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~ _ _ _ _ _ _~Four macrocyclic ligands have been synthesized: 1-oxa-4,7,10,13-tetraazdcyc~opentadecane (I), 1,4dioxa-7,10,13-triazacyclopentadecane (Z), 1,4-dioxa-7,11.14-triazacyclohexadecane (3), l,4-dioxa-7,1lj 15-triazacycloheptadecane (4), one of them, 3, for the first time. The protonation constants of the ligands and the stability constants of the complexes formed by the four ligands with some divalent first-series transition-metal ions, Cd2+ and Pb*+, were determined by potentiometric methods, in aqueous solution, at 25" and I = 0 . 1 0~ (KNO,). The sequence of protonation of ligand 1 was studied by 'H-NMR spectroscopy. The Iroing-WiUiams' order of stability is obeyed for the complexes of all the ligands, and the metal complexes of 1 present the higher values of stability. A drop in the stability of all the metal complexes studied is observed when the metal complexes of 1 are compared with the corresponding complexes of 2. The effedt of the increase of the ring size of the macrocycle can be observed for metal complexes of the series of ligands 2 4 , where, in spite of the slight increase of the overall basicity of the ligands (20.28, 22.25, and 24.96 for 2, 3, and 4 respectively), small differences in stability are found for the corresponding complexes of 2 and 3, but a significant drop occurs for all the metal complexes formed with the 17-membered ligand, specially for the larger metal ions like Mn2+ and Pb2+.Introduction. -The ability to predict the selectivity of metal complexes is of great interest in many fields, as in analytical chemistry for the selective separation or determination of metals [l] [2], in medicine for the treatment of metal intoxications [3] or for imaging and therapy agents [4] [5]. In the last few decades, many works have been published on metal complexes using macrocyclic ligands, but, contrary to the conclusions of the first studies on this subject which suggested that metal ions were most strongly complexed in the case of closest match between the size of the metal ion and the cavity of the macrocycle (size-match selectivity) [6], the prediction of the selectivity is much more complicated, as many other factors are generally to be considered [7] [8]. It is known that even minor variations in the structure of the macrocycle may lead to considerable differences in the behavior of the metal complexes that cannot be anticipated.Our aim is to understand the factors which control the selectivity of metal complexes formed by simple macrocyclic ligands. Although a very large volume of work has been published on tetraaza-macrocyclic ligands (especially the 14-membered ligands) [9], and some research has been made on metal complexation of pentaaza-macrocyclic ligands [lo], much less information is available on ligands containing both oxygen and nitrogen as donor atoms, especially in the case of larger ring systems. In the present work, we have synthesized four potentially pentadentate ligands, 1 4 , and studied their stability with several divalent first-series transition-metal ions. We...

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The present work addresses the role of two ortho-substituted Mn(III) N-alkylpyridylporphyrins, alkyl being ethyl in MnTE-2-PyP(5+) and n-hexyl in MnTnHex-2-PyP(5+), on the protection against the oxidant tert-butylhydroperoxide (TBHP). Their protective role was studied in V79 cells using endpoints of cell viability (MTT and crystal violet assays), intracellular O(2)*- generation (dihydroethidium assay) and glutathione status (DTNB and monochlorobimane assays). MnPs per se did not show cytotoxicity (up to 25 microM, 24 h). The exposure to TBHP resulted in a significant decrease in cell viability and in an increase in the intracellular O(2)(*-) levels. Also, TBHP depleted total and reduced glutathione and increased GSSG. The two MnPs counteracted remarkably the effects of TBHP. Even at low concentrations, both MnPs were protective in terms of cell viability and abrogated the intracellular O(2)(*-) increase in a significant way. Also, they augmented markedly the total and reduced glutathione contents in TBHP-treated cells, highlighting the multiple mechanisms of protection of these SOD mimics, which at least in part may be ascribed to their electron-donating ability.

Multiple mechanisms related to metastases undergo redox regulation. Cu[15]pyN5 is a redox-active copper(II) complex previously studied as a chemotherapy sensitizer in mammary cells. The effects of a cotreatment with Cu[15]pyN5 and doxorubicin (dox) were evaluated in two human breast cancer cell lines: MCF7 (low aggressiveness) and MDA-MB-231 (highly aggressive). Cu[15]pyN5 decreased MCF7-directed cell migration. In addition, a cotreatment with dox and Cu[15]pyN5 reduced the proteolytic invasion of MDA-MB-231 cells. Cell detachment was not affected by exposure to these agents. Cu[15]pyN5 and dox significantly increased intracellular ROS in both cell lines. This increase could be at least partially due to H2 O2 accumulation. The combination of Cu[15]pyN5 with dox may be beneficial in breast cancer treatment as it could help reduce cancer cell migration and invasion. Moreover, the ligand [15]pyN5 has a high affinity for copper(II) and displays potential anti-angiogenic properties. Overall, we present a potential drug that might arrest the progression of breast cancer by different and complementary mechanisms.