Paramagnetic Gd Research Articles

Mössbauer, electron paramagnetic resonance, and magnetic susceptibility studies on members of a new family of cyano-bridged 3d-4f complexes. Demonstration of anisotropic exchange in a Fe-Gd complex.

The synthesis and crystallographic characterization of a new family of M(mu-CN)Ln complexes are reported. Two structural series have been prepared by reacting in water rare earth nitrates (Ln(III) = La, Pr, Nd, Sm, Eu, Gd, Dy, Ho) with K(3)[M(CN)(6)] (M(III) = Fe, Co) in the presence of hexamethylenetetramine (hmt). The first series consists of six isomorphous heterobinuclear complexes, [(CN)(5)M-CN-Ln(H(2)O)(8)].2hmt ([FeLa] 1, [FePr] 2, [FeNd] 3, [FeSm] 4, [FeEu] 5, [FeGd] 6), while the second series consists of four isostructural ionic complexes, [M(CN)(6)][Ln(H(2)O)(8)].hmt ([FeDy] 7, [FeHo] 8, [CoEu] 9, [CoGd] 10). The hexamethylenetetramine molecules contribute to the stabilization of the crystals by participating in an extended network of hydrogen bond interactions. In both series the aqua ligands are hydrogen bonded to the nitrogen atoms from both the terminal CN(-) groups and the hmt molecules. The [FeGd] complex has been analyzed with (57)Fe Mossbauer spectroscopy and magnetic susceptibility measurements. We have also analyzed the [FeLa] complex, in which the paramagnetic Gd(III) is replaced by diamagnetic La(III), with (57)Fe Mossbauer spectroscopy, electron paramagnetic resonance (EPR), and magnetic susceptibility measurements, to obtain information about the low-spin Fe(III) site that is not accessible in the presence of a paramagnetic ion at the complementary site. For the same reason, the [CoGd] complex, containing diamagnetic Co(III), was studied with EPR and magnetic susceptibility measurements, which confirmed the S = 7/2 spin of Gd(III). Prior knowledge about the paramagnetic sites in [FeGd] allows a detailed analysis of the exchange interactions between them. In particular, the question of whether the exchange interaction in [FeGd] is isotropic or anisotropic has been addressed. Standard variable-temperature magnetic susceptibility measurements provide only the value for a linear combination of J(x), J(y), and J(z) but contain no information about the values of the individual exchange parameters J(x), J(y), and J(z). In contrast, the spin-Hamiltonian analysis of the variable-field, variable-temperature Mossbauer spectra reveals an exquisite sensitivity on the anisotropic exchange parameters. Analysis of these dependencies in conjunction with adopting the g-values obtained for [FeLa], yielded the values J(x) = +0.11 cm(-1), J(y) = +0.33 cm(-1), and J(z) = +1.20 cm(-1) (S(1).J.S(2) convention). The consistency of these results with magnetic susceptibility data is analyzed. The exchange anisotropy is rooted in the spatial anisotropy of the low-spin Fe(III) ion. The condition for anisotropic exchange is the presence of low-lying orbital excited states at the ferric site that (i) effectively interact through spin-orbit coupling with the orbital ground state and (ii) have an exchange parameter with the Gd site with a value different from that for the ground state. Density functional theory (DFT) calculations, without spin-orbit coupling, reveal that the unpaired electron of the t(2g)(5) ground configuration of the Fe(III) ion occupies the xy orbital, that is, the orbital along the plane perpendicular to the Fe...Gd vector. The exchange-coupling constants for this orbital, j(xy), and for the other t(2g) orbitals, j(yz) and j(xz), have been determined using a theoretical model that relates them to the anisotropic exchange parameters and the g-values of Fe(III). The resulting values, j(yz) = -5.7 cm(-1), j(xz) = -4.9 cm(-1), and j(xy) = +0.3 cm(-1) are quite different. The origin of the difference is briefly discussed.

