Structural variations across the lanthanide series of macrocyclic DOTA complexes: insights into the design of contrast agents for magnetic resonance imaging

It was early shown that the macrocyclic Ln(DOTA) complexes (DOTA = 1,4,7,10-tetra-azacyclododecane-N,N',N' ',N' "-tetraacetic acid) exists in solution as a mixture of two enantiomeric pairs of diastereoisomers differing in the ligand conformation, namely, square antiprismatic (SA) and twisted square antiprismatic (TSA) geometries, respectively. Later, extensive (1)H NMR investigations suggested that a coordination change may be superimposed on this conformational equilibrium involving two additional structures in which the metal ion possesses a coordination number of eight (CN 8). It was predicted that these two species, lacking the apical coordinated water molecule, would maintain the SA and TSA coordination geometries, and therefore, they have been labeled as SA' and TSA', respectively. In this work we report the X-ray solid-state crystal structure determination of six Ln(DOTA) complexes representative of all four coordination geometry typologies deduced from NMR solution studies. A distinctive structural feature that discriminates SA (and SA') and TSA (and TSA') structures is represented by the twist angle between the two square planes of the antiprism, the basal four nitrogen, and the apical four oxygen planes. [Ce(DOTA)(H(2)O)](-) displays a TSA structural typology with a twist angle of 25 degrees and a Ce-O(water) distance of 2.59 A. The SA-type structure has been found in the case of complexes with Pr(III), Nd(III), and Dy(III), where the twist angle is 39, 39, and 38 degrees, respectively, and the metal-water oxygen distance varies significantly (Pr-O(w) 2.529 A; Nd-O(w) 2.508 A; and Dy-O(w) 2.474 A). [Tm(DOTA)](-) displays a TSA'-type structure with a twist angle of 24 degrees. As compared with the TSA structure of the corresponding Ce(III) complex, the Tm(III) complex shows an overall marked shrinkage of all metal-nitrogen and metal-oxygen distances (ca. 0.2 A), which reflects the contraction of the metal ionic radius across the series but also the effect associated with the decrease of the CN from 9 to 8. In [Sc(DOTA)](-), the even smaller ionic radius of Sc(III) shifts the geometry of the coordination cage to the more compact SA' typology with a twist angle of 41 degrees, a value very similar to that found in the SA structures of lanthanide(III) ions with CN 9. Finally, an investigation was made into the hydration spheres of the complexes with SA and TSA geometries to account for the experimental evidence of a markedly different rate of water exchange for the two isomeric structures. This is of fundamental importance to the understanding of the corresponding Gd(III) complexes as MRI contrast agents.     

Enantiomeric self-recognition in homo- and heterodinuclear macrocyclic lanthanide(III) complexes

The controlled formation of lanthanide(III) dinuclear μ-hydroxo-bridged [Ln(2)L(2)(μ-OH)(2)X(2)](n+) complexes (where X = H(2)O, NO(3)(-), or Cl(-)) of the enantiopure chiral macrocycle L is reported. The (1)H and (13)C NMR resonances of these complexes have been assigned on the basis of COSY, NOESY, TOCSY, and HMQC spectra. The observed NOE connectivities confirm that the dimeric solid-state structure is retained in solution. The enantiomeric nature of the obtained chiral complexes and binding of hydroxide anions are reflected in their CD spectra. The formation of the dimeric complexes is accompanied by a complete enantiomeric self-recognition of the chiral macrocyclic units. The reaction of NaOH with a mixture of two different mononuclear lanthanide(III) complexes, [Ln(1)L](3+) and [Ln(2)L](3+), results in formation of the heterodinuclear [Ln(1)Ln(2)L(2)(μ-OH)(2)X(2)](n+) complexes as well as the corresponding homodinuclear complexes. The formation of the heterodinuclear complex is directly confirmed by the NOESY spectra of [EuLuL(2)(μ-OH)(2)(H(2)O)(2)](4+), which reveal close contacts between the macrocyclic unit containing the Eu(III) ion and the macrocyclic unit containing the Lu(III) ion. While the relative amounts of homo- and heterodinuclear complexes are statistical for the two lanthanide(III) ions of similar radii, a clear preference for the formation of heterodinuclear species is observed when the two mononuclear complexes contain lanthanide(III) ions of markedly different sizes, e.g., La(III) and Yb(III). The formation of heterodinuclear complexes is accompanied by the self-sorting of the chiral macrocyclic units based on their chirality. The reactions of NaOH with a pair of homochiral or racemic mononuclear complexes, [Ln(1)L(RRRR)](3+)/[Ln(2)L(RRRR)](3+), [Ln(1)L(SSSS)](3+)/[Ln(2)L(SSSS)](3+), or [Ln(1)L(rac)](3+)/[Ln(2)L(rac)](3+), results in mixtures of homochiral, homodinuclear and homochiral, heterodinuclear complexes. On the contrary, no heterochiral, heterodinuclear complexes [Ln(1)L(RRRR)Ln(2)L(SSSS)(μ-OH)(2)X(2)](n+) are formed in the reactions of two different mononuclear complexes of opposite chirality.     

