An Iridium/Aluminum Cooperative Strategy for the ß-C(sp3 )-H Borylation of Saturated Cyclic Amines.

Despite the widespread success in the functionalization of C(sp2 )-H bonds, the deliberate functionalization of C(sp3 )-H bonds in a highly site- and stereoselective manner remains a longstanding challenge. Herein, we report an iridium/aluminum cooperative catalytic system that enables the ß-selective C-H borylation of saturated cyclic amines and lactams. Furthermore, we have accomplished an enantioselective variant using binaphthol-derived chiral aluminum catalysts to forge C-B bonds with high levels of stereocontrol. Computational studies suggest that the formation of a Lewis pair with the substrates is crucial to lower the energy of the transition state for the rate-determining reductive elimination step.

Synthesis of Sequence-specific Poly(ester-carbonate) Copolymers via Chemoselective Terpolymerization Controlled by the Stoichiometric Ratio of Phosphazene/Triethylborane.

Chemoselective terpolymerization can produce polymer materials with diverse compositions and sequential structures, and thus have attracted considerable attention in the field of polymer synthesis. However, the intrinsic complexity of three-component system also brings great chanllenge, in regard to the reactivity and selectivity of different monomers. Herein, we report the terpolymerization of CO2 /epoxide/anhydride by a binary organocatalytic C3 N3 -Py-P3 /TEB (triethylborane) system. Both the activity and chemoselectivity were highly dependent upon the molar ratio of C3 N3 -Py-P3 to TEB, and sequence-controlled poly(ester-carbonate) copolymers were readily synthesized through one-pot/one-step methodology by tuning the stoichiometric ratio of phosphazene/TEB. In particular, C3 N3 -Py-P3 /TEB with a molar ratio of 1/0.5 exhibited an unprecedentedly high chemoselectivity for ring-opening alternating copolymerization (ROAC) of cyclohexene oxide (CHO) and phthalic anhydride (PA) first and then ROAC of CO2 /CHO. Thus, well-defined triblock polycarbonate-b-polyester-b-polycarbonate copolymers can be produced from the mixture of CO2 , CHO and PA using a bifunctional initiator. With C3 N3 -Py-P3 /TEB=1/1, tapered copolymers were obtained, while random copolymers with high content of polycarbonate (PC) were synthesized with further increasing the amount of TEB. The mechanism of the unexpected chemoselectivity was further investigated by DFT calculations.

Atropisomeric Phosphine Ligands Bearing C-N Axial Chirality: Applications in Enantioselective Suzuki-Miyaura Cross-Coupling Towards the Assembly of Tetra-ortho-Substituted Biaryls.

Biaryl phosphines bearing C(Ar)-C(Ar) axial chirality are commonly known and have been successfully applied in many asymmetric catalyses. Nevertheless, the development of a chiral ligand having an axially chiral C(Ar)-N backbone remains elusive due to its undesirable less restricted rotational barrier. In fact, it is highly attractive to overcome this challenge in ligand development as the incorporation of an N-donor component at the chiral axis is more favorable toward the transient metal coordination, and thus, a better outcome of stereocommunication is anticipated to the approaching substrates. Herein, we present a rational design of a new collection of chiral phosphines featuring a C-N axial chirality and their applications in enantioselective Suzuki-Miyaura cross-coupling for accessing highly steric hindered tetra-ortho-substituted biaryls (26 examples up to 98:2 er). It is worth noting that the embodied carbazolyl framework is crucial to succeed the reaction, by the fruitful steric relief of bulky substrate coordination and transmetalation via a fleeting Pd-N jumping to Pd-π fashion. DFT calculation reveals an interesting Pd-arene-walking characteristic across the carbazolyl plane for attaining a lower energy-preferred route in a catalytic cycle. The theoretical study successfully predicts the stereooutcome and matches the enantioselectivity with the experimental results.

Theoretical Insight into the Multiple Roles of LiHMDS in Pd-Catalyzed Borylation of Fluorobenzene.

Pd-catalyzed borylation of fluorobenzene was theoretically studied. DFT calculations revealed that the reaction occurs through an unprecedented 3 + 6-membered ring transition state, in which one LiHMDS (HMDS = hexamethyldisilazane) acts as a ligand and another LiHMDS is essential to provide Li···N and Li···F interactions, overcoming the large destabilization of the strong phenyl-F bond distortion. The characteristic feature of LiHMDS was elucidated by comparing it with HMDS and NaHMDS analogues.

