Biomedical subjects
Publications and source records attributed to Monique Biesemans.
The hydrolysis of a bridged alpha,omega-bis(trialkynylstannylated) compound leads to a hybrid material ordered by self-assembly where the spacer forms two six-membered [1,2]oxastanninane rings by intramolecular coordination.
Dialkyltin dichloride grafted to a cross-linked polystyrene, with the formula [P-H]((1-t))[P-(CH2)nSnBuCl2]t (P=[CH2CH(pC6H4)], t=the degree of functionalization, and n=6 or 11), is investigated as a recyclable catalyst in the ring-opening polymerization (ROP) of epsilon-caprolactone (CL). It is demonstrated that high-resolution magic-angle-spinning (HR-MAS) NMR spectroscopy is an invaluable tool to characterize completely the supported catalyst. The 2D 1H-13C HSQC HR-MAS spectrum, in particular, allowed extensive assignment of the 1H and 13C resonances, as well as accurate measurement of the (n)J((1)H-(117/119)Sn) and (n)J((13)C-(117/119)Sn) coupling constants. 1H and 119Sn HR-MAS NMR spectroscopy is presented as a monitoring tool for catalytic processes based on organotin compounds, particularly for the investigation of the extent to which polymerization residues are observable in situ in the material pores and for the assessment of the chemical integrity and recycling conditions of the grafted catalyst. From polymerization experiments with CL, initiated by n-propanol and with [P-H]((1-t))[P-(CH2)nSnBuCl2]t of various compositions as the supported catalyst, it appears that a partial 'burst' of the polystyrene support occurs when the length of the alkyl spacer is limited to n=6, as a result of polymer chains growing within the pores of the support. However, extension of the length of the aliphatic polymethylene spacer from 6 to 11 carbon atoms preserves the support integrity and allows the production of catalyst-deprived poly(epsilon-caprolactone) (PCL) oligomers. A preliminary attempt to recycle the heterogeneous catalyst has shown that very good reproducibility can be obtained, in terms of both catalyst activity and molecular-weight parameters of the as-recovered PCL polyester chains.
Insoluble polystyrene grafted compounds of the type (P-H)(1-t){P-(CH2)n SnBu(p)Cl(3-p)}(t), (P-H)(1-t){P-(CH2)n SnBuO}(t) and (P-H)(1-t)[{P-(CH2)n SnBuCl}2O](t/2), in which (P-H) is a cross-linked polystyrene; n=4, 6, and 11; p=0 and 1; and t the degree of functionalisation, were synthesised from Amberlite XE-305, a polystyrene cross-linked with divinylbenzene. The compounds were characterised by using elemental analysis, and IR, Raman, solid-state 117Sn NMR, and 1H and 119Sn high-resolution MAS NMR spectroscopy. The influence of the spacer length and the tin functionality on the catalytic activity of these compounds, as well as their recycling ability, was assessed in the transesterification reaction of ethyl acetate with various alcohols. These studies showed significant differences in the activity of the catalysts interpreted in terms of changes in the mobility of the catalytic centres. Some of the supported catalysts could be recycled at least seven times without noticeable loss of activity. The residual tin content in the reaction products was found to be as low as 3 ppm.
Complexation affinity of laurate ligands (C(12)H(23)O(2)) grafted onto the surface of cerium(IV) oxide nanoparticles can be probed and quantified in situ, by pulsed field gradient (1)H NMR through the dependence of the diffusion coefficient on the size of a species.
Pulsed field gradient (1)H NMR spectroscopy has been applied to investigate the association behavior of the Sn(12)-oxo cluster macrocation [(BuSn)(12)O(14)(OH)(6)](2+) with two different and smaller anions, p-toluenesulfonate (PTS(-)) and diphenylphosphinate (Ph(2)PO(2) (-)). By monitoring the translational diffusion coefficients of the various species involved, it is shown that the association depends on the anion involved and on the solvent used. Moreover, the possibility to individually monitor the diffusion characteristics of multiple anionic and cationic species in mixtures, by virtue of resolved (1)H resonances available from each species, allows us to evidence the occurrence of ion exchange in such systems. Thus when [(BuSn)(12)O(14)(OH)(6)](PTS)(2) is mixed with two equivalents of Ph(2)PO(2)NMe(4), PTS(-) is displaced by Ph(2)PO(2) (-), highlighting the greater affinity of the organotin macrocation for the diphenylphosphinate. This example clearly illustrates the potential of pulsed field gradient (1)H NMR spectroscopy in inorganic/organometallic chemistry, to follow preferential ion pairing in multi-ion systems at the level of each individually charged species.