A simple thermodynamic model for rationalizing the formation of self-assembled multimetallic edifices: application to triple-stranded helicates

Reaction of the bis-tridentate ligand bis[1-ethyl-2-[6'-(N,N-diethylcarbamoyl)pyridin-2'-yl]benzimidazol-5-yl]methane (L2) with Ln(CF(3)SO(3))(3).xH(2)O in acetonitrile (Ln = La-Lu) demonstrates the successive formation of three stable complexes [Ln(L2)(3)](3+), [Ln(2)(L2)(3)](6+), and [Ln(2)(L2)(2)](6+). Crystal-field independent NMR methods establish that the crystal structure of [Tb(2)(L2)(3)](6+) is a satisfying model for the helical structure observed in solution. This allows the qualitative and quantitative beta23 (bi,Ln1,Ln2)characterization of the heterobimetallic helicates [(Ln(1))(Ln(2))(L2)(3)](6+). A simple free energy thermodynamic model based on (i) an absolute affinity for each nine-coordinate lanthanide occupying a terminal N(6)O(3) site and (ii) a single intermetallic interaction between two adjacent metal ions in the complexes (DeltaE) successfully models the experimental macroscopic constants and allows the rational molecular programming of the extended trimetallic homologues [Ln(3)(L5)(3)](9+).     

Synthesis and structural characterization of lanthanide(III) nitrate complexes of a tetraiminodiphenol macrocycle in the solid state and in solution

The lanthanide(III) complexes [Ln(LH2)(NO3)3] 1-11(La-Er), 15(Y) and [Ln(LH2)(NO3)2(H2O)](NO3) 12-14 (Tm-Lu) of the tetraiminodiphenolate macrocycle L2- have been prepared by the transmetallation reaction between [Pb(LH2)(NO3)2] and Ln(NO3)3.nH2O. In these compounds, the uncoordinated imino nitrogens are protonated and are hydrogen bonded to the phenolate oxygens. The X-ray crystal structures of the La (1), Ho (10) and Lu (14) compounds have been determined. Compounds 1 and 10, in which all the three nitrates are bound in bidentate fashion, are isostructural with distorted bicapped square antiprism geometry for the metal centre. In [Lu(LH2)(NO3)2(H2O)](NO3) 14, of the two metal bound nitrates one is bidentate and the other is unidentate, while the metal centre obtains a distorted square antiprism coordination environment. Proton NMR spectra of the paramagnetic lanthanide complexes have been studied in detail. Contributions of contact and pseudo-contact shifts to the lanthanide induced isotropic shifts (LIS) of the macrocycle protons have been separated and good agreement has been obtained between the calculated LIS values and the experimentally observed values. Analysis of the NMR data has led us to conclude that all the complexes in dimethyl sulfoxide solution attain similar configurations. The absorption and emission spectral characteristic of several compounds have been investigated. The complexes of samarium (5) and europium (6) on photoexcitation at 400 nm exhibit well-resolved luminescence spectra at 77 K both in the solid state and a methanol-ethanol (1 : 4) glassy matrix. For the terbium (8) and dysprosium (9) complexes, however, the observed luminescence peaks are less resolved and weak in intensity.     

Structural analysis of nine-coordinate lanthanide complexes: steric control of the metal-water distance across the series

The structures of 10 isomorphous lanthanide (Ln) complexes of a chiral DOTA tetra-amide ligand (L(1)), [LnL(1)(H(2)O)](CF(3)SO(3))(3).3H(2)O, crystallizing in space group P2(1), have been studied by single-crystal X-ray diffraction. The Ln coordination is a O(4)N(4) square antiprism, the O(4) base of which is capped by an aqua ligand. The sterically demanding position of the latter results in the lengthening of the Ln-OH(2) distance along the Pr to Lu series by 0.06 A (after allowing for the lanthanide contraction). In parallel, the distance between the bound water oxygen and the second-sphere water oxygen is reduced from 3.17 A (Pr) to 3.04 A (Lu), consistent with the enhanced hydrogen bond acceptor ability of the coordinated water oxygen across the series. A Cambridge Structural Database survey of [Ln(H(2)O)(9)](CF(3)SO(3))(3) salts (space group P6(3)/m) and of six reported isostructural complexes of DOTA [L(2)] revealed a similar trend. The implications of the resultant destabilization of the ground state structure for the water interchange process are discussed.     

Coordination of rare-earth elements in complexes with monovacant Wells-Dawson polyoxoanions

