Visible-light-induced, photocatalyst-free generation of glycosyl radicals: Emerging routes for glycosylation.

A brief account of the application of glycosyl halide as glycosyl radical precursor towards glycosylation through visible light catalysis.

In synthetic carbohydrate chemistry, the modification of glycosyl radicals pathway stands as a central area of focus. The radical‐based reactions often demonstrate remarkable compatibility with various functional groups owing to the mild initiation conditions. In particular, the identification of novel glycosyl radical precursors, combined with advanced reaction techniques, has substantially broadened the scope of glycosyl compound synthesis. Despite the presence of versatile donors, the synthesis of noble donors is still addressed as a synthetic need and challenges associated with sugar chemistry. Currently, a new class of glycosyl radical precursors has been developed which enables the production of C‐, S‐, O‐, and N‐glycosides efficiently. In this light, we highlight strategies towards bench‐stable glycosyl sulfoxides, sulphone, and sulfite donors that can enable the site‐, regio‐ and stereoselective transformation of protected or naked sugar synthons in synthetic carbohydrate chemistry. Here, this review article covers the recent developments in the selective glycosyl radical diversification such as glycosyl alkylation, arylation, alkenylation, sulfuration, C−H activation, and DNA conjugation via the bench‐stable donors along with mechanistic aspects, challenges, and future directions.

The need to develop environmentally friendly analytical approaches has driven the pharmaceutical industry to seek greener alternatives. Ultra-Performance Liquid Chromatography (UPLC) is known for its efficiency but traditionally relies on toxic solvents. Integrating Green Analytical Chemistry (GAC) principles aims to address environmental concerns while maintaining analytical performance. This work aims to advance and authenticate a green, efficient UPLC method for the concurrent quantification of Metformin (MET) and Empagliflozin (EPI) in tablet formulations, adhering to green chemistry principles and ensuring high analytical accuracy. The method was optimized using a UPLC-PDA system with a phenyl column and a mobile phase of ethanol and perchloric acid. Analytical Quality by Design (AQbD) was employed to optimize critical method parameters. Environmental impact was assessed using metrics such as GAPI, AMGS, and AGREE. Degradation studies under various stress conditions were performed to test method robustness. The method achieved high recovery rates for MET and EPI, with minimal interference from excipients. The environmental evaluation showed a high Analytical Eco-Score (AES) of 97, indicating low environmental impact. The AGREE score of 0.89 confirmed excellent alignment with green chemistry principles. Degradation studies confirmed the method's stability and reliability under stress conditions. The developed UPLC method demonstrates a significant advancement in analytical sustainability, offering an eco-friendly, efficient, and precise approach to drug analysis. The method's high alignment with green chemistry principles and its effectiveness in quantifying MET and EPI highlight its potential as a model for sustainable analytical practices in pharmaceutical analysis.

Palladium catalyzed tandem reaction represents a one-pot synthetic approach to efficiently synthesize complex functionalized molecules while reducing synthetic steps, aligning with the principles of green chemistry. However, achieving a direct cascade of the aza-Wacker and Povarov reactions in one-pot synthesis presents a challenge due to substrate compatibility issues between the two reactions. In this work, we describe an aza-Wacker/Povarov reaction employing a highly electrophilic palladium catalyst, which effectively converts anilines and 1,6-dienes into hexahydro-cyclopenta[b]quinolines. The optimized conditions yield up to 79%, with a diastereoselectivity > 20:1. Substrate range testing reveals compatibility with various sensitive functional groups, and successful late-stage modifications are performed on several natural products and drug molecules, demonstrating the versatility and practicality of the method. Additionally, a preliminary investigation into the reaction mechanism suggests an aza-Wacker process followed by a Povarov process.