Efficient Electron Transfer from Electron-Sponge Polyoxometalate to Single-Metal Site Metal-Organic Frameworks for Highly Selective Electroreduction of Carbon Dioxide.

In this work, by combining the superiority of polyoxometalates (POMs) and catalytic single-metal site Co of metalloporphyrin, a series of mixed-valence POM-based metal-organic frameworks (MOFs) composites is synthesized by a post-modification method. The electron-transfer property of POM@PCN-222(Co) composite is significantly enhanced owing to the directional electron-transfer from POM to single-metal site Co in PCN-222(Co). In particular, H-POM@PCN-222(Co) gives a high Faradaic efficiency of 96.2% for electroreduction of CO2 into CO and good stability over 10 h. DFT calculations confirm that the directional electron transfer, which accelerates the multi-electron transfer from the electrode to active single-metal site Co, enriches the electron density of the Co center, and ultimately reduces the energy of the rate-determining step, thus increasing the catalytic activity of CO2 reduction reaction (CO2 RR). This work therefore suggests some new insight for the design of efficient electrocatalysts for CO2 RR.

Methane Borylation Catalyzed by Ru, Rh, and Ir Complexes in Comparison with Cyclohexane Borylation: Theoretical Understanding and Prediction.

Methane borylation catalyzed by Cp*M(Bpin)n (M = Ru or Rh; HBpin = pinacolborane; n = 2 or 3) and (TMPhen)Ir(Bpin)3 (TMPhen = 3,4,7,8-tetramethyl-1,10-phenanthroline) was investigated by DFT in comparison with cyclohexane borylation. Because Ru-catalyzed borylation has not been theoretically investigated yet, its reaction mechanism was first elucidated; Cp*Ru(Bpin)3 1-Ru is an active species, and Cp*Ru(Bpin)3(H)(CH3) 4-Ru is a key intermediate. In 4-Ru, the Ru is understood to have an ambiguous oxidation state between +IV and +VI because it has a H··Bpin bonding interaction with a bond order of about 0.5. Methane borylation occurs through oxidative addition of methane C-H bond followed by reductive elimination of borylmethane in all of these catalysts. The catalytic activity for methane borylation increases following the order Cp*Ru(Bpin)3 < (TMPhen)Ir(Bpin)3 < Cp*Rh(Bpin)2. Cyclohexane borylation occurs in the same mechanism except for the presence of isomerization of a key intermediate. Chemoselectivity of methane over cyclohexane increases following the order Ir < Ru < Rh. In all of these catalysts, the rate-determining step (RDS) of cyclohexane borylation needs a larger ΔG°‡ than the RDS of methane borylation because the more bulky cyclohexyl group induces larger steric repulsion with the ligand than methyl. One reason for the worse chemoselectivity of the Ir catalyst is its less congested transition state of the reductive elimination of borylcyclohexane. Herein, use of a strongly electron-donating ligand consisting of pyridine and N-heterocyclic carbene with bulky substituents is computationally proposed as a good ligand for the Ir catalyst; actually, the Ir complex of this ligand is calculated to be more active and more chemoselective than Cp*Rh(Bpin)2 for methane borylation.

Computational Study of spx (x=1-3)-Hybridized Be-Be Bonds Stabilized by Amidinate Ligands.

Complexes containing odd-electron Be-Be bonds are still rare until now. Hereby, a series of neutral di-beryllium amidinate complexes containing a Be-Be bond were explored theoretically. The complexes with direct chelation with the Be2 dimer by the bidentate amidinate (AMD) ligands are always corresponding to their global minimum structures. The detailed bonding analyses reveal that the localized electrons of the Be-Be fragment can be adjusted by the amount of AMD ligands because each AMD ligand only takes one electron from the Be2 fragment. Meanwhile, the hybridization of the central Be atom also changes as the number of AMD ligands increases. In particular, the sp3 -hybridized single-electron Be-Be bond is firstly identified in the tri-AMD-ligands-chelated neutral D3h -Be2 (AMD)3 complex, which also possesses the higher stability compared to its monoanionic D3h -Be2 (AMD)3 - and monocationic C3 -Be2 (AMD)3 + analogues. Importantly, our study provides a new approach to obtain a neutral odd-electron Be-Be bond, namely by the use of radical ligands through side-on chelation.