The alpha-1 and alpha-2 isomers of the monovacant Wells-Dawson heteropolyoxoanion [P(2)W(17)O(61)](10-) are complexants of trivalent rare-earth (RE) ions and serve to stabilize otherwise reactive tetravalent lanthanide (Ln) and actinide (An) ions in aqueous solution. Aspects of the bonding of Ln ions with alpha-1-[P(2)W(17)O(61)](10-) and alpha-2-[P(2)W(17)O(61)](10-) were investigated to address issues of complex formation and stability. We present structural insights about the Ln(III) coordination environment and hydration in two types of stoichiometric complexes, [Ln(alpha-1-P(2)W(17)O(61))](7-) and [Ln(alpha-2-X(2)W(17)O(61))(2)](17-) (for Ln identical with Sm, Eu, Lu; X identical with P, As). The crystal and molecular structures of [(H(2)O)(4)Lu(alpha-1-P(2)W(17)O(61))](7-) (1) and [Lu(alpha-2-P(2)W(17)O(61))(2)](17-) (2) were solved and refined through use of single-crystal X-ray diffraction. The crystallographic results are supported with corresponding insights from XAFS (X-ray absorption fine structure) for a series of nine solid-state complexes as well as from optical luminescence spectroscopy of the Eu(III) analogues in aqueous solution. All the Ln ions are eight-coordinate with oxygen atoms in a square antiprism arrangement. For the 1:1 stoichiometric Ln/alpha-1-[P(2)W(17)O(61)](10-) complexes, the Ln ions are bound to four O atoms of the lacunary polyoxometalate framework in addition to four O atoms from solvent (water) molecules as [(H(2)O)(4)Ln(alpha-1-P(2)W(17)O(61))](7-). This structure (1) is the first of its kind for any metal complex of alpha-1-[P(2)W(17)O(61)](10-), and the data indicate that the general stoichiometry [(H(2)O)(4)Ln(alpha-1-P(2)W(17)O(61))](7-) is maintained throughout the lanthanide series. For the 1:2 stoichiometric Ln/alpha-2-[X(2)W(17)O(61)](10-) complexes, no water molecules are in the Ln-O(8) coordination sphere. The Ln ions are bound to eight O atoms-four from each of two heteropolyanions-as [Ln(alpha-2-X(2)W(17)O(61))(2)](17-). The average Ln-O interatomic distances decrease across the lanthanide series, consistent with the decreasing Ln ionic radius.     

The first self-assembled trimetallic lanthanide helicates driven by positive cooperativity

The segmental tris-tridentate ligand L7 reacts with stoichiometric quantities of Ln(III) (Ln=La-Lu) in acetonitrile to give the complexes [Ln(2)(L7)(3)](6+) and [Ln(3)(L7)(3)](9+). Formation constants point to negligible size-discriminating effects along the lanthanide series, but Scatchard plots suggest that the self-assembly of the trimetallic triple-stranded helicates [Ln(3)(L7)(3)](9+) is driven to completion by positive cooperativity, despite strong intermetallic electrostatic repulsions. Crystallization provides quantitatively [Ln(3)(L7)(3)](CF(3)SO(3))(9) (Ln=La, Eu, Gd, Tb, Lu) and the X-ray crystal structure of [Eu(3)(L7)(3)](CF(3)SO(3))(9).(CH(3)CN)(9).(H(2)O)(2) (Eu(3)C(216)H(226)N(48)O(35)F(27)S(9), triclinic, P1, Z=2) shows the three ligand strands wrapped around a pseudo-threefold axis defined by the three metal ions rigidly held at about 9 A. Each metal ion is coordinated by nine donor atoms in a pseudo-trigonal prismatic arrangement, but the existence of terminal carboxamide units in the ligand strands differentiates the electronic properties of the terminal and the central metallic sites. Photophysical data confirm that the three coordination sites possess comparable pseudo-trigonal symmetries in the solid state and in solution. High-resolution luminescence analyses evidence a low-lying LMCT state affecting the central EuN(9) site, so that multi-metal-centered luminescence is essentially dominated by the emission from the two terminal EuN(6)O(3) sites in [Eu(3)(L7)(3)](9+). New multicenter equations have been developed for investigating the solution structure of [Ln(3)(L7)(3)](9+) by paramagnetic NMR spectroscopy and linear correlations for Ln=Ce-Tb imply isostructurality for these larger lanthanides. NMR spectra point to the triple helical structure being maintained in solution, but an inversion of the magnitude of the second-rank crystal-field parameters, obtained by LIS analysis, for the LnN(6)O(3) and LnN(9) sites with respect to the parameters extracted for Eu(III) from luminescence data, suggests that the geometry of the central LnN(9) site is somewhat relaxed in solution.     

Lanthanide chelates containing pyridine units with potential application as contrast agents in magnetic resonance imaging

A new pyridine-containing ligand, N,N'-bis(6-carboxy-2-pyridylmethyl)ethylenediamine-N,N'-diacetic acid (H(4)L), has been designed for the complexation of lanthanide ions. (1)H and (13)C NMR studies in D(2)O solutions show octadentate binding of the ligand to the Ln(III) ions through the nitrogen atoms of two amine groups, the oxygen atoms of four carboxylates, and the two nitrogen atoms of the pyridine rings. Luminescence measurements demonstrate that both Eu(III) and Tb(III) complexes are nine-coordinate, whereby a water molecule completes the Ln(III) coordination sphere. Ligand L can sensitize both the Eu(III) and Tb(III) luminescence; however, the quantum yields of the Eu(III)- and Tb(III)-centered luminescence remain modest. This is explained in terms of energy differences between the singlet and triplet states on the one hand, and between the 0-phonon transition of the triplet state and the excited metal ion states on the other. The anionic [Ln(L)(H2O)]- complexes (Ln=La, Pr, and Gd) were also characterized by theoretical calculations both in vacuo and in aqueous solution (PCM model) at the HF level by means of the 3-21G* basis set for the ligand atoms and a 46+4 f(n) effective core potential for the lanthanides. The structures obtained from these theoretical calculations are in very good agreement with the experimental solution structures, as demonstrated by paramagnetic NMR measurements (lanthanide-induced shifts and relaxation-rate enhancements). Data sets obtained from variable-temperature (17)O NMR at 7.05 T and variable-temperature (1)H nuclear magnetic relaxation dispersion (NMRD) on the Gd(III) complex were fitted simultaneously to give insight into the parameters that govern the water (1)H relaxivity. The water exchange rate (k(298)(ex)=5.0 x 10(6) s(-1)) is slightly faster than in [Gd(dota)(H2O)]- (DOTA=1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane). Fast rotation limits the relaxivity under the usual MRI conditions.     