Chapter 1 - Polymer green chemistry: principles of polymer synthetic green chemistry

ConspectusThe study of carbohydrates has emerged as a crucial research area in various disciplines due to their pivotal roles in cellular processes. To facilitate in-depth exploration of their biological functions, chemical glycosylation reactions that allow facile access of glycoconjugates to a broad research community are highly needed. In classical glycosylation reactions, a glycosyl donor is activated by an acid to generate a reactive electrophilic intermediate, which subsequently forms a glycosidic bond upon reaction with a nucleophilic acceptor. Such an ionic pathway glycosylation has been the mainstay technique for glycoconjugate synthesis and allowed the synthesis of numerous intricate structures. Nevertheless, limitations still exist. For instance, when labile glycosyl donors or harsh activating conditions are required, these methods show limited tolerance to hydroxyl groups that are abundant on sugar rings. In addition, achieving good stereocontrol represents another longstanding obstacle. In recent years, new modes of donor activation have been sought to tackle the above challenges.We noted that glycosylation methods passing through the intermediacy of glycosyl radicals via a cascade of single-electron transfer steps possess significant but underexplored potential. Progress in this area has been slow due in large part to a dearth of handy methods to generate and maneuver glycosyl radicals. Most existing methods call for either forcing conditions or unstable/inconvenient starting materials. In order to better exploit the power of the radical pathway glycosylation, we have developed a range of glycosyl donors─namely, glycosyl sulfoxides, glycosyl sulfones, and glycosyl sulfinates─that are bench stable and can be readily prepared from simple starting materials. These donors can be activated to form glycosyl radicals under mild conditions. Enabled by the use of these donors, we have developed a series of glycosylation methods that could be used for making O-, S-, or C-glycosides, some of which were previously difficult to access. In many cases, no protecting group on glycosyl donors is required. As an illustration of their potential utility, our methods have been adopted in the preparation of sugar-drug conjugates, sugar-DNA conjugates, glycopeptides, and even glycoproteins. While in most cases the intrinsic reactivity of glycosyl radical intermediates can be explored to access axially configured products, some of the methods also allow the utilization of external, delicate reagents, or catalysts to override such innate preference and achieve catalyst-controlled stereoselectivity.We believe that radical pathway glycosylation has enormous potential and can inspire the development of novel methods for glycoside synthesis. In this Account, we highlight the design principles for the development of our glycosyl donors, summarize our recent advancements in radical pathway glycosylation enabled by their use, and provide an outlook on the future directions of this field.

Rapid gelation remains essential in maintaining uniform network structures and mechanical properties under mild conditions. Here, we report a strategy based on a glycosyl radical to achieve rapid gelation within tens of seconds. Mechanistically, glycosyl sulfinates serve as efficient precursors to glycosyl radicals upon treatment with potassium persulfate (KPS) through a single-electron transfer process. The following polymerization process exhibits a gentle increase in exotherms and viscosity, which promotes the homogeneity of the polymer network. Glycosyl units are partially incorporated into polymer chains as hydroxyl-rich termini with the remainder freely dispersed throughout the hydrogel matrix, both forming extensive dynamic hydrogen bonds with polymer backbones. Consequently, the hydrogels exhibit exceptional mechanical performance, including high strength, toughness, elasticity, and fatigue resistance. This robust method is compatible with various vinyl monomers, glycosyl sulfinate derivatives, and even harsh environmental conditions. As a proof-of-concept application, the precursor solution can rapidly form uniform gel films via controlled spraying, highlighting potential applications in flexible electronics, wearable sensors, and biomedical dressings.

We here report glycosyl sulfoxides appended with an aryl iodide moiety as readily available, air and moisture stable precursors to glycosyl radicals. These glycosyl sulfoxides could be converted to glycosyl radicals by way of a rapid and efficient intramolecular radical substitution event. The use of this type of precursors enabled the synthesis of various complexC‐linked glycoconjugates under mild conditions. This reaction could be performed in aqueous media and is amenable to the synthesis of glycopeptidomimetics and carbohydrate‐DNA conjugates.

We here report glycosyl sulfoxides appended with an aryl iodide moiety as readily available, air and moisture stable precursors to glycosyl radicals. These glycosyl sulfoxides could be converted to glycosyl radicals by way of a rapid and efficient intramolecular radical substitution event. The use of this type of precursors enabled the synthesis of various complex C-linked glycoconjugates under mild conditions. This reaction could be performed in aqueous media and is amenable to the synthesis of glycopeptidomimetics and carbohydrate-DNA conjugates.

