Amphiphilic pentaazamacrocyclic manganese superoxide dismutase mimetics

Inorg Chem. 2014 Jan 21;53(2):1009-20. doi: 10.1021/ic402469t. Epub 2013 Dec 26.

Abstract

Five newly functionalized pentaazamacrocyclic manganese complexes, with variable lengths and amounts of the aliphatic groups (three compounds with one linear chain containing 12, 16, and 22 carbon atoms, i.e., MnL1, MnL2, and MnL3, respectively, as well as two compounds containing two C12 and C16 chains, MnL4 and MnL5, respectively) that are derivatives of the known SOD mimetic, Mn(Me2-Pyane), have been synthesized. These amphiphilic complexes were characterized by the ESI mass spectrometry, potentiometric titrations, light scattering, cyclic voltammetry, and direct stopped-flow determination of their SOD activity at pH 8.1 and 7.4 (in phosphate and HEPES buffers). The formation of supramolecular aggregates that predominantly exist in the solution as a defined micellar/nanostructure assembly, with an average 400 nm size, has been demonstrated for MnL1. The biological effects of the selected complexes (MnL1 and MnL2) on the superoxide level in cytosol and mitochondria have been tested, as well as their effects on the prevention of the lipid peroxidation induced by paraquat. Advantages and disadvantages of the lipophilic pentaazamacrocyclic manganese SOD mimetics in comparison to the corresponding nonsubstituted SOD active complex have been discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomimetic Materials / chemical synthesis
  • Biomimetic Materials / chemistry*
  • Biomimetic Materials / pharmacology
  • Cell Line
  • Electrochemistry
  • Hydrophobic and Hydrophilic Interactions*
  • Macrocyclic Compounds / chemical synthesis
  • Macrocyclic Compounds / chemistry*
  • Macrocyclic Compounds / pharmacology
  • Macrophages / drug effects
  • Manganese / chemistry
  • Mice
  • Superoxide Dismutase / metabolism*

Substances

  • Macrocyclic Compounds
  • Manganese
  • Superoxide Dismutase