Novel macrocyclic EuII complexes: fast water exchange related to an extreme M-O water distance

Eu(II) complexes are potential candidates for pO(2)-responsive contrast agents in magnetic resonance imaging. In this regard, we have characterized two novel macrocyclic Eu(II) chelates, [Eu(II)(DOTA)(H(2)O)](2-) and [Eu(II)(TETA)](2-) (H(4)DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, H(4)TETA=1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid) in terms of redox and thermodynamic complex stability, proton relaxivity, water exchange, rotation and electron spin relaxation. Additionally, solid-state structures were determined for the Sr(II) analogues. They revealed no inner-sphere water in the TETA and one inner-sphere water molecule in the DOTA complex. This hydration pattern is retained in solution, as the (17)O chemical shifts and (1)H relaxation rates proved for the corresponding Eu(II) compounds. The thermodynamic complex stability, determined from the formal redox potential and by pH potentiometry, of [Eu(II)(DOTA)(H(2)O)](2-) (lg K(Eu(II))=16.75) is the highest among all known Eu(II) complexes, whereas the redox stabilities of both [Eu(II)(DOTA)(H(2)O)](2-) and [Eu(II)(TETA)](2-) are inferior to that of 18-membered macrocyclic Eu(II) chelates. Variable-temperature (17)O NMR, NMRD and EPR studies yielded the rates of water exchange, rotation and electron spin relaxation. Water exchange on [Eu(II)(DOTA)(H(2)O)](2-) is remarkably fast (k298(ex)=2.5 x 10(9) s(-1)). The near zero activation volume (DeltaV++ =+0.1+/-1.0 cm(3) mol(-1)), determined by variable-pressure (17)O NMR spectroscopy, points to an interchange mechanism. The fast water exchange can be related to the low charge density on Eu(II), to an unexpectedly long M-O(water) distance (2.85 A) and to the consequent interchange mechanism. Electron spin relaxation is considerably slower on [Eu(II)(DOTA)(H(2)O)](2-) than on the linear [Eu(II)(DTPA)(H(2)O)](3-) (H(5)DTPA=diethylenetriaminepentaacetic acid), and this difference is responsible for its 25 percent higher proton relaxivity (r(1)=4.32 mM(-1) s(-1) for [Eu(II)(DOTA)(H(2)O)](2-) versus 3.49 mM(-1) s(-1) for [Eu(II)(DTPA)(H(2)O)](3-); 20 MHz, 298 K).     

Gadolinium(III) complexes of mono- and diethyl esters of monophosphonic acid analogue of DOTA as potential MRI contrast agents: solution structures and relaxometric studies

Two new macrocyclic DOTA-like chelates containing one phosphonate pendant arm were synthesised as potential contrast agents for MRI (magnetic resonance imaging). The chelates bind to the lanthanide(III) in an octadentate manner, via four nitrogen atoms, three carboxylate and one phosphonate oxygen atoms. Solution structures of [Ln(do3ap(OEt2))(H(2)O)] and [Ln(do3ap(OEt))(H(2)O)](-) were studied using (31)P and (1)H NMR spectroscopy and SAP (square-antiprismatic)/TSAP (twisted square-antiprismatic) isomerism was observed. Depending on the nature of the lanthanide(III) ion, the lanthanide(III) complexes of H(4)do3ap(OEt) are present in solution as up to four different diastereoisomers observable with NMR. The TSAP isomer is the most abundant at the beginning of the lanthanide series and, with a decrease of the ionic radius of lanthanide(III) ions, both TSAP and SAP forms were observed. A second interconversion (SAP<-->TSAP') becomes important at the end of the series (TSAP' means the TSAP species without a coordinated water molecule). The remaining axial coordination site is occupied by one water molecule for the Gd(3+)-complex. The calculated fraction of the TSAP isomer in the gadolinium(III) complexes increases in the order [Gd(DOTA)(H(2)O)](-) < [Gd(do3ap(OEt2))(H(2)O)] < [Gd(do3ap(OEt))(H(2)O)](-) < [Gd(do3ap)(H(2)O)](2-). Gadolinium(III) complexes of phosphorus-containing chelates, generally, have the advantage of a relatively fast water exchange rate due to a greater sterical demand of the phosphorus acid moiety and of the presence of the second-sphere water shell, which also contributes to the overall relaxivity. The [Gd(do3ap(OEt2))(H(2)O)] and [Gd(do3ap(OEt))(H(2)O)](-) complexes were studied by variable-temperature (17)O NMR and (1)H NMRD. The experimental data were evaluated simultaneously with commonly used equations based on Solomon-Bloembergen-Morgan approximation, extended by a contribution of the second coordination sphere. The water exchange rates were found to be strongly dependent on the TSAP/SAP isomeric ratio and the overall charge of the complex: the monoanionic [Gd(do3ap(OEt))(H(2)O)](-) complex with TSAP molar fraction equal to 0.36 has the water exchange rate of 20 x 10(6) s(-1) (tau(M) = 50 ns) while neutral [Gd(do3ap(OEt2))(H(2)O)] complex with TSAP molar fraction 0.28 has an exchange rate equal to 4.4 x 10(6) s(-1) (tau(M) = 227 ns).     

