维生素B1催化制备2-噻吩偶姻的研究

以维生素B1为催化剂,在三乙胺为碱的条件下,催化2-噻吩甲醛发生安息香缩合反应制备噻吩偶姻,产率15％。     

Intrinsic factor and vitamin B12 complex‐loaded poly[lactic‐co‐(glycolic acid)] microspheres: preparation,characterization and drug release

BACKGROUND: Vitamin B12 is an essential vitamin required by all mammals. Absorption of vitamin B12 is facilitated by binding of intrinsic factor–vitamin B₁₂ complex to specific receptors in the ileum. In humans a deficiency of this vitamin or a lack of intrinsic factor leads to pernicious anaemia. The major objective of the present study was to prepare intrinsic factor–vitamin B12 complex‐loaded poly[lactic‐co‐(glycolic acid)] (PLGA)‐based microparticles and to investigate their release kinetics. RESULTS: PLGA copolymer was synthesized by the ring‐opening polymerization method and characterized using gel permeation chromatography, Fourier transform infrared spectroscopy and ¹H NMR. The glass transition temperature measurement showed a single T_g at 40 °C. The intrinsic factor–vitamin B12 complex‐loaded PLGA microspheres were prepared by a water‐in‐oil‐in‐water double emulsion solvent extraction/evaporation technique. An environmental scanning electron microscopy investigation demonstrated that the PLGA particles had a mean particle diameter of 38 µm. Interestingly, different drug release patterns (bi‐ and triphasic ones) were observed for vitamin B12‐loaded and intrinsic factor–vitamin B12 complex‐loaded microspheres. In contrast to the rapid release of vitamin B12 by itself, in vitro release tests showed that intrinsic factor and vitamin B12 in the complex were released from PLGA microspheres in a sustained manner over 15 days. CONCLUSION: PLGA microspheres can be an effective carrier for the intrinsic factor–vitamin B12 complex. Copyright © 2007 Society of Chemical Industry     

氨基三溴苯基荧光酮化学发光法测定维生素B_(12)中的钴

用氨基三溴苯基荧光酮 (ATB- PF)为化学发光剂建立了与 CTMAB- H2 O2 化学发光法测定的新体系 ,线性响应范围为 5× 1 0 - 10～ 2× 1 0 - 8g· m L- 1,检测限为 4× 1 0 - 11g· m L- 1,应用于维生素 B12 样品的测定 ,结果满意。     

Solution Structure and Constrained Molecular Dynamics Study of Vitamin B12 Conjugates of the Anorectic Peptide PYY(3–36)

Vitamin B₁₂–peptide conjugates have considerable therapeutic potential through improved pharmacokinetic and/or pharmacodynamic properties imparted on the peptide upon covalent attachment to vitamin B₁₂ (B₁₂). There remains a lack of structural studies investigating the effects of B₁₂ conjugation on peptide secondary structure. Determining the solution structure of a B₁₂–peptide conjugate or conjugates and measuring functions of the conjugate(s) at the target peptide receptor may offer considerable insight concerning the future design of fully optimized conjugates. This methodology is especially useful in tandem with constrained molecular dynamics (MD) studies, such that predictions may be made about conjugates not yet synthesized. Focusing on two B₁₂ conjugates of the anorectic peptide PYY(3–36), one of which was previously demonstrated to have improved food intake reduction compared with PYY(3–36), we performed NMR structural analyses and used the information to conduct MD simulations. The study provides rare structural insight into vitamin B₁₂ conjugates and validates the fact that B₁₂ can be conjugated to a peptide without markedly affecting peptide secondary structure.     

Release of vitamin B12 from poly(N‐vinyl‐2‐pyrrolidone)‐crosslinked polyacrylamide hydrogels: A kinetic study

Hydrogels, composed of poly(N‐vinyl‐2‐pyrrolidone) and crosslinked polyacrylamide, were synthesized and the release of vitamin B₁₂ from these hydrogels was studied as a function of the degree of crosslinking and pH of the external swelling media. The three drug‐loaded hydrogel samples synthesized with different crosslinking ratios of 0.3, 0.7, and 1.2 (in mol %) follow different drug‐release mechanisms, that is, chain relaxation with zero‐order, non‐Fickian and Fickian, or diffusion‐controlled mechanisms. To establish a correlation between their swelling behavior and drug‐release mechanism, the former was studied by the weight‐gain method and, at the same time, the concentration of the drug released was studied colorimetrically. Various swelling parameters such as the swelling exponent n, gel‐characteristic constant k, penetration velocity v, and diffusion coefficient D were evaluated to reflect the quantitative aspect of the swelling behavior of these hydrogels. Finally, the drug‐release behavior of the hydrogels was explained by proposing the swelling‐dependent mechanism. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 1706–1714, 2000     

Dityrosine Crosslinking of Collagen and Amyloid-β Peptides Is Formed by Vitamin B12 Deficiency-Generated Oxidative Stress in Caenorhabditis elegans

