Search

The stability constants of complexes of the macrocyclic ligand do3a-pic4– (H4do3a-pic = 2,2′,2″-{10-[(6-carboxypyridin-2-yl)methyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triyl}triacetic acid) with several divalent metal ions (Pb2+, Cd2+, Zn2+, Cu2+, Ca2+, and Mg2+) have been determined by using pH-potentiometric titrations (I = 0.1 M KCl, 25 °C). The stability of these complexes follows the trend Cu2+ > Cd2+ ≈ Pb2+ ≈ Zn2+ >> Ca2+ >> Mg2+. A particularly high stability constant has been determined for the Cu2+ complex [log KCuL = 23.20(4)]. Analysis of the titration curves indicate the presence of protonated forms of the complexes in solution, with protonation constants of log KM(HxL) = 6.9–2.0 (x = 1, 2, or 3). The structure of the complexes in solution has been investigated by using 1H and 13C NMR spectroscopy and DFT calculations performed in aqueous solution at the TPSSh/6-31G(d) level. In the case of the Pb2+ and Cd2+ complexes, relativistic effects were considered with the use of relativistic effective core potentials. Calculations show that the complexes with the largest metal ions (Pb2+ and Ca2+) are nine-coordinate, with their coordination polyhedra being best described as capped twisted square antiprisms. The Cd2+ and Mg2+ complexes are seven-coordinate, with the metal ions being bound to the four nitrogen atoms of the cyclen unit and the three acetate pendant arms. Finally, in the Cu2+ and Zn2+ complexes, the metal ions are six-coordinated, with the metal ions being asymmetrically placed inside the macrocyclic cavity of the ligand, and the coordination polyhedra can be described as an octahedron and a trigonal prism, respectively.

Paramagnetic lanthanide(III) complexes stable in aqueous solutions have gained increasing interest in the recent years due to their importance as contrast agents in magnetic resonance imaging (MRI). Lanthanide(III) complexes with macrocyclic ligands derived from 1,4,7,10-tetraazacyclododecane (cyclen) are widely used for the design of MRI probes because of their high thermodynamic stability and kinetic inertness. The rational design of more efficient contrast agents requires a better understanding of the structure and dynamics of these systems in solution. This contribution reviews the work of the author and his collaborators on the solution structure and dynamics of lanthanide(III) complexes with different cyclen-based ligands and closely related systems. DFT calculations provide molecular geometries and relative energies of the different stereoisomers of these complexes in good agreement with the experimental data. The conformational analysis performed with the aid of density functional theory (DFT) calculations was validated with the investigation of the YbIII-induced 1H NMR paramagnetic shifts, which encode information on the position of the observed NMR nuclei with respect to the LnIII ion. Additionally, DFT calculations provide a better understanding of the dynamic processes responsible for the interconversion between the square-antiprismatic (SAP) and twisted-square-antiprismatic (TSAP) isomers of these complexes in solution, which might proceed through the inversion of the cyclen unit or the rotation of the pendant arms. The activation barriers obtained from theoretical calculations show a good agreement with the experimental values obtained from variable-temperature NMR spectroscopy. The work presented in this paper shows that DFT calculations in combination with NMR spectroscopy provide detailed information on the structure and dynamics of lanthanide(III) complexes at the molecular level and represent a powerful tool for the characterization of lanthanide(III) complexes relevant to the field of MRI contrast agents.

[Abstract] The coordinative properties towards lead(II) of two lateral macrobicyclic receptors that incorporate either a 1,10‐diaza‐[15]crown‐5 (L7) or a 4,13‐diaza‐[18]crown‐6 (L8) fragment are reported. Spectrophotometric titrations performed in acetonitrile solution indicate only the formation of mononuclear complexes in solution. The X‐ray crystal structures of the two receptors show that the conformation adopted by the ligand is imposed by the presence of intramolecular hydrogen‐bonding interactions that involve the secondary amine groups and the pivotal nitrogen atoms. The solid‐state structure of [Pb(L7)(NCS)](SCN)·0.5H2O shows that the metal ion is asymmetrically coordinated inside the macrobicyclic cavity. The PbII ion is coordinated to the nitrogen atom of the pyridine unit, the two secondary amine atoms, two oxygen atoms of the crown moiety, and a nitrogen atom of an isothiocyanate group. The distances between the PbII ion and the two pivotal nitrogen atoms as well as one of the oxygen atoms of the crown moiety are too long (>2.92 Å) to be considered unequivocal bonds, and should be regarded only as weak interactions. The protonation constants of L7 and L8 as well as the stability constants of their PbII complexes were investigated by using potentiometric titrations in 95 % methanol (I = 0.1 M, nBu4NClO4, 25 °C). The two receptors undergo two protonation processes in the pH range investigated (2.0 < pH < 12.0), which correspond to the protonation of the nitrogen atoms of the oxa–aza moiety. The log KPbL value obtained for L7 [9.906(1)] is approximately 1.1 log K units higher than the one determined for L8 [8.75(1)]. Xunta de Galicia; PGIDIT06TAM10301PR Xunta de Galicia; INCITE09E1R103013ES

