A Cubic Tinkertoy-like Heterometallic Cluster with a Record Magnetocaloric Effect.

Clusters showing a giant magnetocaloric effect (MCE) are of interest as molecular coolants for magnetic refrigeration. Herein, we report two heterometallic clusters, denoted as Gd152Ni14@Cl24 and Sm152Ni8, just to highlight their inorganic core motifs, obtained by ligand-controlled co-hydrolysis of Ni2+ and Ln3+ (Ln = Gd, Sm) in the presence of N-(2-hydroxyethyl)iminodiacetic acid (H2HEIDA). Both clusters display fascinating cubic Tinkertoy-like structures, with the core motifs being built of multiple metallic shells of Platonic and Archimedean polyhedra. The isothermal magnetic entropy change─a direct measurement of MCE─was determined to be 52.65 J·kg-1·K-1 at 2.5 K and 7.0 T for the Gd-containing cluster; this value is the highest known for any molecular clusters so far reported.

Substituent Positioning Effects on the Magnetic Properties of Sandwich-Type Erbium(III) Complexes with Bis(trimethylsilyl)-Substituted Cyclooctatetraenyl Ligands.

Lanthanide complexes with judiciously designed ligands have been extensively studied for their potential applications as single-molecule magnets. With the influence of ligands on their magnetic properties generally established, recent research has unearthed certain effects inherent to site differentiation due to the different types and varying numbers of substituents on the same ligand platform. Using two new sandwich-type Er(III) complexes with cyclooctatetraenyl (COT) ligands featuring two differently positioned trimethylsilyl (TMS) substituents, namely, [Li(DME)Er(COT1,5-TMS2)2]n (Er1) and [Na(DME)3][Er(COT1,3-TMS2)2] (Er2) [COT1,3-TMS2 and COT1,5-TMS2 donate 1,3- and 1,5-bis(trimethylsilyl)-substituted cyclooctatetraenyl ligands, respectively; DME = 1,2-dimethoxyethane], and with reference to previously reported [Li(DME)3][Er(COT1,4-TMS2)2] (A) and [K(DME)2][Er(COT1,4-TMS2)2] (B), any possible substituent position effects have been explored for the first time. The rearrangement of the TMS substituents from the starting COT1,4-TMS2 to COT1,3-TMS2 and COT1,5-TMS2, by way of formal migration of the TMS group, was thermally induced in the case of Er1, while for the formation of Er2, the use of Na+ in the placement of its Li+ and K+ congeners is essential. Both Er1 and Er2 display single-molecule magnetic behaviors with energy barriers of 170(3) and 172(6) K, respectively. Magnetic hysteresis loops, butterfly-shaped for Er1 and wide open for Er2, were observed up to 12 K for Er1 and 13 K for Er2. Studies of magnetic dynamics reveal the different pathways for relaxation of magnetization below 10 K, mainly by the Raman process for Er1 and by quantum tunneling of magnetization for Er2, leading to the order of magnitude difference in magnetic relaxation times and sharply different magnetic hysteresis loops.

A Bis-Cyclopentadienyl Ligand-Supported Di-Iron Trihydride Motif as a Synthon for Access to Heterobimetallic Trinuclear Complexes.

Herein, we report the synthesis of a flexible bis-cyclopentadienyl ligand L (the doubly deprotonated form of H2L (1,3-bis(2,4-di-tert-butylcyclopentadienyldimethylsilyl)benzene)), demonstrating its ability to stabilize a series of di-iron hydrido complexes. Notably, this ligand facilitates the isolation of an unprecedented anionic cyclopentadienyl ligand-supported di-iron trihydride complex, LFe2(µ-H)3Li(THF) (2), functioning as a synthon for the [Fe2(µ-H)3]- core and providing access to heterobimetallic complexes 4-6 with coinage metals.

Three-Dimensional Analysis of Bone Remodeling After Closed Treatment for Mandibular Condylar Head Fracture.

