New complexes of La(III), Ce(III), Pr(III), Nd(III), Sm(III), Eu(III) and Gd(III) ions with morin

New solid complex compounds of La(III), Ce(III), Pr(III), Nd(III), Sm(III), Eu(III) and Gd(III) ions with morin were synthesized. The molecular formula of the complexes is Ln(C₁₅H₉O₇)₃ · nH₂O, where Ln is the cation of lanthanide and n = 6 for La(III), Sm(III), Gd(III) or n = 8 for Ce(III), Pr(III), Nd(III) and Eu(III). Thermogravimetric studies and the values of dehydration enthalpy indicate that water occurring in the compounds is not present in the inner coordination sphere of the complex. The structure of the complexes was determined on the basis of UV-visible, IR, MS, ¹H NMR and ¹³C NMR analyses. It was found that in binding the lanthanide ions the following groups of morin take part: 3OH and 4CO in the case of complexes of La, Pr, Nd, Sm and Eu, or 5OH and 4CO in the case of complexes of Ce and Gd. The complexes are five- and six-membered chelate compounds.     

Nature and composition of La(III), Ce(III), Pr(III), Nd(III), Sm(III), Gd(III), Dy(III) and Ho(III) complexes of embelin

The isolation and characterization of nine polymeric complexes of the general formula [M(L)_1.5S₂]_n (where M is the metal ion, L the ligand and S the solvent, C₂H₅OH) of La(III) and Ce(III), Pr(III), Nd(III), Sm(III), Gd(III), Tb(III), Dy(III), Ho(III) with.the biologically active compound embelin using elemental and thermal analysis, infrared and electronic spectral studies is reported.     

Lanthanide nitrate complexes of 4-N-(2′-Hydroxy-1 ′-naphthylidene)-aminoantipyrine

Lanthanide nitrates form with 4-N-(2′-hydroxy-l′- naphthylidene)aminoantipyrine (HNAAP) complexes of the type [Ln(HNAAP)₂(NO₃)₃] (where Ln = La, Pr, Nd, Sm, Gd, Tb, Dy, Ho and Y). The IR spectra of these complexes show that HNAAP acts as a bidentate neutral ligand and nitrate group is coordinated monodentately. The electronic spectra of the Nd complex show reasonable covalency in the metal-ligand bond. The magnetic moments of these complexes are in better agreement with the Van Vleck values. All these complexes are thermally stable up to200 °C.     

Towards MRI contrast agents of improved efficacy. NMR relaxometric investigations of the binding interaction to HSA of a novel heptadentate macrocyclic triphosphonate Gd(III)-complex

 A novel heptacoordinating ligand consisting of a thirteen-membered tetraazamacrocycle containing the pyridine ring and bearing three methylenephosphonate groups (PCTP-[13]) has been synthesized. Its Gd(III) complex displays a remarkably high longitudinal water proton relaxivity (7.7 mM^–1 s^–1 at 25  °C, 20 MHz and pH 7.5) which has been accounted for in terms of contributions arising from (1) one water molecule bound to the metal ion, (2) hydrogen-bonded water molecules in the second coordination sphere, or (3) water molecules diffusing near the paramagnetic chelate. Variable-temperature ¹⁷O-NMR transverse relaxation data indicate that the residence lifetime of the metal-bound water molecule is very short (8.0 ns at 25  °C) with respect to the Gd(III) complexes currently considered as contrast agents for magnetic resonance imaging. Furthermore, GdPCTP-[13] interacts with human serum albumin (HSA), likely through electrostatic forces. By comparing water proton relaxivity data for the GdPCTP-[13]-HSA adduct, measured as a function of temperature and magnetic field strength, with those for the analogous adduct with GdDOTP (a twelve-membered tetraaza macrocyclic tetramethylenephosphonate complex lacking a metal-bound water molecule), it has been possible to propose a general picture accounting for the main determinants of the relaxation enhancement observed when a paramagnetic Gd(III) complex is bound to HSA. Basically, the relaxation enhancement in these systems arises from (1) water molecules in the hydration shell of the macromolecule and protein exchangeable protons which lie close to the interaction site of the paramagnetic complex and (2) the metal bound water molecule(s). As far as the latter contribution is concerned, the interaction with the protein causes an elongation of the residence lifetime of the metal-bound water molecule, which limits, to some extent, the potential relaxivity enhancement expected upon the binding of the paramagnetic complex to HSA. Received: 27 January 1997 / Accepted: 12 May 1997     

