Complexation of Mn(II) by Rigid Pyclen Diacetates: Equilibrium, Kinetic, Relaxometric, Density Functional Theory, and Superoxide Dismutase Activity Studies.

We report the Mn(II) complexes with two pyclen-based ligands (pyclen = 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene) functionalized with acetate pendant arms at either positions 3,6 (3,6-PC2A) or 3,9 (3,9-PC2A) of the macrocyclic fragment. The 3,6-PC2A ligand was synthesized in five steps from pyclen oxalate by protecting one of the secondary amine groups of pyclen using Alloc protecting chemistry. The complex with 3,9-PC2A is characterized by a higher thermodynamic stability [log KMnL = 17.09(2)] than the 3,6-PC2A analogue [log KMnL = 15.53(1); 0.15 M NaCl]. Both complexes contain a water molecule coordinated to the metal ion, which results in relatively high 1H relaxivities (r1p = 2.72 and 2.91 mM-1 s-1 for the complexes with 3,6-PC2A and 3,9-PC2A, respectively, at 25 °C and 0.49 T). The coordinated water molecule displays fast exchange kinetics with the bulk in both cases; the rates (kex298) are 140 × 106 and 126 × 106 s-1 for [Mn(3,6-PC2A)(H2O)] and [Mn(3,9-PC2A)(H2O)], respectively. The two complexes were found to be remarkably inert with respect to their dissociation, with half-lives of 63 and 21 h, respectively, at pH = 7.4 in the presence of excess Cu(II). The r1p values recorded in blood serum remain constant at least over a period of 120 h. Cyclic voltammetry experiments show irreversible oxidation features shifted to higher potentials with respect to [Mn(EDTA)(H2O)]2- (H4EDTA = ethylenediaminetetraacetic acid) and [Mn(PhDTA)(H2O)]2- (H4PhDTA = phenylenediamine-N,N,N',N'-tetraacetic acid), indicating that the PC2A complexes reported here have a lower tendency to stabilize Mn(III). The superoxide dismutase activity of the Mn(II) complexes was tested using the xanthine/xanthine oxidase/p-nitro blue tetrazolium chloride assay at pH = 7.8. The Mn(II) complexes of 3,6-PC2A and 3,9-PC2A are capable of assisting decomposition of the superoxide anion radical. The kinetic rate constant of the complex of 3,9-PC2A is smaller by 1 order of magnitude than that of 3,6-PC2A.

The role of ligand to metal charge-transfer states on the luminescence of Europium complexes with 18-membered macrocyclic ligands.

We report a detailed study of the photophysical properties of EuIII and TbIII complexes with two ligands based on a 3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane platform containing either four pyridine-2yl-methyl (L1) or four hydroxyethyl (L2) pendant arms. The [TbL1]3+ and [TbL2]3+ complexes present moderate luminescence quantum yields upon excitation through the ligand bands (φH2O = 7.4 and 21%, respectively). The [EuL2]3+ complex displays a relatively low quantum yield in H2O (φH2O = 1.6%) that increases considerably in D2O (φD2O = 5.3%), which highlights the strong quenching effect of the four ligand O-H oscillators. The emission spectrum of [EuL1]3+ is rather unusual in that it shows a relatively high intensity of the 5D0 → 7F5,6 transitions, which appears to be also related to the distorted D4d symmetry of the coordination polyhedron. Surprisingly, the quantum yield of the [EuL1]3+ complex is very low (φH2O = 0.10%), considering the good protection of the EuIII coordination environment offered by the ligand. Cyclic voltammograms recorded from aqueous solutions of [EuL1]3+ display a reversible curve with a half-wave potential of -620 mV (versus Ag/AgCl), while [EuL2]3+ presents a reduction peak at more negative potential (-1040 mV). Thus, the L1 ligand provides a rather good stabilisation of divalent Eu compared to the L2 analogue, suggesting that the presence of a low-lying ligand-to-metal charge-transfer (LMCT) state might be responsible for the low quantum yield determined for [EuL1]3+. A density functional theory (DFT) study provides very similar energies for the ligand-centered excited singlet (1ππ*) and triplet (3ππ*) states of [EuL1]3+ and [EuL2]3+. The energy of the 9LMCT state of [EuL1]3+ was estimated to be 20 760 cm-1 by using all-electron relativistic calculations based on the DKH2 approach, a value that decreases to 15 940 cm-1 upon geometry relaxation.

