17-Black Natural Conductors
Black is everywere, on earth and in stellar interspaces. Black is melanin, no matter what the extensively conjugated carbonium skeleton was formed from. Melanin is a conductor as it is a radical-polarone. It is a stable free radical, holding positive charges, balanced by counter anions and exhibiting a small gap, 1,4 eV. Experimental data, molecular modelling studies and molecular quantum mechanics calculations agree describing DHI-melanin, as a structure fundamentally constituted by repetitive units of 5-gem-diol-indol-6-one linked at 4,7 positions. Linear filaments in two low-energy conformational states, helix and alternate sheet, can arrange to form stratum and cage by further C2 bonds, taking in account for gas and ion keeping and metal chelate formation. Electric and conformational properties explain different roles of melanins. As UV filter and radical scavenger black has a protective function in epithelial tissue; in dopaminergic neurons of Substantia nigra, an area of brain involved in fine motor control, it can act as a conductor allowing rapid electron passage which, generating a magnetic field, can feel the earth-field and control movements. Melanin destruction, in Parkinson’s disease can participate to symptoms and development of neuro-degenerative process.
Many others pigments are found in nature and are candidates to semiconductivity or superconductivity 24 like biline derivatives, metalloporphyrins, ommins, pterins, pheomelanins ( link 9 ), pheochromes, benzothiazines, benzothiazinones, dibenzothiazinones indigoids, cyanines, humic acids, fulvic acids etc..All the pigments are radical-polarones with the characteristic polyconjugate chain of acetilene-black.
A revision of the biological, chemical, and physical properties of the natural pigments is desiderable.
reported by Raper1,2 in 1927 melanin is formed by action of
tyrosinase on tyrosine. Many products of the process tyrosine--melanin have
been isolated or identified like DOPA, dopachrome, cyclodopa,
5,6-dihydroxyindole (DHI), 5,6-dihydroxyindole-2-carboxylic acid (DHICA).The
process of melanogenesis of the DHI which seems to occur in Sepia although
conflicting with experimental date is generally accepted.
melanin, carbon dioxide and H2O2 are also
The role played by H2O2 in melanogenesis was not undertaken.
Carbon dioxide arises from heating of many melanins but its significance remains uncertain2,8. DHI-melanin prepared in the presence of catalase, by heating, produces CO2 (4.7%)
Four possibilities exist for eumelanins to explain carbon dioxide evolution:
a. CO2 could arises from DHICA, Dopachrome or Cyclodopa units although is known that the carboxylic group is firmly bound in these substances,
b. CO2 arises from COOH groups formed from the breakdown of catechol units. 8
c. CO2 arises from gem-diols groups.
d. CO2 arises from the cationic center of the polymer.
recently3,30 it was found that the melanin precursor in Sepia
is DHI . In other words DHI-melanin would represent an interesting model for
melanin structure studies.Unfortunately theory don’t agree with experiment
sepiomelanin having many carboxylic groups
( cyclodopa units ? ).
Analytical results showed by different authors are variable depending to the
melanin extraction and purification method adopted .The most frequently
reactions occuring during extraction and purification of melanosome and
premelanosome34 are :
a. oxidative degradations
e. modification of the counteranion16
papers fail in describing the elemental composition of the melanin 2,
4, 6, 8, 11, 33. All the proposed structures have, for each indole
unit, one oxygen less than the requirement of analytical results. Numerous
adjustments have been claimed, included the presence of water molecules,
DHICA or Dopachrome units, indole and benzene breakdown forming COOH groups23,
etc., to justify the differences between found and calculated values of the
In this paper, the 5-gem-diol-indol-6-one structure is proposed, as a repetitive unit of the precursor to explain analytical data and chemical-physical behaviour.
Actually, elemental analysis of DHI-melanin and sepiomelanin, a well known pigment from Sepia officinalis6,7,8,27 are in apparent agreement with polymers containing units (Table 1) with one more oxygen atom that there is in the precursor.
