional choice due to its mild reaction conditions, energy efficiency, and compatibility with functional groups. This article offers a comprehensive review of photochemical strategies employed for the direct and selective methylation of C(sp3 )-H, C(sp2 )-H, and C(sp)-H bonds in various organic molecules. The discussed methodologies encompass transition-metal-based photocatalysis, organophotocatalysis, as well as other metal-free approaches, including electron donor-acceptor (EDA)-enabled transformations. Importantly, a wide range of easily accessible agents such as tert-butyl peroxide, methanol, DMSO, methyl tert-butyl ether, TsOMe, N-(acetoxy)phthalimide, acetic acid, methyl halides, and even methane can serve as effective methylating reagents for modifying diverse targets. These advancements in photochemical C-H methylation are anticipated to drive further progress in the fields of organic synthesis, photocatalysis, and pharmaceutical development, opening up exciting avenues for creating novel organic molecules and discovering new drug compounds.

Visible light-triggered selective C(sp2)-H/C(sp3)-H coupling of benzenes with aliphatic hydrocarbons.

The direct and selective coupling of benzenes with aliphatic hydrocarbons is a promising strategy for C(sp2)-C(sp3) bond formation using readily available starting materials, yet it remains a significant challenge. In this study, we have developed a simplified photochemical system that incorporates catalytic amounts of iron(III) halides as multifunctional reagents and air as a green oxidant to address this synthetic problem. Under mild conditions, the reaction between a strong C(sp2)-H bond and a robust C(sp3)-H bond has been achieved, affording a broad range of cross-coupling products with high yields and commendable chemo-, site-selectivity. The iron halide acts as a multifunctional reagent that responds to visible light, initiates C-centered radicals, induces single-electron oxidation to carbocations, and participates in a subsequent Friedel-Crafts-type process. The gradual release of radical species and carbocation intermediates appears to be critical for achieving desirable reactivity and selectivity. This eco-friendly, cost-efficient approach offers access to various building blocks from abundant hydrocarbon feedstocks, and demonstrates the potential of iron halides in sustainable synthesis.

Synthesis of metalla-dual-azulenes with fluoride ion recognition properties.

Azulene-based conjugated systems are of great interests due to their unusual structures and photophysical properties. Incorporation of a transition metal into azulene skeleton presents an intriguing opportunity to combine the dπ-pπ and pπ-pπ conjugated properties. No such metallaazulene skeleton however has been reported to date. Here, we describe our development of an efficient [5 + 2] annulation reaction to rapid construction of a unique metal-containing [5-5-7] scaffold, termed metalla-dual-azulene (MDA), which includes a metallaazulene and a metal-free organic azulene intertwined by sharing the tropylium motif. The two azulene motifs in MDA exhibit distinct reactivities. The azulene motif readily undergoes nucleophilic addition, leading to N-, O- and S-substituted cycloheptanetrienyl species. Demetalation of the metallaazulene moiety occurs when it reacts with nBu4NF, which enables highly selective recognition of fluoride anion and a noticeable color change. The practical [5 + 2] annulation methodology, facile functional-group modification, high and selective fluoride detection make this new π-conjugated polycyclic system very suitable for potential applications in photoelectric and sensing materials.

Recent Advances in Photochemical Asymmetric Three-Component Reactions.

Over the past decades, asymmetric photochemical synthesis has garnered significant attention for its sustainability and unique ability to generate enantio-enriched molecules through distinct reaction pathways. Photochemical asymmetric three-component reactions have demonstrated significant potential for the rapid construction of chiral compounds with molecular diversity and complexity. However, noteworthy challenges persist, including the participation of high-energy intermediates such as radical species, difficulties in precise control of stereoselectivity, and the presence of competing background and side reactions. Recent breakthroughs have led to the development of sophisticated strategies in this field. This review explores the intricate mechanisms, synthetic applications, and limitations of these methods. We anticipate that it will contribute towards advancing asymmetric catalysis, photochemical synthesis, and green chemistry.

Photochemical Synthesis of S,N,O-Containing Polyheterocycles via an α-C(sp3)-H Functionalization/Radical Cyclization Cascade.

