Iron(III) Complexes as Superoxide Dismutase Mimics: Synthesis, Characterization, Crystal Structure, and Superoxide Dismutase (SOD) Activity of Iron(III) Complexes Containing Pentaaza Macrocyclic Ligands

Iron(III) complexes with four pentaaza macrocylic ligands, [Fe(L)Cl 2 ](PF 6 ), have been synthesized, where the ligand L is 1,4,7,10,13-pentaazacyclopentadecane (L 1 ), 2 R,3 R,8 S,9 S -dicyclohexano-1,4,7,10,13-pentaazacyclopentadecane (L 2 ), 2 R,3 R,8 R,9 R -dicyclohexano-1,4,7,10,13-pentaazacyclopentadecane (L 3 ), or 2 S,5R,8S,11R,14S -pentamethyl-1,4,7,10,13-pentaazacyclopentadecane (L 4 ), respectively. Conductivity measurements in acetonitrile are consistent with two chloro anions coordinated to iron(III). In acetonitrile solution, all four iron complexes exhibit a reversible or quasi-reversible redox couple in the experimental range −1.5 to +1.5 V vs E Ag/Ag +, and the redox potentials for those four complexes are similar (from −0.15 to −0.19 V vs NHE). In aqueous solutions, the electrochemical properties of those complexes are different from those in acetonitrile solution; the redox peaks shift more than 0.5 V more positive. The complexes with L 1, L 2, and L 3 display a reversible redox at 0.35, 0.45, and 0.43 V vs NHE, respectively, while [Fe(L 4 )Cl 2 ](PF 6 ) shows a cathodic peak at 0.44 V and two anodic peaks at 0.31 and 0.14 V vs NHE, respectively. The base titration results reveal that two water molecules are coordinated to the iron(III) in these complexes. p K a 1 and p K a 2: 3.46(7) and 7.31(7) for [Fe(L 1 )Cl 2 ](PF 6 ); 3.7(1) and 7.50(2) for [Fe(L 2 )Cl 2 ](PF 6 ); 4.1(1) and 7.73(2) for [Fe(L 3 )Cl 2 ](PF 6 ); 3.6(7) and 7.4(2) for [Fe(L 4 )Cl 2 ](PF 6 ). The superoxide dismutase (SOD) activity, assessed by stopped-flow experiments, reveals that all four metal complexes catalyze the fast disproportionation of superoxide in aqueous solution: at pH = 7.8, the catalyic rate constants for the complexes were 0.81 × 10 7, 1.42 × 10 7, 1.41 × 10 7, and 0.29 × 10 7 M - 1 s - 1 for [Fe(L 1 )Cl 2 ](PF 6 ), [Fe(L 2 )Cl 2 ](PF 6 ), [Fe(L 3 )Cl 2 ](PF 6 ), and [Fe(L 4 )Cl 2 ](PF 6 ), respectively. The crystal structure of [Fe(L 2 )Cl 2 ](PF 6 ) was determined. Crystal data: triclinic, P 1̄; a = 7.367(2), b = 10.707(2), c = 17.632(2) Å; α = 81.27(2), β = 79.74(2), γ = 83.38(2)°; R = 0.0465 for observed data ( I > 2σ( I )). The iron is seven-coordinate with five nitrogen atoms from the pentaaza macrocylic ligand and trans- chloro anions in a pentagonal bipyramidal arrangement. The average bond lengths for Fe−N and Fe−Cl are 2.271 and 2.339 Å, respectively.