Elemental Composition of DHI-melanin, sepiomelanin and its derivatives. 20,31
Samples Found %
DHI-melanin 8 C, 58.8 H, 3.3 N, 9.3
DHI-melanin 4,5,30 C, 55.3 H, 3.2 N, 8.3
DHICA-melanin 27 C, 56.1 H, 3.1 N, 7.6
Sepiomelanin6,7,8,33 C, 59.9 H, 3.4 N, 8.2
DHI-melanin methyl ether8 C, 61.6 H, 5.7 N, 8.6 OCH3, 21.5
Sepiomelanin methyl ether 8 C,64.1 H, 5.5 N, 7.4 OCH3, 18.5
C, 66.2 H, 2.1 N, 9.6
(C9H3O4N) C, 57.1 H, 1.6 N, 7.4
(C8H5O3N )x C, 58.9 H, 3.0 N, 8.5
(C8H7O4N)x C, 53.0 H, 3.8 N, 7.7
(C9H7O3N)x C, 61.0 H, 4 N, 7.9 OCH3, 17.5
(C10H1004N) C, 57.7 H, 4.8 N, 6.7 OCH3, 29.8
(C10H504N) C, 59.4 H, 2.4 N, 6.9 OCH3, 15.3
reaction, by diazomethane, suggests the presence of a methoxy group on each
indole, in contrast with proposed
structures. This contrast has been resolved by a conformational study on
oligomers formed by units linked
in4-7 in the
preferential sites of polymerization reaction
In the structure considered an hydroxyl group is available to methylation, but the oligomers stabilized by hydrogen bonds assume two low energy conformations: an alternate sheet and the more stable helix. A 60° dihedral angle between two indole planes is formed.
Torsional angles and formation heats are reported. Constrained by steric hindrance, the alternated pleated sheet and the helix are held in their shapes by hydrogen bonds between a hydroxyl group and the heterocyclic NH. The hydroxyl group over (or under) the indolic plane and the heterocyclic NH generates a helix, whereas a bond between the hydroxyl group alternatively over and under the indole plane and the heterocyclic NH determines the alternate pleated sheet.
Many different equilibria of quinone and reduced forms of monomers and oligomers may occur in the process of melanogenesis. The equilibrium water-quinone,quinone-quinone hydrated, dopachrome-DHICA, decarboxydopachrome-DHI were not considered at present.
Currently, it is not possible to establish when the gem-diol formation take place ,even if after or before polymerization. Nevertheless, ab initio quantum-mechanical calculations indicate that the 5-gem-diol is more, about 13 Kcal, stable than the corresponding 6-gem-diol and that the orbital coefficients (LUMO) of indole-5,6-dione make the 5-carbon the more suitable to water nucleophilic attack.
Hydration of quinone carbonyl groups of indole 5,6-dione, resulting on the 5-gem-diol is a less studied process and it is very similar to hydration of ketone compounds19. This reaction is favoured by electron-withdrawing groups like the a-b unsaturated system and the condensed pyrrolic ring of indol-5,6-dione. The hydrogen bond formation between the pyrrolic NH of an indole unit and a 5-hydroxyl group on the next indole unit can further stabilize the 5-gem-diol formation.
Thermogravimetric analysis of dried natural sepiomelanin and synthetic DHI-melanin showed that water is removed at a transition temperature of 96.4° (about 10%), according to a quinone monohydrate structure 36.
Actually, if DHI-melanin held a polyindolquinone structure, according to the widespread hypothesis reported in literature 2,11 a very easy reduction reaction and high stability to oxidation should be expected, whereas melanin is a substance sensible to oxygen, oxidizing agents and halogens and is not reducible with quinone typical reducing agents and catalytic hydrogen.
Reactivity of other positions of DHI can be responsible of a further link between the polymeric chains to form sheaf stratum or cage structure (Figure 3). This structure explains the water, gas, ions, organic and inorganic products, high binding affinity of melanins.
Figures shows the melanin structure together with the acetylene black, which can be considered an un-substituted melanin.
In all melanins, the unpaired electrons (one of two hundred indole units calculated on the EPR signal), the positive charges (one per eight units calculated on the amount of the counteranion; Cl- in sepiomelanin) distributed along the unsaturated, conjugated skeletons, the red line (the spine, a conductive wire into the molecule)) are responsible of their conductivity.24-26,29,30
Biological electrical fields may be generated by the spine changing the superficial properties of the pigment. This would be an ideal equipment for cell assembly and cell movement. The system would be easily removed by H2O2.