A highly effective approach based on an organophotocatalytic α-C(sp3)-H functionalization/radical cyclization cascade has been developed. This method enables the synthesis of various tricyclic heterocycles containing S, O, and N atoms with excellent site selectivity and diastereoselectivity. Mechanistic investigations have confirmed that the reaction involves photoredox-triggered C(sp3)-H cleavage followed by a radical cyclization and aromatization process. These findings are expected to pave the way for developing cost-effective tandem radical reactions and synthesizing heterocyclic drugs.

Does the periportal end of a double-lumen endobronchial tube need to be fixed to prevent dislocation of the cuffed end caused by a change in position? A randomized controlled trial.

OBJECTIVE: This study aimed to evaluate the effects on the dislocation and misalignment of the cuffed end of a double-lumen endobronchial tube (DLT) when a patient moves from a horizontal to a lateral position without fixation. METHODS: A total of 148 patients who had undergone video-assisted thoracoscope surgery were enrolled and randomly divided into two groups: a group in which the periportal end of the DLT was fixed with tape (group I; n = 74) and a group in which the periportal end of the DLT remained unfixed (group II; n = 74). Both groups were given an intravenous induction for double-lumen endobronchial intubation and then moved from a horizontal position to a lateral position, after which the alignment of the bronchial cuffed end of the DLT was assessed using a fiberoptic bronchoscope. RESULTS: After lateral position, the dislocation rate of group I and group II was 44.6% and 20.2%, and the misalignment rate was 27.0% and 8.1%, respectively, the incidence of dislocation and misalignment was significantly lower in group II than in group I after the change to a lateral position (p < 0.05). After lateral position, the total rate of airway injury was 25.7% in group I and 5.4% in group II, the incidence of airway injury was significantly lower in group II than in group I (p < 0.05), as was the incidence of sore throat, hoarseness, and cough on postoperative day 1 (p < 0.05). The average outward dislocation of the periportal end of the DLT in group II was 1.5 cm. CONCLUSION: A DLT without periportal fixation is less likely to be displaced and poorly aligned when the patient moves from a horizontal to a lateral position, which could facilitate intra-operative management and reduce the incidence of postoperative complications.

Through a randomized controlled trial, this study innovatively found that no double-lumen endobronchial tube (DLT) peripheral tape binding can prevent the dislocation and misalignment of the DLT bronchial cuffed end in patients undergoing thoracic surgery from horizontal to lateral position.

A transition metal- and photosensitizer-free approach for site-selective (hetero)arylation of polychlorinated heteroarenes.

We have developed an effective photochemical method for site-selective (hetero)arylation of polychlorinated heteroarenes. This approach eliminates the need for transition metal catalysts and photosensitizers by relying on in situ formation of unconventional electron donor-acceptor (EDA) complexes between two substrates and a basic additive. Our protocol yields chlorine-containing biaryl heterocyclic compounds with high levels of site-selectivity, which are of significant importance in both synthetic and medicinal chemistry.

Effect of individualized PEEP titration by ultrasonography on perioperative pulmonary protection and postoperative cognitive function in patients with chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the effect of the individualized positive end-expiratory pressure (PEEP) lung protection ventilation strategy by combining driving pressure (ΔP) and pulmonary ultrasound (LUS)-based titration on lung function and postoperative cognitive function in patients with chronic obstructive pulmonary disease (COPD) during laparoscopic surgery. METHODS: A total of 108 patients with COPD undergoing laparoscopic gastrointestinal surgery under general anesthesia were included in this study. They were randomly divided into three groups (n = 36): traditional volume ventilation group (Group C), fixed PEEP 5 cmH2O group (Group P), and ΔP combined with LUS-based PEEP titration in the resuscitation room group (Group T). All three groups were given volume ventilation mode, I:E = 1:2; In group C, VT was 10 mL/kg and PEEP was 0 cmH2O; In groups P and T, VT was 6 mL/kg and PEEP was 5 cmH2O; After mechanical ventilation for 15 min in Group T, ΔP in combination with LUS was used to titrate PEEP. The oxygenation index (PaO2/FiO2), airway platform pressure (Pplat), dynamic lung compliance (Cdyn), Montreal Cognitive Assessment (MoCA), and venous interleukin-6(IL-6) were recorded at the corresponding time points, and the final PEEP value in Group T was recorded. RESULTS: The final PEEP value of Group T was (6.4 ± 1.2) cmH2O; Compared with groups C and P: PaO2/FiO2 and Cdyn in Group T were significantly increased (P < 0.05) and value of IL-6 was significantly decreased (P < 0.05) at the corresponding time points. Compared with group C, the MoCA score on day 7 after surgery in Group T was significantly higher (P < 0.05). CONCLUSION: Compared with the traditional ventilation strategy, the individualized ΔP combined with LUS-based PEEP titration in patients with COPD during the perioperative period of laparoscopic surgery can play a better role in lung protection and can improve postoperative cognitive function.