Lanthanide ion catalysis of the trans-cis isomerization of trans-bis(oxalato)-diaquochromate(III) and trans-bis(malonato)diaquochromate(III) [1]

The lanthanide ion catalyzed trans-cis isomerizations of trans-bis(oxalato)diaquochromate(II) and trans-bis(malonato)diaquochromate(III) have been studied. A linear free energy relationship was found correlating the catalytic rate constants for the oxalate reaction with the corresponding formation constants of complexes formed between simple monocarboxylic acids and the light (LaGd) members of the lanthanide series. The results indicates that for this portion of the series, the reaction mechanism is related to the formation of monocarboxylate complex intermediates. When the ionic radius of the lanthanide ion decreases below a particular value (as in the latter half of the series), the metal ion remains coordinated to both carboxylates of the oxalate ion rather than simply binding to only one carboxylate. In either situation, isomerization to the cis product eventually occurs, and the lanthanide ion is released.The reaction rates associated with the trans-bis(malonato)diaquochromate(III) reaction were found to be significantly slower than those of the corresponding oxalate system. However, in the malonate system, no linear free energy relationship was found relating the catalytic rate constants with the corresponding formation constants of monocarboxylic acids. One does find a linear relationship between the catalytic rate constants for the malonate reaction and the log K₁ values for the corresponding lanthanide/malonate complexes. During the course of the trans-cis isomerization, the lanthanide ion chelates the dissociated malonate group of a pentavalent Cr(III) intermediate. In the mechanism the lanthanide ion does not aid in ring opening, and neither does it singly bond to the intermediate     

Complexes of lanthanoid salts with macrocyclic ligands. Part 32. Synthesis and characterization of the complexes between lanthanoid nitrates and a tetraoxadiaza macrocycle

Lanthanoid nitrates react with 1,7,10,16-tetraoxa- 4,13-diaza-N,N′-dimethylcyclooctadecane, Me₂(2,2), to give complexes with two different metal:ligand ratios, 1:1 (Ln = La, Ce, Tb) and 4:3 (Ln = Pr, Nd, Sm, Eu, Gd, Th, Dy, Ho). The complexes were isolated from anhydrous solutions in acetonitrile and characterized by elemental analysis, X-ray diffraction, magnetic susceptibility measurements and vibrational analysis.The La and Ce 1:1 complexes are non-ionic and probably 12-coordinated, with the metal ion bound to the six donor atoms of the ligand and to three bidentate nitrate ions. The 4:3 complexes are ionic; they contain three bis(nitrato) complex cations [Ln(NO₃)₂·Me₂(2,2)]⁺ and one hexakis(nitrato) anion [Ln(NO₃)₆]³⁻. Spectroscopic data, including luminescence spectra, point to the 1:1 Tb-complex as being a 4:3 complex with an additional outer-sphere coordinated molecule of ligand.In solution, the 1:1 complexes remain essentially non-ionic, although some dissociation cannot be ruled out, whereas the 4:3 complexes behave as 2:1 (of even 3:1) electrolytes.     

Lanthanide(III) solvation: N,N-dimethylformamide as a unidentate O-donor

Structure determinations for the lanthanide (Ln) complexes [(CH₃)₂NH₂][Gd(dmf)₈](ClO₄)₄, [Tb(dmf)₈](ClO₄)₃ and [Ho(dmf)₇(OH₂)](ClO₄)₃ (dmf=N,N-dimethylformamide) show all three to contain an LnO₈ coordination unit of essentially square-antiprismatic geometry. The geometry of the inner coordination sphere appears to be little perturbed by quite major differences in the lattice environment of the cations. Attractive interactions between coordinated dmf molecules may be one contributor to the stability of the primary coordination sphere.     

