Physico-chemical evaluation of rationally designed melanins as novel nature-inspired radioprotectors

Andrew D. Schweitzer, Robertha C. Howell, Zewei Jiang, Ruth A. Bryan, Gary Gerfen, Chin Cheng Chen, Dennis Mah, Sean Cahill, Arturo Casadevall, Ekaterina Dadachova

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Background: Melanin, a high-molecular weight pigment that is ubiquitous in nature, protects melanized microorganisms against high doses of ionizing radiation. However, the physics of melanin interaction with ionizing radiation is unknown. Methodology/Principal Findings: We rationally designed melanins from either 5-S-cysteinyl-DOPA, L-cysteine/L-DOPA, or LDOPA with diverse structures as shown by elemental analysis and HPLC. Sulfur-containing melanins had higher predicted attenuation coefficients than non-sulfur-containing melanins. All synthetic melanins displayed strong electron paramagnetic resonance (2.14.1018, 7.09.1018, and 9.05.1017 spins/g, respectively), with sulfur-containing melanins demonstrating more complex spectra and higher numbers of stable free radicals. There was no change in the quality or quantity of the stable free radicals after high-dose (30,000 cGy), high-energy (137Cs, 661.6 keV) irradiation, indicating a high degree of radical stability as well as a robust resistance to the ionizing effects of gamma irradiation. The rationally designed melanins protected mammalian cells against ionizing radiation of different energies. Conclusions/Significance: We propose that due to melanin's numerous aromatic oligomers containing multiple p-electron system, a generated Compton recoil electron gradually loses energy while passing through the pigment, until its energy is sufficiently low that it can be trapped by stable free radicals present in the pigment. Controlled dissipation of high-energy recoil electrons by melanin prevents secondary ionizations and the generation of damaging free radical species.

Original languageEnglish (US)
Article numbere7229
JournalPloS one
Volume4
Issue number9
DOIs
StatePublished - Sep 30 2009

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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