Electron paramagnetic resonance and Mössbauer studies of metal chelation by adriamycin

Jay L. Zweier, Abraham Levy

Research output: Contribution to journalArticlepeer-review


EPR and Mössbauer studies demonstrate that iron chelation by adriamycin is complex, with several different chelation structures. At physiological pH in aqueous solution, three different EPR spectra are observed: a spectrum at g = 4.2 of Fe3+ in a rhombic crystal field (type 1); a spectrum at g = 2.01 with symmetric Gaussian lineshape linewidth 225 G (1 G = 10−4 T), suggestive of Fe3+ bound in an octahedral crystal field (type 2); and a broad spectrum centered at g = 2.0 suggestive of ferromagnetically coupled Fe3+ (type 3). The type 1 and 2 spectra are observed at adriamycin/Fe3+ ratios >4, the type 3 spectrum is observed at ratios <4 and at ratios <2 an increasing amount of Fe3+ gives rise to EPR silent iron(III) hydroxide polymers. At 4 K the type 1 and 2 complexes exhibit a broad doublet Mössbauer signal with an isomer shift δ = 0.56 (1) mm s−1 and quadrupole splitting δEQ = 0.74 (1) mm s−1. The type 3 complex gives rise to a sextet signal with isomer shift ΔEq = 0.47 (1) mm s−1 and hyperfine splitting HF = 476 (1) kG with exhibits superparamagnetic relaxation behavior with a blocking temperature of 23 K, consistent with a microcrystal size of 25 Å. Cu2+ binds to adriamycin at adriamycin/Cu2+ ratios >4:1 giving rise to an EPR spectrum with axial symmetry g = 2.26, g = 2.066, A = 188 G, while 2:1 complexes exhibit a single Gaussian line at g = 2.09 indicative of exchange‐coupled Cu2+. The exchange‐coupled Cu2+ and ferromagnetically coupled Fe3+ complexes can be explained by the formation of stacked 2:1 adriamycin‐metal polymers. On titration of adriamycin with Fe3+‐nitrilotriacetate a different spectrum is observed at g = 4.3 and its intensity plateaus at an adriamycin/iron ratio of 2. The iron adriamycin complexes cycle to reduce molecular oxygen and this cycle has been hypothesized to be a mechanism mediating the therapeutic and toxic effects of the drug. Both EPR and Mössbauer experiments demonstrate that the type 1 and 2 chelates reduce their Fe3+ to Fe2+ while the type 3 chelate does not. Therefore, the stoichiometry and method of complex preparation can profoundly effect the properties of these complexes.

Original languageEnglish (US)
Pages (from-to)S114-S122
JournalMagnetic Resonance in Chemistry
Issue number13
StatePublished - 1995


  • adriamycin
  • coordination structure
  • electron paramagnetic resonance
  • free radical
  • iron
  • metal chelation

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)


Dive into the research topics of 'Electron paramagnetic resonance and Mössbauer studies of metal chelation by adriamycin'. Together they form a unique fingerprint.

Cite this