All-Metallic Zn=Zn Double-π Bonded Octahedral Zn2 M4 (M=Li, Na) Clusters with Negative Oxidation State of Zinc.

Zn=Zn double bonded-especially double-π bonded-systems are scarce due to strong Coulomb repulsion caused by the Zn atom's internally crowded d electrons and very high energy of the virtual π orbitals in Zn2 fragments. It is also rare for Zn atoms to exhibit negative oxidation states within reported Zn-Zn bonded complexes. Herein, we report Zn=Zn double-π bonded octahedral clusters Zn2 M4 (M=Li, Na) bridged by four alkali metal ligands, in which the central Zn atom is in a negative oxidation state. Especially in D4h -Zn2 Na4 , the natural population analysis shows that the charge of the Zn atom reaches up to -0.89 |e| (-1.11 |e| for AIM charge). Although this cooperation inevitably increases the repulsion between two Zn atoms, the introduction of the s1 -type ligands results in occupation of degenerated π orbitals and the electrons being delocalized over the whole octahedral framework as well, in turn stabilizing the octahedral molecular structure. This study demonstrates that maintaining the degeneracy of the π orbitals and introducing electrons from equatorial plane are effective means to construct double-π bonds between transitional metals.

sp3 C-H Borylation Catalyzed by Iridium(III) Triboryl Complex: Comprehensive Theoretical Study of Reactivity, Regioselectivity, and Prediction of Excellent Ligand.

Iridium-catalyzed C-H borylation of THF was theoretically investigated as example of sp3 C-H functionalization. DFT computations show that ß-regioselective borylation occurs more easily than does α-regioselective, as reported experimentally, through oxidative addition of C-H bond to iridium(III) species and reductive elimination of B-C bond. The reductive elimination is both a rate-determining step and a regioselectivity-determining step. The lower energy transition state (TS) of the reductive elimination of ß-boryloxolane arises from the Ir···(ß-oxolanyl) interaction at TS being stronger than the Ir···(α-oxolanyl) one. The Ir···(ß-oxolanyl) interaction being stronger than the Ir···(α-oxolanyl) one is a result of the valence orbital energy of the α-oxolanyl group being higher than that of the ß-oxolanyl group due to antibonding overlap of the valence orbital with O 2p orbital, where SOMO of oxolanyl radical is taken as valence orbital hereinafter. Reactivity of substrate decreases following the order primary (ß) C-H of ethyl ether > primary C-H of n-pentane ∼ secondary (ß) C-H of THF > secondary C-H of cyclopentane > secondary (α) C-H of THF ∼ secondary C-H of n-pentane > secondary (α) C-H of ethyl ether. The primary C-H bond is more reactive than the secondary one because of its smaller steric repulsion and lower energy valence orbital of the primary alkyl group. The ß-C-H bond of THF is more reactive than the secondary C-H bond of cyclopentane because of valence orbital energy of the ß-oxolanyl group being lower than that of the cyclopentyl group. Both steric and electronic factors are important for determining reactivity of substrate. Bidentate ligand consisting of pyridine and N-heterocyclic carbene is predicted to be better than 3,4,7,8-tetramethyl-1,10-phenanthroline used experimentally.

Strong Pancake 2e/12c Bond in π-Stacking Phenalenyl Derivatives Avoiding Bond Conversion.

The nature of the 2e/12c bond and its conversion to a carbon-carbon single bond in phenalenyl dimers have prompted a great deal of interests recently. In this work, we theoretically investigated a series of π-stacking phenalenyl derivatives with 2e/12c bonding character by density functional theory (DFT) calculations to elucidate origin of this unusual bond conversion. Results show that bond-conversion of the phenalenyl dimer easily occurs at room-temperature both dynamically and thermodynamically. However, bond-conversion of hetero π-stacking adducts, in which the two center carbon atoms were substituted by boron and nitrogen atoms, respectively, is much more difficult, because the 2e/12c bond is stabilized by its charge transfer character. Consequently, the bond-conversion is an endothermic process, albeit with a low conversion barrier. Interestingly, Lewis acid-base interactions would be induced by substitution of the center nitrogen atom to phosphorus atom. The 2e/12c bond is further stabilized by 5.9 kcal mol-1 and its conversion is also thermodynamically unfavorable.

