Affinity and efficacy studies of buprenorphine analogues at opioid receptors

Buprenorphine is a widely used analgesic. Its in vivo properties are partial agonism at μ-receptors and antagonism at κ-receptors. For the investigation of the role of the tertiary alcohol function in the pharmacology of buprenorphine, a series of ring constrained analogues of buprenorphine, in which the tertiary hydroxyl substituent on C19 is fixed in different positions either above (BU46 and BU95) or below (BU47, BU96, BU48 and BU61) the plane of the ring, have been studied in several biological test systems, include binding assays, isolated tissue bioassays and intracellular assays. [Continues.

Initial Reactivity of Linkages and Monomer Rings in Lignin Pyrolysis Revealed by ReaxFF Molecular Dynamics

The initial conversion pathways of linkages and their linked monomer units in lignin pyrolysis were investigated comprehensively by ReaxFF MD simulations facilitated by the unique VARxMD for reaction analysis. The simulated molecular model contains 15 920 atoms and was constructed on the basis of Adler’s softwood lignin model. The simulations uncover the initial conversion ratio of various linkages and their linked aryl monomers. For linkages and their linked monomer aryl rings of α-O-4, β-O-4 and α-O-4 & β-5, the C_α/C_β ether bond cracking dominates the initial pathway accounting for at least up to 80% of their consumption. For the linkage of β–β & γ-O-α, both the C_α–O ether bond cracking and its linked monomer aryl ring opening are equally important. Ring-opening reactions dominate the initial consumption of other 4-O-5, 5-5, β-1, β-2, and β-5 linkages and their linked monomers. The ether bond cracking of C_α–O and C_β–O occurs at low temperature, and the aryl ring-opening reactions take place at relatively high temperature. The important intermediates leading to the stable aryl ring opening are the phenoxy radicals, the bridged five-membered and three-membered rings and the bridged six-membered and three-membered rings. In addition, the reactivity of a linkage and its monomer aryl ring may be affected by other linkages. The ether bond cracking of α-O-4 and β-O-4 linkages can activate its neighboring linkage or monomer ring through the formed phenoxy radicals as intermediates. The important intermediates revealed in this article should be of help in deepening the understanding of the controlling mechanism for producing aromatic chemicals from lignin pyrolysis

Investigation of model scale effects on coal pyrolysis using ReaxFF MD simulation

<p>ReaxFF MD is a promising method for exploring complex chemical reactions, allowing large coal molecular systems simulated at high temperature. Due to the amorphous and diverse nature of coal chemical structure, model scale effect on the simulation of coal pyrolysis can be a big issue, which was investigated by comparing heat-up ReaxFF MD simulations of three Liulin coal models with 2338, 13,498 and 98,900 atoms. ReaxFF MD simulation results show its consistency in the observed trends of weight loss profiles and product generations lumped by C number for different model scales. The small-scale coal model facilitates observation of reaction sites, but can hardly access reasonable evolving trends of products and reactions. ReaxFF MD simulations of the coal model in middle scale can obtain much better evolving trends of pyrolyzates and reproduce some reaction pathways. But certain fluctuations or randomness of reactions still exist in the evolution trends of representative products. The diversity of chemical reactions in coal pyrolysis can be much more accessible by employing the large-scale coal model, thus permitting distinguishable evolving trends in pyrolyzates.</p

Sex and age of different types of patella fractures (n, %).

Sex and age of different types of patella fractures (n, %).</p

A: Coronal T1-weighted MR image; B: Coronal fat-suppressed proton density-weighted MR image.

Female, 46 years old, longitudinal fracture. The T1WI signal of the patellar is reduced, and the patellar is divided into two parts: the right and the left.</p

Different types of patellar fractures combined with ligament injuries (n, %).

Different types of patellar fractures combined with ligament injuries (n, %).</p

A: Coronal T1-weighted MR image; B: Coronal fat-suppressed proton density-weighted MR image.

Male, 60 years old, oblique fracture. The fracture line is at an angle to the mid-axis of the body.</p

Measurement of trochlear groove angle on axial T1WI image.

Measurement of trochlear groove angle on axial T1WI image.</p

A: Axial T1-weighted MR image; B: Axial fat-suppressed proton density-weighted MR image.

Female, 26 years old, tangential fracture. Patellar subluxation with localized osteochondral defects in the medial portion of the patellar, patchy osteoedema of the lateral femoral condyle on axial fat-suppressed proton density-weighted MR image, and grade II signal in the medial patellar retinaculum. Simple effusion in the joint capsule.</p

Comparison of patellofemoral joint morphology among patients with different types of patellar fractures (cases, %).

Comparison of patellofemoral joint morphology among patients with different types of patellar fractures (cases, %).</p