PubMed Health⌕ Search

Biomedical subjects

Paul Tordo

Publications and source records attributed to Paul Tordo.

At least 19 recordsLinked to original sources
PubMed2006

Nitroxide bound beta-cyclodextrin: is there an inclusion complex?

236CDTIPNO, a derivative of the persistent free radical TIPNO (1,1-dimethylethyl 2-methyl-1-phenylpropyl nitroxide) covalently bound to a permethylated-beta-cyclodextrin, was prepared. Self-association of 236CDTIPNO in water was proved by solvent- and competition-dependent EPR spectroscopy experiments with 2,6-di-O-Me-beta-cyclodextrin (DIMEB) and permethylated-beta-cyclodextrin (TRIMEB) as external hosts competing for accommodation of the TIPNO moiety. Temperature-dependent EPR spectra were simulated with a novel two-dimensional (field-temperature) EPR simulation program that afforded a full determination of the thermodynamic parameters characterizing the rate constants of the self-inclusion reaction derived from Arrhenius and Eyring models. This method allows separating the line broadening effects due to relaxation from a chemical exchange, even if only the fast exchange regime is accessible experimentally. The activation parameters for the forward and backward steps were consistent with an equilibrium between a nonassociated form and a weakly associated form, with activation free enthalpies for each reaction of around 34 kJ.mol(-)(1).

Journal Article↗
PubMed2006

Persilylated phosphoranyl radicals: the first persistent noncyclic phosphoranyl radicals.

Persistent noncyclic phosphoranyl radicals have been prepared and observed by electron paramagnetic resonance (EPR) for the first time. They were obtained by UV-photolysis of a solution containing a bis(trialkylsilyl) peroxide (R = Me, Et) and a tris(trialkylsilyl) phosphite (R = Me, Et, iPr). EPR parameters (a(P) approximately 100 mT) are typical of phosphoranyl radicals exhibiting a trigonal-bipyramidal structure, with the odd electron in an equatorial site. Analysis of the pseudo-first-order decay shows that these phosphoranyl radicals decay by S(H)2 homolytic substitution on the bis(trialkylsilyl) peroxide and by loss of a trialkylsilyloxyl radical (alpha-scission reaction). Both the S(H)2 and alpha-scission reactions depend on the steric bulk of the alkyl groups, that is, the bulkier the alkyl group, the slower the S(H)2 and alpha-scission reactions.

Journal Article↗
PubMed2006

Thermodynamic analysis of the chemical exchange of beta-phosphorylated cyclic nitroxides by using two-dimensional (temperature versus magnetic field) simulation of ESR spectra: the impact of labile solvent-solute interactions on molecular dynamics.

A complete thermodynamic characterization of the chair-to-chair interconversion in beta-diphosphorylated piperidine-N-oxyl radicals was achieved by means of the analysis of temperature-dependent ESR spectra. A new two-dimensional simulation method was developed with the coordinates temperature and magnetic field, in which the entire set of spectra was simulated simultaneously by adjusting the coefficients in the power expansion, giving the temperature-dependent ESR parameters and the thermodynamic and kinetic parameters determining the site populations and exchange rates, respectively. The new method promotes elimination of the ambiguities inherent in the spectroscopic determination of thermodynamic parameters. Labile solvent-solute interactions can strongly influence the chemical exchange, producing a complex network of symmetric and asymmetric interconversions. The solvent dependence of magnetic relaxation was also analyzed.

Journal Article↗
PubMed2006

Inclusion complexes of EMPO derivatives with 2,6-di-O-methyl-beta-cyclodextrin: synthesis, NMR and EPR investigations for enhanced superoxide detection.

The free radical trapping properties of eight 5-alkoxycarbonyl-5-methyl-1-pyrroline N-oxide (EMPO) type nitrones and those of 5,5-dimethyl-1-pyrroline N-oxide (DMPO) were evaluated for trapping of superoxide anion radicals in the presence of 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-CD). (1)H-NMR titrations were performed to determine both stoichiometries and binding constants for the diamagnetic nitrone-DM-beta-CD equilibria. EPR titrations were then performed and analyzed using a two-dimensional EPR simulation program affording 1 : 1 and 1 : 2 stoichiometries for the nitroxide spin adducts with DM-beta-CD and the associated binding constants after spin trapping. The nitroxide spin adducts associate more strongly with DM-beta-CD than the nitrones. The ability of the nitrones to trap superoxide, the enhancement of the EPR signal intensity and the supramolecular protection by DM-beta-CD against sodium L-ascorbate reduction were evaluated.

Electron Spin Resonance Spectroscopy↗
PubMed2006

Homolysis of N-alkoxyamines: a computational study.

