Mixed Azines of Naloxone with Dihydromorphinone Derivatives

The mixed azines 4 and 5 were prepared by reaction of naloxazone ( 2 ) with either oxymorphone ( 6 ) or 14-O-methyloxymorphone ( 7 ) and tested in vitro using opioid receptor binding assays and in vivo using the AcOH-writhing test in mice. Compound 4 was found to be a partial agonist, while compound 5 was a potent opioid agonist with higher potency than morphine.     

Theoretical conformational analysis of a simple sulphilimine model

The topomerization (bond rotation andS-pyramidal inversion) of a simple sulphilimine model, H₂SNH has been studied with the aid ofab initio SCF MO calculations. The highest rotation barrier occurs when the H₂SN moiety is planar, < HSN = 120 °. The maxima of the inversion crossections occur at the planar conformation for all rotation angles α as expected, however, the minima belong to different values when α is varied. The minimum energy path between the two lowest minima of the conformational energy surface consists of a pure inversion section and a section which is mostly rotation. The optimum values of the < HSN bond angles are significantly smaller than the corresponding < RSN bond angles of sulphilimines of bulkierR substituents.     

Cyclic sulfonium salts with S ... O interactions 2. Molecular structures with six-membered rings

1-[2-(N-methylcarbamoyl)phenyl]-3H-2,1-naphto-(1,8-d,e)-oxathiin-1-ium chloride (2), 1-[2-(N-methylcarbamoyl)-phenyl]-2-methyl-3-oxo-3H-1, 2-naphto-(1,8-d,e)-thiazin-1-ium chloride (3), 1-[8-(N-methylcarbamoyl)naphtyl]-2-methyl-3-oxo-3H-1, 2-naphto-(1,8-d,e)-thiazin-1-ium chloride (4) and 1-(8-carboxylatonaphtyl)-2-methyl-3-oxo-3H-1,2-naphto-(1,8-d,e)-thiazin-1-ium dipolar ion (5) cyclic sulfonium salts were prepared and their chemical properties investigated (spirosulfurane-formation, hydrolysis). The molecular structures obtained from x-ray diffraction can be described with a considerably distorted trigonal bipyramidal arrangement of the ligands about the sulfonium center, with O/N—S ... O=apical angles of 173.9, 164.9, 156.6, and 159.0°, as well as with S—O/N apical bond lengths of 1.648, 1.671, 1.664, and 1.682 Å. The structures exhibit relatively short S ... O close contacts with interatomic distances of 2.253, 2.448, 2.795, and 2.619 Å.     

Acid-catalysed hydrolysis of S(IV)N bond in N-sulphonyl sulphilimines—I : Mechanism and substituent effect

The acid-catalysed hydrolysis of sulphilimines of XC₆H₄(Me)SNTs and MePhSNSO₂C₆H₄Y type has been studied by a kinetic method in moderately concentrated (1–6 M) aqueous H₂SO₄ and HClO₄ solutions. The rate law: rate = k_ψ[sulphilimine] is valid for hydrolysis leading to sulphoxides and sulphonamides. The dependence of k_ψ on acidity, temperature and substituents X and Y has been measured and interpreted, ?_X, ?_Y and ΔS^‡ data (+ 1·19, + 1·00 and −18·7- - 22·6 e.u., resp) show that the nucleophilic attack of water on the positively polarized S(IV) atom of protonated sulphilimines can be regarded as the rate-determining step of the hydrolysis. From φ parameters (0·94−1·5) calculated for the hydrolysis of MePhSNTs it follows that water participates in the reaction as a nucleophile and proton-transfer agent.     

On the character of operational solutions of the time-fractional diffusion equation

The nonhomogeneous time-fractional diffusion equation is analyzed in the frames of the Mikusiński calculus. The exact and the approximate solution of the considered problem are constructed and their character is analyzed.     

Modeling rate-controlling solvent effects. The pericyclic meisenheimer rearrangement of N-propargylmorpholine N-oxide

The activation parameters of the pericyclic Meisenheimer rearrangement and a competitive rearrangement of N-propargylmorpholine N-oxide were determined by experimental and computational methods. A number of aprotic and protic solvents of different polarities and hydrogen bond-forming abilities and the roles of electron-pair acceptor additives were investigated. The reaction kinetics were followed by means of NMR. In protic solvents, isotope-labeling experiments revealed a novel inverse secondary kinetic isotope effect (k(H)/k(D) about 0.8) for the rate-determining cyclization step, probably occurring because of a C(sp) --> C(sp(2)) change in hybridization at the reaction center. In molecular computations at the B3LYP/6-31++G(d,p) level of theory, implicit, explicit, and joint explicit-implicit solvent models were used. The explicit-implicit model and molecular dynamic simulations gave the most accurate results. The components of the rate-controlling solvent effect are discussed, and general equations are proposed for accurate prediction of the solvent-dependent activation parameters.     

Stereochemistry of sulphilimine and sulphoxide formations in reactions of sulphides with chlorinating agents and nucleophiles

The stereochemistry of sulphilimine and sulphoxide formations was studied in reactions of chiral alkyl aryl sulphides either with N-chloro toluenesulphonamides or with t-BuOCl followed by TsNH^?Na⁺ both leading to unequal amounts of diastereomers of products. Configurations were determined by spectroscopic methods and stereospecific reactions, and diastereomeric product distributions were measured by hplc. Results are discussed and reaction pathways are suggested for the product-controlling steps. From sulphonium type intermediates sulphoxides are formed by hydrolysis with inversion, while sulphilimines with retention or inversion of configuration at sulphur depending on manner of attack by N-nucleophile. In reactions of ortho-carboxy-substituted sulphides both sulphilimines and sulphoxides are formed from cyclic acyloxysulphonium intermediates with inversion of configuration at sulphur.     

Small-Maturity Asymptotics for the At-The-Money Implied Volatility Slope in Lévy Models

We consider the at-the-money (ATM) strike derivative of implied volatility as the maturity tends to zero. Our main results quantify the behaviour of the slope for infinite activity exponential Lévy models including a Brownian component. As auxiliary results, we obtain asymptotic expansions of short maturity ATM digital call options, using Mellin transform asymptotics. Finally, we discuss when the ATM slope is consistent with the steepness of the smile wings, as given by Lee’s moment formula.     

High resolution applications of laser-induced breakdown spectroscopy for environmental and forensic applications

Laser-induced breakdown spectroscopy (LIBS) has been used in the elemental analysis for a variety of environmental samples and as a proof of concept for a host of forensic applications. In the first application, LIBS was used for the rapid detection of carbon from a number of different soil types. In this application, a major breakthrough was achieved by using a multivariate analytical approach that has brought us closer towards a “universal calibration curve”. In a second application, it has been demonstrated that LIBS in combination with multivariate analysis can be employed to analyze the chemical composition of annual tree growth rings and correlate them to external parameters such as changes in climate, forest fires, and disturbances involving human activity. The objectives of using this technology in fire scar determinations are: 1) To determine the characteristic spectra of wood exposed to forest fires and 2) To examine the viability of this technique for detecting fire occurrences in stems that did not develop fire scars. These examples demonstrate that LIBS-based techniques are inherently well suited for diverse environmental applications. LIBS was also applied to a variety of proof of concept forensic applications such as the analysis of cremains (human cremation remains) and elemental composition analysis of prosthetic implants.