A copper-activated magnetic resonance imaging contrast agent with improved turn-on relaxivity response and anion compatibility

We present the synthesis and characterization of Copper-Gad-7 (CG7), a new copper-activated magnetic resonance imaging (MRI) contrast agent that possesses a Gd(3+)-DO3A scaffold with an appended thioether-rich receptor for copper recognition. Installation of additional carboxylate groups on the periphery of the CG scaffold affords a practical strategy to increase the absolute relaxivity of these types of copper-responsive MRI sensors as well as reduce their sensitivity to biologically abundant anions. Due in large part to restricted access of inner-sphere water molecules to the paramagnetic Gd(3+) core, in the absence of copper ions, CG7 exhibits a relatively low relaxivity value of r(1) = 2.6 mM(-1) s(-1); addition of Cu(+) triggers a 340% enhancement in relaxivity to r(1) = 11.4 mM(-1) s(-1). For comparison, the relaxivity of the analogous CG2 sensor without peripheral carboxylates increases from r(1) = 1.5 to 6.9 mM(-1) s(-1) upon Cu(+) binding. CG7 features high selectivity for Cu(+) over a range of biologically relevant metal ions, including the cellular abundant alkali and alkaline earth cations and d-block ions Zn(2+) and Cu(2+). Moreover, the Cu(+)-response of the CG7 sensor is not significantly affected by bicarbonate, phosphate, citrate, and lactate anions at cellular levels. (17)O NMR dysprosium-induced shift (DIS) and nuclear magnetic relaxation dispersion (NMRD) experiments suggest that the origin of the improved anion compatibility of CG7 is a reduced q modulation compared to previous members of the CG family, and T(1)-weighted phantom images confirm that CG7 can monitor changes in copper levels by MRI at clinically relevant field strengths.

Nanostructured T1 MRI contrast agents

Recent advances on new T1 MRI contrast agents using nanostructured materials will be presented. Paramagnetic Gd3+ ions have been immobilized in nanostructured matrices such as liposomes, perfluorocarbons, silica-based nanoparticles, emulsions, and carbon nanotube to generate nanostructured ionic T1 MRI contrast agents with high relaxivity. Inorganic nanoparticles of gadolinium compounds and manganese oxides have been recently developed as new types of T1 MRI contrast agents using the large surface concentration of metal ions with high magnetic moments. Functionalization of these nanostructured T1 contrast agents enabled targeted imaging, multimodal imaging, and simultaneous imaging and drug delivery.

Mechanisms of ZnII-Activated Magnetic Resonance Imaging Agents

We report on the mechanism of a series of Zn (II)-activated magnetic resonance contrast agents that modulate the access of water to a paramagnetic Gd (III) ion to create an increase in relaxivity upon binding of Zn (II). In the absence and presence of Zn (II), the coordination at the Gd (III) center is modulated by appended Zn (II) binding groups. These groups were systematically varied to optimize the change in coordination upon Zn (II) binding. We observe that at least one appended aminoacetate must be present as a coordinating group to bind Gd (III) and effectively inhibit access of water. At least two binding groups are required to efficiently bind Zn (II), creating an unsaturated complex and allowing access of water. (13)C isotopic labeling of the acetate binding groups for NMR spectroscopy provides evidence of a change in the metal coordination of these groups upon the addition of Zn (II) supporting our proposed mechanism of activation as presented.

Lanthanide Triflate-Catalyzed Arene Acylation. Relation to Classical Friedel–Crafts Acylation

Lanthanide trifluoromethanesulfonates, Ln(OTf) 3 (OTf (-) = trifluoromethanesulfonate), serve as effective precatalysts for the rapid, regioselective, intermolecular acylation of activated arenes. This contribution probes mechanism and metal ionic radius effects in the catalytic lanthanide triflate-mediated acylation of anisole with acetic anhydride. Kinetic studies of Ln(OTf) 3 (Ln = La, Eu, Yb, Lu)-mediated anisole acylation with acetic anhydride in nitromethane reveal the rate law nu approximately k 3 [Ln (3+)] (1)[acetic anhydride] (1)[anisole] (1). Eyring and Arrhenius analyses yield Delta H++ = 12.9 (4) kcal.mol (-1), Delta S++ = -44.8 (1.3) e.u., and E a = 13.1 (4) kcal.mol (-1) for Ln = Yb, with the negative Delta S++ implying a highly organized transition state. The observed primary kinetic isotope effect of k H/ k D = 2.6 +/- 0.15 is consistent with arene C-H bond scission in the turnover-limiting step. The proposed catalytic pathway involves precatalyst formation via interaction of Ln(OTf) 3 with acetic anhydride, followed by Ln (3+)-anisole pi-complexation, substrate-electrophile sigma-complex formation, and turnover-limiting C-H bond scission. Lanthanide size effects on turnover frequencies are consistent with a transition state lacking significant ionic radius-dependent steric constraints. Substrate-Ln (3+) interactions using paramagnetic Gd (3+) and Yb (3+) NMR probes and factors affecting reaction rates such as arene substituent and added LiClO 4 cocatalyst are also explored.

