Teresa Rodríguez-Blas

Lanthanide dota-like Complexes Containing a Picolinate Pendant: Structural Entry for the Design of LnIII-Based Luminescent Probes

In this contribution we present two ligands based on a do3a platform containing a picolinate group attached to the fourth nitrogen atom of the cyclen unit, which are designed for stable lanthanide complexation in aqueous solutions. Potentiometric measurements reveal that the thermodynamic stability of the complexes is very high (log K = 21.2-23.5), being comparable to that of the dota analogues. Luminescence lifetime measurements performed on solutions of the Eu(III) and Tb(III) complexes indicate that the complexes are nine coordinate with no inner-sphere water molecules. A combination of density functional theory (DFT) calculations and NMR measurements shows that for the complexes of the heaviest lanthanides there is a major isomer in solution consisting of the enantiomeric pair Λ(δδδδ) and Δ(λλλλ), which provides square antiprismatic coordination (SAP) around the metal ion. Analysis of the Yb(III)-induced paramagnetic shifts unambiguously confirms that these complexes have SAP coordination in aqueous solution. For the light lanthanide ions however both the SAP and twisted-square antiprismatic (TSAP) isomers are present in solution. Inversion of the cyclen ring appears to be the rate-determining step for the Λ(δδδδ) ↔ Δ(λλλλ) enantiomerization process observed in the Lu(III) complexes. The energy barriers obtained from NMR measurements for this dynamic process are in excellent agreement with those predicted by DFT calculations. The energy barriers calculated for the arm-rotation process are considerably lower than those obtained for the ring-inversion path. Kinetic studies show that replacement of an acetate arm of dota by a picolinate pendant results in a 3-fold increase in the formation rate of the corresponding Eu(III) complexes and a significant increase of the rates of acid-catalyzed dissociation of the complexes. However, these rates are 1-2 orders of magnitude lower than those of do3a analogues, which shows that the complexes reported herein are remarkably inert with respect to metal ion dissociation.

Hyperfine coupling constants on inner-sphere water molecules of Gd(III)-based MRI contrast agents.

Herein we present a theoretical investigation of the hyperfine coupling constants (HFCCs) on the inner-sphere water molecules of [Gd(H(2)O)(8)](3+) and different Gd(III)-based magnetic resonance imaging contrast agents such as [Gd(DOTA)(H(2)O)](-), [Gd(DTPA)(H(2)O)](2-), [Gd(DTPA-BMA)(H(2)O)] and [Gd(HP-DO3A)(H(2)O)]. DFT calculations performed on the [Gd(H(2)O)(8)](3+) model system show that both hybrid-GGA functionals (BH&HLYP, B3PW91 and PBE1PBE) and the hybrid meta-GGA functional TPSSh provide (17)O HFCCs in close agreement with the experimental data. The use of all-electron relativistic approaches based on the DKH2 approximation and the use of relativistic effective core potentials (RECP) provide results of essentially the same quality. The accurate calculation of HFCCs on the [Gd(DOTA)(H(2)O)](-), [Gd(DTPA)(H(2)O)](2-), [Gd(DTPA-BMA)(H(2)O)] and [Gd(HP-DO3A)(H(2)O)] complexes requires an adequate description of solvent effects. This was achieved by using a mixed cluster/continuum approach that includes explicitly two second-sphere water molecules. The calculated isotropic (17)O HFCCs (A(iso)) fall within the range 0.40-0.56 MHz, and show deviations from the corresponding experimental values typically lower than 0.05 MHz. The A(iso) values are significantly affected by the distance between the oxygen atom of the coordinated water molecule and the Gd(III) ion, as well as by the orientation of the water molecule plane with respect to the Gd-O vector. (1)H HFCCs of coordinated water molecules and (17)O HFCCs of second-sphere water molecules take values close to zero.

Solution Structure and Dynamics, Stability, and NIR Emission Properties of Lanthanide Complexes with a Carboxylated Bispyrazolylpyridyl Ligand