The importance of levoglucosenone (LGO) as a bio-derived platform molecule has been significantly elevated through its transformation into Cyrene™, a widely adopted green solvent. In this study, we investigate the interactions of LGO with water, a key component of biorefinery systems, revealing a new, efficient route to monohydroxycyrene (MHC). This transformation involves the slow, aqueous-based conversion of LGO to a triol intermediate, followed by selective dehydration to form MHC—a chiral molecule with dual functional groups and promising synthetic potential. MHC was synthesised in two simple and green steps without the need for catalysts or reagents, achieving an 88% yield and 98% purity under mild conditions. This environmentally benign approach aligns with the principles of green chemistry by eliminating the need for hazardous reagents and employing water as a sustainable solvent. The structure of MHC was confirmed using a combination of NMR, IR, UV-Vis, CHN, MS, and thermal analyses. Our results also highlight the role of temperature in influencing product formation, with lower temperatures (45–65 °C) enhancing yield, while higher temperatures (e.g., 95 °C) reduce conversion efficiency. MHC exhibits favourable physical and chemical properties, including polarity, solubility, and thermal stability, making it a promising candidate for future applications in green chemistry, pharmaceuticals, and materials science. The combined reactivity of the carbonyl and hydroxyl groups makes MHC a promissing platform molecule for synthesising polymers, pharmaceuticals, and advanced bio-based materials. Moreover, the mild reaction conditions and catalyst-free nature of the process contribute to reduced energy input and lower environmental impact. This work offers new insights into sustainable chemical pathways and provides a strong foundation for scaling up the production of novel biomass-derived building blocks.

Glycosyl radical functionalization is one of the central topics in synthetic carbohydrate chemistry. Recent advances in metal-catalyzed cross-coupling chemistry and metallaphotoredox catalysis provided powerful platforms for glycosyl radical diversification. In particular, the discovery of new glycosyl radical precursors in conjunction with these advanced reaction technologies have significantly expanded the space for glycosyl compound synthesis. In this Minireview, we highlight the most recent progress in this area starting from 2021, and the reports included will be categorized based on different reaction types for better clarity.

Green Stereoregular Polymerization of Poly(methyl methacrylate)s Through Vesicular Catalysis

Reversible generation of glycosyl radicals from telluroglycosides under photochemical and thermal conditions

The aim of the research is to: Identify the level of knowledge of middle school students about the principles of green chemistry and thenature of their attitudes towards it. Identify the correlation between middle school students' knowledge of the principles of green chemistry and their attitudes towards the principles. The descriptive research method was followed and a questionnaire was prepared with two areas, the first related to the principles of green chemistry consisting of 20 paragraphs and the second about the attitude towards the principles of green chemistry consisting of 20 paragraphs. They were valid and reliable, and were applied to a sample of (362) male and female students,(219) male and (143) female students. The results of the research showed that the level of knowledge of middle school students about the principles of green chemistry was average. The degree of attitude ofmiddle school students towards the principles of green chemistry was high.