Effects of citric acid and the siderophore desferrioxamine B (DFO-B) on the mobility of germanium and rare earth elements in soil and uptake in Phalaris arundinacea

Effects of citric acid and desferrioxamine B (DFO-B) on the availability of Ge and selected rare earth elements (REEs) (La, Nd, Gd, Er) to Phalaris arundinacea were investigated. A soil dissolution experiment was conducted to elucidate the effect of citric acid and DFO-B at different concentrations (1 and 10 mmol L^?1 citric acid) on the release of Ge and REEs from soil. In a greenhouse, plants of P. arundinacea were cultivated on soil and on sand cultures to investigate the effects of citric acid and DFO-B on the uptake of Ge and REEs by the plants. Addition of 10 mmol L^?1 citric acid significantly enhanced desorption of Ge and REEs from soil and uptake into soil-grown plants. Applying DFO-B enhanced the dissolution and the uptake of REEs, while no effect on Ge was observed. In sand cultures, the presence of citric acid and DFO-B significantly decreased the uptake of Ge and REEs, indicating a discrimination of the formed complexes during uptake. This study clearly indicates that citric acid and the microbial siderophore DFO-B may enhance phytoextraction of Ge and REEs due to the formation of soluble complexes that increase the migration of elements in the rhizosphere.     

Gd(III) complexes as contrast agents for magnetic resonance imaging: a proton relaxation enhancement study of the interaction with human serum albumin

 The non-covalent interaction between human serum albumin (HSA) and DOTA-like Gd(III) complexes containing hydrophobic benzyloxymethyl (BOM) substituents has been thoroughly investigated by measuring the solvent proton relaxation rates of their aqueous solutions. The binding association constants (K _A) to HSA are directly related to the number of hydrophobic substituents present on the surface of the complexes. Furthermore, an estimation of ΔH° and ΔS° has been obtained by the temperature dependence of K _A. Assays performed with the competitor probes warfarin and ibuprofen established that the complexes interact with HSA through two nearly equivalent binding sites located in the subdomains IIA and IIIA of the protein. Strong relaxation enhancements, promoted by the formation of slowly tumbling paramagnetic adducts, have been measured at 20 MHz for complexes containing two and three hydrophobic substituents. The macromolecular adduct with the latter species has a relaxivity of 53.2±0.7 mM^–1 s^–1, which represents the highest value so far reported for a Gd(III) complex. The temperature dependence of the relaxivity for the paramagnetic adducts with HSA indicates long exchange lifetimes for the water molecules dipolarly interacting with the paramagnetic centre. This is likely to be related to the formation, upon hydrophobic interaction of the complexes with HSA, of a clathrate-like, second-coordination-sphere arrangement of water molecules. Besides affecting the dissociative pathway of the coordinated water molecule, this water arrangement may itself significantly contribute to enhancement of the bulk solvent relaxation rate. Received: 6 November 1995 / Accepted: 17 April 1996     

Diethyl and diisopropyl phosphite complexes of lanthanide(III) chlorides

Lanthanide chlorides form adducts of the type [Ln(L)_nCl₃] (where Ln = La, Pr, Nd, Sm, Eu, when n = 6; and Ln = Gd, Tb, Dy or Yb when n = 5; and L = (EtO)₂P(O)H or (PrⁱO)₂P(O)H upon interacting with the diethyl and diisopropyl phosphites in dry ethyl and isopropyl alcohol, respectively. Complexes were recrystallised from ethanol or isopropanol and washed with n-hexane. On the basis of elemental analysis, infrared, ¹H NMR and ³¹P NMR spectral studies, it is concluded that these phosphites coordinate to the lanthanide metal atom through the oxygen atom which has the greatest affinity for lanthanides in these adducts.     