Constructing Stable π-Dimers: Two Parallel Pancake π-π Bonds.

Stable phenalenyl (PLY) radical π-dimers still play an important role for new multifunctional materials owing to their intriguing molecular structure and unusual pancake π-π bonding mode. Herein, we design a new biphenalenyl biradicaloid (1) consisting of two PLYs and one benzene ring linkage tethered by single bonds, which presents an open-shell character. Further, three π-dimers (a1, b1, and c1) combined with 1 and conventional biphenalenyl biradicaloid (a, b, and c), which are capable of forming two staggered PLY dimers, exhibiting a short interlayer distance between the monomers. Interestingly, the analysis of the frontier molecular orbital reveals that two bonding orbitals, namely, the two highest occupied molecular orbitals (HOMO and HOMO-1) are doubly occupied. The results reveal that three π-dimers display two parallel pancake bonds. Moreover, they have small diradical and tetraradical characters, large interaction energies, and strong aromaticity, which indicate the stability of these π-dimers. The present work creates a new class of strong pancake bonding and might be utilized in devising an array of materials.

The Suzuki-Miyaura Coupling of Nitroarenes.

Synthesis of biaryls via the Suzuki-Miyaura coupling (SMC) reaction using nitroarenes as an electrophilic coupling partners is described. Mechanistic studies have revealed that the catalytic cycle of this reaction is initiated by the cleavage of the aryl-nitro (Ar-NO2) bond by palladium, which represents an unprecedented elemental reaction.

Connecting effect on the first hyperpolarizability of armchair carbon-boron-nitride heteronanotubes: pattern versus proportion.

Carbon-boron-nitride heteronanotubes (BNCNT) have attracted a lot of attention because of their adjustable properties and potential applications in many fields. In this work, a series of CA, PA and HA armchair BNCNT models were designed to explore their nonlinear optical (NLO) properties and provide physical insight into the structure-property relationships; CA, PA and HA represent the models that are obtained by doping the carbon segment into pristine boron nitride nanotube (BNNT) fragments circularly around the tube axis, parallel to the tube axis and helically to the tube axis, respectively. Results show that the first hyperpolarizability (ß0) of an armchair BNCNT model is dramatically dependent on the connecting patterns of carbon with the boron nitride fragment. Significantly, the ß0 value of PA-6 is 2.00 × 10(4) au, which is almost two orders of magnitude larger than those (6.07 × 10(2) and 1.55 × 10(2) au) of HA-6 and CA-6. In addition, the ß0 values of PA and CA models increase with the increase in carbon proportion, whereas those of HA models show a different tendency. Further investigations on transition properties show that the curved charge transfer from N-connecting carbon atoms to B-connecting carbon atoms of PA models is essentially the origin of the big difference among these models. This new knowledge about armchair BNCNTs may provide important information for the design and preparation of advanced NLO nano-materials.

Two-electron/24-center (2e/24c) bonding in novel diradical π-dimers.

A series of diradical π-dimers 2 with interesting pancake-shaped 2e/24c π-π bonding character were designed and investigated based on the famous phenalenyl (PLY) π-dimer with 2e/12c π-π bonding character. The position of stronger interaction between two layers of radicals was found by the Wiberg bond index (WBI) maximum component. Further, the different contributions of the interaction energy were analyzed quantitatively by energy decomposition analysis (EDA). Among these new diradical π-dimers, 2180 has the smallest layer distance and the largest interaction between two layers of radicals. The unusual PLY analogues can provide new insights into the unique features of two-electron/multicenter (2e/mc) π-π bonding.

The polar 2e/12c bond in phenalenyl-azaphenalenyl hetero-dimers: Stronger stacking interaction and fascinating interlayer charge transfer.

An increasing number of chemists have focused on the two-electron/multicenter bond (2e/mc) that was first introduced to interpret the bonding mechanism of radical dimers. Herein, we report the polar two-electron/twelve center (2e/12c) bonding character in a series of phenalenyl-azaphenalenyl radical hetero-dimers. Interestingly, the bonding energy of weaker polar hetero-dimer (P-TAP) is dominated by the overlap of the two different singly occupied molecular orbital of radicals, while that of stronger polar hetero-dimer (P-HAP) is dominated by the electrostatic attraction. Results show that the difference between the electronegativity of the monomers plays a prominent role in the essential attribution of the polar 2e/12c bond. Correspondingly, a stronger stacking interaction in the hetero-dimer could be effectively achieved by increasing the difference of nitrogen atoms number between the monomers. It is worthy of note that an interesting interlayer charge transfer character is induced in the polar hetero-dimers, which is dependent on the difference between the electronegativity of the monomers. It is our expectation that the new knowledge about the bonding nature of radical hetero-dimers might provide important information for designing radical based functional materials with various applications.