Open AccessCCS ChemistryCOMMUNICATION1 Dec 2021Transition-Metal-Free Reductive Cross-Coupling Employing Metabisulfite as a Connector: General Construction of Alkyl–Alkyl Sulfones Yingying Meng, Ming Wang and Xuefeng Jiang Yingying Meng Shanghai Key Laboratory of Green Chemistry and Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062 , Ming Wang *Corresponding authors: E-mail Address: [email protected] E-mail Address: [email protected] Shanghai Key Laboratory of Green Chemistry and Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062 and Xuefeng Jiang *Corresponding authors: E-mail Address: [email protected] E-mail Address: [email protected] Shanghai Key Laboratory of Green Chemistry and Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062 State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071 https://doi.org/10.31635/ccschem.021.202000638 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail A multicomponent reductive cross-coupling of unactivated alkyl halides and alkyl tosylates connected via sodium metabisulfite was established for the general construction of alkyl–alkyl sulfones. Neither a metal catalyst nor a metal reductant is required in this "green" reductive cross-coupling. Inorganic sodium metabisulfite served as both the sulfur dioxide source and the robust connector. Safe formate was used as a highly efficient single-electron reductant. Both intramolecular and intermolecular reductive cross-couplings were achieved with broad substrate scopes. Diverse biologically important molecules were efficiently cross-linked with steroids, saccharides, amino acids, peptides, and pharmaceuticals with sensitive functional groups, affording sulfone-bridged hybrid molecules. Mechanistic studies demonstrated that alkyl radicals were involved in the singly occupied molecular orbital (SOMO) of the metabisulfite salt, initiating the transformation. Download figure Download PowerPoint Introduction Sulfone motifs have attracted considerable interest in drug discovery because of their dramatic effects on stability, liposolubility, and metabolism.1–4 The linkage of carbon chains to sulfone motifs always improves drug metabolism. Alkyl–alkyl sulfones are among the most frequently occurring sulfone motifs in pharmaceuticals due to their excellent effects on the balance between water solubility and lipid solubility. Several representative and well-known pharmaceutical inhibitors containing alkyl–alkyl sulfones are shown in Scheme 1a.5–10 Conventionally, sulfones are prepared via the oxidation of sulfides with strong oxidants after thiol-involved couplings,11,12 resulting in low functional group compatibility. Strategies for sulfone construction via the introduction of hypervalent sulfur in the same oxidation state into organic frameworks are of great interest due to the oxidative economy and step economy of such processes.13–20 For instance, transition-metal-catalyzed syntheses of aryl–aryl(alkyl) sulfones have been well developed via halides and organometallic reagents.21–26 However, a general approach for the introduction of sulfone motifs into C(sp3)−C(sp3) organic frameworks is lacking since the β-hydrogen in alkyl coupling partners is likely to be poorly compatible with transition-metal-catalyzed systems.27,28 Although we have achieved the construction of aryl–alkyl sulfone by virtue of the distinction between aryl and alkyl halides, tin is still necessary as a stoichiometric metal reductant.29,30 Developing cheap salts for green and safe hydrogen storage and for replacing environmentally unfriendly metals as reductants in reductive cross-couplings is a long-standing goal.31–38 In addition, the smaller distinction between two different alkyl coupling partners is a tough challenge compared with the distinction between aryl and alkyl halide coupling partners.39 Traditionally, the direct reductive cross-couplings of electrophilic partners are realized via preactivation of alkyl halides by a metal reductant to avoid precast organometallic reagents (Scheme 1b). Previously, we showed that the SO2 motif in inorganic sulfur dioxide salts possesses a sufficiently active hybridized singly occupied molecular orbital (SOMO) to participate in a radical process.29,40–51 Alkyl halides can be used as precursors for alkyl radicals, leading to radical capture with inorganic sulfur dioxide salts for the generation of sulfonyl radicals. Due to the slightly higher electronegativity of sulfur atoms than carbon atoms, sulfonyl radicals were apt to be reduced than alkyl radicals. A release-controlled hydrogen storage salt instead of rapid electron transfer from reductive metal powders is the key factor for the highly selective reduction of sulfonyl radicals. Alkyl tosylates are rather inert during the