Solid state and solution structures of the lanthanide complexes with cryptand (2.2.1): Crystallographic and NMR studies of a dimeric praseodymium (2.2.1) cryptate containing two μ-hydroxo bridges

A dimeric lanthanide cryptate was obtained by the addition of an excess of cryptand (2.2.1) to a slightly hydrated solution of the monomeric praseodymium (2.2.1) perchlorate complex in acetonitrile. This new lanthanide compound is centrosymmetric and displays the space groupP2₁/n. The encryptated metal ions are nine-coordinated, they are bonded to all the heteroatoms of a (2.2.1) ligand and they are linked to each other by two -hydroxo bridges. The hydroxyl groups are relegating the cryptands to both end of the dimer and the praseodymium ions are less effectively accomodated in the macrocylic internal cavities than in the case of the monomeric Pr(2.2.1) complex. The formation of both the monomeric and the dimeric lanthanide complexes is readily observed by proton NMR. Supplementary data relevant to this article are deposited with the British Library Lending Division as Supplementary Publication No. 82050 (24 pages).Presented at the Fourth International Symposium on Inclusion Phenomena and the Third International Symposium on Cyclodextrins, Lancaster, U.K., 20–25 July 1986.     

Auto-assembling of ditopic macrocyclic lanthanide chelates with transition-metal ions. Rigid multimetallic high relaxivity contrast agents for magnetic resonance imaging

PhenHDO3A is a ditopic ligand featuring a tetraazacyclododecane unit substituted by three acetate arms and one 6-hydroxy-5,6-dihydro-1,10-phenanthroline group (PhenHDO3A = rel-10-[(5R,6R)-5,6-dihydro-6-hydroxy-1,10-phenantholin-5-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid). This ligand was specially designed so as to obtain highly stable heteropolymetallic assemblies. PhenHDO3A has been prepared starting from phenanthroline epoxide and either a triprotected tetraazacyclododecane or tert-butyl triester of N,N',N' '-tetraazacyclododecane-triacetic acid. The latter yields PhenHDO3A in a single step. PhenHDO3A forms kinetically stable lanthanide complexes (acid-catalyzed kinetic constant kH = (1.2 +/- 0.2) x 10(-3) s(-1) M(-1)) whose solution structure has been deduced from a quantitative analysis of the paramagnetic shifts and the longitudinal relaxation times of the proton nuclei of YbPhenHDO3A. The alcohol group of the dihydro-phenanthroline unit remains coordinated to the encapsulated metal ion despite the steric crowding brought about by this group. Furthermore, the complexes are monohydrated, as shown by luminescence lifetime measurements on EuPhenHDO3A solutions. Relaxivity titrations at 20 MHz clearly indicate that the phenanthroline unit of GdPhenHDO3A is available for the spontaneous formation of highly stable tris complexes with the Fe2+ and Ni2+ ions. The water-exchange times and the rotational correlation times of GdPhenHDO3A and Fe(GdPhenHDO3A)32+ have been deduced from variable temperature 17O NMR studies and from nuclear relaxation dispersion curves. Despite rather slow water-exchange rates (taum0 = 1.0-1.2 x 10(-6) s), relaxivity gains of 90% have been observed upon the formation of the heterometallic tris complexes. The latter rotate about four times more slowly (taur0= 398 ps) than the monomeric unit (taur0 = 105 ps) and their relaxivity is, accordingly, twice as high. The relaxivity of the tris complexes between 10 and 50 MHz is comparable to relaxivities reported for Gd3+-containing dendrimers of much higher molecular weights. The high relaxivity of the tris-PhenHDO3A lanthanide complexes is attributed to their internal rigidity.     