Lanthanide-transition-metal carbonyl complexes: new [Co4(CO)11]2- clusters and lanthanide(II) isocarbonyl polymeric arrays

Two types of Ln(II)-Co(4) isocarbonyl polymeric arrays, [(Et(2)O)(3)(-)(x)()(THF)(x)()Ln[Co(4)(CO)(11)]]( infinity ) (1-3; x = 0, 1) and [(THF)(5)Eu[Co(4)(CO)(11)]]( infinity ) (4), were prepared and structurally characterized. Transmetalation involving Ln(0) and Hg[Co(CO)(4)](2) in Et(2)O yields [(Et(2)O)(3)Ln[Co(4)(CO)(11)]]( infinity ) (1, Ln = Yb; 2, Ln = Eu). Dissolution of the solvent-separated ion pairs [Ln(THF)(x)()][Co(CO)(4)](2) (Ln = Yb, x = 6; Ln = Eu) in Et(2)O affords [(Et(2)O)(2)(THF)Yb[Co(4)(CO)(11)]]( infinity ) (3) and [(THF)(5)Eu[Co(4)(CO)(11)]]( infinity ) (4). In these reactions, oxidation and condensation of the [Co(CO)(4)](-) anions result in formation of the new tetrahedral cluster [Co(4)(CO)(11)](2)(-). The two types of Ln(II)-Co(4) compounds contain different isomers of [Co(4)(CO)(11)](2)(-), and, consequently, the structures of the infinite isocarbonyl networks are distinct. The cluster in [(Et(2)O)(3)(-)(x)()(THF)(x)()Ln[Co(4)(CO)(11)]]( infinity ) (1-3) possesses pseudo C(3)(v)() symmetry (an apical Co, three basal Co atoms; one face-bridging, three edge-bridging, seven terminal carbonyls) and connects to Ln(II) centers through eta(2),micro(4)- and eta(2),micro(3)-carbonyls to generate a 2-D puckered sheet. In contrast, [(THF)(5)Eu[Co(4)(CO)(11)]]( infinity ) (4) incorporates a C(2)(v)() symmetric cluster (two unique Co environments; two face-bridging, one edge-bridging, eight terminal carbonyls), and isocarbonyl linkages (eta(2),micro(4)-carbonyls) to Eu(II) atoms create a 1-D zigzag chain. Complexes 1-4 contain the first reported eta(2),micro(4)-CO bridges between a Ln and a transition-metal carbonyl cluster. Infrared spectroscopic studies revealed that the isocarbonyl associations to Ln(II) persist in solution. The solution structure and dynamic behavior of the [Co(4)(CO)(11)](2)(-) cluster in 1 was investigated by variable-temperature (59)Co and (13)C NMR spectroscopies.     

Assignment of the electronic spectra of [Mo(CN)(8)](4)(-) and [W(CN)(8)](4)(-) by Ab initio calculations

CASPT2 calculations are performed on the dodecahedral and square antiprismatic isomers of the [Mo(CN)(8)](4)(-) and [W(CN)(8)](4)(-) complexes. The high-energy experimental bands above 40000 cm(-)(1) are assigned to MLCT transitions. The experimental observed trend of the extinction coefficients for the molybdenum and tungsten complex is reproduced by our CASSCF oscillator strengths. All bands below 40000 cm(-)(1) can be ascribed to ligand-field transitions, although small contributions from forbidden MLCT transitions cannot be excluded. In order to account for all experimental bands in the electronic spectrum of these octacyanocomplexes, a dynamic equilibrium in solution between the two isomeric forms must be hypothesized. Spin-orbit coupling effects are found to be more important for the square antiprismatic isomers; in particular, large singlet-triplet mixings are calculated for this isomer of [W(CN)(8)](4)(-). Ligand-field and Racah parameters as well as spin-orbit coupling constants are determined on the basis of the calculated transition energies. The obtained values for these parameters support the recently proposed model for exchange interactions in magnetic clusters and networks containing pentavalent octocyanometalates of molybdenum and tungsten.     

