Peracid-mediated n-oxidation and rearrangement of dimethylphosphoramides: plausible model for oxidative bioactivation of the carcinogen hexamethylphosphoramide (HMPA)

Dimethylphosphoramides react with $\text{m}$-chloroperoxybenzoic acid (MCPBA) in anhydrous acetone to yield the previously unknown $\text{P}$-dimdethylamino-oxyphosphonous derivatives $\text{via}$$\text{N}$-oxidation and rearrangement. Further MCPBA oxidation yields formaldehyde and nitrosomethane, isolated as its $\text{trans}$-dimer. These reactions provide a possible biomimetic model for the metabolic activation of hexamethylphosphoramide as a mutagen and carcinogen.     

Compatibility study of tobramycin and pharmaceutical excipients using differential scanning calorimetry,FTIR, DRX,and HPLC

Differential scanning calorimetry (DSC), isothermal stress testing–Fourier transform infrared spectroscopy (IST–FTIR), isothermal stress testing–high-performance liquid chromatography, and powder X-ray diffraction (PDRX) were used as screening techniques for assessing the compatibility of tobramycin with some currently employed ophthalmic excipients. In the first phase of the study, DSC was used as a tool to detect any interaction. The absolute value of the difference between the enthalpy of the pure tobramycin melting peak and that of its melting peak in the different analyzed mixtures was chosen as a parameter of the drug–excipient interaction degree. DSC results demonstrated that benzalkonium chloride, monobasic sodium phosphate, boric acid, edetate disodium, sodium metabisulfite, thimerosal, and potassium sorbate interact with tobramycin. Taking into account these results, it could be suggested that some of the changes observed in the IST–FTIR spectra of binary blends of tobramycin and some of the excipients would account for a possible interaction between the mixture component. In this study, PDRX did not provide much information, since only tobramycin–thimerosal interactions could be detected. DSC and IST–FTIR are suitable and simple methods for the detection of potential incompatibilities between active pharmaceutical ingredient (API) and excipients.

     

Reaction of Proposed Phosphorothiolate S-Oxide Intermediates with Alcohols

Abstract

S-Oxide 2 is an extremely reactive intermediate. Its phosphorylation vs rearrangement rates, strongly depend upon the nature of the nucleophile.     

Studies of the Synthesis of Diethyl Cyclopropylphosphonate and Its Thio and Seleno Analogs

Two methods for the synthesis of unsubstituted diethyl cyclopropylphosphonate are described. One method is a reaction between cyclopropylmagnesium bromide and diethyl chlorophosphite to give diethyl cyclopropylphosphonite, followed by oxidation with sodium periodate to the corresponding phosphonate. Alternatively, diethyl cyclopropylphosphonite was reacted with elemental sulfur or selenium to give the thio and seleno analogs, respectively. The second method involves exclusive 1,3‐elimination of HBr from diethyl 3‐bromopropylphosphonate. This method can be directed to either the 1,2‐ or the 1,3‐elimination reaction, leading to propenylphosphonate or cyclopropylphosphonate, depending on the solvent used.     

Deterministic Mathematical Modelling for the Spatial Allocation of Multi-Categorical Resources: with an Application to Real Health Data

This paper presents some mathematical formulations of deterministic non-linear optimization models for planning the spatial distribution of public service facilities and their utilization. The modelling is performed as a function of multi-categorical resource types and the consumer's zone of residence over a large geographical domain. The mathematical solution to the deterministic model, its parameter estimation by log-linear regression, and some preliminary results of simulation for a Massachusetts hospital database are presented.     

The dislocation distribution in copper after fatigue at elevated temperature

A qualitative explanation for the absence of hardening in the saturation region of the fatigue-hardening curve is proposed on the basis of observations of the spatial dislocation distribution and the distribution of Burgers vectors.We are indebted to the Ministry of Technology for financial support for this work. We are also very grateful to Dr. A. Gittins of the Central Electricity Research Laboratories who provided us with a number of fatigue specimens used in some preliminary experiments and to Dr. Saimoto of Queens University who provided details of his unpublished work.     

Energy transfer in constant period free-electron lasers

A simple single particle model of a free-electron laser (FEL) amplifier has been used in a computer simulation to determine the maximum fractional conversion of electron kinetic energy to laser energy. The simulation results can be represented by a single universal curve. A simple scaling relationship for the length of the optimized constant period helix together with the universal curve permit one to predict maximum fractional energy conversion for any set of values of initial electron energy, initial laser intensity, magnetic field amplitude, and magnet period.     

Photoelectric energy distributions associated with interconduction band transitions in Cu,Ag and Au

The photoelectric energy distributions associated with direct transitions between the bulk conduction bands in the three noble metals have been calculated using the interconduction band structures determined in analyses of the piezo-optical response. The good overall agreement between the calculated and observed line shapes strongly corroborates the piezo-optical determinations. However, small discrepancies for initial energies around the Fermi energy are noted which we believe can not be attributed to direct transitions in the bulk.     

Selective site controlled nucleophilic attacks in 5-membered ring phosphate esters: unusual C-O vs. common P-O bond cleavage

Clean endocyclic C-O bond cleavage has been achieved in the reactions of 5-membered phosphate triesters with various nucleophiles.