The complexation behavior of the ligand 2,6-bis{3-[N,N-bis(carboxymethyl)aminomethyl]pyrazol-1-yl}-pyridine, L, toward lanthanide cations was investigated throughout the series. Potentiometric titration experiments on L (0.1 M KCl) revealed the presence of four protonation steps in the 2-12 pH domain, associated with the protonation of the two tertiary amine nitrogen atoms and with two of the four carboxylate functions. The stability constants for the formation of the [LnL](-) complexes (Ln = La, Nd, Eu, Ho, and Lu) were determined in water and evidenced a hill-shaped complexation trend along the series, with log K increasing from 14.56(9) (La) to 16.68(2) (Ho) and decreasing to 15.42(2) (Lu). Geometry optimizations showed the [LnL](-) complexes (Ln = La, Nd, Eu, Ho, Yb, and Lu) adopting a C(2) symmetry with the symmetry axis going through the metal atom and the nitrogen atom of the central pyridine ring, leading to the presence of Delta and Lambda helical enantiomers. Analysis of the calculated Ln-O and Ln-N bond lengths showed a marked deviation from the expected values at the end of the series, which accounts for the observed decreased complexation affinity. (1)H and (13)C NMR experiments in D(2)O (room temperature) showed the shortening of the bond distances in [LnL](-) complexes from La to Lu to be accompanied by a rigidification of the structure, leading to a decreased C(2) symmetry for the Lu complex compared to C(2v) for La. This decreased symmetry was attributed to a slow Delta <--> Lambda interconversion that was followed by variable-temperature (13)C NMR experiments on the Lu complex. The activation parameters determined by line broadening analysis for this interconversion process point to an associatively assisted interconversion process. The (1)H NMR spectrum of the paramagnetic [YbL](-) complex was investigated in D(2)O, and a lanthanide induced shift analysis showed good agreement between the observed paramagnetic chemical shifts and those calculated from the DFT optimized structures using a dipolar model, especially when solvent effects are taken into account. The UV-vis absorption and near-infrared luminescence spectra of the Pr, Nd, Er, and Yb complexes were measured in water and showed the complexation pocket provided by the ligand to be well-suited for the protection of the cations, all of them displaying typical Ln-centered emission spectra, the Yb complex having a relatively long lifetime of 3.0 micros in water.

Stability, Water Exchange, and Anion Binding Studies on Lanthanide(III) Complexes with a Macrocyclic Ligand Based on 1,7-Diaza-12-crown-4: Extremely Fast Water Exchange on the Gd3+ Complex

The picolinate-derivative ligand based on the 1,7-diaza-12-crown-4 platform (bp12c4(2-)) forms stable Ln(3+) complexes with stability constants increasing from the early to the middle lanthanides, then being relatively constant for the rest of the series (logK(LnL) = 16.81(0.06), 18.82(0.01), and 18.08(0.05) for Ln = La, Gd, and Yb, respectively). The complex formation is fast, allowing for direct potentiometric titrations to assess the stability constants. In the presence of Zn(2+), the dissociation of [Gd(bp12c4)](+) proceeds both via proton- and metal-assisted pathways, and in this respect, this system is intermediate between DTPA-type and macrocyclic, DOTA-type chelates, for which the dissociation is predominated by metal- or proton-assisted pathways, respectively. The Cu(2+) exchange shows an unexpected pH dependency, with the observed rate constants decreasing with increasing proton concentration. The rate of water exchange, assessed by (17)O NMR, is extremely high on the [Gd(bp12c4)(H(2)O)(q)](+) complex (k(ex)(298) = (2.20 +/- 0.15) x 10(8) s(-1)), and is in the same order of magnitude as for the Gd(3+) aqua ion (k(ex)(298) = 8.0 x 10(8) s(-1)). In aqueous solution, the [Gd(bp12c4)(H(2)O)(q)](+) complex is present in hydration equilibrium between nine-coordinate, monohydrated, and ten-coordinate, bishydrated species. We attribute the fast exchange to the hydration equilibrium and to the flexible nature of the inner coordination sphere. The large negative value of the activation entropy (DeltaS = -35 +/- 8 J mol(-1) K(-1)) points to an associative character for the water exchange and suggests that water exchange on the nine-coordinate, monohydrated species is predominant in the overall exchange. Relaxometric and luminescence measurements on the Gd(3+) and Eu(3+) analogues, respectively, indicate strong binding of endogenous anions such as citrate, hydrogencarbonate, or phosphate to [Ln(bp12c4)](+) complexes (K(aff) = 280 +/- 20 M(-1), 630 +/- 50 M(-1), and 250 +/- 20 M(-1), respectively). In the ternary complexes, the inner sphere water molecules are fully replaced by the corresponding anion. Anion binding is favored by the positive charge of the [Ln(bp12c4)](+) complexes and the adjacent position of the two inner sphere water molecules. To obtain information about the structure of the ternary complexes, the [Gd(bp12c4)(HCO(3))] and [Gd(bp12c4)(H(2)PO(4))] systems were investigated by means of density functional theory calculations (B3LYP model). They show that anion coordination provokes an important lengthening of the distances between the donor atoms and the lanthanide ion. The coordination of phosphate induces a more important distortion of the metal coordination environment than the coordination of hydrogencarbonate, in accordance with a higher binding constant for HCO(3)(-) and a more important steric demand of phosphate.