Syntheses and structural characterizations of sheet- and column-like lanthanide-transition metal arrays: the effect of hydrogen bonding on the structure when K(+) is replaced by [NH4]+

Sheet- and column-like cyanide bridged lanthanide-transition metal arrays were synthesized through metathesis reactions between anhydrous LnCl(3) (Ln = Eu, Yb) and A(2)[M(CN)(4)] (A = K(+), NH(4)(+); M = Ni, Pt) in a 1:2 molar ratio in DMF (DMF = N,N-dimethylformamide) solution. Single-crystal X-ray analysis revealed that complexes of formula [K(DMF)(7)Ln[M(CN)(4)](2)](infinity) (Ln = Eu, M = Ni, 1; Ln = Yb, M = Pt, 2) consist of infinite layers of neutral, puckered sheets that contain hexagonal rings of composition [(DMF)(10)Ln(2)[M(CN)(4)](3)](6) with interstitial (DMF)(4)K(2)[M(CN)(4)] units located between the layers. The sheet structure is generated through the repeating (DMF)(10)Ln(2)[M(CN)(4)](3) unit with trans cyanide ligands in [M(CN)(4)](2)(-) serving as bridges. The column-like complex [(NH(4))(DMF)(4)Yb[Pt(CN)(4)](2)](infinity), 3, is formed when NH(4)(+) replaces K(+). It consists of infinite, negatively charged, square, parallel columns bundled through N-H...NC hydrogen bonds between NH(4)(+) and terminal CN from the columns. Cis cyanide ligands in [Pt(CN)(4)](2)(-) units serve as bridges. Complex 3 is the first known example where Ln(III) centers are coordinated to four [M(CN)(4)](2)(-) units. Bicapped (square face) trigonal prismatic coordination geometries were observed for Ln(III) centers in 1 and 2. Square antiprismatic geometry for Yb(III) centers are observed in 3. Crystal data for 1: triclinic space group P1, a = 8.797(2) A, b = 15.621(3) A, c = 17.973(6) A, alpha = 105.48(2) degrees, beta = 98.60(2) degrees, gamma = 98.15(2) degrees, Z = 2. Crystal data for 2: triclinic space group P1, a = 8.825(1) A, b = 15.673(1) A, c = 17.946(1) A, alpha = 105.46(2) degrees, beta = 99.10(1) degrees, gamma = 98.59(1) degrees, Z = 2. Crystal data for 3: monoclinic space group P2(1)/c, a = 9.032(1) A, b = 29.062(1) A, c = 15.316(1) A, beta = 94.51(1) degrees, Z = 2.     

Towards Binuclear Polyaminocarboxylate MRI Contrast Agents? Spectroscopic and MD Study of the Peculiar Aqueous Behavior of the LnIII Chelates of OHEC (Ln=Eu,Gd, and Tb): Implications for Relaxivity

We report the study of binuclear Ln(III) chelates of OHEC (OHEC=octaazacyclohexacosane-1,4,7,10,14,17,20,23-octaacetate). The interconversion between two isomeric forms, which occurs in aqueous solution, has been studied by NMR, UV/Vis, EPR, and luminescence spectroscopy, as well as by classical molecular dynamics (MD) simulations. For the first time we have characterized an isomerization equilibrium for a Ln(III) polyaminocarboxylate complex (Ln(III)=Y, Eu, Gd and Tb) in which the metal centre changes its coordination number from nine to eight, such that: [Ln(2)(ohec)(H(2)O)(2)](2-) r<==>[Ln(2)(ohec)](2-)+2 H(2)O. The variable temperature and pressure NMR measurements conducted on this isomerization reaction give the following thermodynamic parameters for Eu(III): K(298)=0.42+/-0.01, DeltaH(0)=+4.0+/-0.2 kJ mol(-1), DeltaS(0)=+6.1+/-0.5 J K(-1) mol(-1) and DeltaV(0)=+3.2+/-0.2 cm(3) mol(-1). The isomerization is slow and the corresponding kinetic parameters obtained by NMR spectroscopy are: k(298)(is)=73.0+/-0.5 s(-1), DeltaH++(is)=75.3+/-1.9 kJ mol(-1), DeltaS++(is)= +43.1+/-5.8 J K(-1) mol(-1) and DeltaV++(is)=+7.9+/-0.7 cm(3) mol(-1). Variable temperature and pressure (17)O NMR studies have shown that water exchange in [Gd(2)(ohec)(H(2)O)(2)](2-) is slow, k(298)(ex)=(0.40+/-0.02)x10(6) s(-1), and that it proceeds through a dissociative interchange I(d) mechanism, DeltaV( not equal )=+7.3+/-0.3 cm(3) mol(-1). The anisotropy of this oblong binuclear complex has been highlighted by MD simulation calculations of different rotational correlation times. The rotational correlation time directed on the Gd-Gd axis is 24 % longer than those based on the axes orthogonal to the Gd-Gd axis. The relaxivity of this binuclear complex has been found to be low, since 1) only [Gd(2)(ohec)(H(2)O)(2)](2-), which constitutes 70 % of the binuclear complex, contributes to the inner-sphere relaxivity and 2) the anisotropy of the complex prevents water molecules from having complete access to both Gd(III) cages; this decreases the outer-sphere relaxivity. Moreover, EPR measurements for the Gd(III) and for the mixed Gd(III)/Y(III) binuclear complexes have clearly shown that the two Gd(III) centres interact intramolecularly; this enhances the electronic relaxation of the Gd(III) electron spins.     