Calix[4]arenes as selective extracting agents. An NMR dynamic and conformational investigation of the lanthanide(III) and thorium(IV) complexes

The lanthanide and Th4+ complexes with calix[4]arene ligands substituted either on the narrow or at the wide rim by four coordinating groups behave totally differently as shown by an NMR investigation of the dia- and paramagnetic complexes. Solutions of complexes were prepared by reacting anhydrous metal perchlorate salts with the ligands in dry acetonitrile (CAUTION). Relaxation time T1 titrations of acetonitrile solutions of Gd3+ by calixarenes indicate that ligands subsituted on the narrow rim form stable 1:1 complexes whether they feature four amide groups (1) or four phosphine oxide functions. In contrast, a ligand substituted by four (carbamoylmethyl)-diphenylphosphine oxide moieties on the wide rim (3) and its derivatives from polymeric species even at a 1:1 ligand/metal concentration ratio. Nuclear magnetic relaxation dispersion (NMRD) curves (relaxation rates 1/T1 vs magnetic field strength) of Gd3+, Gd3+.1 and Gd3+.3 perchlorates in acetonitrile are analyzed by an extended version of the Solomon-Bloembergen-Morgan equations. A comparison of the calculated rotational correlation times tau r shows that ligand 3 forms oligomeric Gd3+ species. The chelates of ligand 1 are axially symmetric (C4 symmetry), and the paramagnetic shifts induced by the Yb3+ ion are accounted for quantitatively. The addition of water or of nitrate ions does not modify the geometry of the complex. The metal chelates of 3 and its derivatives adopt a C2 symmetry, and the paramagnetic shifts are interpreted on a semiquantitative basis only. Water and NO3- ions completely labilize the complexes of the heavy lanthanides. The very high selectivity of ligand 3 through the lanthanide series stems from a complex interplay of factors.     

Polymethylated DOTA ligands. 2. Synthesis of rigidified lanthanide chelates and studies on the effect of alkyl substitution on conformational mobility and relaxivity

M4DOTA, [(2S,5S,8S,11S)-4,7,10-tris-carboxymethyl-2,5,8,11-tetramethyl-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid (2e), and M4DOTMA, (R)-2-[(2S,5S,8S,11S)-4,7,10-tris-((R)-1-carboxyethyl)-2,5,8,11-tetramethyl-1,4,7,10-tetraazacyclododecan-1-yl]propionic acid (3e), are derivatives of ligand DOTA (1e) that form sterically crowded lanthanide chelates. M4DOTMA forms highly symmetric and totally rigid single Y(3+) and Yb(3+) species in which the ring substituents occupy corner positions in a square antiprismatic arrangement as shown by molecular mechanics calculations and by a quantitative interpretation of the relative magnitudes of the paramagnetic (1)H NMR shifts of dipolar origin. The NMR spectrum of YbM4DOTMA(-) displays two intense methyl peaks outside the 0-10 ppm range whose shift difference is strongly temperature dependent. YbM4DOTMA(-) (3d) could be a useful probe in magnetic resonance thermometric imaging. With only four methyl substituents on the tetraaza ring, M4DOTA forms three Yb(3+) species in solution. The methyl substituents prevent the inversion of configuration of the ethylenic groups but not of the acetate arms. Although the methyl groups are likely to preferably occupy ring corner positions, the dipolar equations do not allow one to distinguish with certainty between the two available corner (equatorial) orientations. Reliably applying the dipolar equations is less obvious than usually assumed. A single methyl substituent as in ligand MDOTA (5e) suffices to rigidify the tetraaza cycle but not the acetate arms. Racemic YbMDOTA(-) (5d) is present in solution as four totally asymmetric topomers with the methyl groups occupying either one of the two equatorial positions. A complete assignment of the solution structures on the basis of the dipolar equations is again uncertain. The nuclear magnetic relaxation dispersion curves of the Gd(3+) chelates of all the methylated DOTA ligands including DOTMA, (R)-2-[4,7,10-tris-((R)-carboxyethyl)- 1,4,7,10- tetraazacyclododecan-1-yl]propionic acid, are very similar, and intermolecular conformational processes appear to have no influence on the relaxivity of these small complexes for which the relaxation T(1) is mainly determined by the rotational correlation time (tau(r)). The hydration number of the Tb(3+) chelates measured by fluorescence decreases from DOTMA to M4DOTMA presumably because steric crowding leads to an increase of the metal-water distance.     

