Search

The correct parametrization of lanthanide complexes is of the utmost importance for their characterization using computational tools such as molecular dynamics simulations. This allows the optimization of their properties for a wide range of applications, including medical imaging. Here we present a systematic study to establish the best strategies for the correct parametrization of lanthanide complexes using [Gd(DOTA)]

Aqueous suspensions of metal organic frameworks (MOF) containing different Ln(3+) ions, consisting of a series of layered Ln(3+) networks formulated as [Ln(H(2)cmp)(H(2)O)] (where H(5)cmp is (carboxymethyl)iminodi(methylphosphonic acid), with a relatively wide size distribution (400 nm to 1 microm) were studied by relaxometry. The water (1)H longitudinal (r(1)) and transverse (r(2)) relaxivities were obtained for aqueous suspensions of these materials with different lanthanide ions. The values of r(1) are very small and varied only slightly with the effective magnetic moment (mu(eff)) of the lanthanide ions, while r(2) values are larger and proportional to the value of mu(eff)(2). The dependence of R(2) on tau(CP) (the time interval between two consecutive refocusing pulses in the train of 180 degrees pulses applied in a CPMG pulse sequence) was evaluated. The value of R(2) initially increases with tau(CP) and then saturates at higher tau(CP) at a value that is about 3 to 5 times lower than R(2p)*. This can be explained by the static dephasing regime (SDR) theory, in which the diffusion effect is taken into account and where the condition tau(D)Delta omega(r(p))(-1) holds (tau(D) = r(p)(2)/D, where D is the diffusion coefficient, r(p) is the radius of the particle, and Delta omega(r(p)) is the Larmor frequency shift at the particle's surface). Separation of the particles into two fractions with different particle sizes led to a significant enhancement of the r(2) relaxivity of the smaller particles with a narrow size distribution. Magnetometric measurements performed with the particles containing Dy(III), Ho(III), and Gd(III) showed a typical paramagnetic behavior from 4 to 100 K, used to determine the Curie constants.

Two cyclen-derived Gd probes, [Gd-DOTAM](3+) and [Gd-DOTP](5-) (DOTAM = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetamide; DOTP = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylenephosphonate)), were assessed as paramagnetic relaxation enhancement (PRE)-inducing probes for characterization of protein-protein interactions. Two proteins, Desulfovibrio gigas rubredoxin and Desulfovibrio gigas cytochrome c(3), were used as model partners. In a (1)H NMR titration it was shown that [Gd-DOTP](5-) binds to cytochrome c(3) near heme IV, causing pronounced PREs, characterized by line width broadenings of the heme methyl resonances at ratios as low as 0.08. A K(d) of 23 ± 1 μM was calculated based on chemical shift perturbation of selected heme methyl resonances belonging to three different heme groups, caused by allosteric effects upon [Gd-DOTP](5-) binding to cytochrome c(3) at a molar ratio of 2. The other probe, [Gd-DOTAM](3+), caused PREs on a well-defined patch near the metal center of rubredoxin (especially the patch constituted by residues D19-G23 and W37-S45, which broaden beyond detection). This effect was partially reversed for some resonances (C6-Y11, in particular) when cytochrome c(3) was added to this system. Both probes were successful in causing reversible PREs at the partner binding site, thus showing to be good probes to identify partners' binding sites and since the interaction is reversible to structurally characterize protein complexes by better defining the complex interface.