A Phosphine‐Mediated Through‐Space Exchange Coupling Pathway for Unpaired Electrons in a Heterobimetallic Lanthanide–Transition Metal Complex

The reaction of P(CH2OH)3 with methyl anthranilate NH2C6H4-2-CO2Me produced the ligand precursor P(CH2NHC6H4-2-CO2Me)3 (1). The reaction of 1 with [Y{N(SiMe3)2}3] produced hexadentate yttrium complex [Y{P(CH2NC6H4-2-CO2Me)3}] (2), in which the metal centre is coordinated by three amido donors and the three carbonyl oxygen atoms of the ester groups. The 31P{1H} NMR spectrum features 1J Y,P=15 Hz, and DFT calculations demonstrate that through-space interaction between the minor lobe of the phosphine lone pair and the yttrium centre allows a large Fermi contact contribution to this spin coupling constant. The EPR spectrum of the analogous paramagnetic Gd complex [Gd{P(CH2NC6H4-2-CO2Me)3}] (3) can be modelled by using a B20 crystal field parameter of +/-0.19 cm(-1). Heterodinuclear complexes were prepared by the reactions of 1 and 3 with [5,10,15,20-tetrakis(4-methoxyphenyl)porphinato]cobalt(II), by binding of the phosphine lone pair to the d(7) cobalt centre. The solid-state EPR spectrum of the heterodinuclear yttrium complex 4 exhibits large superhyperfine coupling to the phosphorus nucleus, indicative of an S=1/2 complex in which the unpaired electron resides in the cobalt dz2 orbital directed at the phosphine donor. The magnetic susceptibility of the heterodinuclear Gd-Co complex 5 demonstrates that through-space antiferromagnetic coupling occurs between unpaired electrons on the gadolinium and cobalt centres.

Micelles Based on Biodegradable Poly(l-glutamic acid)-b-Polylactide with Paramagnetic Gd Ions Chelated to the Shell Layer as a Potential Nanoscale MRI−Visible Delivery System

There is much interest in the development of a nanoscale drug delivery system with MRI visibility to optimize the delivery efficiency and therapeutic efficacy under image guidance. Here we report on the successful fabrication of nanoscale micelles based on biodegradable poly( L-glutamic acid)- b-polylactide (PG- b-PLA) block copolymer with paramagnetic Gd3+ ions chelated to their shell. PG- b-PLA was synthesized by sequential polymerization reactions: anionic polymerization of L-lactide followed by ring-opening polymerization of benzyl glutamate N-carboxylic anhydride. The metal chelator p-aminobenzyldiethylenetriaminepenta(acetic acid) (DTPA) was readily conjugated to the side chain carboxylic acids of poly( L-glutamic acid). The resulting copolymer formed spherical micelles in aqueous solution with an average diameter of 230 nm at pH 7.4. The size of PG(DTPA)- b-PLA micelles decreased with increasing pH value. DTPA-Gd chelated to the shell layer of the micelles exhibited significantly higher spin-lattice relaxivity (r1) than a small-molecular-weight MRI contrast agent, indicating that water molecules could readily access the Gd ions in the micelles. Because of the presence of multiple carboxylic acid functional groups in the shell layer, polymeric micelles based on biodegradable PG(DTPA-Gd)- b-PLA may be a suitable platform for the development of MRI-visible, targeted nanoscale drug delivery systems.