Cu(II)–poly(L-arginine) complexes. Potentiometric and spectral characterization of amine and peptide nitrogen ligands

The study of Cu(II)–poly(L -arginine) complexes by potentiometric titration, as well as by optical, circular dichroism, and infrared spectra, provides information about the nature of ligands and the coordination sphere around the metal ion. Three different complexes have been identified. The first, which is formed below pH 8, contains two guanidinium nitrogens and two water molecules at the corners of the coordination square. The constant of the overall process as determined by the Gregor method equals 2.0 ± 0.1 × 10^?9. The two other complexes form between pH 8 and 10.5 and they contain two guanidinium and two peptide nitrogens as nearest ligands. One of them is a monomer and the other probably a dimer, which differ in the symmetry of the coordination sphere around the cupric ion. The optical spectra of the three complexes show an absorption band at 260 nm that we have assigned to a charge-transfer transition between a σ metal nitrogen (amine) molecular orbital and a d_x2_?y2 metal orbital. The spectra of the two complexes containing peptide nitrogens exhibit another absorption band at 320 nm, which we have assigned to a charge transfer from a π orbital of the amide group to the d_x2_?y2 metal orbital.     

Spectroscopic study of lanthanide(III) complexes with aliphatic dicarboxylic acids

The complexation of trivalent lanthanides with aliphatic dicarboxylic acids (malonic, succinic, glutaric and adipic) were studied at 25°C and 0.1 M (NaClO₄) ionic strength by luminescence and absorption spectroscopy and luminescence lifetime measurements. The luminescence spectra and decay constants indicate that ML and ML₂ complexes were formed. The stability constants of Eu(III) complexes with the dicarboxylic acids were calculated from the changes of the ⁵D₀←⁷F₀ excitation spectra of Eu(III). For the four dicarboxylic acids studied, both the stability constant and the number of water molecules released from the inner sphere of Eu(III) upon complexation decrease from malonate to adipate for both the ML and ML₂ complexes. The results are interpreted as reflecting an increasing tendency from chelation to monodentation as the carbon chain length increases between carboxylate groups. The trend in the oscillator strength in the hypersensitive transition of the Nd(III)and Ho(III) complexes is the same as that in the ligand basicity.     

Ternary Gd(III)L-HSA adducts: evidence for the replacement of inner-sphere water molecules by coordinating groups of the protein. Implications for the design of contrast agents for MRI

Two novel gadolinium(III) chelates based on the structure of the heptadentate macrocyclic 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) ligand have been synthesized and their relaxometric and luminescent properties thoroughly investigated. They contain two water molecules in the inner coordination sphere in fast exchange with the bulk solvent and bear either a p-bromobenzyl or a p-phosphonatomethylbenzanilido substituent for promoting further interaction with macromolecular substrates. Upon interaction with human serum albumin the expected relaxation enhancement is not observed owing to displacement of the two inner-sphere water molecules of the complexes by a donor atom (likely from a carboxylate group) on the protein and possibly the phosphate anion of the buffered solution, respectively. We modeled the observed behavior by measuring the decrease of the relaxation rate of the water protons upon addition of malonate anion to aqueous solutions of the complexes. Conversely, no change in the hydratation state of the Gd(III) center for both complexes has been observed when the substrate for the formation of the macromolecular adduct is represented by poly-beta-cyclodextrin.     

Rare earth thiocyanate complexes with tripiperidinophosphine oxide: synthesis and characterization. Crystal structure of Pr(SCN)3(tpppO)3