During nitroxide-mediated polymerization (NMP) in the presence of a nitroxide R2(R1)NO*, the reversible formation of N-alkoxyamines [P-ON(R1)R2] reduces significantly the concentration of polymer radicals (P*) and their involvement in termination reactions. The control of the livingness and polydispersity of the resulting polymer depends strongly on the magnitude of the bond dissociation energy (BDE) of the C-ON(R1)R2 bond. In this study, theoretical BDEs of a large series of model N-alkoxyamines are calculated with the PM3 method. In order to provide a predictive tool, correlations between the calculated BDEs and the cleavage temperature (Tc), and the dissociation rate constant (k(d)), of the N-alkoxyamines are established. The homolytic cleavage of the N-OC bond is also investigated at the B3P86/6-311++G(d,p)//B3LYP/6-31G(d), level. Furthermore, a natural bond orbital analysis is carried out for some N-alkoxyamines with a O-C-ON(R1)R2 fragment, and the strengthening of their C-ON(R1)R2 bond is interpreted in terms of stabilizing anomeric interactions.

Journal Article↗
PubMed2005

Synthesis and spin-trapping behavior of 5-ChEPMPO, a cholesteryl ester analogue of the spin trap DEPMPO.

[structure: see text] 5-(Cholesteryloxyethoxyphosphoryl)-5-methylpyrroline N-oxide (5-ChEPMPO), a DEPMPO analogue bearing a cholesterol group on the phosphorus atom, has been prepared and used to trap peroxyl-, alkoxyl-, thiyl-, and carbon-centered radicals in organic solvent. The important steric hindrance in 5-ChEPMPO does not affect the properties of 5-ChEPMPO in comparison to DEPMPO for the spin trapping of an enantiopure linoleic acid hydroperoxide. The 5-ChEPMPO-OOL spin adduct was observed by ESR and confirmed by ESI-MS/MS experiments. The relaxation terms of the 5-ChEPMPO-lipid peroxyl spin adduct were compared with those of other peroxyl spin adducts, and it was shown that the cholesteryl group has only a weak influence on the exchange rate between adduct conformers.

Cholesterol↗
PubMed2005

Inclusion complexes of PBN-type nitrone spin traps and their superoxide spin adducts with cyclodextrin derivatives: parallel determination of the association constants by NMR titrations and 2D-EPR simulations.

(1)H NMR and electron paramagnetic resonance (EPR) titrations were used to determine the association constants of the complexes of alpha-phenyl-N-tert-butylnitrone (PBN) analogues and their superoxide spin adducts, respectively, with methylated beta-cyclodextrins. A 1:1 stoichiometry for the nitrones with randomly methylated beta-cyclodextrin and 2,6-di-O-methyl-beta-cyclodextrin and 1:1 and 1:2 stoichiometries for the corresponding cyclodextrin-nitroxide complexes were observed. After the superoxide radical spin trapping reaction, EPR titrations afforded the association constants of the corresponding cyclodextrin-nitroxide complexes. Two-dimensional EPR simulations indicated a bimodal inclusion of the nitroxide free radical spin adducts into the cyclodextrins. For all the nitrone-cyclodextrin and nitroxide-cyclodextrin complexes, the association constants were always higher for the nitroxide complexes than for the nitrone complexes. A cooperative system concerning the complexation of the nitroxide spin adduct with a cyclodextrin was evidenced by EPR titrations. The efficiency of the cyclodextrin inclusion technique to trap superoxide and to resist bioreduction by sodium l-ascorbate was also investigated.

Cyclodextrins↗
PubMed2005

Diastereoselective synthesis and ESR study of 4-phenylDEPMPO spin traps.

[reaction: see text] The cis and trans diastereoisomers of 5-(diethoxyphosphoryl)-5-methyl-4-phenylpyrroline N-oxide (4-PhDEPMPOt 8 and 4-PhDEPMPOc 9) were prepared stereoselectively and used as spin traps for hydroxyl and superoxide radicals. The spin adduct formed by reaction of the cis stereoisomer 9with superoxide radical anion exhibited an 8-line ESR spectrum, showing only a reduced alternating line width phenomenon. This spectrum is simpler than the 12-line spectrum of DEPMPO-OOH, which exhibits a strong alternating line width phenomenon. The half-life times of the 4-PhDEPMPOc-OOH and DEPMPO-OOH adducts were of the same order: 14.5 and 15.5 min, respectively.

Electron Spin Resonance Spectroscopy↗
PubMed2005

Assignment of the EPR spectrum of 5,5-dimethyl-1-pyrroline N-oxide (DMPO) superoxide spin adduct.