Séparation chromatographique des lanthanides en deux groupes basée sur des différences dans la cinétique de décomposition des complexes lanthanides-macrocyclesChromatographic separation of lanthanides into two groups based on kinetic differences in the decomposition of macrocycle/lanthanide complexes

The separation of the lanthanides in two groups, based on differences in decomplexation rates of the LnDOTA entities (DOTA = 1,4,7,10-tetraazacyclododecane-N,N′,N″,N?-tetraacetic acid), is achieved on a sulphonate cation-exchange column (H⁺ form). The yttrium earths, from terbium to lutetium, are eluted first as Ln-DOTA-H species with 1.25 M HCl; the light lanthanides, from lanthanum to samarium inclusive, are eluted as uncomplexed ions at the end of the chromatogram, with more concentrated hydrochloric acid. Given an equimolar mixture of the Eu-DOTA and Gd-DOTA complexes as starting solution, 40% of the gadolinium can be recovered free from europium at the start of elution and 47% of the europium free from gadolinium at the end of the elution.     

Investigation of the quantitative properties of the quadrupole orthogonal acceleration time-of-flight mass spectrometer with electrospray ionisation using 3,4-methylenedioxymethamphetamine

This paper describes the investigation of the potential of a quadrupole orthogonal acceleration time-of-flight mass spectrometer (Q-TOF) equipped with an atmospheric pressure ionisation interface for quantitative measurements of small molecules separated by reversed phase liquid chromatography. To this end, the detection limits and linear dynamic range in particular were studied in an LC/MS/MS experiment using 3,4-methylenedioxymethamphetamine standards and 3,4-methylenedioxyethylamphetamine for internal standardisation. In a second phase, the experiment was repeated with real biological extracts (whole blood, serum, and vitreous humour). A calibration for 3,4-methylenedioxymethamphetamine and its metabolite 3,4-methylenedioxyamphetamine was prepared in each of these matrices again using 3,4-methylenedioxyethylamphetamine as internal standard. The resulting quantitative data were compared with those obtained by liquid chromatography with fluorescence detection for the same extracts. The Q-TOF results revealed excellent sensitivity and a linear dynamic range of nearly four decades (2-10 000 pg on-column, r(2) = 0.9998, 1/x weighting). Furthermore, all the calibration curves prepared in biological material were superimposable, LC/MS/MS and LC-fluorescence, and the quantitative results for actual samples compared very favourably. It was concluded that the Q-TOF achieves a linear dynamic range for quantitative LC/MS/MS work exceeding that of fluorescence detection and at much better absolute sensitivity. Copyright 1999 John Wiley & Sons, Ltd.     

Finite element approximation of a model for phase separation of a multi-component alloy with a concentration-dependent mobility matrix

We consider a model for phase separation of a multi-componentalloy with a concentration-dependent mobility matrix and logarithmicfree energy. In particular we prove that there exists a uniquesolution for sufficiently smooth initial data. Further, we provean error bound for a fully practical piecewise linear finiteelement approximation in one and two space dimensions. Finallynumerical experiments with three components in one space dimensionare presented.     

Carbamoylmethylphosphinoxide derivatives based on the triphenylmethane skeleton. Synthesis and extraction properties

Two different strategies were used to synthesize tri(2-alkoxy-5-nitrophenyl)methanes 6a,b. The X-ray structures of 6a and its precursor 5 show the molecules in a conformation with a syn-orientation of the nitro and alkoxy groups. Hydrogenation and acylation by the appropriate active ester gave the corresponding tri-CMPO derivatives 4a,b. Their ability to complex lanthanide ions was studied by NMR spectroscopy and by nuclear magnetic relaxation dispersion and further characterized by quantum mechanical calculations. Extraction experiments from acidic solution to dichloromethane reveal a reasonable selectivity of Am(III) over Eu(III), but in contrast to similar tetra-CMPOs derivatives of calix[4]arenes the distribution coefficients strongly decrease with increasing concentration of HNO(3).