The synthesis and characterization of rare-earth (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu and Y) thiocyanate adducts with tripiperidinophosphine oxide (tpppO) with general formula (RE)(SCN)₃(tpppO)₃ are reported. Conductance measurements in acetonitrile indicate the non-electrolytic nature of the complexes. Infrared absorption spectra evidence that the SCN⁻ ion coordinates through the nitrogen atom (isothiocyanate form) and that tpppO coordinates through the phosphoryl oxygen. X-ray powder patterns suggest the existence of three different crystal forms: (1) La; (2) an isomorphous series including Ce, Nd and Pr; and (3) another isomorphous series, including Sm, Gd, Eu, Ho, Er, Tb, Lu and Y. The visible spectra of the Nd adduct and the calculated parameters β = 0.98, b^1/2 = 0.072 and δ = 1.06 indicate that the metal-ligand bonds are essentially electrostactic. The emission spectra of the Eu compound showed ⁵D₀ → ⁷F_J bands (J = 0, 1, 2), suggesting a C_3v symmetry for the coordination polyhedron. The lifetime of the ⁵D₀ state is 1.28 ms. The emission spectra of the Tb complex presented ⁵D₄ → ⁷F_J bands (J = 4, 5, 6) and the Dy complex showed the ⁴F_9/2 → ⁶H_13/2 band. The structure of the Pr complex showed that the coordination polyhedron is a trigonal antiprism, with the isothiocyanate anions in one base and three tpppO ligands in the other. Thermal analyses (TG-DTG) were carried out for the Ce, Nd and Gd adducts. Mass losses start between 250 and 334 °C. The final residues at 1300 °C are the corresponding phosphates.     

Comparative study of glutamine synthetase bound lanthanide(III) ions using NMR relaxation and lanthanide(III) luminescence techniques

Changes in the intrinsic fluorescence intensity of glutamine synthetase induced by lanthanide(III) ion binding demonstrate the existence of three types of sites for these ions. The sites are populated sequentially during titrations of the enzyme, and the first two have a stoichiometry of 1 per enzyme subunit. The number of water molecules coordinated to Eu(III) bound to the first site was determined by luminescence lifetime techniques to be 4.1 +/- 0.5. The hydration of Gd(III) bound to the same site was studied by magnetic field dependent water proton longitudinal relaxation rate measurements, and by water proton and deuteron relaxation measurements of one sample at single magnetic fields. The magnetic resonance techniques also yield a value of 4 for the hydration number.     

Formation and phosphodiesterolytic activity of lanthanide(III) N,N-bis(2-hydroxyethyl)glycine hydroxo complexes

Potentiometric titrations of N,N-bis(2-hydroxyethyl)glycine (bicine) in the presence of Ln(III) cations (Ln=La, Pr, Nd and Eu) in the pH range extended to ca. 9.5 reveal formation of two types of binuclear hydroxo complexes Ln₂(bic)₂(OH)₄ and Ln₂(bic)(OH)₄ ⁺ (bicH=bicine) in addition to previously reported mononuclear mono- and bis-complexes Ln(bic)²⁺ and Ln(bic)₂ ⁺, which predominate at pH below 8. ¹H NMR titrations of La(III)-bicine mixtures in D₂O show that the complex formation with bicine is slow in the NMR time scale and confirm formation of hydroxide rather than alkoxide complexes in basic solutions. Formation of a different type of hydroxide species under conditions of an excess of metal over ligand is confirmed by studying the absorption spectra of the Nd(III)-bicine system in the hypersensitive region. The binuclear hydroxide complexes are predominant species at pH above 9 and their stabilities increase in the order La < Pr ≈ Nd < Eu. They show fairly high catalytic activity in the hydrolysis of bis(4-nitrophenyl) phosphate (BNPP) at room temperature. Comparison of concentration and pH-dependences of the reaction rates with the species distribution diagrams shows that the catalytic hydrolysis of BNPP proceeds via a Michaelis-Menten type mechanism, which involves the Ln₂(bic)(OH)₄ ⁺ complex as the reactive species. The values of the catalytic rate constants and the Michaelis constants are in the range 0.002-0.004 s⁻¹ and 0.35-1.5 mM, respectively, for all lanthanides studied. The half-life for the hydrolysis of BNPP is reduced from 2000 years to ca. 10 min at 25 °C and pH 9.2 in the presence of 5 mM La(III) and 2.5 mM bicine.     

