We report the Mn(II) complexes with two pyclen-based ligands (pyclen = 3,6,9,15tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene) functionalized with acetate pendant arms either at 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 pyclenoxalate 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 (logKMnL = 17.09(2) than the 3,6-PC2A analogue (logKMnL = 15.53(1), 0.15 M NaCl). Both complexes contain a water molecule coordinated to the metal ion, which results in relatively high 1 H relaxivities (r1p = 2.72 and 2.91 mM -1 s -1 for the complexes with 3,6-and 3,9-PC2A, respectively, 25 ºC, 0.49 T). The coordinated water molecule displays fast exchange kinetics with the bulk in both cases; the rates (kex 298 ) are 14010 6 and 12610 6 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)] 2and [Mn(PhDTA)(H2O)] 2-, 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/NBT assay at pH 7.8. The Mn(II) complexes of 3,6-PC2A and 3,9-PC2A are capable to assist the decomposition of superoxide anion radical. The kinetic rate constant of the complex of 3,9-PC2A is smaller by one order of magnitude than that of 3,6-PC2A.

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The systems formed by the V(IV)O(2+) ion with tridentate ligands provided with the (O, N(imine), O) donor set were described. The ligands studied were 2,2'-dihydroxyazobenzene (Hdhab), α-(2-hydroxy-5-methylphenylimino)-o-cresol (Hhmpic), calmagite (H2calm), anthracene chrome red A (H3anth), calcon (H2calc), and calconcarboxylic acid (H3calc(C)). They can bind vanadium with the two deprotonated phenol groups and the imine nitrogen to give (5,6)-membered chelate rings. The systems were studied with EPR, UV-vis and IR spectroscopy, pH-potentiometry, and DFT methods. The ligands form unusual non-oxido V(IV) compounds both in aqueous solution and in the solid state. [V(anthH(-1))2](4-) and [V(calmH(-1))2](2-) (formed in water at the physiological pH) and [V(dhabH(-1))2] and [V(hmpicH(-1))2] (formed in the solid state in MeOH) are hexa-coordinated with geometry intermediate between the octahedron and the trigonal prism and an unsymmetric facial arrangement of the two ligand molecules. DFT calculations were used to predict the structure and (51)V hyperfine coupling tensor A of the non-oxido species. The EPR behavior of 13 non-oxido V(IV) species was put into relationship with the relevant geometrical parameters and was rationalized in terms of the spin density on the d(xy) orbital. Depending on the geometric isomer formed (meridional or facial), d(z)(2) mixes with the d(xy) orbital, and this effect causes the lowering of the highest (51)V A value.

Copper(II) complexes of the N‐terminal peptide fragments of tau protein have been studied by potentiometric and various spectroscopic techniques (UV‐vis, CD, ESR and ESI‐MS). The octapeptide Tau(9‐16) (Ac−EVMEDHAG−NH2) contains the H14 residue of the native protein, while Tau(26‐33) (Ac−QGGYTMHQ−NH2) and its mutants Tau(Q26K‐Q33K) (Ac−KGGYTMHK−NH2) and Tau(Q26K‐Y29A‐Q33K) (Ac−KGGATMHK−NH2) include the H32 residue. To compare the binding ability of H14 and H32 in a single molecule the decapeptide Ac−EDHAGTMHQD−NH2 (Tau(12‐16)(30‐34)) has also been synthesized and studied. The histidyl residue is the primary metal binding site for metal ions in all the peptide models studied. In the case of Tau(9‐16) the side chain carboxylate functions enhance the stability of the M−Nim coordinated complexes compared to Tau(26‐33) (logK(Cu−Nim)=5.04 and 3.78, respectively). Deprotonation and metal ion coordination of amide groups occur around the physiological pH range for copper(II). The formation of the imidazole‐ and amide‐coordinated species changes the metal ion preference and the complexes formed with the peptides containing the H32 residue predominate over those of H14 at physiological pH values (90 %–10 %) and in alkaline samples (96 %–4 %).

Detailed equilibrium and spectroscopic characterization of the complex formation processes of the nickel binding loop in NiSOD and its related fragments is reported in the slightly acidic–alkaline pH range. The N-terminally free and protected nonapeptides HCDLPCGVY-NH2 (NiSODM 1 ), HCDLACGVY-NH2 (NiSODM 3 ), and Ac-HCDLPCGVY-NH2 (NiSODM 2 ) and the N-terminally shortened analogues HCDL-NH2 and HCA-NH2 were synthesized, and their nickel­(II) complexes were studied by potentiometric and several spectroscopic techniques. EPR spectroscopy was also used to assign the coordinating donor sites after the in situ oxidation of nickel­(II) complexes. The terminal amino groups are the primary metal binding sites for nickel­(II) ion in NiSODM 1 and NiSODM 3 , resulting in the high nickel­(II) binding affinity of this peptide via the formation of a square-planar, (NH2,N–,S–,S–) or (NH2,NImN–,S–) coordinated species in a wide pH range. The latter coordination sphere prevents the formation of the active structure of NiSOD under physiological pH, reflecting the crucial role of proline in nickel­(II) binding. In situ oxidation of the Ni­(II) complexes yielded Ni­(III) transient species in the case of nonapeptides. The square-pyramidal coordination environment with axial imidazole ligation provides the active structure of the oxidized form of NiSOD in the case of N-terminally free peptides. Consequently, these ligands are promising candidates for modeling NiSOD. The acylation of the amino terminus significantly reduces the nickel­(II) binding affinity of the nonapeptide, while the oxidation results in coordination isomers.