ESR study of the spin adducts of three analogues of DEPMPO substituted at C-4 or C-3

In the research program of some new derivatives of spin-trap DEPMPO (5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide) leading to various radical adducts with photogenic ESR signals, three phosphorylated pyrroline-N-oxides were studied in spin trapping. These nitrones were proved to trap a variety of free radicals to afford adducts presenting characteristic ESR signals enabling unambiguous identification of the radical species trapped. From the general patterns of the signals, the adduct geometries were determined. Two of the nitrones bore a hydroxylmethyl substituent (HM) on the pyrroline ring, either at C-3 or at C-4. The two diastereoisomers of nitrone 4-HMDEPMPO, whose synthesis has been already described, were separately studied. The isomer (4R*,5R*) of 4-HMDEPMPO afforded stereoselectively, with superoxide or peroxyl radicals, trans adducts versus the phosphoryl group, however, they formed two rotamer sets in chemical exchange. In comparison with DEPMPO adducts, the exchanges rates of the conformer sets of 4-HMcisDEPMPO-OOH and 4-HMcisDEPMPO-(OOBu)-Bu-t were 9-fold or 2-fold smaller respectively. The eight-line signals of theses adducts were easily recognisable. The trapping of the same radicals with the other diastereoisomer (4S*,5R*)-4-HMDEPMPO or with (3S*,5R*)-3-HMDEPMPO, obtained via oxidation of a phosphorylated pyrroline, led to more complicated spectra owing to the formation of diastereoisomer adducts. The signal of each diastereoisomer adduct was simulated with two species in conformational exchange. In comparison with DEPMPO, the cis-C-4-substitution was proved to slow by 26-fold the exchange rate between the two rotamer sets of the trans superoxide adduct versus the phosphoryl group. The trans-C-3-substitution was proved to slow by 18-fold, at 223 K, the exchange rate between the two rotamer sets of the trans terbutylperoxyl adduct. The last nitrone, a bicyclic one, named MEOOPPO (6a-methyl-(6-ethoxy-5-oxa-6-oxaphospholan-6-yl)-1-pyrroline-N-oxide) was obtained directly from (4R*,5R*)-4-HMDEPMPO in basic conditions. Superoxide with the rigid MEOOPPO reacts exclusively in trans addition versus the phosphoryl group, however, the adduct obtained in aqueous buffer was not very persistent and the nitrone was partially degraded during 30 min storage. For every nitrone, the hydroxyl radical was not added stereoselectively on one ring face and some diasteroisomer adducts were obtained

Synthèse et application au piégeage radicalaire de nitrones de type DEPMPO

Le premier objectif de ce travail était d'étudier l'effet de la substitution en position 4 de nitrones de type DEPMPO sur la géométrie des adduits superoxyde, sur leur persistance et sur l'allure de leurs spectres RPE. Le deuxième objectif était de fournir des précurseurs pour la synthèse de nitrones plus spécifiques. Mon travail de doctorat a consisté en la synthèse et l'étude RPE de deux séries de nitrones fonctionnalisées par un groupement phényl en position 4. Les deux diastéréoisomères : la 4 PhDEPMPOt et la 4 PhDEPMPOc furent préparés et utilisés pour le piégeage de plusieurs espèces radicalaires. L'adduit de spin formé par réaction de la 4 PhDEPMPOc avec le superoxyde a présenté un signal composé de 8 raies montrant seulement un léger phénomène de largeur de raie alternée. Les temps de demi-vie de la 4PhDEPMPOc-OOH sont similaire ( ~15mm). La deuxième série de molécules, ce sont les nitrones dérivées de la 4HMDEPMPO. Cette molécule fut obtenu en trois étapes et utilisée comme précurseur pour la préparation de nitrones vectorisées. L'adduit de spin formé par réaction de la 4HMDEPMPOc avec le superoxyde a présenté un signal composé de 8 raies montrant seulement un phénomène de largeur de raie alternée résiduel. Le temps de demi-vie de la 4HMDEPMPO-cOOH est plus grand (21mn) que celui de la DEPMPO-OOH. Un premier test de vectorisation par une molécule présentant une activité biologique a été concluant puisque la 4BIODEPMPOc fut synthétisée et l'étude RPE a démontré que l'introduction du motif biotine est compatible avec le piégeage de radicaux libres et a présenté un adduit du superoxyde dont le signal fut facilement attribuableAIX-MARSEILLE1-BU Sci.St Charles (130552104) / SudocSudocFranceF

Alkylperoxyl spin adducts of pyrroline-N-oxide spin traps: Experimental and theoretical CASSCF study of the unimolecular decomposition in organic solvent, potential applications in water

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EPR Studies of the Binding Properties, Guest Dynamics, and Inner-Space Dimensions of a Water-Soluble Resorcinarene Capsule

International audienceNitroxide free radicals have been used to studythe inner space of one of Rebek’s water-soluble capsules.EPR and1HNMR spectroscopy,ESI-MS, and DFT calculationsshowed apreference for the formation of 1:2complexes.EPR titrationsallowed us to determin ebinding constants (Ka)in the order of 107m¢2.EPR spectral-shape analysisprovidedinformation on the guest rotational dynamics within thecapsule. The interplay between optimum hydrogen bondingupon capsuleformation and steric strain for guest accom-modationhighlights some degree of flexibility for guest in-clusion,particularly at the center of the capsule where thehydrogen bond seam can be barely distorted or slightly dis-turbed

Frontispiece: EPR Studies of the Binding Properties, Guest Dynamics, and Inner-Space Dimensions of a Water-Soluble Resorcinarene Capsule.

International audienceHost-Guest Systems After extensive work toward the creation of molecular capsules in which two cavitands self-assemble to produce a constricted space amenable to guest encapsulation, a water-soluble version of Rebek's capsules was recently introduced. By combining EPR and NMR spectroscopy and ESI-MS, O. Ouari and co-workers have investigated the inner space metrics (width and height) of these supramolecular objects in water, as well as their binding constants and guest rotational dynamics. Nitroxides have been shown to be powerful probes affording a wealth of information. Read more in the Full Paper on page 16404 ff

Comprehensive synthesis of monohydroxy-cucurbit[n]urils (n = 5, 6, 7, 8): High purity and high conversions

We describe a photochemical method to introduce a single alcohol function directly on cucurbit[n]urils (n = 5, 6, 7, 8) with conversions of the order 95-100% using hydrogen peroxide and UV light. The reaction was easily scaled up to 1 g for CB[6] and CB[7]. Spin trapping of cucurbituril radicals combined with MS experiments allowed us to get insights about the reaction mechanism and characterize CB[5], CB[6], CB[7], and CB[8] monofunctional compounds. Experiments involving 18O isotopically labeled water indicated that the mechanism was complex and showed signs of both radical and ionic intermediates. DFT calculations allowed estimating the Bond Dissociation Energies (BDEs) of each hydrogen atom type in the CB series, providing an explanation of the higher reactivity of the "equatorial" C-H position of CB[n] compounds. These results also showed that, for CB[8], direct functionalization on the cucurbituril skeleton is more difficult because one of the methylene hydrogen atoms (H<inf>b</inf>) has its BDE lowering within the series and coming close to that of H<inf>c</inf>, thus opening the way to other types of free radicals generated on the CB[8] skeleton leading to several side products. Yet CB[5]-(OH)<inf>1</inf> and CB[8]-(OH)<inf>1</inf>, the first CB[8] derivative, were obtained in excellent yields thanks to the soft method presented here.Peer reviewed: YesNRC publication: Ye