Closed treatment of mandibular condylar fractures has been used for its indications based on the fracture site, fracture status, and patient age. Posttreatment mandibular condyle size is associated with mandibular function; however, a few studies have reported bone remodeling patterns and volume changes in the condyle and glenoid fossa after mandibular condylar head fractures (CHFs). Therefore, volumetric changes in the mandibular condyle and glenoid fossa were analyzed in the present study, and bone remodeling patterns were evaluated after mandibular CHFs. The present study included 16 condyles from 12 patients who received closed treatment for CHF. After reconstruction of a 3-dimensional skull model, including the mandible, using computed tomography data taken immediately after injury and 6 months after treatment, volume changes in the mandibular condyle and glenoid fossa were analyzed. The condylar volume increased by 0.32±0.66 cm3 during the 6-month healing period without statistical significance (P=0.093). Regarding the glenoid fossa, the fossa showed a statistically significant volume increase of 0.41±0.59 cm3 (P=0.021), and 12 glenoid fossae (75%) showed downward bone apposition; however, no change or only mild bone resorption was observed in 4 glenoid fossae (25%). The results of this study indicated that the volume changes in the mandibular condyle after closed treatment of a mandibular CHF are not significant, and the glenoid fossa adapts to the displaced mandibular condyle through downward growth accompanied by volume increase.

Determinative Effect of Axial Linearity on Single-Molecule Magnet Performance in Dinuclear Dysprosium Complexes.

Two dichloride-bridged dinuclear dysprosium(III) complexes based on salen ligands, namely, [Dy(L1 )(µ-Cl)(thf)]2 (1; H2 L1 =N,N'-bis(3,5-di-tert-butylsalicylidene)phenylenediamine) and [Dy2 (L2 )2 (µ-Cl)2 (thf)2 ]2 (2; H2 L2 =N,N'-bis(3,5-di-tert-butylsalicylidene)ethylenediamine) are reported. These two complexes have two short Dy-O(PhO) bonds that exhibit angles of ∼90° for 1 and ∼143° for 2, leading to clear slow relaxation of the magnetization for 2 and not for 1. Compound 2 has a near-identical core to the recently reported compound [Dy2 (L3 )2 (µ-Cl)2 (thf)2 ] (3; H2 L3 =N-(2-pyridylmethyl)-N,N-bis(2'-hydroxy-3',5'-di-tert-butylbenzyl)amine). The only substantial difference is the relative angle of the two O(PhO) -Dy-O(PhO) vectors, which is collinear in 2 owing to inversion symmetry and ∼68° in 3 due to a molecular C2 axis. It is shown that this subtle structural difference leads to large differences in the dipolar ground states, giving rise to open magnetic hysteresis for 3 and not for 2.

Electron Paramagnetic Resonance Spectra of Pentagonal Bipyramidal Gadolinium Complexes.

Gadolinium is a special case in spectroscopy because of the near isotropic nature of the 4f7 configuration of the +3 oxidation state. Gd3+ complexes have been studied in several symmetries to understand the underlying mechanisms of the ground state splitting. The abundance of information in Gd3+ spectra can be used as a probe for properties of the other rare earth ions in the same complexes. In this work, the zero-field splitting (ZFS) of a series of Gd3+ pentagonal bipyramidal complexes of the form [GdX1X2(Leq)5]n+ [n = 1, X = axial ligands: Cl-, -OtBu, -OArF5 or n = 3, X = tBuPO(NHiPr)2, Leq = equatorial ligand: Py, THF or H2O] with near fivefold symmetry axes along X1-Gd-X2 was investigated. The ZFS parameters were determined by fitting of room-temperature continuous wave electron paramagnetic resonance (EPR) spectra (at X-, K-, and Q-band) to a spin Hamiltonian incorporating extended Stevens operators compatible with C5 symmetry. Examination of the acquired parameters led to the conclusion that the ZFS is dominated by the B20 term and that the magnitude of B20 is almost entirely dependent on, and inversely proportional to, the donor strength of the axial ligands. Surveying the continuous shape measure and the X1-Gd-X2 angle of the complexes showed that there is some correlation between the proximity of each complex to D5h symmetry and the magnitude of the B65 parameter, but that the deformation of the X1-Gd-X2 angle is more significant than other distortions. Finally, the magnitude of B20 was found to be inversely proportional to the thermal barrier for the reversal of the magnetic moment (Ueff) of the corresponding isostructural Dy3+ complexes.

