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

Abstract

A new class of macrocyclic ligands based on 1-oxa-4,7-diazacyclononane was synthesized and their Mn²⁺ complexes were investigated with respect to stability and relaxation properties. Each ligand has two pendant arms involving carboxylic (H₂L¹ — 1-oxa-4,7-diazacyclononane-4,7-diacetic acid), phosphonic (H₄L² — 1-oxa-4,7-diazacyclononane-4,7-bis(methylenephosphonic acid)), phosphinic (H₂L³ — 1-oxa-4,7-diazacyclononane-4,7-bis(methylenephosphinic acid)) or phenylphosphinic (H₂L⁴ — 1-oxa-4,7-diazacyclononane-4,7-bis[methylene(phenyl)phosphinic acid]) acid moieties. H₂L³ and H₂L⁴ were synthesized for the first time. The crystal structure of the Mn²⁺ complex with H₂L⁴ confirmed a coordination number of 6 for Mn²⁺. The protonation constants of all ligands and the stability constants of their complexes with Mn²⁺ and some biologically or biomedically relevant metal ions were determined by potentiometry. The protonation sequence of H₂L³ was followed by ¹H and ³¹P 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 Mn²⁺ complexes with all ligands investigated. For H₂L³ and H₂L⁴, full Mn²⁺ complexation cannot be achieved even with 100% ligand excess. The transmetallation of MnL¹ and MnL² with Zn²⁺ was too fast to be followed at pH 6. Variable temperature ¹H NMRD and ¹⁷O NMR measurements have been performed on MnL¹ and MnL² to provide information on water exchange and rotational dynamics. The ¹⁷O chemical shifts indicate hydration equilibrium between mono- and bishydrated species for MnL¹, while MnL² is monohydrated. The water exchange is considerably faster on MnL¹ (k_ex²⁹⁸ = 1.2 × 10⁹ s⁻¹) than on MnL² (k_ex²⁹⁸ = 1.2 × 10⁷ 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 Mn²⁺ complexes are stable toward air-oxidation.