Influence of medium and temperature on the hydrolysis kinetics of propacetamol hydrochloride: determination using derivative spectrophotometry

Propacetamol hydrochloride (PRO) is a water-soluble prodrug of paracetamol (PA) which can be parenterally administered as analgesic for the treatment of postoperative pain, acute trauma, and gastric and/or intestinal disorders where oral administration is not possible. In these circumstances, PRO can be administered in physiologic or glucose solutions since it is rapidly and quantitatively hydrolyzed into PA by plasma estearases. We have studied the degradation kinetics of PRO in 5% glucose and 0.9% saline solutions at 4 degrees C and 25 degrees C (storage and room temperatures, respectively). The analytic technique used to determine PRO and PA quantitatively was first-derivative spectrophotometry. The degradation process of PRO can be best fitted to a second-order kinetics with independence of the medium used (saline or glucose solution). The hydrolysis kinetics of PRO conversion into PA depends on the temperature but not on the assay medium (saline or glucose solution). The degradation rate constants obtained for PRO were approximately 4.5 times higher at 25 degrees C than at 4 degrees C. The values of t(90%) for PRO were 3.17 h and 3.61 h at 25 degrees C, and 13.42 h and 12.36 h at 4 degrees C when the tests were performed in 5% glucose and 0.9% saline solutions, respectively.     

A new lignan glycoside and other constituents from Cephalaria ambrosioides

A new lignan glycoside, 1,5-dihydroxy-2-(4"-beta-D-glucopyranosyloxy-3"-methoxyphenyl)-6-(4'-hydroxy-3'-methoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane, named ambrosidine ([structure: see text]), along with seven known compounds (four iridoids and three hydroxycinnamic esters) were isolated from the roots of Cephalaria ambrosioides. The structures of these compounds were determined by use of NMR and MS techniques and by chemical transformations. The cytotoxic activity of the novel compound [structure: see text] was evaluated against five human solid tumour cell lines.     

A new insight on the structural changes of linear quadrupole liquids

Molecular-dynamics simulations for linear quadrupole liquids are presented. The study is carried out for two different molecular lengths at constant density and a number of temperatures and quadrupole moments. All the simulated thermodynamic states correspond to the condensed phases and some of them show typical features of a solid structure. Furthermore, a change on the preferred intermolecular orientation in the liquid phase is observed from a shifted parallel molecular arrangement to a perpendicular orientation as the quadrupole raises. This change depends on the quadrupole moment as well as on the molecular length and is put in relation with the solid structure of different "diatomic" molecules such as nitrogen, ethane, and acetylene. The appearance of a plastic solid phase at low quadrupole moment and density is also justified. A thoroughly discussion about the availability of classical perturbation theories for this kind of systems is presented.     

Search of ligands for the amyloidogenic protein beta2-microglobulin by capillary electrophoresis and other techniques

Beta2-microglobulin (beta2-m) is a small amyloidogenic protein normally present on the surface of most nucleated cells and responsible for dialysis-related amyloidosis, which represents a severe complication of long-term hemodialysis. A therapeutic approach for this amyloidosis could be based on the stabilization of beta2-m through the binding to a small molecule, and consequent inhibition of protein misfolding and amyloid fibril formation. A few compounds have been described to weakly bind beta2-m, including the drug suramin. The lack of a binding site for nonpolypeptidic ligands on the beta2-m structure makes it difficult for both the identification of functional groups responsible for the binding and the search of hits to be optimized. The characterization of the binding properties of suramin for beta2-m by using three different techniques (surface plasmon resonance, affinity CE (ACE), ultrafiltration) is here described and the results obtained are compared. The common features of the chemical structures of the compounds known to bind the protein led us to select 200 sulfonated/suramin-like molecules from a wider chemical library on the basis of similarity rules, so as to possibly single out some interesting hits and to gain more information on the functional groups involved in the binding. The development of screening methods to test the compounds by using ultrafiltration and ACE is described.     

