Yves Leroux

A mild and efficient one-pot synthesis of 1-hydroxymethylene-1,1-bisphosphonic acids. Preparation of new tripod ligands

Abstract A simple and efficient one-pot procedure for synthesis of 1-hydroxymethylene-1,1-bisphosphonic acids by reaction of acyl chlorides and tris(trimethylsilyl)phosphite is described. This method was applied to the synthesis of new phosphonated chelating tripod ligands.

Bisphosphonate chelating agents: Coordination ability of 1-phenyl-1-hydroxymethylene bisphosphonate towards Cu2+ ions

Potentiometric and EPR data allow for evaluation of the coordination equilibria in the Cu(2+)-bisphosphonate system. The bisphosphonic ligand was found very efficient in Cu(2+) chelation with formation of monomeric and dimeric species. Two phosphonate groups are basic binding sites for metal ion. The involvement of hydroxyl in metal ion coordination is also likely, especially when one phosphonate is protected by dimethyl ester. As the metal bound phosphonate groups are relatively bulky (six oxygens) and their negative charge above pH 4 is high (four per ligand) the equimolar species is a dominant complex at physiological pH.

Bisphosphonate chelating agents: complexation of Fe(III) and Al(III) by 1-phenyl-1-hydroxymethylene bisphosphonate and its analogues

Abstract Bisphosphonate ligands were found to be very efficient chelating agents for both Al(III) and Fe(III) ions. Potentiometric and spectroscopic data allow evaluation of the coordination equilibria in the solutions containing 1-phenyl-1-hydroxymethylene bisphosphonate and its three analogues with Al(III) and Fe(III) ions. At pH below 4 the bis-complexes are formed, while above pH 4 the major species are equimolar, monomeric for Al(III) or dimeric for Fe(III) complexes. The large steric hindrance and high electric charge are the major factors influencing the complex stoichiometry. The formation of the dimeric Fe(III) with μ-oxo or μ-hydroxo bridges were supported by measurements of the magnetic moments using Evans’ method. The stabilities of the complexes formed are higher than those found for deferiprone, L1, used in clinics as a chelating agent.

Synthese et structure d'un trialcoxy-1,1,1 phospholev premier modele pentacoordine contenant le cycle phosphole

Abstract Addition of a trivalent phosphorus compound to dimethyl acetylenedicarboxylate gives a carbanionic species which can be trapped by dimethyl acetylenedicarboxylate; a trialkoxy-1,1,1 phosphole v is obtained.

Aminoglycoside and glycopeptide renal toxicity in intensive care patients studied by proton magnetic resonance spectroscopy of urine.

ObjectiveAminoglycoside and glycopeptide antibiotics are responsible for renal toxicity. In most cases, the nephrotoxicity is limited to a reversible tubular injury, but an acute and sustained renal failure may occur. The aim of our study was to explore the renal function of patients given these antimicrobial agents with proton magnetic resonance spectroscopy of urine. This technique is able to detect, in urine samples, a wide range of metabolites reflecting renal tubular function. The variables assessed by magnetic resonance spectroscopy were compared with the routine markers of renal function: creatinine, urea, and 24-hr urine volume. DesignProspective clinical study. SettingIntensive care unit. PatientsAll patients in an intensive care unit receiving an aminoglycoside and/or a glycopeptide were included in the study if they presented with signs of renal dysfunction. All experiments were performed on urine samples collected for the routine follow-up of these patients. InterventionProton spectra were acquired with water suppression, and the peak intensity of each metabolite was reported in relationship to the intensity of the creatinine peak. Measurements and Main ResultsThe ratio values obtained by magnetic resonance spectroscopy were compared with the values of creatininemia and blood urea obtained routinely by biochemistry and with the value of the 24-hr urine volume by logistic regression and general linear models. This statistical analysis showed that the ratio of dimethylamine to creatinine was highly correlated with creatininemia. ConclusionsDimethylamine is an osmolyte released from the medullar region of the kidney. Thus, our study demonstrated that nephrotoxicity from aminoglycosides and glycopeptides is not limited to proximal tubular toxicity but also may involve the medullar region (Henle loop and collecting duct) of the nephron.

Etude par RMN des organomagnesiens heterocycliques de la serie du furanne, du thiofene, du selenofene et de la pyridine

Abstract Various Grignard reagents, derived from bromopyridine, furan, thiophene and selenophene have been synthesized via an exchange reaction between heterocyclic bromides and isopropylmagnesium chloride. The NMR parameters were determined and related to the electronic structure; an “ ortho effect” is evidenced in the pyridine derivatives but is not apparent in the pentagonal heterocycles. The exchange mechanisms were studied and the activation functions were evaluated for the rate-determining step of the formation and for the Schlenk equilibrium.

Synthesis of New Phosphonated Tripod Ligands as Putative New Therapeutic Agents in the Chelation Treatment of Metal Intoxications

In a quest for new chelation therapy drugs for the treatment of intoxication by actinides, some new phosphonated chelating tripod ligands have been synthesized. They have been obtained by means of a coupling reaction between a diethylphosphonoalkanoic acid activated with N,N′-disuccinimidyl carbonate (DSC) and a series of polyamines, with subsequent deprotection of the phosphonate groups.

Existence d'un dianion allénique derivant du méthoxy-3 phényl-1 propyne-1 synthèse de derivés alléniques éthers fonctionnels et de composés carbonylés α,β éthylèniques

Abstract 3-Methoxy-1-phenyl-1-propyne treated at −75° by two equivalents of butyl-lithium in ether gives a dianion whose structure is allenic. This dianion offers various possibilities of selective mono and bialkylation rections with excellent yields. Hydrolysis of allenic ether derivatives liberates α-ethylenic aldehydes or ketones.

1-Hydroxyalkane-1,1-diyldiphosphonates as potent chelating agents for metal ions. Potentiometric and spectroscopic studies of copper(II) co-ordination

Potentiometric and spectroscopic (EPR and absorption) studies have shown that two phosphonic groups bound to the same carbon atom serve as a very powerful binding site for Cu2+ ion in spite of the very high negative charge centred on these groups. The steric effects as well as a high negative charge enforce unusual geometries around the metal ion and the formation of 1:2 complexes is less favourable. These features of the diphosphonic moiety mean that alkoxo-bridged dimer formation via the adjacent hydroxyl groups is less likely.

Trapping of carbanionic species synthesis of new salt-free ylids and phosphoranes

Abstract Syntheses of new salt-free ylids and phosphoranes by addition of a trivalent phosphorus compound with dimethylacetylene dicarboxylate in presence of a trapping reagent are described. The results are consistent with trapping of carbanionic species.