Studies of the Temperature Dependence of the Structure and Magnetism of a Hexagonal-Bipyramidal Dysprosium(III) Single-Molecule Magnet.

The hexagonal-bipyramidal lanthanide(III) complex [Dy(OtBu)Cl(18-C-6)][BPh4] (1; 18-C-6 = 1,4,7,10,13,16-hexaoxacyclooctadecane ether) displays an energy barrier for magnetization reversal (Ueff) of ca. 1000 K in a zero direct-current field. Temperature-dependent X-ray diffraction studies of 1 down to 30 K reveal bending of the Cl-Ln-OtBu angle at low temperature. Using ab initio calculations, we show that significant bending of the O-Dy-Cl angle upon cooling from 273 to 100 K leads to a ca. 10% decrease in the energy of the excited electronic states. A thorough exploration of the temperature and field dependencies of the magnetic relaxation rate reveals that magnetic relaxation is dictated by five mechanisms in different regimes: Orbach, Raman-I, quantum tunnelling of magnetization, and Raman-II, in addition to the observation of a phonon bottleneck effect.

Access to Monomeric Lead(II) Hydrides with Remarkable Thermostability and Their Use in Catalytic Hydroboration of Carbonyl Derivatives.

We report on the remarkable stability of unprecedented, monomeric lead(II) hydrides M+[LPb(II)H]- (M[1-H]), where L = 2,6-bis(3,5-diphenylpyrrolyl)pyridine and M = (18-crown-6)potassium or ([2.2.2]-cryptand)potassium. The half-life of [K18c6][1-H] of ∼2 days in tetrahydrofuran at 25 °C is significantly longer than those reported for dimeric lead(II) hydrides supported by bulky terphenyl ligands (few hours at low temperatures), which are the only examples known for lead(II) hydride compounds. The presence of a Pb-H bond in [1-H]- was unambiguously identified by multinuclear NMR spectroscopy. Remarkably, a 1H resonance of the hydride ligand was found at δ = 41.43 ppm (1JPbH = 1312 Hz). For reactivity study, [1-H]- serves as an excellent hydroboration catalyst with high turnover numbers and turnover frequencies for several carbonyl compounds.

Efficient synthesis of an apremilast precursor and chiral ß-hydroxy sulfones via ketoreductase-catalyzed asymmetric reduction.

Ketoreductase (KRED)-catalyzed asymmetric reduction of prochiral ketones is an attractive method to synthesize chiral alcohols. Herein, two KREDs LfSDR1-V186A/E141I and CgKR1-F92I with complementary stereopreference were identified towards reduction of apremilast prochiral ketone intermediate 1a. LfSDR1-V186A/E141I exhibited >99% conversion and 99.2% ee yielding an apremilast chiral alcohol intermediate ((R)-2a) at 50 g L-1 substrate loading. Furthermore, we investigated the substrate scope of ß-keto sulfones by using LfSDR1-V186A/E141I and CgKR1-F92I to produce both enantiomers of the corresponding ß-hydroxy sulfones, with good-to-excellent conversion (up to >99%) and enantioselectivity (up to 99.9% ee) being obtained in most cases. Finally, the gram-scale synthesis of (R)-2a was performed by employing the crude enzyme of LfSDR1-V186A/E141I and BsGDH to afford the desired enantiomer with >99% conversion, 85.9% isolated yield and 99.2% ee. This study presents a biocatalytic strategy to synthesize chiral ß-hydroxy sulfones.

[Chinese medicine dispensing granules: history, status quo, and development prospect in "post-pilot era"].

Chinese medicine dispensing granules, the result of the efforts to transform Chinese medicinal decoction pieces in China, features portability and ease of storage. Thus, it is destined to be an indispensible dosage form in the modernization drive of Chinese medicine. The Announcement on Ending the Pilot Project of Chinese Medicine Dispensing Granules was released in February 2021 and relevant regulations went into force in November 2021, which marks the a new journey for the development of Chinese medicine dispensing granules and the beginning of the "post-pilot era". However, it faces the challenges in quality and standard. This study reviewed the history of Chinese medicine dispensing granules, analyzed the technical progress, market, and main problems in development, and proposed suggestions and prospects for its development in the "post-pilot era", which is expected to serve as a reference for its industry development and rational use.