Improvement of an old spectrophotometric method for the microdetermination of ascorbic acid by the use of a micellar medium

₃]²⁺. Whereas the initial method is carried out in an aqueous solution, the improved one employs an aqueous micellar medium formed by the cationic surfactant cetylpyridinium bromide (CPBR). The λmax in both methods is the same, i.e. 510 nm. The mean apparent molar absorptivity (ɛ) and Sandell’s sensitivity (Ss) were calculated as ɛ=2.10×10⁴ Lmol^-1 cm^-1 and Ss=8.37 ng cm^-2 for the initial procedure, and ɛ=2.62×10⁴ Lmol^-1 cm^-1 and Ss=6.72 ng cm^-2 for the improved one. The regression line equation for the improved method was: A=1.487×10^-1C −1.415×10^-2 (r=0.9998). The accuracy and the precision of the improved method were investigated and the conclusions were satisfactory. The results obtained for ASCA by both the described method and an official one, were statistically compared by means of the Student’s t-test and by the variance ratio F-test; and no significant difference was observed. Received: 15 January 1996/Revised: 7 March 1996/Accepted: 13 March 1996     

A new bis(3-hydroxy-4-pyridinone)-IDA derivative as a potential therapeutic chelating agent. Synthesis, metal-complexation and biological assays

A new bis(3-hydroxy-4-pyridinone) derivative of iminodiacetic acid, imino-bis(acetyl(1-(3'-aminopropyl)-3-hydroxy-2-methyl-4-pyridinone)), IDAPr(3,4-HP)(2), has been prepared and studied in its interaction with a set of hard metal ions. This tetradentate ligand presents a much higher chelating efficiency for trivalent hard metal ions (Fe, Ga, Al) than the monodentate derivative Deferriprone, namely at the diluted conditions prevailing in physiological conditions and at low clinical doses. A similar behaviour was also observed for the complexation with Zn(II) but at a significantly lower extent. This compound presents a moderate hydrophilic character at physiological pH (logD=-1.72). In vivo assays showed much more rapid clearance of (67)Ga from most tissues of metal-loaded mice than the drug Deferriprone and the radioactivity excretion occurs mostly through the kidneys. Therefore, results from in vitro and in vivo studies indicated good perspectives for this compound to be a potential decorporating agent for hard metal ions in overload situations without depletion of essential metal ions such as zinc.     

Crystallization specifics of carbonate-hydroxylapatite in the presence of strontium-containing agents

The effect of strontium-containing compounds on the crystallization of strontium-substituted carbonate- hydroxylapatite from a human synovial fluid prototype was studied. Synthesis products were investigated by FT-IR spectroscopy, X-ray diffraction, and differential thermal analysis. The amount of strontium in samples was determined by atomic emission analysis. For the synthesized phases, crystallite sizes were calculated by the Selyakov–Sherer formula, and the unit cell parameters were determined. The kinetically stable brushite phase was shown to transform into the more thermodynamically stable phase of strontium-containing carbonate-hydroxylapatite with increasing exposure time of precipitates under the mother solution. Some schemes were proposed for phase transformations under heat treatment.     

Reactivity of B‐Xanthyl N‐Heterocyclic Carbene‐Boranes

The synthesis and reactivity of mono‐ and bis‐S‐xanthyl NHC‐boranes is reported. The new NHC‐boranes are prepared through nucleophilic exchange at boron from either mono‐ or bis‐triflyl NHC‐boranes, themselves obtained by protolysis of the NHC‐BH₃ starting compounds. The B?H bond of the S‐xanthyl NHC‐boranes can be cleaved both homolytically and heterolytically, albeit the latter is more synthetically useful. The S‐xanthyl NHC‐boranes can reduce both aldehydes and imines. The B?S bond can also be cleaved homolytically. Under UV irradiation, the S‐xanthyl NHC‐boranes generate NHC‐boryl radicals that can initiate radical polymerizations of acrylates.     

Structural and phase characteristics of the diamond/matrix interfacial zone in high-resistant diamond composites

The structural-phase state of the contact zone and the factors that influence on the strength of diamond retention in the diamond carbide composites were determined. Composites were obtained by the new hybrid technology that eliminates the reheating of the metalized coating. The elaborated technology combines the thermal diffusion metallization of a diamond and the sintering by the scheme of self-dosed impregnation in a one-stage technological cycle. By the methods of electron microscopy, X-ray diffraction analysis, and Raman spectroscopy the structural and phase characteristics of the interphase boundary were investigated. The improvement of chemical and mechanical adhesion between the diamond and carbide matrix was obtained. It was shown that the specific productivity of the samples with a metalized diamond component is 39% higher than those without metallization.