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 language | English (US) |
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Pages (from-to) | 9066-9074 |
Number of pages | 9 |
Journal | Inorganic Chemistry |
Volume | 54 |
Issue number | 18 |
DOIs | |
State | Published - Sep 2 2015 |
Externally published | Yes |
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Inorganic Chemistry