Ligand Fluorination to Mitigate the Raman Relaxation of DyIII Single-Molecule Magnets: A Combined Terahertz, Far-IR and Vibronic Barrier Model Study.

The fast Raman relaxation process via a virtual energy level has become a puzzle for how to chemically engineer single-molecule magnets (SMMs) with better performance. Here, we use the trifluoromethyl group to systematically substitute the methyl groups in the axial position of the parent bis-butoxide pentapyridyl dysprosium(III) SMM. The resulting complexes-[Dy(OLA )2 py5 ][BPh4 ] (LA =CH(CF3 )2 - 1, CH2 CF3 - 2, CMe2 CF3 - 3)-show progressively enhanced TB hys (@100 Oe s-1 ) from 17 K (for 3), 20 K (for 2) to 23 K (for 1). By experimentally identifying the varied under barrier relaxation energy in the 5-500 cm-1 regime, we are able to identify that the C-F bond related vibration energy of the axial ligand ranging from 200 to 350 cm-1 is the key variant for this improvement. Thus, this finding not only reveals a correlation between the structure and the Raman process but also provides a paradigm for how to apply the vibronic barrier model to analyze multi-phonon relaxation processes in lanthanide SMMs.

A Local D4h Symmetric Dysprosium(III) Single-Molecule Magnet with an Energy Barrier Exceeding 2000†K*.

Three six-coordinate DyIII single-molecule magnets (SMMs) [Dy(Ot Bu)2 (L)4 ]+ with local D4h symmetry are obtained by optimizing the equatorial ligands. One of the compounds with L=4-phenylpyridine shows an energy barrier (Ueff ) of 2075(11) K, which is the third largest Ueff , and the first Ueff >2000 K for SMMs with axial-type symmetry so far. Ab initio analysis indicates that the exceptional uniaxial magnetic anisotropy is deeply related to the axially compressed octahedral geometry. This work provides a new insight into the local D4h symmetry for high-performance SMMs.

Inosine induces acute hyperuricaemia in rhesus monkey (Macaca mulatta) as a potential disease animal model.

CONTEXT: The uric acid metabolism pathway is more similar in primates and humans than in rodents. However, there are no reports of using primates to establish animal models of hyperuricaemia (HUA). OBJECTIVES: To establish an animal model highly related to HUA in humans. MATERIALS AND METHODS: Inosine (75, 100 and 200 mg/kg) was intraperitoneally administered to adult male rhesus monkeys (n = 5/group). Blood samples were collected over 8 h, and serum uric acid (SUA) level was determined using commercial assay kits. XO and PNP expression in the liver and URAT1, OAT4 and ABCG2 expression in the kidneys were examined by qPCR and Western blotting to assess the effects of inosine on purine and uric acid metabolism. The validity of the acute HUA model was assessed using ulodesine, allopurinol and febuxostat. RESULTS: Inosine (200 mg/kg) effectively increased the SUA level in rhesus monkeys from 51.77 ± 14.48 at 0 h to 178.32 ± 14.47 µmol/L within 30 min and to peak levels (201.41 ± 42.73 µmol/L) at 1 h. PNP mRNA level was increased, whereas XO mRNA and protein levels in the liver were decreased by the inosine group compared with those in the control group. No changes in mRNA and protein levels of the renal uric acid transporter were observed. Ulodesine, allopurinol and febuxostat eliminated the inosine-induced elevation in SUA in tested monkeys. CONCLUSIONS: An acute HUA animal model with high reproducibility was induced; it can be applied to evaluate new anti-HUA drugs in vivo and explore the disease pathogenesis.