Lanthanide(III) complexes with ligands derived from a cyclen framework containing pyridinecarboxylate pendants. The effect of steric hindrance on the hydration number.

Two new macrocyclic ligands, 6,6′-((1,4,7,10-tetraazacyclododecane-1,7-diyl)bis(methylene))dipicolinic acid (H2DODPA) and 6,6′-((4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diyl)bis(methylene))dipicolinic acid (H2Me-DODPA), designed for complexation of lanthanide ions in aqueous solution, have been synthesized and studied. The X-ray crystal structure of [Yb(DODPA)](PF6)·H2O shows that the metal ion is directly bound to the eight donor atoms of the ligand, which results in a square-antiprismatic coordination around the metal ion. The hydration numbers (q) obtained from luminescence lifetime measurements in aqueous solution of the Eu(III) and Tb(III) complexes indicate that the DODPA complexes contain one inner-sphere water molecule, while those of the methylated analogue H2Me-DODPA are q = 0. The structure of the complexes in solution has been investigated by 1H and 13C NMR spectroscopy, as well as by theoretical calculations performed at the density functional theory (DFT; mPWB95) level. The minimum energy conformation calculated for the Yb(III) complex [Λ(λλλλ)] is in good agreement with the experimental structure in solution, as demonstrated by the analysis of the Yb(III)-induced paramagnetic 1H shifts. The nuclear magnetic relaxation dispersion (NMRD) profiles recorded for [Gd(Me-DODPA)]+ are typical of a complex with q = 0, where the observed relaxivity can be accounted for by the outer-sphere mechanism. However, [Gd(DODPA)]+ shows NMRD profiles consistent with the presence of both inner- and outer-sphere contributions to relaxivity. A simultaneous fitting of the NMRD profiles and variable temperature 17O NMR chemical shifts and transversal relaxation rates provided the parameters governing the relaxivity in [Gd(DODPA)]+. The results show that this system is endowed with a relatively fast water exchange rate k(ex)(298) = 58 × 10(6) s(–1).

Synthesis and Characterization of Some Metal Complexes with New Nitrogen–Oxygen Donor Macrocyclic Ligands – X‐ray Crystal Structures of a 26‐Membered Reduced Monoprotonated Macrocycle and a 20‐Membered Pendant‐Arm Schiff‐Base Macrocyclic Cadmium(II) Complex

New series of macrocyclic Schiff-base lanthanide(III), yttrium(III), and cadmium(II) complexes, [M(1)]Xn (X = NO, M = Y, Ln = La–Yb except Pm and Dy; X = ClO, M = Cd, La, Ce, Pr, Sm, Gd, or Er) and [M(3)]Xn (X = NO, M = Dy; X = ClO, M = Er and Cd), have been prepared by cyclocondensation of O1,O7-bis(2-formylphenyl)-1,4,7-trioxaheptane with O1,O7-bis(2-aninyl)-1,4,7-trioxaheptane (1) or tris(2-aminoethyl)amine (3) in the presence of the appropriate metal salt as a template agent. The Schiff-base macrocycles 1 and 3 are also formed in the absence of a metal ion. Treatment of 1 with NaBH4 in methanol gives the diamine macrocycle 2. The reactions of LnIII, CdII, and YIII ions with 2 have also been investigated. The crystal structures of the monoprotonated ligand 2 and of the complex [Cd(3)](ClO4)2 have been determined by X-ray diffraction analysis.

An NMR and DFT Investigation on the Conformational Properties of Lanthanide(III) 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetate Analogues Containing Methylenephosphonate Pendant Arms