NMR Structural Studies of the Supramolecular Adducts between a Liver Cytosolic Bile Acid Binding Protein and Gadolinium(III)-Chelates Bearing Bile Acids Residues: Molecular Determinants of the Binding of a Hepatospecific Magnetic Resonance Imaging Contrast Agent

The binding affinities of a selected series of Gd(III) chelates bearing bile acid residues, potential hepatospecific MRI contrast agents, to a liver cytosolic bile acid transporter, have been determined through relaxivity measurements. The Ln(III) complexes of compound 1 were selected for further NMR structural analysis aimed at assessing the molecular determinants of binding. A number of NMR experiments have been carried out on the bile acid-like adduct, using both diamagnetic Y(III) and paramagnetic Gd(III) complexes, bound to a liver bile acid binding protein. The identified protein "hot spots" defined a single binding site located at the protein portal region. The presented findings will serve in a medicinal chemistry approach for the design of hepatocytes-selective gadolinium chelates for liver malignancies detection.

Peptides and Gd Complexes Containing Colloidal Assemblies as Tumor-Specific Contrast Agents in MRI: Physicochemical Characterization

The aggregation behavior of an amphiphilic supramolecular system, with potential application as a tumor-specific magnetic resonance imaging contrast agent, has been studied in detail by dynamic light scattering, small-angle neutron scattering and cryotransmission electron microscopy. The system was constituted of mixed aggregates formed by an anionic unimer containing the DTPAGlu, a chelating agent for the paramagnetic Gd 3+ ion, and an uncharged unimer containing the bioactive peptide CCK8, capable of directing the assembly toward tumor cells. Mixed aggregates formed by both unimers, and in the case of the DTPAGlu unimer with the chelating agent as free base or as Gd 3+ complex, have been investigated. A number of interesting features of the aggregation behavior were revealed: at physiological pH, micelles and bilayer structures were present, whereas upon decreasing solution pH or increasing ionic strength, the formation of bilayer structures was favored. On the basis of the above observations, the aggregating mechanism has been elucidated by considering the screening effect on intra- and interaggregate electrostatic repulsions.

Gadolinium (III) ion in liquid water: Structure, dynamics, and magnetic interactions from first principles

We applied first principles molecular dynamics (MD) technique to study structure, dynamics, and magnetic interactions of the Gd(3+) aqua ion dissolved in liquid water, a prototypical system for Gd-based complexes used as contrast agents for magnetic resonance imaging. The first coordination sphere contains eight water molecules with an average Gd-O distance of 2.37 A and an average geometric arrangement close to a square antiprism. The mean tilt angle of the electric dipole vector of these water molecules is theta=145 degrees . In our picosecond time scale simulation we observe no exchange event from the first coordination sphere but only fast "wagging" motions. The second coordination sphere is well pronounced though water molecules in this sphere are subjected to large amplitude dynamic motions. The isotropic hyperfine coupling constants for the inner sphere water molecules [A(iso)((17)O(I))=0.65+/-0.03 MHz, A(iso)((1)H(I))=0.085+/-0.005 MHz] are in good agreement with experimental data and with an earlier study using classical MD. Second sphere Fermi contact hyperfine coupling constants calculated are more than one order of magnitude smaller and of opposite sign as those of the first coordination sphere. The effect of spin polarization induced by the paramagnetic Gd(3+) ion on the dipolar hyperfine interaction was found to be sizable only for the (17)O nuclei of inner sphere water molecules and has a screening character.

Rapid and exothermic solid-state synthesis of metal oxyhalides and their solid solutions via energetic metathesis reactions

Rapid solid-state metathesis reaction chemistry has been extended to the production of layered metal oxyhalide systems. This article describes the successful synthesis of crystalline BiO X ( X=Cl, I), and lanthanide oxychlorides ( LnOCl, Ln=La, Sm, Gd) from metal trihalides and Na 2O 2 in seconds. These known materials contain halide double layers separating M–O layers. Powder X-ray diffraction results on the metathesis metal oxyhalide products agree with prior literature reports. The morphological and compositional properties of the metal oxyhalide products are described. The rapid production of well-mixed paramagnetic Gd x Sm 1− x OCl solid-solution materials was achieved using physical mixtures of SmCl 3 and GdCl 3 precursors reacted with Na 2O 2. The room-temperature magnetic properties of these materials with varying compositions are also described. As expected, magnetism, unit cell parameters, and M–O vibrational bands are all dependent on metal composition in the solid-solution products and vary in an approximately linear Vegard's law fashion.