It is demonstrated that long-range nJ(1H,117Sn) coupling constants down to 0.3 Hz, can be accurately quantified from non-linear fitting of the sine modulation of the associated 1H-117Sn correlation cross-peak intensities sampled as a function of the heteronuclear antiphase coherence preparation time in the 1H-117Sn J-HMQC pulse sequence. The contribution of additional, undesired modulations is illustrated and assessed using the product operator formalism, and is traced back to contributions that arise from miss-setting of the wandering 180 degrees pulse angle in the constant time period. The power of the method and its use in the characterization of weak intramolecular donor-acceptor interactions are illustrated by the determination of long-range nJ(1H,117Sn) coupling constants of bis[3-(dimethylamino)propyl]tin derivatives, [Me2N(CH2)3]2SnR2 (', R = Me; 3, R = Ph; 4, R = t-Bu). By comparing these with the values found for the corresponding bis(4-methylpentyl)tin derivatives, [Me2CH(CH2)3]2SnR2 (2', R = Me; 3', R = Ph), which lack such interactions, the use of long-range coupling constants to detect intramolecular donor-acceptor interactions is evaluated. It is concluded that nJ(1H,117Sn) couplings up to six bonds through an organic carbon chain can be quantified, whether donor-acceptor interactions are present or not. Furthermore, evidence is presented that, when two scalar coupling pathways co-exist, the pathway involving an intramolecular donor-acceptor interaction can have opposite sign, thus decreasing the overall coupling constant to a value smaller than that actually measured in the absence of a donor-acceptor interaction, where only one coupling pathway is active. There is nevertheless clear numerical value discrimination in the series of compounds investigated between long-range couplings in derivatives without weak intramolecular donor-acceptor interactions and those where such interactions can exist.
The anomeric specificity of D-glucose metabolism and functional effects is currently assessed either over about 5 min at 37 degrees C or longer periods at much lower temperatures. In the present study, the half-life for the interconversion of D-glucose anomers at 30 degrees C was found to be increased (P<0.005) from 17.2+/-0.9 min in a mixture of H2O/D2O (9/1, v/v) to 58.6+/-1.9 min in pure D2O. It is proposed that advantage can be taken from this delayed interconversion in D2O in experiments dealing with the anomeric specificity of D-glucose metabolic fate and functional effects. Thus, even over 60-min incubation at 30 degrees C, the integrated mean abundance of alpha- and beta-D-glucose would remain close to 82 and 89%, respectively, of the corresponding initial value (100%).
The ring-opening polymerization (ROP) of epsilon-caprolactone (CL) was carried out in toluene at 100 degrees C with n-propanol (nPrOH) in the presence of Bu(2)SnCl(2). It comes out that the molar mass of the polyester chains can be predicted from the initial monomer-to-alcohol molar ratio in accordance with a controlled ROP mechanism involving an O-acyl cleavage of the monomer to selectively form (alpha-propyloxy)(omega-hydroxy)poly(epsilon-caprolactone) chains. In order to gain fundamental understanding of the mechanistic factors governing the polyester chain growth, advanced (1)H, (13)C, and (119)Sn NMR investigations were performed in situ in [D(8)]toluene, as well as with model solutions that contained Bu(2)SnCl(2) and binary mixtures of the components at various concentrations and temperatures. This has enabled us to propose a mechanism in which Bu(2)SnCl(2) behaves as a catalyst, while nPrOH is the actual initiator. It involves non-aggregated, six-coordinate Bu(2)SnCl(2) complexes in which ligands exchange fast on the (119)Sn NMR observational timescale, and the simultaneous interactions of CL and alcohol function in such a way that it favors insertion/propagation reactions over transesterification ones, up to high monomer conversion.