The conformational properties of lanthanide(III) complexes with the mono- and biphosphonate analogues of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA) are investigated by means of density functional theory (DFT) calculations and NMR spectroscopy. Geometry optimizations performed at the B3LYP/6-31G(d) level and using a 46 + 4f(n) effective core potential for lanthanides provide two energy minima corresponding to the square-antiprismatic (SAP) and twisted square-antiprismatic (TSAP) geometries. Our calculations give relative free energies between the SAP and TSAP isomers in fairly good agreement with the experimental values. The SAP isomer presents the highest binding energy of the ligand to the metal ion, which further increases with respect to that of the TSAP isomer across the lanthanide series as the charge density of the metal ion increases. The stabilization of the TSAP isomer upon substitution of the acetate arms of DOTA by methylenephosphonate ones is attributed to the higher steric demand of the phosphonate groups and the higher strain of the ligand in the SAP isomer. A (1)H NMR band-shape analysis performed on the [Ln(DO2A2P)](3-) (Ln = La and Lu) complexes provided the activation parameters for enantiomerization of the TSAP form of the complexes. The TSAP isomerization process was also investigated by using DFT calculations on the [Lu(DOTA)](-) and [Ln(DO2A2P)](3-) (Ln = La and Lu) systems. Our results confirm that enantiomerization requires both rotation of the pendant arms and inversion of the four five-membered chelate rings formed upon coordination of the macrocyclic unit. According to our calculations, the arm rotation pathway in [Lu(DOTA)](-) is a one-step process involving the simultaneous rotation of the four acetate arms, while in the DO2A2P analogue, the arm-rotation process is a multistep path involving the stepwise rotation of each of the four pendant arms. The calculated activation free energies are in reasonably good agreement with the experimental data. A comparison of the experimental (13)C NMR shifts of [Ln(DO2A2P)](3-) (Ln = La and Lu) complexes and those calculated by using the GIAO method confirms that the major isomer observed in solution for these complexes corresponds to the TSAP isomer.

Lead(II) complexes with macrocyclic receptors derived from 4,13-diaza-18-crown-6.

Pages 5883, 5884, 5886, 5888. Several reference numbers in the text are incorrect. Page 5883: The reference number 14 should be 20; 15 and 16 near the bottom of the left-hand column should be 21 and 22; 21 should be 27. Page 5884: The 28 should be 34; 29 should be 35. Page 5886: The 31 should be 37. Page 5888: The 33 should be 39. The version with corrected reference numbers is available electronically.

Copper complexes with bibracchial lariat ethers: from mono- to binuclear structures

Abstract Copper(II) complexes with a series of bibracchial lariat ethers are described. Independently of the nature of the counterion present (nitrate or perchlorate), the lariat ether N,N′-bis(2-aminobenzyl)-1,10-diaza-15-crown-5 (L1) always forms mononuclear complexes, whereas the lariat ethers N,N′-bis(2-aminobenzyl)-4,13-diaza-18-crown-6 (L2) and N,N′-bis(2-salicylaldiminobenzyl)-4,13-diaza-18-crown-6 (L3) only give binuclear compounds. The X-ray crystal structure of [CuL1](ClO4)2 shows a seven-coordinated copper(II) ion in a distorted (axially compressed) pentagonal-bipyramidal geometry. The X-ray crystal structure of [Cu2(L3-2H)](ClO4)2 confirms the binuclear nature of the compound with both metal ions having identical coordination environments and each one placed out of the crown hole but efficiently encapsulated by the corresponding pendant arm; each copper(II) ion is five-coordinated with an intermediate geometry between trigonal-bipyramidal and square-pyramidal (τ=0.40). The EPR spectra in frozen solution samples are in accordance with a stable coordinate pattern for the metal centre of ligand L1, yielding a rhombic distorted complex with axial compression in solution, in agreement with the X-ray crystal structure of [CuL1](ClO4)2. For the binuclear complexes of L2 and L3, the Cu(II) centres in solution can be distorted from their tetragonally elongated structures via interaction with ethanol and/or the nitrate counterion, leading to more than one species.

Complexes of lead(II) and lanthanide(III) ions with two novel 26-membered-imine and -amine macrocycles derived from 2,6-bis(2-formylphenoxymethyl)pyridine☆

Abstract acrocyclic Schiff-base lanthanide(III) complexes, [LnL1] [X]3 (X = NO3, Ln = La, Ce, Pr, Ce, Pr, Nd, Sm, Eu, Gd Tb, Ho, Er, Tm, Yb or Lu: X = ClO4, Ln = La, Ce, Pr, Nd, Sm, Eu, Tb, Dy or Er) and the complex [PbL1] [ClO4]2 have been prepared by cyclocondensation of 2,6-bis(2-formylphenoxymethyl)pyridine and 1,5-bis(2-aminophenoxyl)-3-oxapentane in the presence of the appropriate metal salt as a template agent. The Schiff-base macrocycle L1 is also formed in the absence of the metal ion. Treatment of L1 with NaBH4 in methanol gave the di-amine macrocycle L2. The reactions of lanthanide(III) ions with L2 were also investigated.