Transport, thermal, and magnetic properties of RuSr2(Gd1.5Ce0.5)Cu2O10−δ, a magnetic superconductor

Resistivity, thermoelectric power, heat capacity, and magnetization for samples of RuSr2(Gd1.5Ce0.5)Cu2O10−δ were investigated in the temperature range 1.8–300K with a magnetic field up to 8T. The resistive transitions to the superconducting state are found to be determined by the inhomogeneous (granular) structure, characterized by the intragranular, Tc0, and intergranular, Tcg, transition temperatures. Heat capacity, C(T), shows a jump at the superconducting transition temperature Tc0≈37.5K. A Schottky-type anomaly is found in C(T) below 20K. This low-temperature anomaly can be attributed to splitting of the ground term S7∕28 of paramagnetic Gd3+ ions by internal and external magnetic fields.

Intracerebral Diffusion of Paramagnetic Cationic Liposomes Containing Gd(DTPA)2- Followed by MRI Spectroscopy: Assessment of Patternc Diffusion and Time Steadiness of a Non-Viral Vector Model

Cationic liposomes are generally considered as the non-viral counterparts of the more common viral vectors used in several gene therapy protocols, but their use as delivery vehicles is limited by their efficiency even if they display a lower toxicity. However, cationic liposomes are promising delivery systems in cell biology due to their ability to incorporate small molecules into their inner aqueous spheres and to deliver them into cells. Additionally, on the external surface they can bind therapeutic molecules such as nucleic acids, oligonucleotides, plasmids, etc. through electrostatic interactions. The aim of this work was to study the diffusion properties of such vehicles in vivo with a non-invasive technique and to monitor their tissue migration in order to collect information to be further used in gene therapy procedures. For this purpose, cationic liposomes containing the paramagnetic contrast agent Gd(DTPA)2- (Gd(III)-diethylenetriamine-N,N,N',N",N"-pentaacetic acid) were investigated because of their extended paramagnetic persistency in vivo, compared to the use of the contrast agent alone, and they were used to monitor the diffusion of such vehicles in an animal model (rat model). In particular, these vectors were injected into the rat brain through a stereotactic frame in a preformed cavity mimicking the lesion which had originated after surgical removal of the primary tumor. For the purpose of comparison, the same injection procedure was also applied to a control series of animals without a preformed brain lesion. Pattern diffusion and steadiness of the reported paramagnetic cationic liposomes were studied by means of Magnetic Resonance Imaging (MRI) which allowed us to monitor their diffusion and assess their intracerebral time availability up to 24 hours.

Separation and Characterization of the Two Diastereomers for [Gd(DTPA-bz-NH2)(H2O)]2-, a Common Synthon in Macromolecular MRI Contrast Agents: Their Water Exchange and Isomerization Kinetics

