Alkaline Hydrolytic Pathway of the Antitumor Drug,Cyclophosphamide

Abstract

In an attempt to clarify the alkaline hydrolytic pathway of the antitumor agent, cyclophosphamide (CP), the time course of its degradation was monitored by ³¹P NMR in 0.5 M KOH solution. After 16 hr at 25°C. 70% of CP is hydrolyzed (t_½ 9 hr) leading to a mixture of 8 phosphorated compounds. among them only 4 represented more than 5% of the initial CP. The chemical shifts and the intensities of these compounds were as follows: 1 1 .1 ppm. 30% of the initial CP (compound 1); 9.5 ppm, 12% (compound 2); 6.4 ppm, 9% (unknown) and 4.8 ppm, 9% (compound 3). The structures of compounds 1–3 were identified by NMR (13C and IH) and mass spectrometry after their isolation. The major degradation compound formed, the nine-membered ring compound I, was also observed during CP hydrolysis at neutral or moderately acid pHsill and was detected in urine of patients treated with CP[2] Compounds 2 and 3 were also formed during the hydrolysis of compound I in 0.5 M KOH solution. Based on the formation in time of the 31P NMR signals in KOH solutions of CP and compound I, the following scheme was established for the major degradation alkaline pathway of CP.     

Alkaline Hydrolysis of the Cytostatic Drug,Ifosfamide, and its N-Dechloroethylated Metabolites

Abstract

I fosfamide (IF) is an alkylating antitumor agent used in the treatment of solid tumors. Up to 50% of IF administered to patients undergoes an oxidative N-dealkylation reaction resulting in the loss or one, other or both chloroethyl side chain(s) to produce 2- or 3-dechloioethylIF (ZDCIF, 3DCIF) or 2,3-didechloroethyllF (DDCIF). The hydrolytic pathway of these four oxazaphosphorines has been studied earlier but only at acidic and neutral pHs^[l] In the present work, we monitored their time courses of hydrolysis at basic pHs using phosphorus-3 1 NMR. The structures of the compounds formed were determined by NMR (13C and 1H) and mass spectrometry. The results are reported in the following scheme.     

Characterization of the interphase in an aluminium/epoxy joint by using controlled pressure scanning electron microscopy coupled with an energy dispersive X-ray spectrometer

The aim of this work is to introduce the use of low vacuum scanning electron microscopy (LVSEM) coupled with an X-ray energy dispersive spectrometer (EDS) in the field of structural adhesives, more precisely aluminium/epoxy resin assembly. Such assembly is characterized by the creation of an interphase resulting from the metal diffusion inside the resin during cross-linking. As the performance of the final bond is strongly links by the interphase properties, fine characterization of this interphase, in particularity the evaluation of its thickness is essential to understand the macroscopic properties of the adhesive assembly. First, the EDS acquisition parameters were investigated in order to limit the sample/resin damage/degradation due to the incident electrons beam irradiation. Then a specific methodology of stacked profiles was defined to improve the precision of the measures. To evaluate the true Al diffusion profile, the impact of the interaction volume of incident electron in the material on the Al signal variation during the interface crossing was calculated and the effect of the gas pressure on the electron beam characteristic and so on the measured profiles was examinated.According to our developed methodology and data treatments, Al diffusion profile was interpreted and interphase thickness was qualitatively determined by comparison with an experimental baseline. This innovative methodology promotes the use of LVSEM–EDS in the field of adhesive structural assemblies, but also, deals with a comparative study on the effect of the gas pressure on the EDS profile analysis.     

Influence of pH and Salt on the Photocrosslinking in Polyelectrolyte Thymine‐Containing Films

Photocrosslinking of thymine‐based water‐soluble polymer films was investigated at varying preparation conditions. Adding salt or decreasing the pH of the solution from which the films were cast resulted in the decreased efficiency of photoimmobilization, while increasing the pH was found to increase the photoimmobilization efficiency. A mechanistic rationale for the observed effects is proposed.     

On the flexibility of the design of multiple try Metropolis schemes

The multiple try Metropolis (MTM) method is a generalization of the classical Metropolis–Hastings algorithm in which the next state of the chain is chosen among a set of samples, according to normalized weights. In the literature, several extensions have been proposed. In this work, we show and remark upon the flexibility of the design of MTM-type methods, fulfilling the detailed balance condition. We discuss several possibilities, show different numerical simulations and discuss the implications of the results.     

Vector magnetisation measurements on thermally evaporated CoCr multilayers and solid solutions for spintronic applications

Structure, morphology and magnetic properties of thermally evaporated Co/Cr multilayers and of the solid solution obtained by isothermal treatment of the layered samples have been studied to evaluate their potential application as high-coercivity materials for hard spin injectors in spintronic devices such as magnetic tunneling junctions. The thermal treatment was performed in a partial pressure of inert gas to allow interdiffusion of Cr and Co. Structure and composition of the materials, as well as the effects of the annealing treatment, have been investigated by field emission scanning electron microscopy and energy-dispersive X-ray analysis. The magnetic configuration of these films was investigated by magnetic force microscopy. Simultaneous measurements of two mutually perpendicular magnetisation components were performed by means of a vector vibrating sample magnetometer, and showed that the in-plane coercivity can be increased by proper thermal treatment from less than 10 Oe to about 240 Oe. However, annealing may result in a loss of compositional and morphologic homogeneity of the films.     

Differentiation among dairy products by combination of fast field cycling NMR relaxometry data and chemometrics

A set of commercial milk and Sicilian cheeses was analysed by a combination of fast field cycling (FFC) nuclear magnetic resonance (NMR) relaxometry and chemometrics. The NMR dispersion (NMRD) curves were successfully analysed with a mathematical model applied on Parmigiano–Reggiano (PR) cheese. Regression parameters were led back to the molecular components of cheeses (water trapped in casein micelles, proteins and fats) and milk samples (water belonging to hydration shells around dispersed colloidal particles of different sizes and bulk water). The application of chemometric analysis on relaxometric data enabled differentiating milk from cheeses and revealing differences within the two sample groups of either cheeses or milk samples. Marked differences among cheeses were evidenced by statistical analysis of the sole quadrupolar peaks parameters, suggesting that these contain information on the nature of the milk used during cheese production. Hence, combination of FFC NMR and chemometrics represents a powerful tool to investigate alterations in dairy products.     

Dependence of the surface roughness of MAPLE-deposited films on the solvent parameters

Matrix-assisted pulsed laser evaporation (MAPLE) was used to deposit layers of poly(9,9-dioctylfluorene) (PFO) to study the relation between the solvent properties (laser light absorption, boiling temperature and solubility parameters) and the morphology of the deposited films. To this end, the polymer was diluted (0.5 wt%) in tetrahydrofuran—THF, toluene and toluene/hexane mixtures. The thickness of the films was equal to 70±20 nm. The morphology and uniformity of the films was investigated by Atomic Force Microscopy and by the photoluminescence emission properties of the polymer films, respectively. It is shown that, although the solubility parameters of the solvents are important in controlling the film roughness and morphology, the optical absorption properties and boiling temperature play a very important role, too. In fact, for matrices characterized by the same total solubility parameter, lower roughness values are obtained for films prepared using solvents with lower penetration depth of the laser radiation and higher boiling temperatures.     

Cross-linked natural IntegroPectin films from citrus biowaste with intrinsic antimicrobial activity

Cellulose - Pectin recovered via hydrodynamic cavitation (IntegroPectin) from lemon and grapefruit agri-food waste intrinsically containing antimicrobial bioactive substances (flavonoids, phenolic...