[structure: see text] Spin trapping consists of using a nitrone or a nitroso compound to "trap" an unstable free radical as a long-lived nitroxide that can be characterized by electron paramagnetic resonance (EPR) spectroscopy. The formation of DMPO-OOH, the spin adduct resulting from trapping superoxide (O(2)(*)(-)) with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), has been exploited to detect the generation of superoxide in a wide variety of biological and chemical systems. The 12-line EPR spectrum of DMPO-OOH has been either reported or mentioned in more than a thousand papers. It has been interpreted as resulting from the following couplings: A(N) approximately 1.42 mT, A(H)beta approximately 1.134 mT, and A(H)gamma(1H) approximately 0.125 mT. However, the DMPO-OOH EPR spectrum has an asymmetry that cannot be reproduced when the spectrum is calculated considering a single species. Recently, it was proposed that the 0.125 mT splitting was misassigned and actually results from the superimposition of two individual EPR spectra associated with different conformers of DMPO-OOH. We have prepared 5,5-dimethyl-[3,3-(2)H(2)]-1-pyrroline N-oxide (DMPO-d(2)), and we showed that the EPR spectrum of the corresponding superoxide spin adduct is composed of only six lines, in agreement with the assignment of the 0.125 mT splitting to a gamma-splitting from a hydrogen atom bonded to carbon 3 of DMPO. This result was supported by DFT calculations including water solvation, and the asymmetry of the DMPO-OOH EPR spectrum was nicely reproduced assuming a chemical exchange between two conformers.

Journal Article↗
PubMed2004

Factors influencing C-ON bond homolysis in alkoxyamines: unexpected behavior of SG1 (N-(2-methyl-2-propyl)- N-(1-diethylphosphono-2,2-dimethylpropyl)-N-oxyl)-based alkoxyamines.

Alkoxyamines and persistent nitroxides are important regulators of nitroxide-mediated radical polymerization (NMP). Since the polymerization time decreases with the increasing equilibrium constant K (k(d)/k(c)), i.e., the increasing rate constant k(d) of the homolysis of the C-ON bond between the polymer chain and the nitroxide moiety, the factors influencing the cleavage rate constants are of considerable interest. SG1-based alkoxyamines have turned out to be the most potent alkoxyamine family to use for NMP of various monomers. Therefore, it is of high interest to determine the factors which make SG1 derivatives better regulators than TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl) derivatives. Contrary to what we had observed with TEMPO derivatives, we observed two relationships for the plot E(a) vs BDE(C-H), one for the nonpolar released alkyl radicals (E(a) (kJ/mol) = -133.0 + 0.72BDE) and the other one for the polar released alkyl radicals (E(a) (kJ/mol) = -137.0 + 0.69BDE). However, for both families (SG1 and TEMPO derivatives), the rate constants k(d) of the C-ON bond homolysis were correlated to the cleavage temperature T(c) (log(k(d)(s(-)(1))) = 1.51 - 0.058T(c)). Such correlations should help to design new alkoxyamines to use as regulators and to improve the tuning of NMP experiments.

Journal Article↗
PubMed2004

ESR study of spin-trapping with two glycosylated analogues of PBN able to target cell membrane lectins.

The spin trapping behaviour of the two galactosylated nitrones LAMPBN and TA1PBN, both of which are able to target cells through recognition by cell membrane lectins, were widely investigated on a variety of free radicals in aqueous media. The ESR spectra of the more amphiphilic nitrone, TA1PBN, were interpreted in the light of the LAMPBN trapping results. The spin adducts of nitrone TA1PBN, which may be better distributed inside the cell, were surrounded by two distinct environments due to the tensioactive organisation of the trap and gave two different ESR signals for each radical trapped.

Cell Membrane↗
PubMed2004

Diastereomeric excess upon cleavage and reformation of diastereomeric alkoxyamines.

The thermal reactions of several TEMPO and DEPN (N-(2-methylpropan-2-yl)-N-(1-diethylphosphono-2,2-dimethylpropyl)-aminoxyl) based alkoxyamines were studied by means of (1)H and (31)P NMR spectroscopy aiming to distinguish the contributions of diastereoselective homolysis and coupling to the total equilibrium diastereomeric distribution. The TEMPO-based compounds reveal no diastereomeric excess while DEPN based compounds show a moderate excess both upon homolysis and coupling. The diastereomeric preference of homolysis for DEPN-(propionate-like) adducts does not depend on the ester group and it is mainly affected by the size of beta-substituents. The diastereoselective coupling is sensitive to the total recombination rate constant k(c) and diastereoselectivity increases with the decrease of k(c). Small diastereoselective coupling is found in the recombination of DEPN with sec-butyl isobutyrate radical, where no prochiral centers are formed upon cleavage of corresponding alkoxyamine.