Evidence of Amine-CO2 Interactions in Two Pillared-Layer MOFs Probed by X-ray Crystallography.

Two pillared-layer metal-organic frameworks (MOFs; PMOF-55 and NH2 -PMOF-55) based on 1,2,4-triazole and terephthalic acid (bdc)/NH2 -bdc ligands were assembled and display framework stabilities, to a certain degree, in both acid/alkaline solutions and toward water. They exhibit high CO2 uptakes and selective CO2 /N2 adsorption capacities, with CO2 /N2 selectivity in the range of 24-27, as calculated by the ideal adsorbed solution theory method. More remarkably, the site and interactions between the host network and the CO2 molecules were investigated by single-crystal X-ray diffraction, which showed that the main interaction between the CO2 molecules and PMOF-55 is due to multipoint supramolecular interactions of C-H⋅⋅⋅O, C⋅⋅⋅O, and O⋅⋅⋅O. Amino functional groups were shown to enhance the CO2 adsorption and identified as strong adsorption sites for CO2 by X-ray crystallography.

Investigating the mechanism and efficacy material basis of Xiehuo Xiaoying decoction for treating Graves' disease via thyroid cell apoptosis based on proteomics and molecular docking techniques.

ETHNOPHARMACOLOGICAL RELEVANCE: For numerous years, the Xiehuo Xiaoying decoction (XHXY), a traditional Chinese medicine formula, has demonstrated substantial promise in treating Graves' disease (GD) in clinical settings, showcasing significant potential. However, the therapeutic mechanism and efficacy material basis of XHXY remains obscure. AIM OF THE STUDY: This work aims to investigate the underlying mechanisms and to study the efficacy material basis of XHXY in anti-GD effect using a combination of TMT quantitative proteomics and molecular docking method. MATERIALS AND METHODS: GD model was initiated by administering Ad-TSH289. Subsequently, the mice underwent a four-week regimen that included oral gavage of XHXY at doses of 17 g/kg·d and 34 g/kg·d, along with intraperitoneal injections of Gentiopicroside (GPS). Utilizing the principles of pharmacological chemistry in traditional Chinese medicine, we employed high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-QTOF/MS) to discern prescribed prototype composition of XHXY in serum samples from mouse. TMT proteomics research provided evidence of XHXY's putative targets and important pathways in vivo. The binding activity of probable action targets and prototype composition was detected by molecular docking. Finally, Immunohistochemistry (IHC) and TUNEL staining were used to verify the mechanism of XHXY and GPS in anti-GD. RESULTS: XHXY and GPS alleviated GD by ameliorating the pathological changes and reducing thyroxine and TRAb levels. In mouse serum, a total of 31 prototypical XHXY ingredients were detected, and the majority of these components were from monarch and minister medicine. Proteomics study results indicated that the XHXY may mainly regulate targets including FAS-associated death domain protein (FADD), Apolipoprotein C-III, etc. and main pathways are Apoptosis, Cholesterol metabolism, TNF signalling pathway, etc. Strong binding activity of the prototypical active ingredient and GPS towards FADD, Caspase 8, and Caspase 3 was demonstrated by molecular docking. XHXY and its primary component, GPS, elevated the expression of FADD, Caspase 8, and Caspase 3, and enhance apoptosis in thyroid cells, as lastly validated by TUNEL and IHC staining. CONCLUSIONS: XHXY exhibits a favorable therapeutic effect in treating GD by promoting apoptosis in thyroid cells through the upregulation of FADD, Caspase 8, and Caspase 3 expression. And GPS is the main efficacy material basis for its therapeutic effect in anti-GD.

Mechanism of Prunella vulgaris L. and luteolin in restoring Tfh/Tfr balance and alleviating oxidative stress in Graves' disease.