1H NMR-Based Metabolic Profiles Delineate the Anticancer Effect of Vitamin C and Oxaliplatin on Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Because of its high recurrence rate and heterogeneity, effective treatment for advanced stage of HCC is currently lacking. There are accumulating evidences showing the therapeutic potential of pharmacologic vitamin C (VC) on HCC. However, the metabolic basis underlying the anticancer property of VC remains to be elucidated. In this study, we used a high-resolution proton nuclear magnetic resonance-based metabolomics technique to assess the global metabolic changes in HCC cells following VC treatment. In addition, the HCC cells were also treated with oxaliplatin (OXA) to explore the potential synergistic effect induced by the combined VC and OXA treatment. The current metabolomics data suggested different mechanisms of OXA and VC in modulating cell growth and metabolism. In general, VC treatment led to inhibition of energy metabolism via NAD+ depletion and amino acid deprivation. On the other hand, OXA caused significant perturbation in phospholipid biosynthesis and phosphatidylcholine biosynthesis pathways. The current results highlighted glutathione metabolism, and pathways related to succinate and choline may play central roles in conferring the combined effect between OXA and VC. Taken together, this study provided metabolic evidence of VC and OXA in treating HCC and may contribute toward the potential application of combined VC and OXA as complementary HCC therapies.

Sox13 promotes hepatocellular carcinoma metastasis by transcriptionally activating Twist1.

SRY (sex-determining region Y)-box 13 (Sox13), a member of group D of the SRY-related high mobility group (HMG) box (Sox) family, is a critical regulator of embryonic development and cartilage formation. Few studies have investigated the role of Sox13 in tumorigenesis. The present study reveals the clinical significance and biological function of Sox13 in hepatocellular carcinoma (HCC). First, the expression of Sox13 in HCC samples was evaluated by qRT-PCR and western blotting, and its association with clinicopathological features and prognosis was determined. We found that Sox13 expression was higher in tumor tissue than in paired nontumor tissue. The upregulation of Sox13 was associated with poor differentiation, metastasis, recurrence and poor overall, and tumor-free survival of HCC patients. The function of Sox13 on HCC cell migration and invasion was then assessed by Transwell assay, and the results demonstrated that Sox13 promoted HCC cell invasion, migration, and epithelial-to-mesenchymal transition (EMT). Notably, the invasion, migration, and EMT of HCC cells induced by Sox13 overexpression could be abolished by Twist1 depletion, and Sox13 was positively correlated with Twist1 at both the mRNA and protein levels. Mechanistically, we revealed that Sox13 activated Twist1 transcription and consequently upregulated Twist1 expression. Furthermore, Sox13 formed a heterodimer with Sox5, and this heterodimer functionally cooperated to enhance the transcriptional activity of Twist1. Our findings suggest that Sox13 serves as an oncogene in HCC, and might be a novel prognostic and therapeutic candidate.

A Study of Magnetic Relaxation in Dysprosium(III) Single-Molecule Magnets.

Although the development of single-molecule magnets (SMMs) is rapid, there are only two families of high energy barrier (Ueff ) dysprosium(III) SMMs known so far: the cyclopentadienyl (Cp) family with a sandwich structure and the pentagonal-bipyramidal (PB) family with D5h symmetry. These high-barrier SMMs, which usually possess Ueff >500 cm-1 allow the separate study of the four magnetic relaxation paths, namely, direct, quantum tunnelling, Raman and Orbach processes, in detail. Whereas the first family is chemically more challenging to modify the Cp rings, it is shown herein that the latter family, with the common formulae [DyX1 X2 (Leq )5 ]+ , such as X1 /X2 =- OCMe3 , - OSiMe3 , - OPh, Cl- or Br- ; Leq =THF/pyridine/4-methylpyridine, can be readily fine-tuned with a range of axial and equatorial ligands by simple substitution reactions. This allows unambiguous confirmation that the Ueff mainly depends on the identity of X1 and X2 , rather than on Leq . More importantly, the fitted parameters are barrier dependent. If X1 is an O donor and X2 is a halide, 500

Exchange-Biasing in a Dinuclear Dysprosium(III) Single-Molecule Magnet with a Large Energy Barrier for Magnetisation Reversal.

A dichlorido-bridged dinuclear dysprosium(III) single-molecule magnet [Dy2 L2 (µ-Cl)2 (thf)2 ] has been made by using a diamine-bis(phenolate) ligand, H2 L. Magnetic studies show an energy barrier for magnetisation reversal (Ueff ) around 1000 K. An exchange-biasing effect is clearly seen in magnetic hysteresis with steps up to 3 K. Ab initio calculations exclude the possibility of a pure dipolar origin of this effect leading to the conclusion that super-exchange through the chloride bridging ligands is important.

