Superoxide radical anion has been demonstrated to be a mediator of many disease states, including inflammatory, autoimmune, and cancerous diseases. As a consequence, we have developed a program to design, synthesize, and test synthetic low-molecular weight superoxide dismutase (SOD) mimics as potential pharmaceutical agents. A critical feature of the design of metal-based drugs is not only high activity as an enzyme mimic but also chemical stability. In this report we describe the synthesis and characterization of a series of C-substituted 1,4,7,-10,13-pentaazacyclopentadecane, [15]aneN 5 , ligands, 1, and their corresponding Mn(II) complexes, 2 and 3, as their dichloro complexes, [Mn([15]aneN 5 )Cl 2 ]. The purpose of the work is to probe the role that substituent (methyl and fused cycloalkyl) groups exert on the catalytic activity and stability of the complexes. All of the 18 new complexes described here are catalysts for the dismutation of superoxide, and substantial substituent effects are observed with k cat values at pH ) 7.4 varying in the range (1.4-9.1) × 10 7 M -1 s -1 . The kinetic and thermodynamic stabilities of these new complexes were studied by a Cu(II) ion competition spectrophotometric assay and by potentiometric titrations, respectively. It is observed that increasing the number of carbon substituents increases the kinetic stability of the complexes, while the thermodynamic stability increases, but less dramatically. The crystal structure for one of these new complexes, [Mn(2,2,3,3-Me 4 [15]aneN 5 )Cl 2 ], 2i, was determined, and reveals that the Mn(II) ion is coordinated by a pentagonal bipyramid array of five macrocyclic derived nitrogen atoms in a plane with the Mn(II) center and capped by trans-dichloro ligands. Crystal data for MnC 14 H 33 N 5 -Cl 2 ‚CH 3 CH 2 OH: triclinic, P1 h-C i 1 (#2), a ) 9.941(2) Å, b ) 11.190(2) Å, c ) 11.613(2) Å, V ) 1125.4(4) Å 3 , Z ) 2, T ) 20 ( 1°C, for 3357 independent absorption-corrected reflections having 2θ(Cu KR) < 120.0°and I > 3σ(Ι), with R int ) 0.027.

The binding of CO to a lacunar Fe(II) cyclidene complex is characterized by very negative values for the activation entropy and activation volume, whereas the reverse dissociation reaction is accompanied by small positive activation entropy and activation volume data. The constructed volume profile suggests that, in the transition state, CO disappears completely into the ligand pocket during partial Fe−CO bond formation, followed by a high-spin to low-spin transition on Fe(II) during which the metal center moves into the ligand plane and accounts for the subsequent volume decrease.