Issue 6, 2014

Coordination-triggered NO release from a dinitrosyl iron complex leads to anti-inflammatory activity

Abstract

Dinitrosyl iron complexes (DNICs) are widely considered NO storage and donor molecules in cells. However, what induces an NO release from iron in DNICs and the subsequent biological consequences remain elusive. The chemistry and biology of the NO release activity of DNICs are reported here. Changes in redox status or coordination number of discrete N-bound DNICs, respectively [Fe(TMEDA)(NO)2] (1) and [Fe(TMEDA)(NO)2I] (2), can generate a metastable {Fe(NO)2}9 DNIC, [Fe(TMEDA)(NO)2]+, with νNO at 1769 and 1835 cm−1 and an EPR signal at g = 2.04, that spontaneously releases NO in solution. The NO release activity of 2 results in the up- and downregulation of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS), respectively, in murine RAW 264.7 macrophages. Furthermore, treatment with 2 leads to downregulation of pro-inflammatory cytokines, TNF-α and IL-6, and upregulation of the anti-inflammatory cytokine, IL-10. Taken together, these results demonstrate that the appropriate control of redox and coordination chemistry of DNICs could enable them to become anti-inflammatory agents, suggesting a potential new role for cellular DNICs.

Graphical abstract: Coordination-triggered NO release from a dinitrosyl iron complex leads to anti-inflammatory activity

Supplementary files

Article information

Article type
Edge Article
Submitted
03 Dec 2013
Accepted
19 Feb 2014
First published
24 Feb 2014

Chem. Sci., 2014,5, 2374-2378

Author version available

Coordination-triggered NO release from a dinitrosyl iron complex leads to anti-inflammatory activity

K. M. Skodje, M. Kwon, S. W. Chung and E. Kim, Chem. Sci., 2014, 5, 2374 DOI: 10.1039/C3SC53319K

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