Enhancing Tris(pyrazolyl)borate-Based Models of Cysteine/Cysteamine Dioxygenases through Steric Effects: Increased Reactivities, Full Product Characterization and Hints to Initial Superoxide Formation

Chemistry. 2020 Sep 10;26(51):11851-11861. doi: 10.1002/chem.202001818. Epub 2020 Aug 13.

Abstract

The design of biomimetic model complexes for the cysteine dioxygenase (CDO) and cysteamine dioxygenase (ADO) is reported, where the 3-His coordination of the iron ion is simulated by three pyrazole donors of a trispyrazolyl borate ligand (Tp) and protected cysteine and cysteamine represent substrate ligands. It is found that the replacement of phenyl groups-attached at the 3-positions of the pyrazole units in a previous model-by mesityl residues has massive consequences, as the latter arrange to a more spacious reaction pocket. Thus, the reaction with O2 proceeds much faster and afterwards the first structural characterization of an iron(II) η2 -O,O-sulfinate product became possible. If one of the three Tp-mesityl groups is placed in the 5-position, an even larger reaction pocket results, which leads to yet faster rates and accumulation of a reaction intermediate at low temperatures, as shown by UV/Vis and Mössbauer spectroscopy. After comparison with the results of investigations on the cobalt analogues this intermediate is tentatively assigned to an iron(III) superoxide species.

Keywords: dioxygenases; enzyme models; nonheme iron; reaction intermediates; spectroscopy.

MeSH terms

  • Biomimetics
  • Borates / chemistry
  • Cobalt / chemistry
  • Crystallography, X-Ray
  • Cysteamine / chemistry*
  • Cysteine / chemistry*
  • Cysteine Dioxygenase / chemistry*
  • Cysteine Dioxygenase / metabolism
  • Dioxygenases / chemistry*
  • Dioxygenases / metabolism
  • Iron / chemistry
  • Ligands
  • Pyrazoles
  • Superoxides / chemistry*

Substances

  • Borates
  • Ligands
  • Pyrazoles
  • tris(pyrazolyl)borate
  • Superoxides
  • Cobalt
  • Cysteamine
  • Iron
  • Dioxygenases
  • cysteamine dioxygenase
  • Cysteine Dioxygenase
  • Cysteine