Advances in the Physicochemical Profiling of Opioid Compounds of Therapeutic Interest

This review focuses on recent developments in the physicochemical profiling of morphine and other opioids. The acid-base properties and lipophilicity of these compounds is discussed at the microscopic, species-specific level. Examples are provided where this type of information can reveal the mechanism of pharmacokinetic processes at the submolecular level. The role of lipophilicity in quantitative structure–activity relationship (QSAR) studies of opioids is reviewed. The physicochemical properties and pharmacology of the main metabolites of morphine are also discussed. Recent studies indicate that the active metabolite morphine-6-glucuronide (M6G) can contribute to the analgesic activity of systemically administered morphine. The unexpectedly high lipophilicity of M6G partly accounts for its analgesic activity. When administered parenterally, another suspected minor metabolite, morphine-6-sulfate (M6S) has superior antinociceptive effects to those of morphine. However, because sulfate esters of morphine derivatives cannot cross the blood-brain barrier these esters may be good candidates to develop peripheral analgesic drugs.     

Organophosphorous ligands in hydrogenase‐inspired iron‐based catalysts: A DFT study on the energetics of metal protonation as a function of P‐atom substitution

The present paper reports a study on the energetics of protonation of a hydrogenase biomimetic complex, [Fe₂(μ‐adt)(CO)₄(PMe₃)₂] (adt = N‐benzylazadithiolate), and of its homologue featuring triphenylphosphine ligands in place of trimethylphosphines. Formation of a terminal hydride on one of the Fe centres was considered first, given the key relevance of terminal hydride species in the enzymatic mechanism. Theoretical calculations highlight that, in a vacuum, terminal protonation of the selected Fe ion in the PPh₃‐bearing organometallic complex is highly favoured when compared to the analogous reaction involving the PMe₃‐containing species, but the trend is inverted in the case of models optimized in a continuum polarizable. An unexpected parallel is thus established between relative basicities of PPh₃ and PMe₃ in vacuum or in solution phase [C. A. Tolman, J. Am. Chem. Soc. 1970 , 92, 2953; G. M. Bancroft, Inorg. Chem. 1986 , 25, 3675], and the energetics of terminal hydride formation upon protonation of [FeFe]‐hydrogenase biomimetic complexes bearing such organophosphorous ligands. Bridging hydride formation was also considered in the present study: calculations showed that protonation of the PMe₃‐bearing organometallic complex is again strongly favoured in vacuo, as compared to the case of the PPh₃‐containing model. However, protonation energies become significantly smaller when solvent effects are taken into account. Such differences between protonation reactions modelled in vacuo and in the polarizable continuum are rationalized in light of the different electrostatic properties of the diiron complexes here considered. Implications for the design and modelling of biomimetic catalysts are briefly discussed in light of recent literature.     

MgO/h-BN复合载体对Ba-Ru/MgO/h-BN氨合成催化剂性能的影响(英文)

采用浸渍法制备了系列不同质量比的MgO/h-BN复合载体负载的Ru基氨合成催化剂,采用X射线衍射、N2低温物理吸附、X射线荧光、扫描电镜、透射电镜、程序升温分析等手段对催化剂进行了详细的表征,并在固定床反应器上考察了它们在氨合成反应中的催化性能.结果表明,MgO/h-BN复合载体中h-BN含量对催化剂活性的影响较大,Ba-Ru[1:1](摩尔比)/MgO/h-BN[8:2](质量比),Ba-Ru[1:1]/MgO/h-BN[6:4]和Ba-Ru[1:1]/MgO/h-BN[5:5]催化剂上氨合成活性均高于Ba-Ru/MgO催化剂.在425°C,5.0MPa,N2/H2=1/3和5000h?1条件下,Ba-Ru[1:1]/MgO/h-BN[8:2]表现出最优催化活性,达506.9ml/(gcat·h).这可归因于MgO/h-BN复合载体上存在较高数量的碱性位,特别是弱碱性位和中等强度碱性位,而这些碱性位可能是由MgO和h-BN之间的相互作用造成.     

Influence of Y2O3 on structural and optical properties of SiO2-BaO-ZnO-xB2O3-(10−x) Y2O3 glasses and glass ceramics

SiO₂-BaO-ZnO-xB₂O₃-(10−x) Y₂O₃, (0 ≤ x ≤ 10) glasses are synthesized. The effect of Y₂O₃ on the structural and optical properties of glasses has been investigated using different characterization techniques. The results are discussed in light of non-bridging oxygens (NBO), optical basicity and heat-treatment of glasses. The band gap has been calculated for as cast and heat-treated glasses. The band gap energy is found to decrease with the increasing content of Y₂O₃ in the glasses and heat-treatment. The presence of the crystalline phase in the glass matrix showed remarkable effect on band gap which decreases to semiconducting range.     

Exploring,Tuning, and Exploiting the Basicity of Hydrotalcites for Applications in Heterogeneous Catalysis

Basic catalysis! The basic properties of hydrotalcites (see picture) make them attractive for numerous catalytic applications. Probing the basicity of the catalysts is crucial to understand the base‐catalysed processes and to optimise the catalyst preparation. Various parameters can be employed to tune the basic properties of hydrotalcite‐based catalysts towards the basicity demanded by each target chemical reaction.

     

Correlation among electronic polarizability, optical basicity and interaction parameter of Bi2O3–B2O3 glasses

For optical basicity and electronic polarizability, the previous studies basically concentrate on the wavelength range of the visible light region. However, heavy metal oxides glasses have a reputation of being good materials for infrared region. In this study, new data of the average electronic polarizability of the oxide ion _O^2-, optical basicity Λ and Yamashita–Kurosawa's interaction parameter A of Bi₂O₃–B₂O₃ glasses have been calculated in a wavelength range from 404.66 to 1083.03 nm. The present investigation suggests that both _O^2- and Λ increase gradually with increasing wave number, and A decreases with increasing wave number. Furthermore, close correlations are studied among _O^2-, Λ, A and refractive index n in this paper. Particularly, it has been found that a quantitative relationship between electronic polarizability and optical basicity is observed in a wavelength range from 404.66 to 1083.03 nm. Our present study extends over a wide range of _O^2-, Λ and A values.     

Donor number estimation for oxygen- and nitrogen-containing solvents via proton NMR shift of chloroform

A linear correlation was determined for oxygen- and nitrogen-containing solvents between the proton NMR shift of chloroform, dilute in a solvent, and the donor number (DN) of that solvent. Results are given for water and for 13 organic solvents. The best straight line is given by DN=7.4–16.6 (CHCl ₃ ) where (CHCl ₃ ) is the shift of pure chloroform relative to that of chloroform in dilute solution. Donor numbers of several solvents were estimated from the correlation.