single-electron transfer (SET) process since the high-lying σ*(C–O) orbital is protected from radical reduction and involved in subsequent nucleophilic substitution. The sequential radical release and coupling limits the undesired homocoupling of the partners (Scheme 1c). Herein, we disclose a transition-metal-free reductive cross-coupling of unactivated alkyl halides, alkyl tosylates, and metabisulfite for the modular construction of alkyl–alkyl sulfone-bridged compounds. Scheme 1 | (a–c) Sulfone-bridged reductive cross-coupling. Download figure Download PowerPoint Results and Discussion We commenced our evaluation of this reductive cross-coupling with unactivated alkyl tosylates 1a, alkyl halides 2a, and sodium metabisulfite in the presence of a base in dimethyl sulfoxide (DMSO). To increase the solubility of inorganic salts, phase-transfer catalyst tetrabuylammonium bromide (TBAB) was added. No desired product 3a was detected in the absence of a reductant in this transformation (Table 1, entry 1). To our delight, bench-stable formic acid and formate reductants could afford the cross-coupled product in moderate yields (Table 1, entries 2–4). Diverse inorganic sulfur dioxide surrogates possessing different masking groups and unique SET abilities were tested as the connector in the current transformation. Sodium metabisulfite was found to provide the best efficiency (65% yield, Table 1, entries 5–7). Further evaluation of bases revealed that the stronger base cesium carbonate delivers 3a in a better yield (Table 1, entries 8–11). Considering the effect of the solvent, DMSO is the best choice since it is beneficial for the dissolution of inorganic salts (Table 1, entries 12–14). Table 1 | Conditions Optimizationa Entry Reductant SO2 Source Base Solvent Yields (%)b 1 — Na2S2O5 K2HPO4 DMSO NP 2 HCO2H Na2S2O5 K2HPO4 DMSO 49 3 HCO2Na Na2S2O5 K2HPO4 DMSO 60 4 HCO2K Na2S2O5 K2HPO4 DMSO 65 5 HCO2K K2S2O5 K2HPO4 DMSO 40 6 HCO2K Na2S2O4 K2HPO4 DMSO 41 7 HCO2K DABSO K2HPO4 DMSO 44 8 HCO2K Na2S2O5 — DMSO 49 9 HCO2K Na2S2O5 NaHCO3 DMSO 44 10 HCO2K Na2S2O5 Et3N DMSO 57 11 HCO 2 K Na 2 S 2 O 5 Cs 2 CO 3 DMSO 77 12 HCO2K Na2S2O5 Cs2CO3 DMA 66 13 HCO2K Na2S2O5 Cs2CO3 DMF 54 14 HCO2K Na2S2O5 Cs2CO3 Toluene 22 Note: NP, no product; DMA, dimethylacetamide; DMF, dimethylformamide. Bold-italic text represents optimal conditions aConditions: 1a (0.2 mmol), SO2 source (0.4 mmol), 2a (0.5 mmol), base (0.4 mmol), reductant (0.5 mmol), TBAB (0.3 mmol), solvent (2.0 mL), 100 °C, N2, 10 h. bIsolated yields. The scope of the reductive cross-coupling employing sodium metabisulfite as a connector is shown in Scheme 2 (for characterizations see the Supporting Information). Aryl propyl sulfones with a broad range of substituents, including those with different electronic properties, at various positions were efficiently afforded ( 3a– 3f). A series of alkyl coupling partners, even linear hexadecane (C16), were well tolerated in the coupling ( 3g– 3k). Heterocycle-containing alkyl tosylates provided the desired alkyl–alkyl products in excellent yields ( 3l). Fused-ring anthracene and pyrene derivatives, common motifs in luminescent materials, successfully underwent the current transformation, furnishing the corresponding sulfone products ( 3m– 3n). Furthermore, this reaction was not only restricted to intermolecular variants but also applicable to the intramolecular synthesis of cyclic sulfones ( 3o–3p). Regretfully, when secondary tosylates were employed, no desired cross-coupling products were detected. Linear alkyl ( 3q– 3s), trifluoropropyl ( 3t), and alkoxyl ( 3u) derivatives successfully participated in the multicomponent reductive cross-coupling. Various nitrogen-containing structures ( 3v– 3y) and even amino acids ( 3y) were compatible with this reductive cross-coupling, efficiently providing the desired sulfones. In addition, secondary alkyl halides are also compatible with this transformation, and these substrates were a notable challenge in C(sp3)−C(sp3) reductive cross-couplings. Both linear ( 3z) and cyclic ( 3aa– 3ae) secondary alkyl halides underwent this transformation. The compatibility with 7- ( 3ad) and 12-membered ( 3ae) rings highlighted the high tolerance of this strategy. The structure of 3ab was confirmed via X-ray diffraction analysis.a Scheme 2 | Collective alkyl sulfone construction. Reaction conditions: 1 (0.2 mmol), Na2S2O5 (0.4 mmol), 2 (potassium formate, 0.5 mmol), HCOOK (0.5 mmol), Cs2CO3 (0.4 mmol), TBAB (0.3 mmol), DMSO (2 mL), 100 °C, 10 h, isolated yields. Download figure Download PowerPoint To further demonstrate the practical applicability of this cross-linking protocol, we sought to link structurally complicated, naturally occurring molecules with pharmaceuticals by employing sodium metabisulfite