Redox properties of iron-dithiocarbamates and their nitrosyl derivatives: implications for their use as traps of nitric oxide in biological systems

While the Fe2+-dithiocarbamate complexes have been commonly used as NO trap s to estimate NO production in biological systems, these complexes can unde rgo complex redox chemistry. Characterization of this redox chemistry is of critical importance for the use of this method as a quantitative assay of NO generation. We observe that the commonly used Fe2+ complexes of N-methyl -D-glucamine dithiocarbamate (MGD) or diethyldithiocarbamate (DETC) are rap idly oxidized under aerobic conditions to form Fe3+ complexes. Following ex posure to NO, diamagnetic NO-Fe3+ complexes are formed as demonstrated by t he optical, electron paramagnetic resonance and gamma-resonance spectroscop y, chemiluminescence and electrochemical methods. Under anaerobic condition s the aqueous NO-Fe3+;MGD and lipid soluble NO-Fe2+-DETC complexes graduall y self transform by reductive nitrosylation into paramagnetic NO-Fe2+-MGD c omplexes with yield of up to 50% and the balance is converted to Fe3+-MGD a nd nitrite. In dimethylsulfoxide this process is greatly accelerated. More efficient transformation of NO-Fe3+-MGD into NO-Fe2+-MGD (60-90% levels) wa s observed after addition of reducing equivalents such as ascorbate, hydroq uinone or cysteine or with addition of excess Fe2+-MGD. With isotope labeli ng of the NOFe3+-MGD with Fe-57, it was shown that these complexes donate N O to Fe2+-MGD. NO-Fe3+-MGD complexes were also formed by reversible oxidati on of NO-Fe3+-MGD in air. The stability of NO-Fe3+-MGD and NO-Fe3+-MGD comp lexes increased with increasing the ratio of MGD to Fe. Thus, the iron-dith iocarbamate complexes and their NO derivatives exhibit complex redox chemis try that should be considered in their application for detection of NO in b iological systems. (C) 2000 Elsevier Science B.V, All rights reserved.