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


RESULTS
We rationally designed melanins from either 5-S-cysteinyl-DOPA, L-cysteine/L-DOPA, or L-DOPA 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 (2.14.10(18), 7.09.10(18), and 9.05.10(17) 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 ((137)Cs, 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
We propose that due to melanin's numerous aromatic oligomers containing multiple pi-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.
Schweitzer
Andrew D
AD
Department of Nuclear Medicine, Albert Einstein College of Medicine, New York, New York, United States of America.
Howell
Robertha C
RC
Jiang
Zewei
Z
Bryan
Ruth A
RA
Gerfen
Gary
G
Chen
Chin-Cheng
CC
Mah
Dennis
D
Cahill
Sean
S
Casadevall
Arturo
A
Dadachova
Ekaterina
E
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003455:Cryptococcus neoformans / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry; D003548:Cysteinyldopa / Q000737:chemistry; D005609:Free Radicals; D005720:Gamma Rays; D007980:Levodopa / Q000737:chemistry; D017895:Manganese Compounds / Q000494:pharmacology; D008543:Melanins / Q000378:metabolism / Q000502:physiology*; D008970:Molecular Weight; D010087:Oxides / Q000494:pharmacology; D010100:Oxygen / Q000737:chemistry; D011836:Radiation Tolerance; D011839:Radiation, Ionizing
D005609:Free Radicals; D017895:Manganese Compounds; D008543:Melanins; D010087:Oxides; C048856:permanganic acid; D003548:Cysteinyldopa; D007980:Levodopa; D003545:Cysteine; D010100:Oxygen