Lanthanide(III) complexes with 10-benzyl-1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane (H 3 L) have been investigated as model compounds of N-alkylated Ln III -do3a complexes (H 3 do3a = 1,4,3,10-tetraazacyclododecane-1,4,7-triacetic acid) with potential application in molecular imaging. The X-ray structures of the [{Ln(L)(H 2 O)} 2 ]·18H 2 O complexes (Ln = Eu or Tb) show that the metal ion is directly bound to the seven donor atoms of the ligand, with the nine-coordination sphere completed by an oxygen atom of an inner-sphere water molecule and an oxygen atom of a carboxylate group from a neighboring [Ln(L)] unit. This results in the formation of tetrameric units through the sharing of carboxylic groups between adjacent [Ln(L)(H 2 O)] complexes. Luminescence lifetime measurements recorded in H 2 O and D 2 O provide a number of coordinated water molecules (q) of 1.2, which indicates that the major species that exists in solution contains one inner-sphere water molecule. The conformational properties of the [Ln(L)(H 2 O)] complexes (Ln = Gd or Lu) have been investigated by using density functional theory (DFT) calculations (B3LYP model). Our results indicate that the Δ(λλλλ) conformation is more stable than the Δ(δδδδ) one for both complexes. The interconversion between these two isomers may proceed either through the inversion of the five-membered rings formed upon coordination of the 1,4,7,10-tetraazacyclododecane (cyclen) unit, or through the stepwise rotation of the three acetate pendant arms. According to our calculations, the activation free energy for the arm-rotation process (5.6 kcalmol -1 ) is much lower than that of the ring-inversion path (14.6 kcalmol -1 ), which in turn is very similar to those determined experimentally for Ln III (dota) complexes. Thus, a low energy barrier for the arm-rotation process appears to be responsible for the relatively fast isomer interconversion observed for Ln III (N-alkylated do3a) complexes.

Lanthanide complexes of a hexaaza macrocyclic ligand containing a pyridine head unit (L) were synthesized (Ln = La–Lu, except Pm). The solid-state structures of the corresponding La, Ce, Pr, Nd, and Lu complexes were determined by single-crystal X-ray crystallography, and they reveal the presence of three different mononuclear complexes with three different conformations of the macrocycle and coordination environments around the metal ions. In all complexes the lanthanide ion is coordinated in an endomacrocyclic manner to the six nitrogen donor atoms of the ligand. In the La, Ce, and Pr complexes the metal ions show a 12-coordinate mononuclear environment in which 3 nitrate anions coordinate in a bidentate fashion. However, in the Nd analogue the metal ion displays a 10-coordinated environment with the coordination of 2 bidentate nitrate groups, whereas Lu shows a 9-coordinate environment interacting with 2 nitrate ligands, one of them acting as bidentate and the second one coordinating in a monodentate fashion. The 1H and 13C NMR spectra of the complexes recorded in CD3CN suggest that the complexes adopt in solution a similar structure to that observed for the Nd complex in the solid state. The [Ln(L)(NO3)3] and [Ln(L)(NO3)2]+ complexes were characterized by density functional theory (DFT) calculations (B3LYP model). The structures obtained from these calculations for La, Ce, Pr, and Nd are in good agreement with the experimental solid-state structures. The relative stabilities of the [Ln(L)(NO3)2]+ complexes with respect to the [Ln(L)(NO3)3] ones (Ln = La, Nd, Gd, Ho, or Lu) were studied both in vacuo and in acetonitrile solution (PCM model) at the same computational level. Our calculations indicate that in solution the [Ln(L)(NO3)2]+ species is the most stable one along the whole lanthanide series, in agreement with the NMR spectroscopic data.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

