Mn2+ complexes of 1-oxa-4,7-diazacyclononane based ligands with acetic, phosphonic and phosphinic acid pendant arms: stability and relaxation studies.

A new class of macrocyclic ligands based on 1-oxa-4,7-diazacyclononane was synthesized and their Mn(2+) complexes were investigated with respect to stability and relaxation properties. Each ligand has two pendant arms involving carboxylic (H(2)L(1)--1-oxa-4,7-diazacyclononane-4,7-diacetic acid), phosphonic (H(4)L(2)--1-oxa-4,7-diazacyclononane-4,7-bis(methylenephosphonic acid)), phosphinic (H(2)L(3)--1-oxa-4,7-diazacyclononane-4,7-bis(methylenephosphinic acid)) or phenylphosphinic (H(2)L(4)--1-oxa-4,7-diazacyclononane-4,7-bis[methylene(phenyl)phosphinic acid]) acid moieties. H(2)L(3) and H(2)L(4) were synthesized for the first time. The crystal structure of the Mn(2+) complex with H(2)L(4) confirmed a coordination number of 6 for Mn(2+). The protonation constants of all ligands and the stability constants of their complexes with Mn(2+) and some biologically or biomedically relevant metal ions were determined by potentiometry. The protonation sequence of H(2)L(3) was followed by (1)H and (31)P NMR titration and the second protonation step was attributed to the second macrocyclic nitrogen atom. The potentiometric data revealed a relatively low thermodynamic stability of the Mn(2+) complexes with all ligands investigated. For H(2)L(3) and H(2)L(4), full Mn(2+) complexation cannot be achieved even with 100% ligand excess. The transmetallation of MnL(1) and MnL(2) with Zn(2+) was too fast to be followed at pH 6. Variable temperature (1)H NMRD and (17)O NMR measurements have been performed on MnL(1) and MnL(2) to provide information on water exchange and rotational dynamics. The (17)O chemical shifts indicate hydration equilibrium between mono- and bishydrated species for MnL(1), while MnL(2) is monohydrated. The water exchange is considerably faster on MnL(1) (k(ex)(298) = 1.2 × 10(9) s(-1)) than on MnL(2) (k(ex)(298) = 1.2 × 10(7) s(-1)). Small endogenous anions (phosphate, carbonate, citrate) do not replace the coordinated water in either of the complexes, but they induce their slow decomposition. All Mn(2+) complexes are stable toward air-oxidation.