Synthesis, Characterization, and Stability of Manganese(II) C-Substituted 1,4,7,10,13-Pentaazacyclopentadecane Complexes Exhibiting Superoxide Dismutase Activity

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]aneN5, ligands, 1, and their corresponding Mn(II) complexes, 2 and 3, as their dichloro complexes, [Mn([15]aneN5)Cl2]. 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 kcat...