Fe-Catalyzed Aliphatic C-H Methylation of Glycine Derivatives and Peptides.

Direct and selective C-H methylation is a powerful tool with which to install methyl groups into organic molecules, and is particularly useful in pharmaceutical chemistry. However, practical methods for such modification of biologically interesting targets have been rarely developed. We here report an iron-catalyzed C(sp3 )-H methylation reaction of glycine derivatives, peptides and drug-like molecules in an alcohol in the presence of di-tert-butyl peroxide. A readily available iron catalyst plays multiple roles in the transformation, which accelerates oxidation of C-N bonds to C=N double bonds, activates imine intermediates as Lewis acids by bidentate chelation, and at the same time facilitates cleavage of the peroxide to generate methyl radicals. A variety of methylated N-aryl glycine derivatives and peptides were obtained in good yield and with excellent chemo- and site-selectivity. This reaction is scalable, easily managed, and can be completed within 1-2 h. It features an economic, bio-friendly catalyst, a green solvent and low toxic reagents, and will provide effective access to precise C-H modification of biomolecules and natural products.

Selectfluor®-enabled photochemical selective C(sp3)-H(sulfonyl)amidation.

Transition metal- and photosensitizer-free C(sp3)-H (sulfonyl)amidation reactions have been realized by employing Selectfluor® as a versatile reagent, functioning as a photoactive component, a HAT precursor and an oxidant. Various toluene derivatives, cycloalkanes, natural products and bioactive molecules can be converted into N-containing products under mild conditions in good yield and with high chemo- and site-selectivity.

Condensed Osmaquinolines with NIR-II Absorption Synthesized by Aryl C-H Annulation and Aromatization.

The structural design and tuning of properties of metallaaromatics are crucial in materials and energy science. Herein, we describe the rapid synthesis of tetracyclic metallaaromatics containing quinoline and pentalene motifs fused by a metal-bridged fragment. These unique compounds display remarkably broad absorption, enabling for the first time the absorption of metallaaromatics to reach the second near-infrared (NIR-II) bio-window. The formation of osmaquinoline unit involves an unconventional C(sp2 )-C(sp3 ) coupling promoted by AgBF4 to achieve [3+3] cycloaddition. The introduction of cyclic dπ -pπ conjugation and extension of the aromatic π-framework can effectively shrink the HOMO-LUMO gap, thus broadening the absorption window. The considerable photothermal conversion efficiency (PCE) in both the NIR-I and NIR-II windows, the high photothermal stability and the excellent electrochemical behavior suggest many potential applications of these condensed metallaquinolines.

Calpain-2 Mediates MBNL2 Degradation and a Developmental RNA Processing Program in Neurodegeneration.