The structure and dynamics of the lanthanide(III) complexes of the bis(propylamide) of diethylenetriaminepentaacetate (DTPA-PA[sub 2]) in aqueous solution have been investigated by [sup 13]C and [sup 17]O NMR. With the use of the longitudinal [sup 13]C relaxation times of the Nd[sup III] complex it is shown that the organic ligand is bound to the lanthanide(III) ion in an octadentate fashion via the three nitrogens of the diethyenetriamine backbone, the three carboxylate groups, and the two amide oxygens. [sup 17]O NMR measurements show that the coordination sphere is completed by one water ligand. The inversion of the lanthanide-bound nitrogens is precluded, and therefore four diastereomeric pairs of isomers are possible for these complexes. Low-temperature [sup 13]C NMR spectra show that all these isomers occur in solution. Three dynamic processes have been identified by means of variable-temperature NMR measurements: (i) rapid rotations of the carboxylate groups, (ii) racemization at the middle N atom via interconversions between the two possible conformations of the ethylene bridges, and (iii) racemization at the terminal N atoms of the diethylenetriamine backbone via decoordination-inversion-coordination. The barriers of the interconversions between the enantiomers have been determined by line-shape analysis and from coalescence temperatures. A comparison is made with themore » Ln[sup III] diethylenetriaminepentaacetate (DTPA) complexes.« less

Various combinations of density functionals and pseudopotentials with associated valence basis-sets are compared for reproducing the known solid-state structure of [V 2O 2(OO) 2 l-lact 2] (2-) cis . Gas-phase optimizations at the B3LYP/SBKJC level have been found to provide a structure that is close to that seen in the solid state by X-ray diffraction. Although this may result in part from error compensation, this optimized structure allowed satisfactory reproduction of solution multinuclear NMR chemical shifts of the complex in all-electron DFT-IGLO calculations (UDFT-IGLO-PW91 level), suggesting that it is probably close to that found in solution. This combination of approaches has subsequently been used to optimize the structures of the vanadium oxoperoxo complexes [V 2O 3(OO) l-lact 2] (2-) cis , [V 2O 3(OO) l-lact 2] (2-) trans , and [VO(OO)( l-lact)(H 2O)] (-) cis . The (1)H, (13)C, (51)V, and (17)O NMR chemical shifts for these complexes have been calculated and compared with the experimental solution chemical shifts. Excellent agreement is seen with the (13)C chemical shifts, while somewhat inferior agreement is found for (1)H shifts. The (51)V and (17)O chemical shifts of the dioxo vanadium centers are well reproduced, with differences between theoretical and experimental shifts ranging from 22.9 to 35.6 ppm and from 25.1 to 43.7 ppm, respectively. Inferior agreement is found for oxoperoxo vanadium centers, with differences varying from 137.3 to 175.0 ppm for (51)V shifts and from 148.7 to 167.0 ppm for (17)O(oxo) shifts. The larger errors are likely to be due to overestimated peroxo O-O distances. The chosen methodology is able to predict and analyze a number of interesting structural features for vanadium(V) oxoperoxocomplexes of alpha-hydroxycarboxylic acids.

Lanthanide shift reagents have been used extensively in multinuclear magnetic resonance (NMR) applications in order to obtain information regarding ion distribution and transport in cellular systems. The aqueous reagents used in this study were Dy(PPP)J-, Tm( PPP)J-, Dy(TTHA)’-, Dy(PcPcP);-, and Dy(DOTP)’-, where Dy3+ and Tm3+ represent dysprosium and thulium ions and PPPs-, TTHA6-, PcPcPs-, and DOTP*- denote the triphosphate, triethylenetetraminehexaacetate, bis(dihydroxyphosphiny1- methyl)phosphinate, and I ,4,7,1 O-tetrazacyclododecane-N,N’,N”,N”’-tetrakis(methanephosphonate) ligands, respectively. The apparent size and shape of Li+-free RBCs (red blood cells), studied by both scanning electron microscopy and Coulter counter methods, were unchanged by the presence of the above shift reagents at concentrations lower than 10 mM. However, Li+ incubation changed both the shape and size of RBCs. The rates of Na+-Li+ exchange in Li+-loaded RBCs measured by 7Li NMR spectroscopy in the presence of Dy(PPP);-, TI~(PPP),~o-r, D~(PcPcP),~w-e re significantly higher than the rates measured in the absence of shift reagents by atomic absorption or in the presence of DY(TTHA)~o-r DY(DOTP)~b-y 7Li NMR spectroscopy. 31P and I9F NMR measurements of the membrane potential of Li+-free RBCs revealed that the shift reagents studied (except for Dy(TTHA)”) do change the membrane potential, with the most negatively charged reagents having the largest effect. Thus, shift reagents must be used with caution in physiological NMR studies and in particular RBC applications. http://dx.doi.org/10.1021/ic00345a014