(1) Background: Vitamin B₁₂ deficiency in Caenorhabditis elegans results in severe oxidative stress and induces morphological abnormality in mutants due to disordered cuticle collagen biosynthesis. We clarified the underlying mechanism leading to such mutant worms due to vitamin B₁₂ deficiency. (2) Results: The deficient worms exhibited decreased collagen levels of up to approximately 59% compared with the control. Although vitamin B₁₂ deficiency did not affect the mRNA expression of prolyl 4-hydroxylase, which catalyzes the formation of 4-hydroxyproline involved in intercellular collagen biosynthesis, the level of ascorbic acid, a prolyl 4-hydroxylase coenzyme, was markedly decreased. Dityrosine crosslinking is involved in the extracellular maturation of worm collagen. The dityrosine level of collagen significantly increased in the deficient worms compared with the control. However, vitamin B₁₂ deficiency hardly affected the mRNA expression levels of bli-3 and mlt-7, which are encoding crosslinking-related enzymes, suggesting that deficiency-induced oxidative stress leads to dityrosine crosslinking. Moreover, using GMC101 mutant worms that express the full-length human amyloid β, we found that vitamin B₁₂ deficiency did not affect the gene and protein expressions of amyloid β but increased the formation of dityrosine crosslinking in the amyloid β protein. (3) Conclusions: Vitamin B₁₂-deficient wild-type worms showed motility dysfunction due to decreased collagen levels and the formation of highly tyrosine-crosslinked collagen, potentially reducing their flexibility. In GMC101 mutant worms, vitamin B₁₂ deficiency-induced oxidative stress triggers dityrosine-crosslinked amyloid β formation, which might promote its stabilization and toxic oligomerization.     

Comparative Efficacy and Safety of P2Y12 Inhibitor Monotherapy and Dual Antiplatelet Therapy in Patients with and without Diabetes Mellitus Undergoing Percutaneous Coronary Intervention

Increasing evidence has shown P2Y12 inhibitor monotherapy is a feasible alternative treatment for patients after percutaneous coronary intervention (PCI) with stent implantation in the modern era. However, patients with diabetes mellitus (DM) have a higher risk of ischemic events and more complex coronary artery disease. The purpose of this study is to evaluate the efficacy and safety of this novel approach among patients with DM and those without DM. We conducted a systematic review and meta-analysis of randomized controlled trials that compared P2Y12 inhibitor monotherapy with 12 months of dual antiplatelet therapy (DAPT) in patients who underwent PCI with stent implantation. PubMed, Embase, Cochrane library database, ClinicalTrials.gov, and three other websites were searched for our data from the earliest report to January 2022. The primary efficacy outcome was major adverse cardiovascular and cerebrovascular events (MACCE): a composite of all-cause mortality, myocardial infarction, stent thrombosis, and stroke. The primary safety outcome was major or minor bleeding events. The secondary endpoint was net adverse clinical events (NACE) which are defined as a composite of major bleeding and adverse cardiac and cerebrovascular events. A total of four randomized controlled trials with 29,136 patients were included in our meta-analysis. The quantitative analysis showed a significant reduction in major or minor bleeding events in patients treated with P2Y12 inhibitor monotherapy compared to standard DAPT (OR: 0.68, 95% CI: 0.46–0.99, p = 0.04) without increasing the risk of MACCE (OR: 0.96, 95% CI: 0.85–1.09, p = 0.50). The number of NACE was significantly lower in the patients treated with P2Y12 inhibitor monotherapy (OR: 0.84, 95% CI: 0.72–0.97, p = 0.019). In DM patients, P2Y12 inhibitor monotherapy was associated with a lower risk of MACCE compared to standard DAPT (OR: 0.85, 95% CI: 0.74–0.98, p = 0.02). Furthermore, P2Y12 inhibitor monotherapy was accompanied by a favorable reduction in major or minor bleeding events (OR: 0.80, 95% CI: 0.64–1.05, p = 0.107). In non-DM patients, P2Y12 inhibitor monotherapy showed a significant reduction in major or minor bleeding events (OR: 0.58, 95% CI: 0.38–0.88, p = 0.01), but without increasing the risk of MACCE (OR: 0.99, 95% CI: 0.82–1.19, p = 0.89). Based on these findings, P2Y12 inhibitor monotherapy could significantly decrease bleeding events without increasing the risk of stent thrombosis or myocardial infarction in the general population. The benefit of reducing bleeding events was much more significant in non-DM patients than in DM patients. Surprisingly, P2Y12 inhibitor monotherapy could lower the risk of MACCE in DM patients. Our study supports that P2Y12 inhibitor monotherapy is a promising alternative choice of medical treatment for patients with DM undergoing PCI with stent implantation in the modern era.     

An unusual dichromium(II,II) compound bearing di-2-pyridyl ketone oximate ligands and prepared by the ligand-assisted reduction of a trichromium(III,III,III) complex in air

The reaction of the oxide-centred triangular, trichromium(III,III,III) complex [Cr₃O(O₂CCMe₃)₆(H₂O)₃](O₂CCMe₃) with di-2-pyridyl ketone oxime, (py)₂CNOH, in MeCN under aerobic and refluxing conditions yields the pivalate-free, dichromium(II,II) complex [Cr₂{(py)₂CNO}₄] · 2H₂O (1 · 2H₂O). The dinuclear complex can also be prepared by the reaction of [Cr(CO)₆] with (py)₂CNOH in refluxing MeCN/H₂O in air. The two high-spin Cr^II atoms are doubly bridged by two 2.1110 oximate ligands, while a chelating 1.0110 (py)₂CNO⁻ ion completes distorted trigonal bipyramidal coordination at each metal centre. The dimers are stabilized by intramolecular stacking interactions between the terminal (py)₂CNO⁻ ligands, and the structural effects of these interactions are discussed.