Tuning Cobalt(III) Schiff Base Complexes as Activated Protein Inhibitors

Marie C. Heffern, Viktorie Reichova, Joseph L. Coomes, Allison S. Harney, Elizabeth A. Bajema, Thomas J. Meade*

*Corresponding author for this work

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Cobalt(III) Schiff base complexes ([Co(acacen)(L)2]+, where L = NH3) inhibit histidine-containing proteins through dissociative exchange of the labile axial ligands (L). This work investigates axial ligand exchange dynamics of [Co(acacen)(L)2]+ complexes toward the development of protein inhibitors that are activated by external triggers such as light irradiation. We sought to investigate ligand exchange dynamics to design a Co(III) complex that is substitutionally inert under normal physiological conditions for selective activation. Fluorescent imidazoles (C3Im) were prepared as axial ligands in [Co(acacen)(L)2]+ to produce complexes (CoC3Im) that could report on ligand exchange and, thus, complex stability. These fluorescent imidazole reporters guided the design of a new dinuclear Co(III) Schiff base complex containing bridging diimidazole ligands, which exhibits enhanced stability to ligand exchange with competing imidazoles and to hydrolysis within a biologically relevant pH range. These studies inform the design of biocompatible Co(III) Schiff base complexes that can be selectively activated for protein inhibition with spatial and temporal specificity.

Original languageEnglish (US)
Pages (from-to)9066-9074
Number of pages9
JournalInorganic chemistry
Volume54
Issue number18
DOIs
StatePublished - Sep 2 2015

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry

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    Heffern, M. C., Reichova, V., Coomes, J. L., Harney, A. S., Bajema, E. A., & Meade, T. J. (2015). Tuning Cobalt(III) Schiff Base Complexes as Activated Protein Inhibitors. Inorganic chemistry, 54(18), 9066-9074. https://doi.org/10.1021/acs.inorgchem.5b01415