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

Schweitzer AD, Howell RC, Jiang Z, Bryan RA, Gerfen G, Chen CC, Mah D, Cahill S, Casadevall A, Dadachova E - PLoS ONE (2009)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Albert Einstein College of Medicine, New York, New York, United States of America.

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 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/significance: 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.

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HPLC (a) and EPR spectra of (b) MELex5, (c) MEL1, (d) MEL2, (e) MEL3b, (f) MEL4.BG, background; PTCA, pyrrole-2,3,5-tricarboxylic acid; PDCA, pyrrole-2,3-dicarboxylic acid; TTCA, 1,3-thiazole-2,4,5-tricarboxylic acid; TDCA, thiazole-4,5-dicarboxylic acid.
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pone-0007229-g001: HPLC (a) and EPR spectra of (b) MELex5, (c) MEL1, (d) MEL2, (e) MEL3b, (f) MEL4.BG, background; PTCA, pyrrole-2,3,5-tricarboxylic acid; PDCA, pyrrole-2,3-dicarboxylic acid; TTCA, 1,3-thiazole-2,4,5-tricarboxylic acid; TDCA, thiazole-4,5-dicarboxylic acid.

Mentions: The HPLC of oxidized synthetic melanins gave additional information about their structure (Fig. 1a). Pyrrole-2,3,5-tricarboxylic acid (PTCA) and pyrrole-2,3-dicarboxylic acid (PDCA), which are oxidation products of DHICA-derived units and DHI-derived units, respectively, were used as standards. MELex5 was characterized by a significant amount of DHICA-derived units and almost no DHI-derived units, while both MEL1 and MEL2 consisted of both DHICA and DHI-derived units, suggesting greater heterogeneity in oligomer unit composition in melanins synthesized via tyrosinase oxidation when compared to melanins synthesized with benzoyl peroxide. MEL3b, synthesized from L-DOPA with L-cysteine, did not show any oxidation products of DHICA or DHI, implying that L-DOPA does not form an appreciable amount of DHICA- or DHI-derived units when oxidized in the presence of L-cysteine. MEL4 contained no oxidation products of DHICA or DHI. However, its chromatogram had peaks assigned to 1,3-thiazole-4,5-dicarboxylic acid (TDCA) and 1,3-thiazole-2,4,5-tricarboxylic acid (TTCA), the oxidation breakdown products of sulfur-containing aromatic structures [15], [27].


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

Schweitzer AD, Howell RC, Jiang Z, Bryan RA, Gerfen G, Chen CC, Mah D, Cahill S, Casadevall A, Dadachova E - PLoS ONE (2009)

HPLC (a) and EPR spectra of (b) MELex5, (c) MEL1, (d) MEL2, (e) MEL3b, (f) MEL4.BG, background; PTCA, pyrrole-2,3,5-tricarboxylic acid; PDCA, pyrrole-2,3-dicarboxylic acid; TTCA, 1,3-thiazole-2,4,5-tricarboxylic acid; TDCA, thiazole-4,5-dicarboxylic acid.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2749938&req=5

pone-0007229-g001: HPLC (a) and EPR spectra of (b) MELex5, (c) MEL1, (d) MEL2, (e) MEL3b, (f) MEL4.BG, background; PTCA, pyrrole-2,3,5-tricarboxylic acid; PDCA, pyrrole-2,3-dicarboxylic acid; TTCA, 1,3-thiazole-2,4,5-tricarboxylic acid; TDCA, thiazole-4,5-dicarboxylic acid.
Mentions: The HPLC of oxidized synthetic melanins gave additional information about their structure (Fig. 1a). Pyrrole-2,3,5-tricarboxylic acid (PTCA) and pyrrole-2,3-dicarboxylic acid (PDCA), which are oxidation products of DHICA-derived units and DHI-derived units, respectively, were used as standards. MELex5 was characterized by a significant amount of DHICA-derived units and almost no DHI-derived units, while both MEL1 and MEL2 consisted of both DHICA and DHI-derived units, suggesting greater heterogeneity in oligomer unit composition in melanins synthesized via tyrosinase oxidation when compared to melanins synthesized with benzoyl peroxide. MEL3b, synthesized from L-DOPA with L-cysteine, did not show any oxidation products of DHICA or DHI, implying that L-DOPA does not form an appreciable amount of DHICA- or DHI-derived units when oxidized in the presence of L-cysteine. MEL4 contained no oxidation products of DHICA or DHI. However, its chromatogram had peaks assigned to 1,3-thiazole-4,5-dicarboxylic acid (TDCA) and 1,3-thiazole-2,4,5-tricarboxylic acid (TTCA), the oxidation breakdown products of sulfur-containing aromatic structures [15], [27].

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Albert Einstein College of Medicine, New York, New York, United States of America.

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 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/significance: 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.

Show MeSH