We studied the efficacy of the tris-glycinatocobaltate(II) complex ([Co(gly)(3)](-)) as a shift reagent (SR) for chloride by (35)Cl NMR spectroscopy and compared to that of Co(2+)((aq)). Due to the relatively low thermodynamic stability of [Co(gly)(3)](-), a 1:3 Co(II)/gly stoichiometric solution at physiological pH is approximately a 2:1 mixture of [Co(gly)(2)(H(2)O)(2)] and [Co(gly)(H(2)O)(4)](+). This SR was found to be stable up to higher pH values than Co(2+)((aq)), better preventing Co(OH)(2) formation at alkaline pH. No significant differences in the (35)Cl(-) NMR chemical shift induced by Co(II)/gly or Co(2+)((aq)) were observed in the presence of physiological concentrations of either Ca(2+) or Mg(2+), or of either Na(+) or K(+). Although Co(2+)((aq)) was almost twice as effective as Co(II)/gly in shifting the (35)Cl(-) NMR resonance at the same high rho ([SR]/[Cl(-)]) value and low ionic strength, Co(2+)((aq)) showed a significant decrease (p < 0.05) in the (35)Cl(-) chemical shift at higher ionic strength. Line widths at half-height were significantly (p < 0.05) less for Co(II)/gly than for Co(2+)((aq)) at rho values in the range 0.066-0.40. Intracellular chloride was clearly detectable by (35)Cl NMR spectroscopy in human skin fibroblast cells suspended in medium containing 40 mM Co(II)/gly SR. We determined that, although Co(2+)((aq)) provides a larger shift than Co(II)/gly at the same rho value, there are significant advantages for using Co(II)/gly, such as pH stability, ionic strength independent chemical shifts, narrow (35)Cl(-) NMR resonances, and reduced cellular toxicity, as a SR in biological systems.

A variable-temperature, -pressure, and -ionic strength (1)H NMR study of the DOTA complexes of different trivalent cations (Sc, Y, La, Ce --> Lu) (DOTA = 1,4,7,10-tetraaza-1,4,7,10-tetrakis(carboxymethyl)cyclododecane) yielded data that are in contradiction with the hitherto used model of only two enantiomeric pairs of diastereoisomers that differ in the ligand conformations. A two-isomer equilibrium cannot explain the newly observed apparent reversal of the isomer ratio at the end of the series. As both conformers may lose their inner sphere water molecule, a coordination equilibrium may be superimposed on this conformational equilibrium, as shown by large positive reaction volumes for the isomerization of [Ln(DOTA)(H(2)O)(x)()](-) (Ln = Yb, Lu; x = 1, 0). The isomerization of [Nd(DOTA)(H(2)O)](-) and [Eu(DOTA)(H(2)O)](-) is purely conformational, as shown by near-zero reaction volumes. The measured isomerization enthalpies and entropies agree with this model. The shift of the isomerization equilibria by a variety of non-coordinative salts depends on the ligand conformation rather than the presence or absence of the inner sphere water molecule. This results from weak ion binding and water solvent stabilization of one ligand conformation, rather than the decrease of the activity of the bulk water in the solution, as shown by UV-vis measurements of the coordination number sensitive transition (5)F(0) --> (7)D(0) of Eu(III) as a function of ionic strength. Fluoride ions replace a water molecule in the inner coordination sphere, preferentially for one of the conformational isomers, as proven by (19)F-NMR shifts and the appearance of a third set of resonances corresponding to [Eu(DOTA)F](2)(-) in the (1)H-NMR spectrum of [Eu(DOTA)(H(2)O)](-).

Macroscopic and microscopic protonation of the title compounds (I)-(III), prepared by published methods, is studied using potentiometry and multinuclear magnetic resonance spectroscopy.

Preparation et etude potentiometrique de la protonation. Determination de constantes de complexation et spectrometrie RMN