The study presented in this paper provides a rare example of a macrocyclic receptor allowing the formation of mono- or binuclear complexes on the same first-row transition-metal guest cation depending on the nature of the counterion present. Reaction of N,N′-bis(benzimidazol-2-ylmethyl)-4,13-diaza-18-crown-6 (L4) with CoII, NiII, CuII, or ZnII perchlorates leads to the formation of the expected mononuclear complexes with the metal ion showing a distorted octahedral coordination environment. In these complexes, the metal ion is placed at one end of the macrocyclic cavity, and two of the oxygen atoms of the crown ether moiety remain uncoordinated. 1H and 13C NMR spectroscopic studies on the diamagnetic [Zn(L4)]2+ complex indicate that the asymmetric coordination of the metal ion inside the macrocyclic cavity is maintained in acetonitrile solution, but translocation of the ZnII ion from one end of the macrobicyclic cavity to the second one occurs. However, reaction of L4 with CoII, NiII, or CuII perchlorates in the presence of chloride anions results in the formation of binuclear complexes where the metal ion is either five-coordinate in a distorted trigonal bipyramidal coordination environment (Co or Cu) or six-coordinate in a distorted octahedral geometry (Ni), and a chloride anion coordinates to each of the two metal ions in all cases. The ZnII ion behaves in a different way, and addition of chloride anions to the ZnII perchlorate in the presence of L4 does not lead to the formation of a binuclear complex. The formation of these binuclear systems was followed by spectrophotometric titrations of the mononuclear [M(L4)](ClO4)2 complexes with [nBu4N]Cl in acetonitrile solution indicating the formation of a [M2(L4)(Cl)]2+ intermediate species, followed by the formation of the binuclear complex [M2(L4)(Cl)2]2+ (M = Co, Ni, or Cu). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

The binding tendencies of the pendant-armed crown ethers L1–L3 [L1 = N,N′-bis(benzimidazol-2-ylmethyl)-1,7-diaza-12-crown-4, L2 = N,N′-bis(benzimidazol-2-ylmethyl)-1,10-diaza-15-crown-5) and L3 = N,N′-bis(benzimidazol-2-ylmethyl)-4,13-diaza-18-crown-6] towards PbII and CdII have been investigated. The X-ray crystal structure of [Cd(L3)](ClO4)2·EtOH shows that, in the solid state, the CdII ion is eight-coordinate and fits quite well into the crown hole, favouring an anti arrangement of the organic receptor. NMR measurements recorded in acetonitrile solution indicate that increasing the crown size induces a conformational change in the series of CdII complexes. The conformation goes from a syn arrangement for L1 to an anti arrangement for L3, passing through a syn [lrarr2] anti equilibrium in the complex derived from L2. On the contrary, no conformational change was observed for the corresponding PbII complexes, which have a syn conformation in all cases. These results have been confirmed by means of density functional theory (DFT) calculations performed by using the B3LYP model. The binding constants obtained from UV/Vis titration experiments in DMSO solution demonstrate that a decrease in the crown size provokes a 102-fold enhancement of the stability for this series of CdII complexes, whereas for PbII a gradual decrease of the binding constants is observed. Receptor L1 shows a certain degree of selectivity for CdII over PbII, with a selectivity factor > 102. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

The macrobicycle receptor L4, derived from 1,10-diaza-15-crown-5 incorporating a phenol Schiff-base spacer, forms stable complexes with lead(II). In [Pb(L4)(ClO4)](ClO4)·CH3CN (1), the lead(II) ion is asymmetrically placed at the one end of the macrobicyclic cavity, because of the intramolecular hydrogen bonding interaction that occurs between an imine nitrogen atom and the phenol group. This asymmetric position of the metal ion inside the macrobicyclic cavity induces chirality in this system. Variable temperature 1H NMR spectroscopic experiments indicate that the asymmetric coordination of the metal ion inside the macrocyclic cavity is maintained in acetonitrile solution, but a translocation of the PbII ion from one end of the macrobicyclic cavity to the second one occurs. This dynamic behaviour, which corresponds to the interconversion between the two possible enantiomeric forms of the complex, is fast on the NMR timescale at 320 K but slow at low temperatures, and we have estimated an activation barrier of ΔG‡ = 68 ± 2 kJ mol–1. We have also studied the effect of the protonation on 1 by NMR and UV/Vis spectroscopy in CH3CN solutions at room temperature, finding that diprotonation causes demetallation of the complex without receptor destruction, recovering L4 in its protonated form. On the other hand, the interaction of compound 1 with anions such as NO3– and SCN– has been evaluated by using spectrophotometric titrations in acetonitrile solution, finding log K values of 5.83(1) for NO3– and 6.27(2) forSCN–. The [Pb(L4)]2+, [Pb(L4)(NO3)]+, [Pb(L4)(NCS)]+ and [Pb(L4)(SCN)]+ systems were characterized by means of density functional theory calculations (DFT) performed by using the B3LYP model, and the coordination geometry as well as the role of the PbII lone pair has been investigated and discussed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)