Increasing loss of structure and function of neurons and decline in cognitive function is commonly seen during the progression of neurologic diseases, although the causes and initial symptoms of individual diseases are distinct. This observation suggests a convergence of common degenerative features. In myotonic dystrophy type 1 (DM1), the expression of expanded CUG RNA induces neurotransmission dysfunction before axon and dendrite degeneration and reduced MBNL2 expression associated with aberrant alternative splicing. The role of loss of function of MBNL2 in the pathogenesis of neurodegeneration and the causal mechanism of neurodegeneration-reduced expression of MBNL2 remain elusive. Here, we show that increased MBNL2 expression is associated with neuronal maturation and required for neuronal morphogenesis and the fetal to adult developmental transition of RNA processing. Neurodegenerative conditions including NMDA receptor (NMDAR)-mediated excitotoxicity and dysregulated calcium homeostasis triggered nuclear translocation of calpain-2, thus resulting in MBNL2 degradation and reversal of MBNL2-regulated RNA processing to developmental patterns. Nuclear expression of calpain-2 resembled its developmental pattern and was associated with MBNL2 degradation. Knock-down of calpain-2 expression or inhibition of calpain-2 nuclear translocation prevented neurodegeneration-reduced MBNL2 expression and dysregulated RNA processing. Increased calpain-2 nuclear translocation associated with reduced MBNL2 expression and aberrant RNA processing occurred in models for DM1 and Alzheimer's disease (AD) including EpA960/CaMKII-Cre mice of either sex and female APP/PS1 and THY-Tau22 mice. Our results identify a regulatory mechanism for MBNL2 downregulation and suggest that calpain-2-mediated MBNL2 degradation accompanied by re-induction of a developmental RNA processing program may be a converging pathway to neurodegeneration.SIGNIFICANCE STATEMENT Neurologic diseases share many features during disease progression, such as cognitive decline and brain atrophy, which suggests a common pathway for developing degenerative features. Here, we show that the neurodegenerative conditions glutamate-induced excitotoxicity and dysregulated calcium homeostasis induced translocation of the cysteine protease calpain-2 into the nucleus, resulting in MBNL2 degradation and reversal of MBNL2-regulated RNA processing to an embryonic pattern. Knock-down or inhibition of nuclear translocation of calpain-2 prevented MBNL2 degradation and maintained MBNL2-regulated RNA processing in the adult pattern. Models of myotonic dystrophy and Alzheimer's disease (AD) also showed calpain-2-mediated MBNL2 degradation and a developmental RNA processing program. Our studies suggest MBNL2 function disrupted by calpain-2 as a common pathway, thus providing an alternative therapeutic strategy for neurodegeneration.

Improvement in the Blood Urea Nitrogen and Serum Creatinine Using New Cultivation of Cordyceps militaris.

Background: Chronic kidney disease (CKD) is a critical public health issue with a huge financial burden for both patients and society worldwide. Unfortunately, there are currently no efficacious therapies to prevent or delay the progression of end-stage renal disease (ESRD). Traditional Chinese medicine practices have shown that Cordyceps militaris (C. militaris) mycelia have a variety of pharmacologically useful properties, including antitumor, immunomodulation, and hepatoprotection. However, the effect of mycelial C. militaris on CKD remains unclear. Methods: Here, we investigated the effects of C. militaris mycelia on mice with CKD using four types of media: HKS, HKS with vitamin A (HKS + A), CM, and CM with vitamin A (CM + A). Results: The results at day 10 revealed that the levels of blood urea nitrogen (BUN) were significantly lower in the HKS (41%), HKS + A (41%), and CM + A (34%) groups compared with those in the corresponding control groups (nephrectomic mice). The level of serum creatinine in the HKS + A group decreased by 35% at day 10, whereas the levels in the HKS and CM + A groups decreased only by 14% and 13%, respectively, on day 30. Taken together, this is the first report using four new media (HKS, HKS + A, CM, and CM + A medium) for C. militaris mycelia. Each medium of mycelial C. militaris on CKD exhibits specific effect on BUN, serum creatinine, body weight, total protein, and uric acid. Conclusions: Taken together, this is the first report using four new media (HKS, HKS + A, CM, and CM + A medium) for C. militaris mycelia. Each medium of mycelial C. militaris on CKD exhibits specific effects on BUN, serum creatinine, body weight, total protein, and uric acid. We concluded that treatment with C. militaris mycelia cultured in HKS or CM + A medium could potentially prevent the deterioration of kidney function in mice with CKD.

Effect of doxofylline on pulmonary inflammatory response and oxidative stress during mechanical ventilation in rats with COPD.

OBJECTIVE: To evaluate the effects of doxofylline on inflammatory responses and oxidative stress during mechanical ventilation in rats with chronic obstructive pulmonary disease (COPD). METHODS: Eight-week-old male Sprague Dawley rats were selected, and the COPD rat model was constructed. The rats were randomly divided into a model group (group M), a model + normal saline group (group N), a doxofylline group (group D), and a control group fed with conventional chow and given normal oxygen supply (group C) (n = 12 in each group). Tracheal intubation and mechanical ventilation were conducted in the rats in each group after anesthesia. A real-time intravenous infusion with 50 mg/kg of doxofylline was conducted in group D, and there was no drug intervention in groups C, N and M. Pathological manifestations of the pulmonary tissues were observed and compared among the groups. And some indicators were evaluated. RESULTS: (1) The pulmonary tissues of the rats in groups M, N, and D exhibited typical pathological histological changes of COPD. (2) Groups M, N, and D showed increased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue and BALF, and decreased PaO2 and IL-10 and SOD levels, compared with group C. (3). Group D showed decreased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue, and increased PaO2 and IL-10 and SOD levels, compared with group N or M. CONCLUSION: Doxofylline was shown to improve ventilation and air exchange during mechanical ventilation in rats with COPD, reduce the inflammatory response and oxidative stress, and mitigate the degree of pulmonary tissue injury.