Mono-, bi-, and trinuclear bis-hydrated Mn(2+) complexes as potential MRI contrast agents.

We report a series of ligands containing pentadentate 6,6'-((methylazanediyl)bis(methylene))dipicolinic acid binding units that form mono- (H2dpama), di- (mX(H2dpama)2), and trinuclear (mX(H2dpama)3) complexes with Mn2+ containing two coordinated water molecules per metal ion, which results in pentagonal bipyramidal coordination around the metal ions. In contrast, the hexadentate ligand 6,6'-((ethane-1,2-diylbis(azanediyl))bis(methylene))dipicolinic acid (H2bcpe) forms a complex with distorted octahedral coordination around Mn2+ that lacks coordinated water molecules. The protonation constants of the ligands and the stability constants of the Mn2+, Cu2+, and Zn2+ complexes were determined using potentiometric and spectrophotometric titrations in 0.15 M NaCl. The pentadentate dpama2­ ligand and the di- and trinucleating mX(dpama)24­ and mX(dpama)36­ ligands provide metal complexes with stabilities that are very similar to that of the complex with the hexadentate ligand bcpe2­, with log ß101 values in the range 10.1­11.6. Cyclic voltammetry experiments on aqueous solutions of the [Mn(bcpe)] complex reveal a quasireversible system with a half-wave potential of +595 mV versus Ag/AgCl. However, [Mn(dpama)] did not suffer oxidation in the range 0.0­1.0 V, revealing a higher resistance toward oxidation. A detailed 1H NMRD and 17O NMR study provided insight into the parameters that govern the relaxivity for these systems. The exchange rate of the coordinated water molecules in [Mn(dpama)] is relatively fast, kex298 = (3.06 ± 0.16) × 108 s­1. The trinuclear [mX(Mn(dpama)(H2O)2)3] complex was found to bind human serum albumin with an association constant of 1286 ± 55 M­1 and a relaxivity of the adduct of 45.2 ± 0.6 mM­1 s­1 at 310 K and 20 MHz.

Stabilizing divalent europium in aqueous solution using size-discrimination and electrostatic effects.

We report two macrocyclic ligands containing a 1,10-diaza-18-crown-6 fragment functionalized with either two picolinamide pendant arms (bpa18c6) or one picolinamide and one picolinate arm (ppa18c6(-)). The X-ray structure of [La(ppa18c6)(H2O)](2+) shows that the ligand binds to the metal ion using the six donor atoms of the crown moiety and the four donor atoms of the pendant arms, 11-coordination being completed by the presence of a coordinated water molecule. The X-ray structure of the [Sr(bpa18c6)(H2O)](2+) was also investigated due to the very similar ionic radii of Sr(2+) and Eu(2+). The structure of this complex is very similar to that of [La(ppa18c6)(H2O)](2+), with the metal ion being 11-coordinated. Potentiometric measurements were used to determine the stability constants of the complexes formed with La(3+) and Eu(3+). Both ligands present a very high selectivity for the large La(3+) ion over the smaller Eu(3+), with a size-discrimination ability that exceeds that of the analogous ligand containing two picolinate pendant arms reported previously (bp18c6(2-)). DFT calculations using the TPSSh functional and the large-core pseudopotential approximation provided stability trends in good agreement with the experimental values, indicating that charge neutral ligands derived from 1,10-diaza-18-crown-6 enhance the selectivity of the ligand for the large Ln(3+) ions. Cyclic voltammetry measurements show that the stabilization of Eu(2+) by these ligands follows the sequence bp18c6(2-) < ppa18c6(-) < bpa18c6 with half-wave potentials of -753 mV (bp18c6(2-)), -610 mV (ppa18c6(-)), and -453 mV (bpa18c6) versus Ag/AgCl. These values reveal that the complex of bpa18c6 possesses higher stability against oxidation than the aquated ion, for which an E1/2 value of -585 mV has been measured.