Investigation on natural melanins recovered from human tumors and on synthetic DHI-melanin, demonstrated that the black pigment, acting as a semiconductor, responds to a critical applied field by changing its conductivity and that the nature of response depends on hydration and temperature of the melanin sample and on external circuity. Drying-hydration equilibrium determinates the switching properties of melanins ( The WEB Advances : Organic Semiconductor ) suggesting that ’‘ strongly linked ‘’ water is involved in melanin conductivity. The electronic characteristics persist in intact melanosomes.12,13
This result and the discovery that melanin responds dynamically to electric field behaving as semiconductor and that this property is connected to hydration are in agreement with the description of DHI-melanin as polyindolquinone monohydrated .
Physical models of natural colours based on measurements of the optical costants of eumelanin and pheomelanin ( Link 14 ) are known. Using the results of exact Mie calculations of the scattering and absorption cross-sections for individual pigment granules we show that the colors produced by dispersions of eumelanin or pheomelanin granules are strongly dependant on the pigment granules size. Measurements of the granule size distribution in hair of differing colors are consistent with the predictions.The colors are found to be strongly dependant on the Mott-Davis optical energy gap parameter EO which controls the dispersion of the optical costant k in amorphous semiconductor. Changes in EO as small as 0.2 eV,out of 1.4 eV, are sufficient to alter color from brown to red hair. Moreover, black color, interpreted on the basis of band theory indicates a gap value about of 1.5 eV, according to a black crystalline semiconductor like SeS.
Acetylene, pyrrole, benzene blacks seem to share common properties; their structural peculiarities may identify a new class of organic semiconductor substances.
DHI, adrenaline, serotonine, tryptamine, dopamine, isoquinoline15 blacks may be also present in nature and can play interesting but still unknown biological roles.
Figure 4 reports a representation of melanin whose backbone arranges in alternate-sheet and helix giving rise to cages. Water plays a crucial role stabilizing secondary and tertiary structures and promote a cooperative phenomenon where hydrogen-bonding is a cohesive interaction. Hydrated indole units may determine the self-assembly of melanin and its pH dependent aggregation, organizing water, or squeezing it out from the internal cages. Folding of the helix backbone upon itself could form spheres, stretched-out zigzag chains and build strata.
As radical-polarone materials, melanins are radical scavengers acting as UV radical-filters in epithelial tissue and bio-organic conductors, allowing a rapid electron passage through the polyconjugated skeleton, ( the red line of the figures, acetylene-black ) An electric conductor in crucial area of brain, could also induce magnetic fields useful to feel the earth's field and to control movements.
Neuromelanin11 the granular black pigment, present in bio-electrical active neurons can be associated with Parkinson’s disease. In fact, biological reactions involving radicals (OH. in Fenton reaction) and nucleophilic attacking agents can easily react on radical and cationic sites, of melanin producing different occurrences iron depletion, local carbon hybrid changes, variations of the conformational structures and fall of conductivity deteriorating the switching functions.
Melanin structure associated with the radical-polarone system of acetylene-black , identify a biological conductors class of large interest in many scientific fields and open doors to still unexplored territory of neurosciences where variations of conformational structure and falls of conductivity dominate together with potential gradients, electron flows and charge transfer processes.
avoid the formation of certain artifacts (oxidation products of H2O2
) we have recently adopted the following procedure for extraction and
purification of sepiomelanin :
animal was frozen to death. The black material was gently squeezed from ink
sac (about 500 mg for each sac) and an excess of
solution was added to freshly
recovered crude pigment to destroy H2O2 present
(about 175 mg). and the mixture frozen for 48 h. New catalase was
added,the mixture was homogenized and
centrifuged repeatedly with a NaCl physiological, degassed, solution to take
away protein components (10’at
5.000 to 15.000g to be tested; granules are taken at low centrifuge speed )
and separate melanosome from granules. Precipitate was washed by
centrifugation three times with H2O, three times with aceton (10
ml), deionised, degassed water obtaining
sepiomelanin or Ca Mg salt of sepiomelanic acid ).
A is washed many times with 2N HCl ( pure reagent ) to remove calcium and magnesium ions.
Supernatant fractions combined and lyophilised were investigated for C, H, N, Ca, Mg, cyclodopa, DHI, DHICA, pyrrolic acids.
