The Critical Role of Ligand Flexibility on the Activity of Free and Immobilized Mn Superoxide Dismutase Mimics

Abstract

In low-molecular-weight Mn superoxide dismutase (SOD) mimics, the ligand plays a key role in tuning the reactivity of the metal center with O2•−. We used three ligands differing in their donor sites, flexibility and/or charge, to compare the redox properties and SOD activity of the resulting Mn complexes: 1,3-bis[(pyridin-2-ylmethyl)(propargyl)amino]propane (pypapn), 1,3-bis(pyridin-2-ylmethyleneamino)propane (py2pn) and 1,4-bis(salicylidenamino)butane (H2salbn). These ligands afford Mn complexes that, in aqueous solution, exist as mononuclear species [Mn(II)(pypapn)(H2O)2]2+, [Mn(II)(py2pn)(H2O)2]2+ and [Mn(III)(salbn)(H2O)2]+. The relative reactivity of these compounds with O2•− at pH 7.8, [Mn(pypapn)(H2O)2]2+ > [Mn(salbn)(H2O)2]+ > [Mn(py2pn)(H2O)2]2+, is independent of the redox potential but strongly depends on the ligand flexibility which becomes a critical feature when the reaction occurs through an inner-sphere electron-transfer mechanism. Immobilization was used to isolate and protect the catalyst from dissociation or dimerization during catalysis. [Mn(pypapn)(H2O)2]2+, with the alkyne group, was covalently grafted to azide functionalized mesoporous silica through click chemistry, while [Mn(py2pn)(solv)2]2+ and [Mn(salbn)(solv)2]+ were encapsulated in SBA-15 mesoporous silica through ionic exchange. The retention or enhancement of the SOD activity and the improved stability of the covalently attached catalyst and the doubly charged complex encapsulated in the silica pores, make them suitable for use in aqueous media.

Effect of Metal Environment and Immobilization on the Catalytic Activity of a Cu Superoxide Dismutase Mimic

“…An effective approach to reducing the complex leaching from the silica consists of the covalent attachment of the catalyst to mesoporous silica employing "click" chemistry [34][35][36][37]. In this work, the SOD activity of the Cu(II) complex formed with an N 4 -tetradentate "clickable" ligand, 1,3-bis[(pyridin-2-ylmethyl)(propargyl)amino]propane (pypapn, Scheme 1) [38], was evaluated in homogeneous phase and covalently grafted to azido functionalized mesoporous silicas, aimed at assessing the role played by this ligand on the catalytic activity and the effect of the covalent anchoring on the catalyst stability. Additionally, the SOD activity of the Cu(II) complex of N,N'-bis(2-pyridylmethylen)propane-1,3-diamine (py 2 pn, Scheme 1), an N 4 -Schiff base ligand, was evaluated after insertion in mesoporous silica by ionic exchange.…”

“…The synthesis of the ligands N,N -bis(2-pyridylmethylen)propane-1,3-diamine (py2pn) [54] and 1,3-bis[(2-pyridilmethyl)(propargyl)amino]propane (pypapn) [38] and the complex [Cu(py2pn)(ClO4)2] [7] were described in previous papers.…”

“…The synthesis of the ligands N,N'-bis(2-pyridylmethylen)propane-1,3-diamine (py 2 pn) [54] and 1,3-bis[(2-pyridilmethyl)(propargyl)amino]propane (pypapn) [38] and the complex [Cu(py 2 pn)(ClO 4 ) 2 ] [7] were described in previous papers. Cu(OAc) 2 •H 2 O (30 mg, 0.15 mmol) was dissolved in methanol (5 mL) and added to a solution of pypapn (50 mg, 0.15 mmol) in methanol (2 mL).…”