Electrochemistry of the anticancer agents methotrexate and alpha-difluoromethylornithine in iminium form.

The electrochemical characteristics of the antitumor agents methotrexate and alpha-difluoromethylornithine were determined as their iminium derivatives. Iminium formation from methotrexate is accomplished in vivo via protonation by enzyme. The requisite imine precursor is generated from alpha-difluoromethylornithine by condensation with enzyme containing pyridoxal phosphate. Electroreduction occurs in the range of -0.2 to -0.6 V. The relationship of reduction to structure is discussed. A possible mode of anticancer action involving electron transfer is presented.