The black solid residue was suspended in degassed, deionised water and pH adjusted to 10 by 1N NaOH solution and was sonicated (15’, 80 W) keeping temperature at 0 °C . The suspension was filtered under nitrogen and the black solution was acidified at pH 1 by pure HCl conc. and centrifuged.The precipitate containing a quasi protein-free sepiomelanin acid, washed very well with water is kept moist in refrigerator.
The black material is additioned with pure HCl conc., maintained for one night in the dark. was dilute and centrifuged and washed many times with deionized water,acetone, water.
The material B (sepiomelanic acid) so obtained is kept moist and deep frozen.
For analysis the pigment is dried in vacuo at room temperature and equilibrated in air of a cleaned-air room.
analysis for A
(sepiomelanin) obtained at 5000 g
C, H, N, S, Ca. Mg, Zn, Cu, Ni, Fe, Cl ( the counteranion sometimes ), ashes.
Same analysis for
fraction obtained at 10000g and 15000g
analysis for B
(sepiomelanic acid ) :
C, H, N, S, Zn, Cu, Cl, Ni, Fe, ashes.
The same analysis is repeated with sepiomelanin-methylether (diazomethane) together with OCH3% determination.
Melanin salts of Fe, Cu, Ni, Zn, are prepared from sonicated solutions at neutral pH and analyzed for elemental composition and conductivity.
Research of the counterion is carried out.
Analytical values obtained with this procedure are in agreement with values calculated for C8H4NO3 or C17H6N2O6 units.
parameters to determine:
Conductivity, PMGE (Proctor and McGinness effect) , superconductivity, doping
effect, MALDI, IR, NMR, X-rays, binding capacity for ions and organic
products, gas adsorbing, cellular assembling capacity.
A similar procedure may be followed for other melanins.Sometimes the procedure may be simplified because the melanin is soluble in water, dilute ammonia or alkalies ( pheomelanins, allomelanins, humic acids, plant melanins, microrganism-melanins). Sonication (80 W for 15 min. in alkaline solution ) is sometimes recommended.
A B B’
Electricity , Galvani
band structure of melanins, Pullman
in melanins, Proctor and McGinness
J.E.Corry, P.Proctor, ‘’
Amorphous semiconductor switching
in melanins ‘’ Science, 183, 853-854, 1974.
The WEB ‘’Advances
: Organic Semiconductors
pigments are amorphous semiconductors (
Science, 177, 896, 1972 ) Melanin
produced synthetically and isolated from biological systems act as an
amorphous semiconductor threshold switch. Switching occurs reversibly as
potential gradients two to three orders of magnitude lower than reported for
inorganic thin films, and comparable to gradients existing in some biological
systems. Of a number of other biological materials tested , only cytochrome c
acted similarly, but at the high potential gradients reported for thin film
the Solid state Physics Correspondent
. Nature, 248, 475, 1974 :
at least one biological material
has been shown to have a strikingly large conductivity when corrected excited.
Mc Ginness,Corry and Proctor, of the University of Texas Cancer Center,
Houston, report in Science 1974, that melanins
can be made to switch from
a poorly conducting to to a higly
conducting state at fairly low electric fields ( say from 10K ohm-cm to 100
ohm-cm at a field of 300 V cm-1 ). This remarkable phenomenon occurs both in
melanin made synthetically from tyrosine and in that extracted from a human
melanoma. The large conduction is not destructive in any way and is reversible
; According to some tests
conduction seems to be electronic rather
G. de Santillana ‘’ Alessandro Volta ‘’ Scientific American, 212, 82-92, 1965
pile or battery opened the age of electrical
power and settled his celebrated argument with Luigi Galvani.Curiously
he then played no part in the epocal developments that his invention made
Born Como 1745 dead Como 1827 ).
( Luigi Galvani born Bologna 1737 dead Bologna 1798 )
and Volta were long in dispute over what Galvani called ‘’ animal
electricity ‘’ and
Volta called ‘’ metallic
Grey Walter ‘’
The Electrical Activity of the Brain
‘’ Scientific American, reprinted from June 1954.
recording the pulsation of tiny currents from various parts of the head the
electroencephalographer diagnose brain disorders and studies the basic
mechanism of mind
W.Holmes ‘’ Le variazioni cromatiche nei cefalopodi ‘’ Endeavour, 14,78-82, 1955.
