ELECTROSPRAY MASS-SPECTROMETRY OF IRON BLEOMYCIN-II - INVESTIGATION OF THE REACTION OF FE(III) BLEOMYCIN WITH IODOSYLBENZENE

The reaction of ferric bleomycin (Fe(III)BLM) with iodosylbenzene (PhIO) has been investigated using electrospray ionization mass spectrometry (ESI-MS) and EPR spectroscopy. A rapid reaction occurs that ultimately yields several cleavage products of the drug, the structures of which have been deduced from their masses. The intermediates observed by ESI-MS suggest a mechanism for the reaction of Fe(III)BLM with PhIO that does not involve hypervalent iron or activated oxygen but, instead, hypervalent iodine I(III) as the oxidant. Indeed, we could not detect the production of an iron oxene complex of BLM (O=Fe(V)BLM) or hydroperoxyferric BLM (HOO-Fe(III)BLM). Furthermore, we show that the products formed when Fe(III)BLM is reacted with PhIO are identical to those formed when Fe(III)BLM is activated in air or when Fe(III)BLM is reacted with H2O2. Surprisingly, the same products are obtained when Zn(II)BLM or metal-free BLM is reacted with PhIO, indicating that a metal ion is not required for the oxidation of BLM by PhIO.