Amines↗
PubMed2003

Synthesis and preliminary biological evaluations of ionic and nonionic amphiphilic alpha-phenyl-N-tert-butylnitrone derivatives.

In this study we report the synthesis of a series of new amphiphilic compounds derived from alpha-phenyl-N-tert-butylnitrone (PBN). The nitrone function was fitted into the core of the molecule between its polar and apolar groups. The polar head consisted of a lactobionamide, an ammonium, or a carboxylate group. The hydrophobic part consisted of a hydro- or a perfluorocarbon chain. The hydrophobic chain was linked to the tert-butyl group of the PBN derivatives using an urethane, a thioether, or an amide bond. The impact of these different parameters on the hydrophilic lipophilic balance of these compounds and their spin trap activity were studied. The various ESR measurements indicated that the aromatic and tert-butyl functional groups of PBN did not affect its spin trap properties. Moreover, these compounds were found to increase the viability of cultured human skin fibroblasts harboring the neurogenic ataxia retinitis pigmentosa mutation and presenting a severe ATPase deficiency.

Adenosine Triphosphatases↗
PubMed2003

Deuterated analogues of the free radical trap DEPMPO: synthesis and EPR studies.

Three analogues of 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DEPMPO, 1) labelled with two (1-d2), five (1-d5) or seven (1-d7)2H were synthesized and used to trap the tert-butylperoxyl radical. The EPR spectra of 1-d2-OOBu(t) and 1-d7-OOBu(t) spin adducts exhibited more straightforward patterns and better signal to noise ratio than those obtained with 1 or 1-d5. The use of the easily available 1-d2 as spin trap could help significantly the analysis of the EPR signals when the signal of either superoxide or alkylperoxyl spin adduct is superimposed with the signals of other spin adducts.

Journal Article↗
PubMed2003

Characterization of the high resolution ESR spectra of the methoxyl radical adducts of 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide (DEPMPO).

Spin-trapping investigators are largely limited by the instability of the radical adducts. Spin trap 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide (DEPMPO) forms very stable alkoxyl radical adducts. However, the presence of two chiral centers in the DEPMPO alkoxyl radical adduct results in two diastereomers with distinctive ESR spectra, which complicates the interpretation of the ESR spectra. We have analyzed the high resolution ESR spectra of the DEPMPO/*OCH3 radical adduct. DEPMPO/*OCH3 has been synthesized by the nucleophilic addition of alcohols to DEPMPO. The electron spin resonance (ESR) spectrum of DEPMPO/*OCH3 in oxygen-free methanol solution reveals superhyperfine structure with hyperfine coupling constants as small as 0.3G. In order to simplify the analysis of the electron spin resonance (ESR) spectrum, we synthesized the DEPMPO/*OCD3 radical adduct. Computer simulation of the DEPMPO/*OCD3 ESR spectrum revealed two diastereomers. Hyperfine coupling constants of gamma-protons and 17O from the -OCH3 group were also determined. ESR spectra of DEPMPO/*OCH3 in phosphate buffer have also been characterized. The presence of specific hyperfine couplings from the -OCH3 group can be used for the unambiguous identification of the DEPMPO/*OCH3 radical adducts. We suggest that the analysis of high resolution ESR spectra can be used for the unambiguous characterization of DEPMPO radical adducts.

Alcohols↗
PubMed2002

Spin trapping of superoxide in the presence of beta-cyclodextrins.

The trapping of superoxide anion with DMPO and DEPMPO has been carried out in the presence of a methylated beta-cyclodextrin, Me-beta-CD; inclusion of the spin adducts in the cavity of Me-beta-CD resulted in a seven-fold increase of their half-life (t1/2 = 96 min for DEPMPO-superoxide spin adduct) and in their protection towards glutathione peroxidase (Gpx) and also ascrobate anion in the case of DEPMPO.

Cyclodextrins↗
PubMed2002

Observation of protein-derived (BSA) oxygen-centered radicals by EPR spin-trapping techniques.

Electron paramagnetic resonance (EPR) spin-trapping experiments, employing the novel spin-trap DEPMPO, provide evidence for the formation of protein-peroxyl radicals from the reaction of bovine serum albumin (BSA) or lysozyme with HO. in the presence of O2. Spin-trapping leads to the detection of anisotropic spectra of partially immobilized protein-peroxyl spin-adducts; positive identification is based on a novel spectrum simulation approach (through which broadened anisotropic spectra are simulated and compared with experiment) and by comparison of results with those obtained when MeO2. is trapped and the adduct frozen in a solid matrix.

Animals↗