Analysis of paramagnetic NMR spectra of triple-helical lanthanide complexes with 2,6-dipicolinic acid revisited: a new assignment of structural changes and crystal-field effects 25 years later

Variable-temperature (1)H and (13)C NMR measurements of the D(3)-symmetrical triple-helical complexes [Ln(L1-2H)(3)](3)(-) (L1 = pyridine-2,6-dicarboxylic acid; Ln = La-Lu) show evidence of dynamic intermolecular ligand-exchange processes whose activation energies depend on the size of the metal ion. At 298 K, the use of diastereotopic probes in [Ln(L3-2H)(3)](3)(-) (L3 = 4-ethyl-pyridine-2,6-dicarboxylic acid) shows that fast intramolecular P <==> M interconversion between the helical enantiomers occurs on the NMR time scale. Detailed analyses of the paramagnetic NMR hyperfine shifts according to crystal-field independent techniques demonstrate the existence of two different helical structures, one for large lanthanides (Ln = La-Eu) and one for small lanthanides (Ln = Tb-Lu), in complete contrast with the isostructurality proposed 25 years ago. A careful reconsideration of the original crystal-field-dependent analysis shows that an abrupt variation of the axial crystal-field parameter A(0)2 parallels the structural change leading to some accidental compensation effects that prevent the detection of structural variations according to the classical one-nucleus method. Crystal structures in the solid state and density functional theory calculations in the gas phase provide structural models that rationalize the paramagnetic NMR data. A regular triple-helical structure is found for small lanthanides (Ln = Tb-Lu) in which the terdentate chelating ligands are rigidly tricoordinated to the metals. A flexible and distorted structure is evidenced for Ln = La-Eu in which the central pyridine rings interact poorly with the metal ion. The origin of the simultaneous variation of structural parameters and crystal-field and hyperfine constants near the middle of the lanthanide series is discussed together with the use of crystal-field-independent techniques for the interpretation of paramagnetic NMR spectra in axial lanthanide complexes.     

Pyridine and phosphonate containing ligands for stable lanthanide complexation. An experimental and theoretical study to assess the solution structure

We report an experimental and theoretical study of the stability and solution structure of lanthanide complexes with two novel ligands containing pyridine units and phosphonate pendant arms on either ethane-1,2-diamine (L2) or cyclohexane-1,2-diamine (L3) backbones. Potentiometric studies have been carried out to determine the protonation constants of the ligands and the stability constants of the complexes with Gd(III) and the endogenous metal ions Zn(II) and Cu(II). While the stability constant of the GdL2 complex is too high to be determined by direct pH-potentiometric titrations, the cyclohexyl derivative GdL3 has a lower and assessable stability (log K(GdL3)=17.62). Due to the presence of the phosphonate groups, various protonated species can be detected up to pH approximately 8 for both ligands and all metal ions studied. The molecular clusters [Ln(L)(H2O)](3-).19H2O (Ln=La, Nd, Ho or Lu; L=L2 or L3) were characterized by theoretical calculations at the HF level. Our calculations provide two minimum energy geometries where the ligand adopts different conformations: twist-wrap (tw), in which the ligand wraps around the metal ion by twisting the pyridyl units relative to each other, and twist-fold (tf), where the slight twisting of the pyridyl units is accompanied by an overall folding of the two pyridine units towards one of the phosphonate groups. The relative free energies of the tw and tf conformations of [Ln(L)(H2O)]3- (L=L2, L3) complexes calculated in aqueous solution (C-PCM) by using the B3LYP model indicate that the tw form is the most stable one along the whole lanthanide series for the complexes of L3, while for those of L2 only the Gd(III) complex is more stable in the tf conformation by ca. 0.5 kcal mol-1. 1H NMR studies of the Eu(III) complex of L3 show the initial formation of the tf complex in aqueous solution, which slowly converts to the thermodynamically stable tw form. The structures calculated for the Nd(III) complexes are in reasonably good agreement with the experimental solution structures, as demonstrated by Nd(III)-induced relaxation rate enhancement effects in the 1H NMR spectra.     

Quantum chemical investigation of hyperfine coupling constants on first coordination sphere water molecule of gadolinium(III) aqua complexes

Hyperfine interactions (HFI) on the nuclei of the first coordination sphere water molecules in a model [Gd(H(2)O)(8)](3+) aqua complex and in the magnetic resonance imaging contrast agent [Gd(DOTA)(H(2)O)](-) were studied theoretically. Density functional theory (DFT) calculations combined with classical molecular dynamics (MD) simulations have been used in order to take into account dynamic effects in aqueous solution. DFT relativistic calculations show a strong spin-polarization of the first coordination sphere water molecules. This spin-polarization leads to a positive (17)O isotropic hyperfine coupling constant (A(iso)((17)O) = 0.58 +/- 0.11 MHz) and to a significant increase of the effective distance (r(eff)(Gd-O) = 2.72 +/- 0.06 A) of dipolar interaction compared to the mean internuclear distance (r(Gd-O) = 2.56 +/- 0.06 A) obtained from the MD trajectory of [Gd(DOTA)(H(2)O)](-) in aqueous solution. The point-dipole model for anisotropic hyperfine interaction overestimates therefore the longitudinal relaxation rate of the (17)O nucleus by approximately 45%. The (1)H isotropic hyperfine coupling constant of the bound water molecule is predicted to be very small (A(iso)((1)H) = 0.03 +/- 0.02 MHz), and the point-dipole approximation for first coordination sphere water protons holds. The calculated hyperfine parameters are in good agreement with available experimental data.     