Total Synthesis of Prostratin, a Bioactive Tigliane Diterpenoid: Access to Multi-Stereocenter Cyclohexanes from a Phenol.

Tiglianes such as prostratin and related diterpenoids are biologically significant natural molecules and long-standing targets for organic synthesis community. Due to the complex polycyclic scaffolds, high oxygenation level, and dense functional groups and stereocenters, their de novo chemical syntheses still face formidable challenges despite extensive efforts in the past 40 years. This account details the development of a modular and concise synthesis of prostratin, a potent anti-HIV and anticancer agent. The key approach in this synthesis involved a sequence of oxidative dearomatization and sequential stereoselective installation of peripheral groups to rapidly build the contiguously substituted cyclohexane C-ring. Inspired by Wender's work, an acid- and solvent-controlled stereodivergent formation of cyclopropane D-ring was developed. Mechanistic investigations by computational methods revealed that the competition between intra- and intermolecular hydrogen bonding led to different conformations, thus favoring different protonation processes. The designed and unexpected chemistry along this campaign reflected the uniqueness of the natural structures and should be amenable to future chemical syntheses of related complex polycyclic molecules.

Old yellow enzymes: structures and structure-guided engineering for stereocomplementary bioreduction.

Since the first discovery of old yellow enzyme 1 (OYE1) from Saccharomyces pastorianus in 1932, biocatalytic asymmetric reduction of activated alkenes by OYEs has become a valuable reaction in organic synthesis. To access stereocomplementary C=C-bond bioreduction, the mining of novel OYEs and especially the protein engineering of existing OYEs have been performed, which successfully achieved the stereocomplementary reduction in several cases and further raise the potential of applications. In this review, we analyzed the structures, active sites, and substrate recognition of OYEs, which are the bases for their substrate specificity and stereospecificity. Sequence similarity network of OYEs superfamily was also constructed to investigate the scope of characterized OYEs. The structure-guided engineering to switch the stereoselectivity of OYEs and thus access stereocomplementary bioreduction over the last decade (2009-2020) was then reviewed and discussed, which might give new insights into the mining and engineering of related biocatalysts. KEY POINTS: • The sequence similarity network of OYEs superfamily was constructed and annotated. • The structures and active sites of OYEs from different classes were compared. • "Left/right" binding mode was used to explain the stereopreferences of OYEs. • Structure-guided engineering of OYEs to switch their stereoselectivity was reviewed.

Evaluation of Bone Remodeling After Simultaneous Sagittal Split Ramus Osteotomy and Mandibular Angle Ostectomy in Patients With Mandibular Prognathism.

PURPOSE: The present study assessed the postoperative bone remodeling after simultaneous sagittal split ramus osteotomy (SSRO) and mandibular angle ostectomy using a 3-dimensional analysis of computed tomography (CT) data. MATERIALS AND METHODS: We designed and implemented a retrospective study that included patients who had undergone SSRO with (study group) or without (control group) mandibular angle ostectomy. Using CT data taken immediately after (T1) and 6 months (T2) after surgery, the vertical and horizontal morphologic changes of the mandibular angle were evaluated and compared between the 2 groups. In the study group, the volumetric changes of the mandibular angle were assessed, and the bone regeneration rate was calculated. RESULTS: A total of 58 mandibular angles were evaluated (32 in the study group and 26 in the control group). The study group exhibited significantly greater vertical bone regrowth at the middle and posterior regions of the mandibular angle ostectomy line compared with that in the control group (middle, P < .001; posterior, P < .001). Both groups showed significant horizontal bone regrowth at 6 months postoperatively (P < .01). In the study group, the postoperative vertical bone regrowth was significantly associated with the extent of exposed bone below the angle ostectomy line at T1 for all regions (P < .001). The percentage of postoperative regenerated bone volume relative to the volume of bone removed intraoperatively was 41.8%. CONCLUSIONS: The present findings suggest that significant bone regrowth could occur after mandibular angle ostectomy with simultaneous SSRO. Therefore, it is necessary to consider bone remodeling patterns in the treatment planning stage for better and more predictable surgical outcomes.