Selective Difunctionalization of Unactivated Aliphatic Alkenes Enabled by a Metal-Metallaaromatic Catalytic System.

The design of organometallic catalysts is crucial in the development of catalytic reactions. Herein, we describe a heterometallic [Os-Cu] complex with the characteristics of bimetallics, metallaaromatics, and pincer complexes. This complex serves as a highly effective catalyst for selective amino- and oxyselenation of unactivated alkenes. More than 80 examples including challenging substrates of unsymmetric aliphatic alkenes and amine-based nucleophiles in such reactions are provided. These reactions produce 1,2-difunctionalized products with good yields and high levels of chemo-, regio-, and stereoselectivity. Our studies revealed the following: (i) The usually inert osmium center activates the N- or O-centered nucleophiles. (ii) The copper-osmium bonding and its cooperative effects play essential roles in control the selectivity by bringing the reaction components into close proximity. (iii) The metallaaromatic moiety helps to stabilize the intermediate. These findings provide a versatile platform for catalyst design based on metal-metallaaromatic cooperative effects that have not been attained previously with bimetallic complexes.

Direct amidation of metallaaromatics: access to N-functionalized osmapentalynes via a 1,5-bromoamidated intermediate.

The direct C-H amidation or imidation of metallaaromatics with N-bromoamides or imides has been achieved under mild conditions and leads to the formation of a family of N-functionalized metallapentalyne derivatives. A unique 1,5-bromoamidated species has been identified, and can be viewed as a σH-adduct intermediate in a nucleophilic aromatic substitution. The 1,5-addition of both electrophilic and nucleophilic moieties into the metallaaromatic framework demonstrates a novel pathway in contrast to the typical radical process of arene C-H amidation involving N-haloamide reagents.

Organophotocatalytic selective deuterodehalogenation of aryl or alkyl chlorides.

Development of practical deuteration reactions is highly valuable for organic synthesis, analytic chemistry and pharmaceutic chemistry. Deuterodehalogenation of organic chlorides tends to be an attractive strategy but remains a challenging task. We here develop a photocatalytic system consisting of an aryl-amine photocatalyst and a disulfide co-catalyst in the presence of sodium formate as an electron and hydrogen donor. Accordingly, many aryl chlorides, alkyl chlorides, and other halides are converted to deuterated products at room temperature in air (>90 examples, up to 99% D-incorporation). The mechanistic studies reveal that the aryl amine serves as reducing photoredox catalyst to initiate cleavage of the C-Cl bond, at the same time as energy transfer catalyst to induce homolysis of the disulfide for consequent deuterium transfer process. This economic and environmentally-friendly method can be used for site-selective D-labeling of a number of bioactive molecules and direct H/D exchange of some drug molecules.

Facile production of chlorophyllides using recombinant CrCLH1 and their cytotoxicity towards multidrug resistant breast cancer cell lines.

The purity of chlorophylls plays one of the key role for the production of chlorophyllides. We have designed a facile method for chlorophyll purification by twice solvent extraction. Twice extraction causes the loss of chlorophylls, but the purity of total chlorophylls can be enhanced 182%. Then, the purified chlorophylls can be converted to relatively pure chlorophyllides facilely. The results show that higher purity of chlorophyllides could be obtained when purified chlorophylls (ethanol-hexane extract) was used as starting materials than that of crude chlorophylls (ethanol-only extract). In biocompatibility test, the results showed that the prepared chlorophyllides can be applied as biomaterials. When the prepared chlorophyllides were applied to anticancer tests, they were active both in MCF7 and MDA-MB-231 (multidrug resistant breast cancer cells) cell lines. In addition, the results suggested that the prepared chlorophyllides could be a potential candidate of combination therapy with doxorubicin to breast cancers.