Computer simulation of Gd(III) speciation in human interstitial fluid

The speciation and distribution of Gd(III) in human interstitial fluid was studied by computer simulation. The results show that at the background concentration, all the Gd(III) species are soluble and no precipitates appear. However as the total concentration of Gd(III) rises above 2.610 × 10^–9 mol/l,the insoluble species become predominant. GdPO₄ is formed first as a precipitate and then Gd₂(CO₃)₃. Among soluble species, free Gd(III), [Gd(HSA)], [Gd(Ox)] and the ternary complexes of Gd(III) with citrate as the primary ligand are main species when the total concentration of Gd(III) is below 2.074 × 10^–2 mol/l. With the total concentration of Gd(III) further rising, [Gd₃(OH)₄] begins to appear and gradually becomes a predominant species.     

Complexation of Al(III) with reduced glutathione in acidic aqueous solutions

The complexation of reduced glutathione (GSH) in its free and Al(III)-bound species in acidic aqueous solutions was characterized by means of multi-analytical techniques: pH-potentiometry, multinuclear (¹H, ¹³C and ²⁷Al) and two-dimensional nuclear Overhauser enhancement NMR spectroscopy (¹H, ¹H-NOESY), electrospray mass spectroscopy (ESI-MS), and ab initio electronic structure calculations. The following results were found. In the 25 °C 0.1 M KCl and 37 °C 0.15 M NaCl ionic medium systems, Al³⁺ coordinates with the important biomolecule GSH through carboxylate groups to form various mononuclear 1:1 (AlHL, AlH₂L and AlH₋₁L), 1:2 (AlL₂) complexes, and dinuclear (Al₂H₅L₂) species, where H₄L⁺ denotes totally protonated GSH. Besides the monodentate complexes through carboxylate groups, the amino groups and the peptide bond imino and carbonyl groups may also be involved in binding with Al³⁺ in the bidentate and tridentate complexes. The present data reinforce that the glycine carboxylate group of GSH has a higher microscopic complex formation constant than γ-glutamyl carboxylate. Compared with simple amino acids, the tripeptide GSH displays a greater affinity for the Al³⁺ ion and thus may interfere with aluminum’s biological role more significantly.     

Differences in the binding modes of phytochelatin to cadmium (II) and Zinc(II) ions

An ¹H NMR (nuclear magnetic resonance) spectroscopic structural analysis of Cd²⁺ complexes formed with the pentapeptide phytochelatin, (NH₃)⁺−(ψ-Glu-Cys)₂−Gly−COO−(PC₂), at a pH of 7.5 showed that the two thiol groups of the Cys residues and either the carbonyl or amide group of the peptide bond between Glu1 and Cys1 act as possible donor groups in the complexes at Cd²⁺/PC₂ ratios up to 0.4. As the ratio increases, the carboxylate group of Glu2 and either the carbonyl or amide group of the peptide bond between Cys1 and Glu2 comes to serve as a donor group. The manner in which Cd²⁺ forms complexes with PC₂ is distinctly different from Zn²⁺ and might account for the role of phytochelatin in Cd²⁺ detoxification. Electron absorption spectrometry demonstrated that the Cd²⁺ complexes are coordinated in a tetrahedral fashion by four thiol groups and that several sulfur atoms might bridge Cd²⁺ ions, resulting in the formation of polynuclear complexes. This contrasts with Zn²⁺ complex formation, which consists exclusively of a 1:1 complex.     

2D coordination polymers of Nd(III) and Gd(III) with the phenoxyacetate ligand

The self-assembly of anionic phenoxyacetate ligands and Nd(III) cations in a 3:1 ratio leads to a 2D {Nd₂(PhOCH₂COO)₆(H₂O)₃ · H₂O}_n coordination polymer 1, which was structurally characterized. The metal centers are bridged by carboxylic groups to form infinite parallel chains separated (19.4 Å) by the π-π and C-H?π-stacked phenoxy groups of the ligands. The thermal dependence of the molar magnetic susceptibility for the isostructural gadolinium polymer 2 has been measured and analyzed according to the analytical expression of an infinite chain of classical spins derived by Fisher. The Gd?Gd interaction is ferromagnetic with a magnitude of 0.015(3) cm⁻¹. Modelling of the field-dependent magnetization at 2 K corroborates this result.