Chiral, bifunctional poly(amino carboxylate) ligands are commonly used for the synthesis of macromolecular, Gd(III)-based MRI contrast agents, prepared in the objective of increasing relaxivity or delivering the paramagnetic Gd(III) to a specific site (targeting). Complex formation with such ligands results in two diastereomeric forms for the complex which can be separated by HPLC. We demonstrated that the diastereomer ratio for Ln(III) DTPA derivatives (approximately 60:40) remains constant throughout the lanthanide series, in contrast to Ln(III) EPTPA derivatives, where it varies as a function of the cation size with a maximum for the middle lanthanides (DTPA(5-) = diethylenetriaminepentaacetate; EPTPA(5-) = ethylenepropylenetriaminepentaacetate). The interconversion of the two diastereomers, studied by HPLC, is a proton-catalyzed process (k(obs) = k(1)[H(+)]). It is relatively fast for [Gd(EPTPA-bz-NH(2))(H(2)O)](2-) but slow enough for [Gd(DTPA-bz-NH(2))(H(2)O)](2-) to allow investigation of pure individual isomers (isomerization rate constants are k(1) = (3.03 +/- 0.07) x 10(4) and 11.6 +/- 0.5 s(-1) M(-1) for [Gd(EPTPA-bz-NH(2))(H(2)O)](2)(-) and [Gd(DTPA-bz-NH(2))(H(2)O)](2-), respectively). Individual water exchange rates have been determined for both diastereomers of [Gd(DTPA-bz-NH(2))(H(2)O)](2-) by a variable-temperature (17)O NMR study. Similarly to Ln(III) EPTPA derivatives, k(ex) values differ by a factor of 2 (k(ex)(298) = (5.7 +/- 0.2) x 10(6) and (3.1 +/- 0.1) x 10(6) s(-1)). This variance in the exchange rate has no consequence on the proton relaxivity of the two diastereomers, since it is solely limited by fast rotation. However, such difference in k(ex) will affect proton relaxivity when these diastereomers are linked to a slowly rotating macromolecule. Once the rotation is optimized, slow water exchange will limit relaxivity; thus, a factor of 2 in the exchange rate can lead to a remarkably different relaxivity for the diastereomer complexes. These results have implications for future development of Gd(III)-based, macromolecular MRI contrast agents, since the use of chiral bifunctional ligands in their synthesis inevitably generates diastereomeric complexes.

Targeting Cells with MR Imaging Probes Based on Paramagnetic Gd(III) Chelates

The low sensitivity is the major disadvantage of MRI as compared to PET. Therefore, amplification strategies are necessary for specific pathway labeling. This survey is aimed at exploring different routes to the entrapment of Gd(III) chelates in various type of cells at amounts sufficiently large to allow MRI visualization. Namely, the obtained results have been summarized in terms of internalization via i) pinocytosis; ii) phagocytosis; iii) receptors; iv) receptor mediated endocytosis; v) transporters; vi) transmembrane carrier peptides. MRI visualization of cells appears possible when the number of internalized Gd(III) chelates is of the order of 10(7)-10(8)/cell. Pinocytosis shows to be particularly useful for labeling cells that can be incubated for several hours in the presence of high concentrations of Gd-agent. This approach appears very effective for labeling stem cells. Nanoparticles filled with Gd-chelates can be used for an efficient loading of cells endowed with a good phagocytic activity. Entrapment via receptors most often results in receptor mediated endocytosis. Suitably functionalized monomeric and multimeric Gd-chelates can be considered for being internalized by this route as well as supramolecular systems such as those formed between Avidin and biotinylated Gd-complexes. Exploitation of up-regulated transporters of nutrients in tumor cells appears to be a promising route for their differentiation from healthy cells. Finally, properly designed systems entering the cells by means of penetrin-like peptides deserve great attention.

Focal‐point anchoring: Large proton relaxivity observed for gadolinium‐cored dendrimer complexes in water

AbstractWater‐soluble Gd3+‐cored poly(ether amide) dendrimer complexes, bearing a diethylenetriaminepentaacetic acid Gd3+ complex (GdDTPA) core, were synthesized. The longitudinal proton relaxivity (R1), governed mainly by the rotation correlation time of the paramagnetic Gd3+ center, was measured in water (37 °C, 20 MHz). An anchor effect at the focal point of the hydrophilic dendrimer was experimentally evaluated for the first time, through a comparison of the R1 values with the ones reported for various Gd3+ complexes, including linear copolymers of GdDTPA linked by various lengths of aliphatic chains via amide bonds. Unusually large R1 values for the first‐ and second‐generation Gd3+‐cored dendrimer complexes (6.1 and 9.3 mM−1 s−1, respectively), even with relatively low molecular weights (1355 and 3877, respectively), suggested a remarkable increase in the local rigidity around the GdDTPA core. The internal rigidity of the dendrimer was supposed to take advantage of the increased nominal molecular weight in water via multihydration to the dendron to increase the rotation correlation time, and this resulted in the observed R1 gain. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 2680–2689, 2004

Insights into the use of paramagnetic Gd(III) complexes in MR-molecular imaging investigations.