The structural characterization of organotin compounds that are grafted onto insoluble cross-linked polymers has necessarily been limited to elemental analysis, infrared spectroscopy, and in a few instances, solid-state NMR spectroscopy. This important bottleneck in the development of such grafted systems has been addressed by using high-resolution magic angle spinning (hr-MAS) NMR spectroscopy. The great potential of this technique is demonstrated through the structural characterization of diphenylbutyl-(3,4) and dichlorobutylstannanes (5,6), grafted onto divinylbenzene cross-linked polystyrene by means of a suitable linker (1, 2). First, conditions suitable for the application of hr-MAS NMR spectroscopy were identified by characterizing the (1)H resonance line widths of the grafted organotin moiety following swelling of the functionalized beads in eight representative solvents. The presence of clearly identifiable tin coupling patterns in both the 1D (13)C and 2D (1)H-(13)C HSQC spectra, and the incorporation of (119)Sn chemical shift and connectivity information from hr-MAS 1D (119)Sn and 2D (1)H-(119)Sn HMQC spectra, provide an unprecedented level of characterization of grafted organotins directly at the solid/liquid interface. In addition, the use of hr-MAS (119)Sn NMR for reaction monitoring, impurity detection, and quantification and assessment of the extent of coordination reveals its promise as a novel tool for the investigation of polymer-grafted organotin compounds. The approach described here should be sufficiently general for extension to a variety of other nuclei of interest in polymer-supported organometallic chemistry.
Di-tert-butyltin oxide, (t-Bu(2)SnO)(3) (1), reacts with 1,2-di-tert-butyltetrachlorodisilane, (t-BuCl(2)Si)(2) (2), to provide the stannasiloxane t-Bu(2)Sn[OSi(OSnCl-t-Bu(2))-t-Bu](2) (4, racemate). The reaction of 1 with 1,2-di-tert-butyltetrafluorodisilane, (t-BuF(2)Si)(2) (3), provides the stannasiloxane [t-Bu(F)SiOSn-t-Bu(2)](2)O (5, meso/racemate mixture) and the tetraorganodistannoxane [t-Bu(2)(F)SnOSn(F)-t-Bu(2)](2) (6). Under loss of (1)/(3) mole equiv of 1, the stannasiloxane 5 is transformed into t-Bu(2)Sn[OSi(F)-t-BuSi(F)-t-BuO](2)Sn-t-Bu(2) (7). Its ten-membered ring structure was elucidated by X-ray analysis. In solution, 7 forms the five-membered ring t-Bu(2)Sn[OSi(F)-t-Bu](2) (7a). The dimeric nature of 6 was confirmed by its crystal structure determination. In solution, 6 exhibits a unique valence tautomerism as evidenced by (19)F and (119)Sn NMR spectroscopy.
The reaction of [(Me(2)Sn)(2)(Me(2)SnO)(ONZOH)(HONZO)(ONZO)] (HONZOH = o-HON=CHC(6)H(4)OH, salicylaldoxime) with ammonium fluoride yields a fluorotris(dimethyltin) disalicylaldoximate complex, compound 4, containing one seven-coordinate and two five-coordinate tin atoms, with a fluoride anion bridging the five-coordinate tin atoms. Though 4 can be obtained in a crystalline form, its crystals are unsuitable for X-ray analysis. Its structure has been completely characterized in solution by 1D (1)H, (13)C, (119)Sn, and (19)F NMR spectra and 2D gradient-assisted (1)H-(119)Sn and (1)H-(13)C HMQC and HMBC NMR spectra. In solution, 4 is involved in an equilibrium with several species. It is shown that the Sn(2)-F-Sn(3) moiety of 4 is the reactive site amenable to nucleophilic substitution with weak nucleophiles like water and methanol. The preservation of the splitting of the (1)J((119/117)Sn(3)-(19)F) coupling but not the (1)J((119/117)Sn(2)-(19)F) coupling evidences a reaction intermediate where the entering nucleophile is bound to the Sn(2) tin atom whereas the fluorine is still linked to the Sn(3) atom. Overall, &mgr;(2)-nucleophilic substitutions on compound 4 with hydroxylated nucleophiles should be viewed as addition-elimination reactions.