Quando nel corso dell’evoluzione i cefalopodi
abbandonarono la protezione di una conchiglia, svilupparono la curiosa facoltà
protettiva di potere cambiare
rapidamente disposizione dei colori sul loro corpo.Questi cambiamenti sono
dovuti alla contrazione e al rilasciamento dei cromatofori controllati dal
sistema nervoso. Ulteriori ricerche su questo fenomeno potranno gettare luce
sulla correlazione tra l’organizzazione del tessuto nervoso ed il
R.D.Keynes ‘’ La produzione di elettricità nei pesci ‘’ Endeavour, 15, 215-222, 1956.
Esistono diverse specie di pesci, per lo più marini
capaci di produrre elettricità
N.Millott, ‘’ La fotosensibilità animale, particolarmente nelle forme prive di occhi’’ Endeavour, 16, 19-28, 1957
‘’ Electric location by fishes ‘’
Scientific American, reprint from March 1963
well known that some fishes generate strong electric
fields to stun their prey
or discourage predators.Gymnarchus niloticuc produce
a weak field to the purpose of sensing its environment.
at room temperature ‘’
Scientific American, 212, 21-27, 1965.
organic materials and polyacetilene-black system are present in melanins ,
porphyrins and other natural pigments.
Raper, H.S. The tyrosinase-tyrosine reaction. VI. Production from tyrosine of
5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid, the precursor
of melanin. Biochem.
J. 21, 86-96 (1927).
2. Nicolaus,R.A.,Melanins,Hermann,Paris(1968). : http://www.tightrope.it/nicolaus/index.htm
3. Palumbo, A., Di Cosmo, A., Gesualdo, I., Hearing, V.J., Subcellular localization and function of melanogenic enzymes in the ink gland of sepia officinalis. Biochem. J. 323,749-756 (1997)
4. Ito, S., Reexamination of the structure of eumelanin. BBA., 883, 155-161 (1986)
5. Beer,R.J.S., Broadhurst,T., Robertson, A. The chemistry of melanins.Part V. The autoxidation of 5,6-Dihydroxyindoles. J. Chem. Soc., 1947-1953 (1954)
6. Panizzi, L., Nicolaus,R., Ricerche sulle Melanine, Gazz.Chim. Ital. 82,435-460, (1952).
7. Piattelli, M.& Nicolaus, R.A., The structure of melanins and melanogenesis. I. The structure of melanin in Sepia. Tetrahedron, 15, 66-75 (1961).
8. Piattelli, M., Fattorusso, E., Magno, S.& Nicolaus, R.A. The strucure of melanins and melanogenesis. II. Sepiomelanin and synthetic pigments. Tetrahedron, 18, 941-949 (1962).
9. MOPAC (version 6.0) available from Quantum Chemistry Program Exchange, No. 455. Vinter, J. G.; Davis, A.; Saunders, M. R. Strategic Approaches to Drug Design. 1. An Integrated Software Framework for Molecular Modelling. J. Comput.-Aided Mol. Design, 1, 31-55 (1987). Treasurywala, A. M.; Jaeger, E. P., Peterson, M. L. Conformational Searching Methods for Small Molecules. III. Study of Stochastic Methods Available in SYBYL and MACROMODEL. J. Comput. Chem. 17, 1171-1182 (1996).
10. Kienz, E., Jellinger, K., Stachelberger, H. & Linert, W. Iron as catayst for oxidative stress in the pathogenesis o f Parkinson's dease? Life Sci,. 65, 1973-1976 (1999)
Prota, G., Melanins and melanogenesis , AP, San Diego (1992).
12. McGinness, J.E., Corry, P., Proctor. P. Amorphous semiconductor switching in melanins. Science 183, 853-854 (1974). www.organicsemiconductors.com
13. Kirkpatrick,D.S., McGinness, J.E., Moorhead, W.D., Corry, P.M., Proctor, P.H. Melanin-water-Ion Dielectric Interactions. Pigment Cell, Vol. 4, 257-262, Karger, Basel (1979) . The WEB ( Advances : Organic Semiconductors ).