Can gadolinium III [Gd(III)] complexes be considered good candidates for magnetic resonance (MR)-molecular imaging studies? In this review article, we examine the principal issues that are the basis of successful use of Gd-based protocols in molecular imaging applications. High relaxivity is the primary requisite. Therefore, the design of such paramagnetic probes has to be pursued keeping in mind the relationships between structure, dynamics, and the relevant parameters involved in paramagnetic relaxation processes. Moreover, the limited number of target molecules on cellular membranes makes it necessary to define strategies aimed at delivering many Gd-containing moieties to the sites of interest. Examples are reported for the attainment of very high relaxivities for the design of new routes for pursuing the accumulation of small sized Gd(III) complexes at the targeting sites. An efficient cellular uptake of Gd-containing probes is the key step for attaining the visualization of targeted cells by MR imaging, and selected examples are reported. In this context, the problem of the assessment of the minimum amount of Gd(III) complexes necessary for the MR imaging-visualization of cells has been addressed by reporting the authors' observations on the cell-internalization of Gd(III) complexes. A particularly efficient delivery system is represented by Gd-loaded apoferritin, which allows the MR visualization of hepatocytes when the number of Gd-complexes per cell is 4 +/- 1 x 10(7). Finally, the potential of responsive systems is considered by outlining the exploitation of the amplification effect brought about by the action of a specific enzymatic activity on the relaxivity of a suitably functionalized Gd(III) complex.

Magnetotransport in Gd1-xSrxCoO3 (0 < x ≤ 0.30) Perovskites

We introduce the magnetotransport properties of Gd1-xSrxCoO3 (0 < x ≤ 0.30) materials. These compounds are semiconducting and show a magnetic transition at Tc ≈ 160 K associated with the onset of magnetic order of cobalt ions within superparamagnetic clusters, which have a freezing point TB < Tc. Very remarkably, the more resistive samples showed rather large magnetoresistance at the lowest available temperature: MRmax(x = 0.10) ≈ −16% at T = 4.2 K under Hmax = 40 kOe. We relate these results to the inhomogeneous electronic structure of these cobaltates and to the presence of the paramagnetic Gd3+ sublattice, which at low temperatures influences the cobalt ions of the superparamagnetic clusters, provoking an increase in the size of the hole-rich regions and in the hopping probability of the charge carriers, and gives rise to the negative magnetoresistance observed.

Innovative magnetic resonance imaging diagnostic agents based on paramagnetic Gd(III) complexes.

Gd(III) complexes are under intense scrutiny as contrast agents for magnetic resonance imaging (MRI). They act by enhancing tissutal proton relaxation rates. Much has already been done in order to get an in-depth understanding of the relationships between structure, dynamics, and contrastographic ability of these paramagnetic complexes. Their potential in the assessment of flow, perfusion, and capillary permeability has already been established. The next challenges are in the field of molecular imaging applications, which would allow the attainment of early diagnosis based on the recognition of specific reporters of the onset of the pathological state. To this end, Gd(III) complexes have to be endowed with improved targeting capabilities by conjugating suitable recognition synthons on their surfaces. Small peptides are candidates of choice for the attainment of this goal. Moreover, the intrinsic low sensitivity of the NMR techniques implies the need to deliver large amounts of contrast agents to the target in order to get its visualization in the resulting images. Highly efficient delivery systems have been identified, which bring a great promise for the development of innovative diagnostic agents based on Gd(III) complexes.

Identification of protein surfaces by NMR measurements with a pramagnetic Gd(III) chelate.

Gd-diethylenetriamine pentaacetic acid-bismethylamide, Gd(DTPA-BMA), is shown to be a reagent suitable for the identification of protein surfaces. Compared to the conventionally used spin-label TEMPOL, Gd(DTPA-BMA) is a stronger relaxation agent, requiring lesser concentrations to achieve the same paramagnetic relaxation enhancement of solvent-exposed protein protons. It is also less hydrophobic and therefore less prone to specific binding to proteins. Relaxation enhancements predicted by a second-sphere interaction model correlated with experimental data recorded with ubiquitin, while the correlation with corresponding data recorded with TEMPOL was poor.