Equilibrium, 1H and 13C NMR spectroscopy,and X-ray diffraction studies on the complexes Bi(DOTA)- and Bi(DO3A-Bu)

Several Bi(III) complexes are used in medicine as drugs. Bi(DO3A-Bu) has recently been proposed as a nonionic contrast agent in X-ray imaging (H(3)DO3A-Bu = 10-[2,3-dihydroxy-(1-hydroxymethyl)propyl]-1,4,7,10-tetraazacyclododecane-1,4,7,-triacetic acid). The solution equilibria and NMR structure and dynamics of Bi(DO3A-Bu) and of the similar Bi(DOTA)(-) have been investigated (H(4)DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). The stability constants were determined with the study of the competition equilibria between Br(-) ions and the ligands DOTA or DO3A-Bu for the Bi(III) by spectrophotometry. The stability constants, obtained for Bi(DOTA)(-) and Bi(DO3A-Bu), are very high, log K = 30.3 and 26.8, respectively. Potentiometric titrations indicated the dissociation of one of the protons among the three alcoholic OH groups in Bi(DO3A-Bu). The dissociation constant is log K = 7.53 (0.09) indicating that at physiological pH about 50% of the species possess -1 charge. It was shown by (1)H and (13)C NMR spectroscopy that the OH group attached to the middle carbon atom of the "butriol" side chain is coordinated to the Bi(III) and starts to deprotonate at pH > 5.5. The crystal structure of NaBi(DOTA).H(2)O shows an octacoordinated arrangement of the donor atoms around the Bi(III), with no water in the inner sphere. The crystals belong to the centrosymmetric space group C2/c. The temperature dependent (1)H and (13)C NMR spectra indicate that both Bi(DOTA)(-) and Bi(DO3A-Bu)(-) complexes are fluxional. For Bi(DOTA), the Delta(deltadeltadeltadelta) right harpoon over left harpoon Lambda(lambdalambdalambdalambda) fluxionality was identified, and on the basis of the activation parameters, a synchronous motion was suggested for the fluxional motion resulting in the change of ring conformation and of the helicity of the complex. The transition state is supposed to be more symmetrical than the initial state. The deprotonated Bi(DO3A-Bu) has a highly asymmetric NMR structure in solution, and its fluxional motion is slower than that of Bi(DOTA)(-).     

Solid state and solution studies of lanthanide(III) complexes of cyclohexanetriols, models of the coordination sites found in sugars

This report covers studies in trivalent lanthanide complexation by two simple cyclohexanetriols that are models of the two coordination sites found in sugars and derivatives. Several complexes of trivalent lanthanide ions with cis,cis-1,3,5-trihydroxycyclohexane (L(1)()) and cis,cis-1,2,3-trihydroxycyclohexane (L(2)()) have been characterized in the solid state, and some of them have been studied in organic solutions. With L(1)(), Ln(L)(2) complexes are obtained when crystallization is performed from acetonitrile solutions whatever the nature of the salt (nitrate or triflate) [Ln(L(1)())(2)(NO(3))(2)](NO(3)) (Ln = Pr, Nd); [Ln(L(1)())(2)(NO(3))H(2)O](NO(3))(2) (Ln = Eu, Ho, Yb); [Ln(L(1)())(2)(OTf)(2)(H(2)O)](OTf) (Ln = Nd, Eu). Lanthanum nitrate itself gives a mixed complex [La(L(1)())(2)(NO(3))(2)][LaL(1)()(NO(3))(4)] from acetonitrile solution while [La(L(1)())(2)(NO(3))(2)](NO(3)) is obtained using dimethoxyethane as reaction solvent and crystallization medium. With L(2)(), Ln(L)(2) complexes have also been crystallized from methanol solution [Ln(L(2)())(2)(NO(3))(2)]NO(3), (Ln = Pr, Nd, Eu). Single-crystal X-ray diffraction analyses are reported for these complexes. Complex formation in solution has been studied for several triflate salts (La, Pr, Nd, Eu, and Yb) with L(1 )()and L(2)(), respectively in acetonitrile and in methanol. In contrast to the solid state, both structures Ln(L) and Ln(L)(2) equilibrate in solution, as was demonstrated by low-temperature (1)H NMR and electrospray ionization mass spectrometry experiments. Competing experiments in complexing abilities of L(1)() and L(2)() with trivalent lanthanide cations have shown that only L(2)() exhibits a small selectivity (Nd > Pr > Yb > La > Eu) in methanol.