14. Becke, A. D. Phys. Rev. A 38, 3098-3100 (1988). Lee, C., Yang, W. & Parr, R. C. Phys. Rev. A 37, 785-789 (1988).
Mosca, L., Blarzino, C., Coccia, R., Foppoli, C. & Rosei, M.A. Melanins
from tetrahydroisoquinolines: spectroscopic characteristics, scavenging
activity and redox transfer properties. Free Radical Biology & Medicine,
24, 161-7 (1998).
16. All the data accumulated in the past half century lead to an unreal picture of melanins function and structure. No research of counteranion has been undertaken.
Melanins are particles and not molecules. For all that literature swarms with
papers on molecular weight of melanins. Some authors quoted a molecular
wlight between 500 and 30000 Da.
18. We propose to assign the igNobel award 2002 to the discovery of melanin molecular weight. Candidates names will be comunicated later.
19. Ogata, Y. & Kawasaki A. The chemistry of the carbonyl group 3-10. Ed Zabicky, J. Interscience Publishers, London 1970.
20. Presence of ashes and counteranions may alter the results.
21. Kroesche, C., Peter, M.G., Detection of Melanochromes by MALDI-TOF Mass Spectrometry, Tetrahedron, 52, 3947-3952 (1996).
22. Bertazzo,A., Costa, C., Allegri, G., Seraglia,R., Traldi,P., Biosinthesys of Melanin from Dopamine.An investigation of Early oligomerization Products, Rapid.Comm. Spectrom. 9, 634-640 (1995).
23. The catecholic fission of indole units (sepiomelanin) may be obtained with alkaline H2O2. The compound isolated as Barium salt C20H17N3O15Ba3 is the precursor of pyrrolic acids (6),(28). This polyacid was also found in MALDI spectra (Napolitano, A., et al. Rapid. Comm. Mass Spectrom. 10, 204, 468 (1996).
24. Nicolaus, B.J.R., Nicolaus, R.A. Speculating on the band colours in Nature, Atti Accademia Pontaniana, XLV, 365-385, ( 1996 ).
25. Nicolaus,R.A. Coloured organic semiconductors: melanins, Rend. Acc. Sci. Fis. Mat., LXIV, 325-340 (1997).
Nicolaus, R.A., Parisi, G., The Nature of Animal Blacks. Atti
Accademia Pontaniana XLIX, 197-233 (2000).
27. Piattelli, M., Fattorusso, E., Magno, S., Nicolaus, R.A. The structure of Melanins and melanogenesis-III-The structure of sepiomelanin, Tetrahedron 19, 2061-2072 (1963).
28. Nicolaus, R.A., MALDI mass spectrometry and melanins, Rend. Acc. Sci. Fis. Mat., LXIV, 315-323 (1997)
29. Nicolaus, G., Nicolaus, R.A., Melanins, Cosmoids, Fullerenes, Rend.Acc.Sci.Fis.Mat. LXVI, 131-158, (1999).
30. Olivieri, M., Nicolaus, R.A., Sulla DHI-melanina, Rend. Acc. Sci. Fis. Mat. LXVI, 85-96 (1999).
31. Results are influenced by extraction and purification methods adopted. Frequently the black material
A tetramer of DHICA has been found in tapetum lucidum of cuttlefish
(Ito, S., et al., Biochem. J., 161, 207-217, 1974 ) but the material was not
33. Benathan, M., Contribution a l'analyse quantitative des melanines, These de Doctorat, Faculte des Sciences, Lausanne, 1-140, Lausanne (1980).
34. Bolognese, A., Nicolaus, R.A., About the structure of sepiomelanin, Atti Accademia Pontaniana, Vol. XLIX, 309-312, (2001).
35. Bolognese, A., Nicolaus, R.A., Melanins and Pheomelanins, Atti Accademia Pontaniana, Vol. L, in press.
36. Nicolaus, R.A., Bolognese, A., Conduttori biologici neri. Atti Accademia Pontaniana, Vol. L, in press.
37. Nicolaus,B.J.R.,Nicolaus,R.A., Olivieri,M., Riflessioni sulla Chimica della materia nera interstellare, Rend. Acc.Sci.Fis.Mat. LXVI, 113-129 (1999)
Nicolaus,B.J.R., Lo scrigno oscuro della vita, Atti della Accademia Pontaniana,
XLVIII, 355-380, (1999).
Revised September 2003