BACKGROUND: The pathophysiology of Graves' disease (GD) involves imbalances between follicular helper T (Tfh) and follicular regulatory T (Tfr) cells, as well as oxidative stress (OS). Prunella vulgaris L. (Xia Ku Cao, XKC) and its primary bioactive compound, luteolin, are recognized for their potential in treating GD. Yet, the mechanism accounting for the immune-modulatory and antioxidant effects of XKC remains elusive. PURPOSE: This study aims to evaluate the pharmacological effects and elucidate the underlying mechanism of XKC and luteolin in a GD mouse model induced by recombinant adenovirus of TSH receptor A subunit (Ad-hTSHR-289). METHODS: High-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (HPLC-QTOF MS) was used to detect the constituents of XKC. The GD model was established through inducing female BALB/c mice with three intramuscular injections of Ad-TSHR-289. Thyroid function, autoantibody and OS parameters were measured by ELISA. Changes of Tfh cells and Tfr cells were detected by flow cytometry. RT-qPCR, Western Blotting, immunohistochemistry were used to explore the related molecular mechanisms. RESULTS: A total of 37 chemical components from XKC were identified by HPLC-QTOF MS, represented by flavonoids, steroids, terpenoids, and luteolin. XKC and luteolin reduced T4, TRAb levels and facilitated the recovery from thyroid damage in GD mice. Meanwhile, XKC and luteolin effectively alleviated OS by decreasing the levels of MDA, NOX2, 4-HNE, 8-OHdG, while increasing GSH level. Flow cytometry showed that XKC and luteolin restored the abnormal proportions of Tfh/Tfr and Tfh/Treg, and the mRNA levels of IL-21, Bcl-6 and Foxp3 in GD mice. In addition, XKC and luteolin inhibited PI3K, Akt, p-PI3K and p-Akt, but activated Nrf2 and HO-1. CONCLUSION: XKC and luteolin could inhibit the development of GD in vivo by rebalancing Tfh/Tfr cells and alleviating OS. This therapeutic mechanism may involve the Nrf2/HO-1 and PI3K/Akt signaling pathways. Luteolin is the main efficacy material basis of XKC in countering GD. For the first time, we revealed the mechanism of XKC and luteolin in the treatment of GD from the perspective of autoimmune and OS.

Function-oriented mechanism discovery of coumarins from Psoralea corylifolia L. in the treatment of ovariectomy-induced osteoporosis based on multi-omics analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (Bu Gu Zhi) is the fruit of Psoralea corylifolia L. (PCL) and has been used for centuries in traditional Chinese medicine formulas to treat osteoporosis (OP). A new drug called "BX" has been developed from PCL, but its mechanism for treating OP is not yet fully understood. AIM OF THE STUDY: To explore the mechanism of action of BX in the treatment of ovariectomy-induced OP based function-oriented multi-omics analysis of gut microbiota (GM) and metabolites. MATERIALS AND METHODS: C57BL/6 mice were bilaterally ovariectomized to replicate the OP model. The therapeutic efficacy of BX was evaluated by bone parameters (BMD, BV/TV, Tb.N, Tb.Sp), hematoxylin and eosin (H&E) staining results, and determination of bone formation markers procollagen type Ⅰ amino-terminal peptide (PⅠNP) and bone-specific alkaline phosphatase (BALP). Serum and fecal metabolomics and high-throughput 16S rDNA sequencing were performed to evaluate effects on endogenous metabolites and GM. In addition, an enzyme-based functional correlation algorithm (EBFC) algorithm was used to investigate functional correlations between GM and metabolites. RESULTS: BX improved OP in OVX mice by increasing BMD, BV/TV, serum PⅠNP, BALP, and improving Tb.N and Tb.Sp. A total of 59 differential metabolites were identified, and 9 metabolic pathways, including arachidonic acid metabolism, glycerophospholipid metabolism, purine metabolism, and tryptophan metabolism, were found to be involved in the progression of OP. EBFC analysis results revealed that the enzymes related to purine and tryptophan metabolism, which are from Lachnospiraceae_NK4A136_group, Blautia, Rs-E47_termite_group, UCG-009, and Clostridia_UCG-014, were identified as the intrinsic link between GM and metabolites. CONCLUSIONS: The regulation of GM and restoration of metabolic disorders may be the mechanisms of action of BX in alleviating OP. This research provides insights into the function-oriented mechanism discovery of traditional Chinese medicine in the treatment of OP.