as a connector (Scheme 3). The linkage of dehydroepiandrosterone, estrone, and a derivative of the anti-inflammatory drug isoxepac was smoothly achieved under the standard conditions ( 3af– 3ah). The linkage of natural cholic acid and tetrahydropyran provided the corresponding product in an excellent yield ( 3ai). The structure of 3ai was confirmed via X-ray diffraction analysisa. The reductive cross-couplings between an amino acid (l-tyrosine), a saccharide (glucose), steroids (dehydroepiandrosterone and estrone), and nonsteroidal anti-inflammatory drug oxaprozin were all successful, affording the corresponding sulfone-bridged hybrid molecules in good yields ( 3aj–3an). Notably, this strategy can efficiently connected long-chain linoleic acids and peptides from the corresponding alkyl precursors ( 3ao). Scheme 3 | The cross-linking of steroids, saccharides, amino acids, and pharmaceuticals. Reaction conditions: 1 (0.2 mmol), Na2S2O5 (0.4 mmol), 2 (0.5 mmol), HCOOK (0.5 mmol), Cs2CO3 (0.4 mmol), TBAB (0.3 mmol), DMSO (2 mL), 100 °C, 10 h, isolated yields. Download figure Download PowerPoint To demonstrate the mechanism of this multicomponent reductive cross-coupling reaction, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) was first added to the system under the standard conditions, and sulfone production was suppressed (Scheme 4a). Subsequently, a radical clock experiment involving (bromomethyl)cyclopropane ( 4) and alkyl tosylates 1a was conducted under the standard conditions (Scheme 4b). Cyclopropane-opened product 5 was generated in 14% yield, indicating that an alkyl radical intermediate was formed from the alkyl bromide substrate during the transformation. These results demonstrated that the multicomponent reductive cross-coupling began with the radical reduction of the alkyl halide followed by SOMO interaction with sodium metabisulfite. Cyclic voltammetric analyses showed that the reduction potentials of alkyl tosylate 1a was −2.75 V and alkyl halide 2a was −2.40 V, which indicated that 2a was likely to be preferentially reduced relative to 1a. Two reduction peaks at −1.50 and −2.40 V were observed in Scheme 4c, corresponding to two successive SETs to alkyl halide 2a, which demonstrated that 2a easily to underwent a single-electron reduction process. Thus, the proposed reaction pathway is depicted in Scheme 4d. Initially, the homolysis of the alkyl halide generated alkyl radical 9 and iodine radical, which was reduced to iodide ion by the slowly released formate. Subsequently, the reaction of alkyl radical 9 and metabisulfite furnished sulfonyl radical 10, which was reduced by formate radical cation, affording sulfonyl anion 11 and sulfinate 11′ in equilibrium. Finally, alkyl coupling of alkyl tosylates 1 and intermediate 11 delivered the desired sulfone product 3. Scheme 4 | (a–d) Mechanistic study. Download figure Download PowerPoint Conclusion A transition-metal-free multicomponent reductive cross-coupling of unactivated alkyl halides, alkyl tosylates, and sodium metabisulfite was achieved for the construction of alkyl–alkyl sulfones. Inorganic sodium metabisulfite salt served both as the sulfur dioxide source and a robust connector. No transition-metal catalyst was necessary, and a controlled-release hydrogen storage salt instead of metal powder reductant allowed the sequential and highly selective reduction of sulfonyl radicals. The linkage of diverse biologically important molecules, such as steroids, saccharides, amino acids, peptides, and pharmaceuticals, was efficiently achieved and delivered sulfone-bridged hybrid molecules. Mechanistic studies demonstrated that alkyl radicals interacted with the SOMO of metabisulfite, initiating the transformation, and the high-lying σ*(C–O) orbital of the alkyl tosylate participated in the subsequent nucleophilic substitution. Further cross-linking protocols with inorganic sulfur salts are being explored in our laboratory. Footnote a CCDC 2007887 ( 3ab) and CCDC 2007888 ( 3ai) can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif Supporting Information Supplemental Information is available and includes general information, general procedure for the synthesis of sulfones, optimization of reaction conditions, characterization of alkyl–alkyl sulfone products, X-ray crystal structures, and electrochemical measurements. Conflict of Interest The authors declare no competing financial or nonfinancial interests. Acknowledgments The authors are grateful for financial support provided by NSFC (nos. 22071057, 21971065, and 21871089), STCSM (nos. 20XD1421500, 20JC1416800, and 18JC1415600), Innovative Research Team of High-Level Local Universities in Shanghai (no. SSMU-ZLCX20180501), and Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning.