Link 21-The BCM story
In the second half of the last
century despite being there intense the study(1-7) of synthetic and natural
melanins this did not lead to good results. Structurally, physically and
functionally our knowledge of the melanins developed in a misleading way.
There are several reasons for this
and many considerations may be made.
Here, we recall a few.
Chemical and biological research
is useful for the study of crystalline substances, of ordered polymers, of
natural organic substances and not for an amorphous material. The belief
that the melanins were polmers created a series of false problems like that of
the positions involved in polymerisation or the problem of the homogenous and
heterogenous polymers. It was said: the question is whether melanin is a
regular, polymer of 5,6-indolequinone (poikilopolymer), or whether it is a
random polymer consisting of several different monomers which are coupled by
means of various bond types.
In itself this question
contains a number of rather special queries, some of which seem of fundamental
Under the principle of
biochemical unitarianism which had proven so fruitful, it was
tempting to assume from the start that melanin, which is clearly an
unusual biological'' polymer '', is synthesized in a manner similar to all
biological polymers, That is, its synthesis is controlled by enzymes
which are specific for substrate and/or bond type. Despite the
complexity of the nucleic acids, proteins, and polysaccharides, they obviously
all have a high degree of order or of non- randomness. These polymers are
each characterized by a single type of linkage, the phosphate
ester bond, the peptide bond and the glycoside bond respectively.
If we follow the unitary principle then, melanin too
should have one characteristic type of linkage which couples the monomers
together. As to the nature of the monomer, the Raper-Mason scheme, as
presented in the past, suggested that it is indole 5,6-quinone.
Perhaps an extreme statement of the homopolymer view would then be
that melanin consists of 5,6-indolequinone linked through a
single bond type(1). This concept requires no special assumption other
than that the premelanosome contains the necessary enzymes to
carry tyrosine through the Raper-Mason scheme, and to direct the
polymerization of the indole 5,6-quinone.
The concept of the
polyindolequinone structure for BCM dominated the scientific scene of the past
The centesimal values for a
polyindolequinone structure (C8H3O2N)
as formed following the Raper-Mason
scheme (an oxidative product of DHI formed
from tyrosine) are:
2. 1 N%
The DHI-melanin analysis (R. J.
S. Beer, T. Broadhurst,A. Robertson, '' The chemistry of melanins-Part V-The
autooxidation of 5,6-Dihydroxyindoles '' Soc. 1947 (1954) gave
C% 56. 6 H%
3. 1 N%
which approximates to the formula
(C8 H5 O3 N)
Surprising the values of BCM
were different as for the ink of cephalopds
C% 54. 3 H%
2. 9 N%
(J. P. Ortonne, C. Voulot, C.
Khatchadourian, A. Palumbo, G. Prota '' A reexamination of melanogeneis in the
ink gland of cephalopods '' in Pigment Cell 1981 page 49-57, Ed. M. Seiji,
University of Tokyo Press, 1981 but may approximate the centesimal value for
C8H3O2N (depending of physical methods of purification adopted) (62a), (62b).
From the start it was clear that
black material obtained from tyrosine
was different to the black material obtained by oxidation of
Natural melanins (BCM) were not
c) In the
oxidation of 5,6-Dihydroxyindole (DHI) the polymer itself must be much more
complex. In the oxidative process CO2 is evolved and H2O2 is formed so that
there may be some very complex
reactions which are not showed in the Raper-Mason scheme. In addition the
black material cannot be reduced by aluminum hydride or Zn+HCl. If it were
a quinone it could be reduced.
. Yet general methods for
the solubilization of natural melanins under physiological conditions have not
yet been found, excepting mild action of H2O2 in alkaline
medium with transformation of the original structure (opening of the benzenoid
part). Once these other biopolymers have been solubilized, they may
be hydrolyzed under physiological conditions with the use of specific enzymes,
or under quite mild conditions of acidic or basic hydrolysis.
Although melanin -in common with any organic substances may be degraded in
mild conditions by H2O2, or photooxidatively
degraded by ultra violet light, in both cases the degradation products are
formed with low yields It is interesting that the colour changes
(black, reddish, gold yellow) during the H2O2 oxidation
corresponds to those of some inorganic sulphides (8). The colour depends
on the gap amplitude of the semiconductor model (8), (27d).
It is now amply confirmed, by EPR,
that natural and also synthetic melanins are paramagnetic and that they
are paramagnetic because they contain unpaired electrons within their molecules
(see acetylene-black) and are amorphous semiconductors : (www.
organicsemiconductors. com ; www. tightrope. it/nicolaus/index. htm ), (27
a-d), (27h), (27l) (27m). The EPR spectra of natural melanins (BCM) and
synthetic material (BSM) are quite similar. The EPR spectra cannot
distinguish between these pigments which we know are in some ways
chemically different (catechol-melanin, dopa-melanin,cyclodopa-melanin,
DHI-melanin), that is the EPR spectra are of no relevance to the melanin problem.
It is our view that the EPR
results raise significant questions : first the EPR signals (electrical
conductivity) which one invariably observes in BCM and BSM, are not seen
in any other biochemical compounds, or in tissues or organisms not containing
Thus melanins (BCM) seem to be
unique among the costituents of living organisms in that they exhibit
intrinsic semiconductivity and have charateristic band gaps 1,2-1,7 eV (black of
the semiconductor model), gas-storage properties and particle structure.
All this eventually requires an explanation in terms of
Some theoretical studies reported
in the past (63) are interesting for understanding the electronic structure and
statistical properties of quasi-particles in polymeric materials that is
solitons, antisolitons, polarons, bipolarons,. Polyacetilene black was used to
study the distortion associated with quasi-particles in oligomers and infinite
The radical-polarone (cationic)
system seems to be present in all the BCM and BSM until now examined. The models
explain a number of properties like optical, magnetic, electrical, chemical
assembling of oligomers. (27 b-d). The description of neutral and
charged defects in conjugate polymers is based on Huckel calculations which have
quantitative limitations. More sophisticated treatment of neutral and
charged defects in polymers differ from Huckel description in quantitative but
not in qualitative conclusions. Whereas Huckel treatment
of a radical defect on polyacetylene yields a distortion of the lattice
extending about seven carbon atoms on either side from the defect, detailed
calculations yield an entity localised on three carbon atoms. The difference has
no important consequence in the application of the theory to the description of
defect formation, trasport in acetylene-black and limits of the applicability of
the soliton model.
Secondly the EPR absorption and
other properties which melanin alone appears to have in living organisms are
found abundantly among products of non-living systems (BSM) including
probably black interstellar matter (27f), (27g).
It is partly because of
these findings that we have seriously entertained the concept that melanin
itself may be formed through a free radical method and without the
intervention of enzymes (except the first step), leading to the formation of an
amorphous material formed by black particles.
Fig 1. The yellow cadmium sulphide has a gap 2,6 eV the
black cadmium 1,6 eV. Colour depends to the gap value.Inorganic pheomelanin and
Study concentrated more on the
molecule than on the particle leads
us to the big scientific mess of the past century. A long time is now
required to get out from this difficult situation but sooner or later the truth
will come to light. Our
ignorance of nanoscience was a negative element for our understanding.
Isolated attempts to introduce the concept of particle for the melanins were
made in 1992 only. (9).
Melanosome are acid-resistant
hydrolysis (60) but easily degraded by physical ( LASER , MALDI, MALDI-TOF ) or
chemical ( H2O2 ) methods.
Extraction of pigments is a
difficult task. Many different methods are used (3), (4), (9), (16), (31), (67),
(76), (77) but none can be recommended.
BCM is made up of small
oligomeric units (43-47), (11),
(10), and the structural morphology
reflects the aggregation of oligomeric molecules.
Even though models of melanins as
substances operating according to “solid state” mechanisms were proposed in
the last decades of the last century, the biological implications of such ideas
(9), (15-16) (20), did not receive
much attention because of the scarcity of reliable experimental confirmation and
also because of the difficulty of accepting a somewhat unconventional point of
view for the biochemical-physical sciences. In more recent years, the
study of the structure of the particles of melanin isolated from the cell or
prepared synthetically (28), (29) has confirmed that both their photophysics and
their photochemistry (17-20) need to be explained in terms of aggregated solids
in which the geometrical and physical characteristics play an essential role in
understanding the physiology of the pigment at a molecular level.
The results of x-ray diffraction
studies (21-25) on granules of melanin are limited to confirming their amorphous
structure in which there are ordered regions, and to the rather speculative
existence of a sort of “fundamental unit” (26). More recent studies of
tunnel effect microscopy have confirmed the previous results and
introduced the concept of a heirarchical structure in the process of
self-aggregation. The electrical conductivity of a black substance may be
notably increased by doping (on this see acetylene black and pyrrol black as
examples) (28-30). Melanins produced synthetically and isolated from
biological systems act as amorphous semiconductors with threshold switching.
Switching is reversible at potential gradients two to three orders of magnitude
lower than reported for inorganic thin films and comparable to
gradients existing in some biological systems. melanins give off a
flash of light when they switch (electroluminiscence). Of a number
of other biological materials tested, only cytochrome C acted similarly,
but at the high potential gradients reported for thin film amorphous
semiconductors. (Science, 183, 853, (1974)
The values reported in literature
should eventually be revised with data obtained from working on integral
This experimental situation
inevitably brings one to consider the melanins as colloidal nanostructures (for
the dimension of their granules) for which the relationship structure-function
must be based on chemical processes in a heterogenous phase. The effect of
light radiation, for example on the processes of charge transfer, must be
interpreted not at a molecular level, but rather as a “photocatalytic”
action of the type studied in certain metallic oxides. Briefly, as in the
colloidal inorganic semiconductors, charges may be stored as band conduction
states and as a consequence energy conversion must always involve
multielectronic transfer processes. The interesting thing is that the
electronic structure of the melanins can give the possibility of such charge
Often the study of melanins (BCM
and BSM) is carried out on artefacts. Artefacts of melanins, little known
from a chemical point of view, form in the course of the synthesis or extraction
from the biological sources, even in the blandest of conditions: processes of
oxidation, decarborboxylation, condensation, or substitution of the natural
cation may all take place during isolation
It should be remembered that all
the ortho. diphenols may produce melanin, by an oxidative process, with a
sufficient number of free positions (at least two) to make the Raper-Mason
scheme difficult to interpret. Black material (melanin) is formed by
oxidation in atmospheric O2 or by H2O2
especially at elevated pH. The material always has one oxygen more than
the number present in the precursor (catechol, 5,6-dioxyindoles, adrenaline,DOPA,
dopammine, methyl-catecholes and methyl-5,6-dihydroxyindoles etc. ).
(Fig. 5-8 )
Attempts of extraction and
purification of melanins by preventative mixing of the various organelles of the
melanocyte have been made (31). The extraction of melanin from the various
biological sources is, effectively, the extraction of granules and of active
melanosomes and premelanosomes. The melanin which is obtained by the
various extractive processes used to date is a set of particles partly formed
during the course of extraction. The melanin which is obtained is,
therefore, an artefact. The subsequent purification process
a. decarboxylation on
b. oxidation of the
benzenoid part (when the precursor is 5,6-dihydroxyindole, DHI) by theH2O2
present in atmospheric oxygen
c. loss of the cation
condensation processes with the use of hot HCl (formation of
pyrroletetracarboxylic acid in the oxidative degradation).
e. conversion of the
dopachromic unit of the”polymer” into a DHI and a DHICA structure.
Wishing to summarise we may claim
that to date nobody has managed to isolate a particle equal to that contained in
a granule of melanocyte. It follows that all the experimental data and
chemo-physical parameters are uncertain and need to be revised.
The application of physical
methods, as for the heterogenous materials used, has not given good results.
Data from NMR and x-ray, for electrical and acoustic conducibility,
photochemistry and photobiology, are all not very reliable. The
interpretation of data obtained by MALDI and MALDI-TOF mass spectrometry is
grotesque, leading to the definition of the melanins as a mixture of oligomers
with low molecular weights. Effectively the black particles built with
oligomers of non-high molecular weight (11) explode (they break like a vase
dropped from a height) under LASER action. The explosion is similar to
that (frantumation) of the graphite, which as is known, brought about the
discovery of the fullerene C60. It is possible that a similar reaction
takes place because of the effect of an undocumented radiation or the collision
of black interstellar particles. (Link 7. Speculation on the chemistry of
interstellar black matter. or Link 8. The dark secret of life).
The BSM of interstellar spaces (Bok globules) and the BCM of Dr A. Satti
a sudanese chemist of Khartoum.
Chemo-biological researchers have
paid little attention to the electrical conducibility of melanin (BCM) and the
Proctor-McGinness effect, (www. organicsemiconductors. com). Chemists have
not considered the new approach for
organic chemistry. Biologists have shown little interest in the
extraordinary capacity-function of the melanin in linking ions and organic
molecules, of forming charge transfer complexes, of transporting and storing gas
(20) (common in fullerene, graphite and helicoid systems), of assembling
molecules, of forming electromagnetic fields, of giving rise to communications
systems between tissue and tissue, and between tissue and the CNS, of the role
played in interstellar space and in the pre-enzymatic era. It is strange that
all this has not stimulated new research on the function of melanin (BCM) in
Considering the biogenesis of the
cellular pigment, it is believed that the melanins are polymers of DHI and/or
DHICA (initially believed to be artefacts by Raper). The reactions, which
lead to 5,6-dioxyindole (DHI) and to 5,6-dioxyindole-2-carboxylic (DHICA), would
thus be under the rigid control of several enzymes and other factors. As a
consequence there should be an enzymatic system which regulates the construction
of the black particle. It should be noted that among other things the
sepia may also yield a melanin from a precursor other than the tyrosine, which
The enzyme seems to be present
not only in the melanocytes of melanoma but also in the melanocyte of sepia ink
(34). A different enzyme which catalyses the conversion of the dopachrome
into DHI seems to be present in insects (4). Analytic studies which
demonstrate that in dopa-melanin the DHICA unit represents only 10% while in
melanoma-melanin (35), only 20% are in contrast. (36). An attempt to
reconcile the action of enzymes with the action of metals
has been presented (4).
To explain the chemical data, in contrast with the Raper-Mason
(www.tightrope.it/nicolaus/index.htm ) (Link
, we suggested that the eumelanins originate from ortho. diphenol
cyclodopa, that the fundamental unit is a hydrated quinonic unit
polymers having one oxygen more than the precursor
(Fig. 7), that the unit which constitutes the black particle may be
described as a radical-polaronic system well represented by acetylene black (Fig.
6) and having a typical EPR signal. This system explains the electrical
conductivity, the colour of the amorphous semiconductor (gap 1,2-1,7 eV), and
the easy breaking of the benzenoid rings (transformation into a substituted
acetylene black). The form of the black particle,( graphite sandwich,
fullerene, and helical of oligomers), rather than the molecular structure,
explains properties like the affinity for ions, organic molecules and gases, the
ability to reduce molecular oxygen, to superoxide ions and hydrogen peroxide.
Particle form may influence colour and conductivity. The concept of the particle
changes the way of studying the melanins (BCM and BSM) and takes us
instinctively to investigate the monomers and oligomers which contribute to the
black particles. The form and size of the particle may be a distinctive
element of the property of different melanins. The era of nanochemistry,
nanophysics and nanobiology has started.In conclusion compared to the past it
seems that a new and more realistic picture of the black material BCM
and BSM may be presented. Oltre che per le sue proprietà assemblatrici tipiche
delle BCM la forma idrata del indolchinone è atossica per la cellula e possiede
molte delle proprietà di superfici del PLGA-collageno, le sue proprietà
elettriche (effetto Proctor-McGinness) rappresentano un elemento di
comunicazione fra tessuto e tessuto e fra tessuto e SNC. Negli acidi umici
la forma idrata reversibile può rappresentare una riserva di acqua da
ridistribuire nel terreno. In forma simile questa acqua solida può essere
trasportata da meteoriti e comete.
Con la formazione di un nero da ciclodopa diversi problemi chimici inerenti alla BCM vengono risolti o messi in condizione di essere risolti. Oligomeri radical polaronici a basso peso molecolare si assemblano per formare la particella. E' probabile che forma, grandezza, struttura possano influenzare la conducibilità elettrica e sonora, il trasporto di gas, ioni, molecole organiche sia della materia nera cellulare (BCM) che della materia nera sintetica (BSM).
Non è sicuro che la melanogenesi proceda attraverso fasi controllate dagli enzimi essendo più probabile l'azione esercitata da metalli quali Fe, Cu, Zn, Ni. L'attività enzimatica è dosata sulla decolorazione, opinabile, della soluzione rossa. Lo studio chimico è carente di analisi C, H, N, S, Cu, Fe, Zn, Ni, e degli spettri di massa.
Per quanto riguarda la funzione della BCM (melanine),una questione assai dibattuta, non si è mai tenuto conto di quanto la chimica e la fisica venivano man mano scoprendo. La conducibilità elettrica e sonora, la proprietà, comune a tutta la materia nera, di legare ioni, molecole organiche, gas, la proprietà di esplodere della melanina e del melanosoma (59) per azione del LASER, la proprietà di assemblaggio molecolare (principio della tensitegrità), la straordinaria sensibilità alla acqua ossigenata.
Infine la conducibilità e la superconducibilita a vari valori del potenziale (effetto Proctor-Mc Ginness) www. organicsemiconductors. com.
Gli studi chimici sulle melanine patologiche sono scarsi. Un vecchio lavoro fatto a Napoli (61) riferisce sulla estrazione da un melanoma di due melanine una nera brillante e l'altra matta, differenti per solubilità in alcali, che potrebbero essere una miscela di DHI-melanina e DHICA-melanina. E' possibile che DHI e DHICA siano coinvolti nella melanogenesi patologica e non in quella fisiologica? In altre parole la particella nera patologica (melanoma) è costruita in prevalenza con indoli e quella fisiologica da dope e ciclodope come segnalato sperimentalmente dalle analisi centesimali ed NMR.
1. H. S. Mason '' Structure of
Melanins'' in Pigment Cell Biology pag. 563-581, Ed. M. Gordon, AP, New York
2. R. H. Thomson '' Melanins ''
in Comparative Biochemistry pag. 727-750, Ed. Florkin-Mason, AP New
York and London 1962
3. R. A. Nicolaus '' Melanins ''
pag. . 1-305, Chemistry of Natural Products, Series Edited by Edgar Lederer,
Hermann Paris 1968.
4. G. Prota "Melanins
and melanogenesis" pag.
1-290, AP, San Diego 1992
5. G. Prota "The
Chemistry of melanins and melanogenesis" in progress in the Chemistry of
Organic Natural Products Ed. W.
Herr, G. W. Kirby, R. E. Moore, W. Steglich, C. H. Tamm,
pag. 113, Springer Verlag Wien New
York 1995 ; Pigment Cell Research 13, 283, 2000.
6. P. A. Riley '' Melanin '', Int. J. Biochem. Cell Biol. , 29, 1235-1240, 1997.
7. R. A. Nicolaus, A. Bolognese, B. Nicolaus '' The Pigment Cell and its Biogenesis '' Accademia Pontaniana 2002.
8. Le Scienze quaderno n° 21, 1985, pag. 69.
9. L. Zeise, Brown L. Murr,
M. R. Chedekel ''Melanin Standard Method : Particelle Description '', Pigment
Cell Research, 5, 132-142, 1992. ; Pigment Cell Research Suppl. 2,
10. C. M. Clancy, J. D.
Simon, '' Ultrastructural organization of eumelanin from Sepia officinalis
measured by atomic force microscopy
'' Biochemistry, 40, 133-153, (2001)
11. C. Kroesche, M. G.
Peter '' Detection of melanochromes by MALDI-TOF mass spectrometry ''
Tetrahedron, 52, 3947-3952, (1996).
12. Cope, F. W. : Eye
melanin free radical kinetics and mechanism in relation to the
Roginsky-Zeldovich (or Elovich) equation and the adsorption of oxygen by
semiconductors. J. Chem. Phys. 40 (1964) 2653-2656
13. McGinness, J. :
Mobility gaps: a mechanism for band gaps in melanins. Science 177 (1972)
14. McGinness, J. , Proctor,
P. : The importance of the fact that melanin is black. J. theor. Biol. 39 (1973) 677-678
15. Crippa, P. R. ,
Cristofoletti, V. , Romeo, N. : A band model for melanin deduced from optical
absorption and photoconductivity experiments. Biochim. Biophys. Acta 538
16. Zeise, L. , Murr, B. L.
, Chedekel, M. R. : Melanin standard method: particle description. Pigment
Cell Res. 5 (1992) 132-142
17. Sarna, T. : Properties
and function of ocular melanin. A photobiophysical view. J.
Photochem. Photobiol. B: Biol. 12 (1992) 215-258
18. Chedekel, M. R. :
Photophysics and photochemistry of melanin. In: Melanin: its role in human
photoprotection (Zeise, Chedekel and Fitzpatrick, eds. ) pp. 11-21 (1995)
19. Menter, J. M. , Willis,
I. : Electron transfer and photoprotective properties of melanins in solution.
Pigment Cell Res. 10 (1997) 214-217
20. Crippa, P. R. : Oxygen
adsorption and photoreduction on fractal melanin particles. Coll. Surf. B:
Biointerf. 20 (2001) 315-319
21. Thathachari, Y. T. ,
Blois, M. S. : Physical studies on melanins. II. X-ray diffraction.
Biophys. J. 9 (1969) 77-89
22. Chio, S. S. : X-ray
diffraction and ESR studies on amorphous melanin. Ph. D. Thesis,
Univ. of Houston (1977)
23. Bridelli, M. G. ,
Crippa, P. R. , Ugozzoli, F. : X-ray diffraction studies on melanins in
lyophylized melanosomes. Pigment Cell Res. 3 (1990) 187-191
24. Cheng, J. , Moss, S. C.
, Eisner, M. , Zschack, P. : X-ray characterization of melanins-I. Pigment
Cell Res. 7 (1994a) 255-262
25. Cheng, J. , Moss, S. C.
, Eisner, M. : X-ray characterization of melanins-II. Pigment Cell Res.
7 (1994b) 263-273.
26. Zajac, G. W. , Gallas,
J. M. , Cheng, J. , Eisner, M. , Moss, S. C. , Alvarado-Swaisgood, A. E. : The
fundamental unit of synthetic melanin: a verification by tunnelling microscopy
of x-ray scattering results. Biochim. Biophys. Acta 1199 (1994) 271-278
a. R. A. Nicolaus, '' Divagazioni sulla struttura a banda del colore in natura : il nero '', Rendiconto della Accademia delle Scienze Fisiche e Matematiche, Vol. LXIV, 145-216, (1998).
b. R. A. Nicolaus, A. Bolognese, B. Nicolaus '' The Pigment Cell and its Biogenesis '' Accademia Pontaniana 2002.
c. B. J. R. Nicolaus, R. A. Nicolaus '' Speculating of the Band Colours in Nature '' Atti Accademia Pontaniana Vol. XLV, 365-385, (1997).
d. R. A. Nicolaus, G. Parisi '' The Nature of Animal Blacks '' Atti Accademia Pontaniana, Vol. XLIX, 197-233, (2001).
e. G. Nicolaus, R. A. Nicolaus ''Melanins, Cosmoida,Fullerenes '' Rend. Acc. Sci. Fis. Mat. , Vol. LXVI, 131-158, (1999).
f. B. J. R. Nicolaus, R. A. Nicolaus, M. Olivieri '' Riflessioni sulla materia nera interstellare '' Rend. Sci. Fis. Mat. , Vol. LXVI, 113-129, (1999).
g. B. J. R. Nicolaus, R. A. Nicolaus '' Lo scrigno oscuro della vita '' Atti Accademia Pontaniana Vol. XLVIII, 155-180, (2000).
h. Comunicazioni Brevi, Atti Accademia Pontaniana, Vol. V, 391-404, (2002).
R. A. Nicolaus,G. Scherillo, '' La Melanina. Un riesame su
struttura,proprietà e sintesi '', Atti Accademia Pontaniana, Vol. XLIV, 265-287, (1995).
l. R. A. Nicolaus '' Coloured organic semiconductors '', Rend. Acc. Sci. Fis. Mat. , Vol. LXIV, 325-352, (1997).
m. Comunicazioni Brevi, Atti Accademia Pontaniana Vol. XLIX, 301-312 (2001).
n. R. A. Nicolaus, G. Misuraca '' Colore 90 '' Atti Accademia Pontaniana, Vol. XL, 83-107, (1991).
o. R. A. Nicolaus '' Melanine '' Quaderni della Accademia Pontaniana n° 4, 1-53, (1984).
R. A. Nicolaus,E. Novellino, G. Prota ''Origine e significato del colore
negli animali '', Rend. Acc. Sci. Fis. Mat.
, Vol. XLII, 1-82, (1976).
28. G. A. Pagani, G. Gardini, ''I metalli organici'', La Chimica e L'Industria, 66, 244-253, (1984).
29. G. Gardini, A. Berlin, '' I polimeri conduttori '', La Chimica e L' Industria, 73, 764-770, (1991).
30. '' Handbook of Organic conductive Molecules
and Polymers '' 4 Volume Set. Edited by H. S. Nalwa, Hitachi Research
Laboratory, Japan (1997).
31. V. J. Hearing, M.
A. Lutzner '' Mammalian Melanosomal Proteins : Characterization on
polyacrylamide Gel Electrophoresis '', Yale Journal of Biology and Medicine, 46,
553-559, (1973);T. Kushimoto,
V. Basrur, J. Valencia, J. Matsunaga, W. D. Vieira, V. J. Ferrans, J. Muller, E. Appella,
V. J. Hearing "A model for melanosome biogenesis based on the purification
and analysis of early melanosomes" Proc. Natl. Acad. Sci.
U. S. A. 98, 10698, (2001).
32 A. Korner et al. J.
Invest. Dermatol. /5,192, 1980.
33. P. Aroca et al. , BBA,1035, 266-275, (1990).
A. Palumbo, M. d'Ischia, G. Misuraca, L. De Martino, G. Prota '' A new
dopachrome-rearranging from the ejected ink of the cuttlefish Sepia officinalis
'' Biochem. J. 299, 839,
(1994) ; BBA, 925, 203, (1987) (preparation of L-dopachrome).
35. P. A. Riley, '' Melanin
''J. Biochem. Cell Biol. , 29, 1235, 1997.
S. Ito, BBA, 883, 155, (1986).
37. R. A. Nicolaus '' Biogenesi delle melanine ''Accademia Nazionale dei Lincei, (Conferenze), Biogenesi delle sostanze naturali, Roma 1964, 291-319. Vedi pag. 317.
R. A. Nicolaus '' Biogenesis of melanins '' Rassegna di Medicina Sperimentale, Anno IX, Suppl. N° 1, (1962). V.
Idelson Ed. , Naples 1962.
C. Lambert, J. N. Chacon, M. R. Chedekel, E. J. Land, P. A. Riley, A.
Thompson, G. Truscott '' A pulse radiolisis investigation of the oxidation of
indolic melanin precursors : Evidence for indolequinone and subsequent
intermediates '' BBA, 993, 12-20,
38. G. A. Duff, J. E.
Roberts, N. Foster, '' Analysis of the structure of synthetic and natural
melanins by solid phase NMR '' Biochemistry 27, 7112-7116, 1988.
39. M. G. Peter, H. Foster,
On the structure of eumelanins : identification of costitutional patterns by
solid-state NMR spectroscopy, Angew. Chem.
Int. Ed. English. 28,741-743, 1989.
40. S. Aime, M.
Fasano, C. Croonbridge, ''
Solid-state 13C NMR characterization of melanin free acids from biosynthetic and
natural melanins. '' Gazz. Chim. Ital. 120, 663-664, 1990
41 Aime, S. Fasano, M. , Terreno,
E. , Croonbridge, C. J. : NMR studies of melanins: Characterization of a
solubile melanin free acid from Sepia ink. Pigment Cell Res. 1991,
42 Hervé, M. , Hirshinger, J. ,
Granger, P. ,Gilard, P. , Deflandre, A. , Goetz, N. : A 13C solid-state NMR
study of the structure and auto-oxidation process of natural and synthetic
melanin. Biochim. Biophys. Acta 1994 1204, 19-27.
43. A. Pezzella, M.
D'Ischia, A. Napolitano, A. Palumbo, G. Prota '' An integrated approach to the
study of sepiomelanin:Evidence for a high proportion of
degraded5,6-dihydroxyindole-2-carboxylic acid units in the pigment backbone ''
Tetrahedron, 53, 8281-8286, (1997)
; Rapid Communications in
Mass Spectrometry, 11, 368-372, (1997).
44. A. Napolitano,A.
Pezzella, G. Prota, R. Seraglia, P. Traldi
'' Structural analysis of
synthetic melanins from 5,6-Dihydroxyindole by Matrix - assisted Laser
desorption / ionization Mass Spectrometry '' Rapid Comm. Mass Spectrom. ,
10, 468-472 (1996).
45. A. Pezzella, A.
Napolitano, M. d'Ischia, G. Prota, R. Seraglia, P. Traldi '' Identification of
partially degraded oligomers of 5,6-Dihydroxyindole-2-carboxylic acid in Sepia
melanin by Matrix-assisted LASER
Spectrometry '' Rapid. Comm. Mass Spectrom. 4, 368-373, 1997
46. A. Bertazzo, C. Costa, G. Allegri, R. Serraglia, P. Traldi ''
Biosynthesis of melanin from dopamine. An
investigation of early oligomerization products '' Rapid Comm. Mass Spectrom. 9, 634-640
47. A. Bertazzo, C. Costa,
G. Allegri, M. Schiavolin, D. Favretto, P. Traldi '' Enzymatic oligomerization
of tyrosine by tyrosinase and
peroxidase studied by Matrix-assisted Laser Desorption/Ionization Mass
Spectrometry '' Rapid Comm.
Mass Spectrom, 13, 542-547, (1999).
48. A. Korner, J.
Pawelek, '' Mammalian tyrosinase catalyzes three reactions in the biosynthesis
of melanin '' Science, 217, 1163-1165,
49. A. Korner, J. Pawelek,
'' Dopachrome conversion : a
possible control point in melanin biosynthesis '', J. Invest. Dermatol. , 75,
J. Pawelek, A. Korner, A.
Bergstrom, J. Bologna ''New Regulators of Melanin biosynthesis
and the autodestruction of
melanoma cell '', Nature, 286, 617-619, (1980).
49 bis. P. Aroca, F. Solano, J. C. Garcia-Borron, J. A. Lozano "Specificity of dopachrome tautomerase and inhibition by carboxylate indoles. Considerations on the enzyme active site" Biochem. J. 277, 393, (1991).
50. B. Kagedal, P. Konradsson,
T. Shibata, Y. Mishima "High-performance liquid-chromatographic
analysis of dopachrome and dihydroxyphenylalanine" Anal. Biochem.
225, 264, (1995)
P. Aroca, F. Solano, J. C Garcia-Borron, J. A. Lozano ''A new
spectrophotometric assay for dopachrome tautomerase
''J. Biol. Biophys.
Methods, 21, 35-46 (1990)
52. F. Solano, C. Jimenez-CervantesJ. H. Martinez-Liarte, J. C. Garcia-Borron, J. R. Jara, J. A. Lozano ''
Molecular Mechanism for catalysis by a new zinc-enzyme,dopachrome tautomerase ''
Biochem. J. , 313, 447-453, (1996).
53. J. L. Pennock, J. M.
Behnke, Q. D. Bickle, E. Devaney, R. K. Grencis, R. E. Isaac, G. W. P. , Joshua,
M. E. Selkirk, Y. Zhang, D. J. Meyer '' Rapid purification and cheracterization of L-dopachrome-metyl
ester tautomerase (macrophage-migration-inhibitory
factor) from Trichinella spiralis, Trichuris muris and Brugia pahangy ''
Biochem. J. , 335, 495-498, (1998).
a. J. Pawelek "
Is dopachrome tautomerase necessary to get DHICA from dopachrome? " Pigment. Cell Res. 7, 126, (1994)
F. Solano, J. C. Garcia-Borron, J. A. Lozano "Is dopachrome
tautomerase necessary to get DHICA from dopachrome? Pigment Cell Res. 7,
c. S. Pavel "Dopachrome tautomerase is not essential for DHICA formation" Pigment Cell Res. 7, 123, (1994).
55. H. Sugimoto, M. Taniguchi, A. Nakagawa, I.
Tanaka, M. Suzuki, J. Nishihira
"Crystallization and preliminary X-ray analysis of human D-dopachrome
tautomerase" J. Struct. Biol. 120, 105, (1997).
56. H. Sugimoto, M. Taniguchi, A. Nakagawa, I. Tanaka, M. Suzuki, J. Nishihira "Crystal Structure of human D-dopachrome tautomerase, a homologue of macrophage migration inhibitory factor, at 1,54 A resolution" Biochem. 38, 3268, (1999).
57. H. Yoshida, J. Nishihira, M. Suzuki, K. Hikichi "NMR characterization of
physicochemical properties of rat D-dopachrome tautomerase" Biochem.
Mol. Biol. Int. 42, 891, (1997).
58. G. Odh, A. Hindemith, A. M.
Rosengren, E. Rosengren, H. Rorsman
"Isolation of a new tautomerase monitored by the conversion of D-dopachrome
to 5,6-dihydroxyindole" Biochem. Biophys.
Res. Commun. 197, 619, (1993).
59. S. L. Jacques, D. J.
McAuliffe '' The melanosome :Threshold temperature for explosive vaporization
and internal absorption coefficient
during pulsed LASER irradiation '' Photochem.
Photobiol. 53, 769, (1991).
60. J. Borovansky, P.
Hach, J. Duchon '' Melanosome : an
unusually resistant subcellular particle '' Cell Biology International Reports,
Vol. 1, 549-554 (1977).
Melanosome are resistant to acid
hydrolysis but they are easily degraded by
LASER or, as occur in vivo, by H2O2.
61. M. Bakunin, G. Dragotti '' Contributo alla conoscenza dei
pigmenti melanici ''Rend. Real. Acc.
Sci. Fis. Mat. Vol. X, 222, (1904)
a. R. A. Nicolaus,M.
Piattelli, G. Narni,, '' The structure of sepiomelanin'' Tetrahedron, Letters
21, 14-17, (1959).
b. M. Piattelli,R. A.
Nicolaus '' The structure of melanins and melanogenesis-I-The structure of
melanin in Sepia '' Tetrahedron 15,
c. M. Piattelli, E.
Fattorusso,S. Magno, R. A. Nicolaus '' The structure of melanins and
melanogenesis-II-Sepiomelanin and synthetic pigments '' Tetrahedron 18, 941-949,
d. M. Piattelli,E.
Fattorusso, S. Magno,R. A. Nicolaus '' The structure of melanins and
melanogenesis -III-The structure of sepiomelanin '' Tetrahedron, 19, 2061-2072
e. R. A. Nicolaus, M.
Piattelli, E. Fattorusso ''The structure of melanins and melanogenesis -IV-On
some natural melanins '' Tetrahedron, 20, 1163-1172 (1964).
63. J. Medrano, D. Dudis ''Quasi-particles
in polymeric conductors '' in Organic Superconductivity, pag. 275. Ed.
V. Z. Kresin, W. A. Little, Plenum Press,New York,
64. R. Nicolaus '' Sugli acidi pirrolcarbonice. Nota I. Acido 2,3,5-pirroltricarbonico '' Gazz. Chim. Ital. 83, 239-251, 1953
65. R. Nicolaus,G. Oriente ''Sugli acidi pirrolcarbonici : acido 2,3,4,5 pirroltetracarbonico '' Gazz. Chim. Ital. 84, 230-241, 1954
66. E. Fattorusso, L. Minale, S. De Stefano, G. Cimino, R. A.
Nicolaus '' Struttura e biogenesi delle feomelanne. Nota V. -Sulla struttura
della gallofeomelanina1 '' Gazz. Chim. Ital. 98,
67. S. Ito, K. Fujita ''
Microanalysis of eumelanin and pheomelanin in hair and melanomas by chemical
dgradation and liquid chromatography '' Analytical Biochemistry
144, 527-536, 1985
68. P. Manini, M. D'Ischia,
M. Milosa, G. Prota '' Acid-promoted competing pathways in the oxidative
polymerization of 5,6-Dihydroxyindoles and related compounds : straightforward
cyclotrimerization routes to diindolocarbazole
derivatives '' J. Org. Chem, 63, 7002-7008, 1998.
69) a G. A. Swan "Chemical
Structure of Melanins" Annals of the New York Academy of Sciences Vol.
100, 1005 (1963)
b. F. Binns, G. A.
Swan "Oxidation of some Synthetic Melanins"
Chemistry and Industry 396 (1957)
G. A. Swan "Some studies on the formation and structure of
melanins" Rendiconti Accademia Scienze
Fisiche Matematiche, Vol. XXXI (1964)
Studies are described of the
formation of melanins in vitro enzymically
and by oxidation from dopa and from dopammine. When these precursors were
labelled with deuterium in the alfa
and beta positions of the side chain, and then converted into melanins large
retention of deuterium in melanin was observed. This means that melanins are not
d. S. N.
Mishra, G. A. Swan "Studies related to the chemistry of Melanins.
-Part II- Synthesis of 5,6-Dihydroxyindoline" Soc. 1424 (1967).
e. S. N.
Mishra, G. A. Swan "Studies related to the chemistry of Melanins
-Part V- Investigations on the Specific Deuteriation of 5,6-Dihydroxyindoline
and 5,6-Dihydroxyindole" Soc. 1431 (1967).
f. F. Binns, J. A.
King, A. Percival, N. C. Robson, G. A. Swan "Studies related
to the Chemistry of Melanins -Part IX- Syntheses of Specifically Deuteriated
3,4-Dihydroxyphenethylamines and 3,4-Dihydroxyphenylalanines" Soc. 1134 (1970).
g. F. Binns,
J. A. King, S. N. Mishra, A.
Percival, N. C. Robson, G. A. Swan, A. Waggott,"Studies
related to the Chemistry of Melanins -Part. XIII- Studies on the structure
of dopamine-melanin" Soc. 2062 (1970).
G. A. Swan "Structure Chemistry and Biosynthesis of Melanins in Fort.
Chem. Org. Natur. Vol. 31,
522, (1974) Springer-Verlag, Wien
The experiments show that 20% of
the polymer units are formed by DOPA and cyclodopa units either in the
autoxidative or enzymatic process. This value was cofirmed by (58) by NMR.
G. A. Swan '' Current knowledge of Melanin Structure '' In Pigment Cell,Vol.
1, Eds. V. J
McGovern,P. Russel. S. Karger,Sydney, (1973), pag. 151.
If the Raper Scheme were
correct it would be expected that the same melanin would be
obtained from tyrosine, DOPA, dopammine,DHI. . Although these melanins
have the same radical- polarone
system, they are,in part, chemically different.
l. J. A. King, A.
Percival, N. C. Robson, G. A. Swan "Studies related to the Chemistry of Melanins -XI- The
distribution of polymeric linkages in dopamelanin" Soc. 1418 (1970).
m. G. W. Kirby, L.
Ogunkoya "Structure of melanin derived from 3,4 -dihydroxy- 1 - (14C, 3H)
-phenylalanine by oxidation with tyrosinase" Soc. Chem. Comm.
21 546 (1965).
V. J. Hearing, T. M. Ekol, P. M. Montague, J. M. Nicholson "Mammalian
Tyrosinase Stoichiometry and measurement of reaction product" BBA
611, 251 (1980).
The authors reported that
there is no incorporation of DOPA,
(cyclodopa), DHICA into dopamelanin. . In other words in melanins
the carboxylic group is not present and
melanins are pure DHI-melanins.
70. M. Seiji, T. B.
Fitzpatrick, R. T. Simpson, M. S. C. Birbeck
''Chemical composition and terminology of specialized organelles (melanosomes
and melanin granules) in mammalian melanocytes '' Nature 197, 1082-1084, 1963.
71. M. Seiji, K. Shimao, M.
S. C. Birbeck, T. B. Fitzpatrick ''Subcellular
localization of melanin biosynthesis '' in The Pigment Cell : Molecular,
Bioogical and Chemical Aspects, Ed. P. Riley, J. C. Fortner, New York
Academy of Sciences, 100, 497, 1963.
72. A. Pezzella, A.
Napolitano, M. D'Ischia, G. Prota,R. Seraglia, P. Traldi '' Identification
partially degraded oligomers of 5,6-dihydroxyindole-2-carboxylic acid in Sepia
melanin by matrix-assisted LASER desorption/ionization mass spectrometry ''
Rapid Comm. Mass Spectr. 11, 368-372, 1997.
73. H. Wyler, J. Chiovini '' Die Synthese von Cyclodopa (leucodopachrome) '' Helv. Chim. Acta 51, 1476-1482, 1968.
74. A. Aroca, F. Solano, C. Solinas, J. C. Garcia-Borron, J. A. Lozano,
Eur. J. Biochem. 208, 155-
75. H. Wyler, '' The
dopachrome-dihydroxyindole '' in Melanogenesis.
Its chemistry as a therapeutic strategy in melanoma. Manchester Meeting
76. M.Benathan et al., Yale
J.Biol.Med. 53, 389,1980 cited by (4)
77. Y.Liu et al., Pigment Cell
Research 16, 355-365, 2003.
78. F. E. Barr, Med Hypothese 11,
79. E.J.Land et al., Pigment Cell
Research 16, 397-406, 2003 .
Melanins are particles with
different shape and size .Melanins are particles built up
from oligomers of unknown molecular
weight. Oligomers, the fundamental stones of the particle, may be optically
active intermediates . Isomeres cis/trans have different conductivity (
pyrrole-black, acetylene-black etc. ) . Such oligomers contribute probably to
the shape and size of the particles and other physical properties.The chemical
and physical study of the fundamental structural units ( aggregates,filaments,
smaller constituents, oligomeric molecules ) of the particles is of great
interest for biology and
presence of particles in light exposed tissues suggest that they are involved in
photoreactions. Tetramers of the melanogen DHICA are found in
the reflecting material of the tapetum lucidum of the sea catfish.
Melanins might show various
hydration and oxidation levels.The acetylene-black radical- polarone system
is see in all natural (BCM)
and synthetic melanins (BSM).
material obtained from the ink sac (sepiomelanin) is a mixture of oligomers,
brocken oligomers, premelanosome,
melanosome, particles at different
maturation grade and activity. Some chemical and physical data obtained from
such a heterogeneous material are
probably to be revisited. The recent results obtained by J.D.Simon (2003) with
atomic force microscopy tecnique will contribute to elucidate the
structure and biological functions of the melanin particle ( melanins,eumelanins,
Papers (1-72)with comment and figures useful for research
improve quality of research any reference should be followed by comment and
( number =
17,18, 31, 37, 39, 50, 51,52, 57, 62, 67
20, 22, 25, 26, 27, 48, 49, 54, 59, 66
23, 24, 58
Neuromelanin 1,10, 11,12,13,
Nanoscience 18, 30, 42,
44,45, 46, 53, 55, 56, 60, 61
Structure 33, 34,
35, 36, 38, 40, 41, 47, 61, 68, 69, 70, 71
are classified into two main groups :
BCM = Black
Cell Matter ( animals,plants, fungi )
BSM = Black
synthetic Matter ( the most famous precursors are DHI, DHICA, Pyrrole,Acetylene,
divided into three groups :
( precursors until now found DOPA, Cyclodopa, DHI,
( precursors until now found the aminoacid cysdopa, with Dibenzothiazine and
Dibenzothiazinonie chromophores )
( precursors until now found catechol, 1,8-dihydroxynaphtalene
To be read
R.A.Nicolaus ‘’ Melanins ‘’ pag
1-310, Hermann, Paris, 1968
R.A.Nicolaus ‘’ Melanins ‘’
in Methodicum Chimicum Vol.11, part 3, pag 190-199, Ed.F.Korte, AP, 1978
‘’ Melanins and melanogenesis
‘’ pag 1-290, AP, San Diego
1) ....melanin a bioelectronic mechanism in brain function....M.E.Lacy,
.....melanin pigmentation in the skin has a protective
value against the harmful effects of ultraviolet UV radiation....W.C.Quevedo
et al., '' Light and skin color in
Sunlight and Man , T.B.Fitzpatrick, M.A.Pathak, I.C.Herber, M.Seiji, A.Kukota,
eds. pag.165-194, University of Tokyo Press,Tokyo (1974).
……. Chemistry of sepiomelanin .Melanin from Sepia
officinalis is present in the
ink sac as the Mg and Ca salt….. M.Piattelli, et al., Tetrahedron, 15, 66-75,
1961; M.Piattelli et al., Tetrahedron, 18,941-949, 1962 ; 19, 2061-2072, 1963 ; R.A.Nicolaus et al. Tetrahedron,
20, 1163-1172, 1964.
H.S.Mason et al., Archives of Biochemistry and
Biophysics (ABB)86, 225-230, 1960 ; T.Sarna et al., Science, 192, 1132-1134,
1976 ; K.Stratton et al., ABB, 123, 477-483, 1968 ; M.A.Pathak, ABB, 123,
Sepiomelanin show a typical EPR (
about g = 2.003 ) signal which
is similar to other BCM and BSM.
) The ink secretion of Octopus contains compounds
capable of paralyzing the olfactory sense of its enemies.
G.E.MacGinitie, N.MacGinitie, ''Natural History of
Marine Animals'' MacGraw Hill,New York (1968).
5) .....pigmentary disorders are well known as in albinism,
vitiligo, mongolian spot, melanoma .... P.A.Riley in '' The Physiology and
Pathophysiology of the skin '' pag.1149-1167,A.Jarret ed.,AP New York
6) Melanins increase the optical efficiency of the eye, are responsible
for production of color patterns, usually of adaptive significance, in the hair
and or the superficial epidermis.
G.Prota ''Melanins and Melanogenesis'' pag.1, AP San Diego (1992).
7) Melanins are able to bind a number of foreign substances
and to keep potentionally harmful substances which are released
after in low,non toxic form.
N.G.Lindquist, Acta Radiol.,325,1-92, (1973) ; Uppsala J. Med. Sci.,
91,238-288 (1986) ; Pigment Cell Research, 1, 133, (1987).
8) Melanins as a matrix for chemical evolution .
M.S.Blois in the ''Origins of Prebiological Systems'' pag 19.
S.W.Fox ed. AP,New York (1965).
9) Melanin acts as a coloured amorphous semiconductor ,the colour
depending to the amplitude of the prohibited Fermi's band.
B.J.R.Nicolaus et al.,
Atti Accademia Pontaniana, Vol.XLV, 365, (1997) ; Rend.Acc.Sci.Fis.Mat.,Vol. LXIV,
325, (1998) ; www.tightrope.it/nicolaus/index.htm
10) Neuromelanin as serving a biocybernetic function.Depletion causes the
substantia nigra to revert from its neuroendocrine role to its original motor
F.M.Forrest, Adv.Biochem.Psychopharmacol., 9, 255, (1974).
11) Degeneration of substantia nigra is associated with Parkinson's
E.Hirsch et al., 334, 345,
12) The binding of drugs aside neuromelanin suggest certain forms
of chemically induced parkinsonism .
R.M.J.Ings, Drug,Metabol., Rev., 15, 1183, (1994)
13) Melanins from tetrahydroisoquinolines found in the brain of
post mortem of Parkinson's patients are similar in dopamelanin regarding NADH
oxidizing properties , oxy-radical scavenging activity, and ability to form
soluble mixed polymers with melanins from opioid peptides .
R.Coccia, C.Foppoli, M.A.Rosei, Free Radical Biology and Medicine, 24, 161,
14) Antimitotic and antibiotic activity is showed by certain allomelanin
of bacteria and fungi.
S.P.Ljach et al., Akad., Nauk SSSR, Institut Mikrobiologii, Izd., Nsuka
Mosckva, 1-86, (1972).
15) Melanin was discussed as a dark screen , lying beneath certain
physical light-reflecting structures whose purely schemochromic colours it
emphasizes merely by absorption of the longer, more deeply penetrating rays .
D.L.Fox, ''Animal Biochromes'' pag.222, Cambridge University Press,
16) Chordate melanins have a mainly protective function, e.g, in
shielding underlying tissue from shortwave irradiation , in heat control,
adaptive coloration. The significance in plants and the more primitive animals
is still obscure .
R.H.Thomson in Comparative Biochemistry pag 727, N.Florkin,
H.S.Mason eds., Vol.III, Part A, AP (1962).
17) Studies on the opticalspecificity of tyrosinases from
different sources reveal the preference for D-isomer of tyrosine
Experientia, 23, 997, (1967).
18) Melanin forms 18-72% of the melanosomes.
J.Duchon, J.Borovansky, P.Hach, Pigment Cell, 1, 165, Karger,Basel,
19) Melatonin administered to the fish induces the change from day to
night colouration .
A.B.Lerner et al., W.Mori, J.Am.Chem.Soc., 80, 2587, (1958).
20) Amorphous melanin is capable of absorbing ultrasound in the I-MHz range and converting this energy into a form which kills the tumor cells.
J.Mc Ginness, P.M.Corry, E.Armour, Pigment Cell, Vol.3, P.Riley ed. ,Karger
Basel (1976). ; U.Mizutani et al., Nature, 259, 505, (1976).
21) Melanin exhibits the
unusual characteristics of an amorphous semiconductor treshold switch.
J McGinness et al., Science, 183, 853, (1974). www.organicsemiconductors.com
22) All black materials are
B.J.R.Nicolaus, et al., Atti della Accademia Pontaniana, Vol.XLV, 365,
(1997); Rend.Acc:Sci.Fis.Mat., Vol.LXIV, 325, (1998) ; www.tightrope.it/nicolaus/index.htm
( Link 19 )
23) Explosive vaporization
during pulsed laser irradiation of melanosome.
S.L.Jacques, D.J.Mc Auliffe, Photochemistry and Photobiology,53,769,
24) Melanin is found to be not volatile in mass spectrometry. www.tightrope/nicolaus/index.htm
25) Melanins natural or prepared
by synthesis are amorphous semicoductors.
A.Pullman,B.Pullman, BBA,54,384,(1961); T.Strzelecka, Physiol. Chem.Phys.
14, 219-233, (1982)
26) It is shown further that the
superconducting state of these polymers should be distinguished by certain
unique chemical properties which could have considerable biological significance.
Physical Review. 134, A1417, (1964).
27) Electrically conducting polymers could provide a noninvasive means
to control the shape and function of adherent cells.
Proc.Natl.Acad.Sci.USA, 91,3201, (1994)
28) The influence of UV
radiation on collagen from rat tail in the presence of melanin was investigated
A.Sionkowska, J.Photochem.Photobiol., 124, 91, (1999)
29) Effects of L-Cysteine on the
oxidation chemistry of Dopamine.
F.Zhang, G.Dryhurst, J.Med:Chem. 37, 1084, (1994).
30) ........the doping effect on melanins is not known.........DHI-black,
Adrenalin-black, Catechol-black are radical-polarone of hydrate polyquinones
......the counterion of melanin is not known........the chemistry of
interstellar black matter is similar to the terrestrial black matter chemistry.......
31) ......dopachrome which is transformed by Sepia
dopachrome-rearranging enzyme to DHI .......
et al., Biochem.J. 299, 839, (1994) ; A.Palumbo et al. Biochem J., 323, 749, (1997)
Apparently sepiomelanin is
similar to DHI- melanin.
32) Many dopachrome units are present in
sepiomelanin.M. Piattelli et al., Tetrahedron,
19, 2061-2072, (1963)
33 ) R.A.Nicolaus et al., Atti Accademia Pontaniana , Vol. XLIX,
197-233, 2000 ;
et al., Atti accademia Pontaniana, Vol. L, 225-243, 2001
.Bolognese et al., Atti Accademia Pontaniana, Vol. LIII
radical polarone system of melanins..Structure
proposed for melanin oligomers taking in account the electric semiconductor
property.The acethylene-black system is shown.
hydrate may be the monomer repetitive unit of DHI-melanin
of o-quinone hydrate three-dimensional arrangement is represented (Chemdraw
software ver. 5.0))
satisfies the elemental analysis requirements for the DHI-melanin with
polyindolquinone structure (Calculated for (C8 H2 N O2):
C%, 65.3; H%, 3.4; N
%, 9.5. Found:
C%, 56.3; H%, 3.0;
N%, 8.2 (Beer)) taking in account the presence of larger amount of oxygen found
and giving a rationale interpretation of the strongly linked water molecules
invoked to justify the non-coherent analytical results.
hydrated quinone participates to stability and to planarize the unsaturated
backbone of melanin and account of the radical-polarone structure related to the
conductive properties of melanin.
Destruction of this hydrated structure pushes the
indole rings about at 90° each from other and, determining a structural
conformation changing, strongly affects the electric properties
34) ...... no melanins (BCM) derived from tyrosine are
35) Cyclodopa precusor of eumelanin (BCM).
A. Bolognese et al.,
Atti Accademia Pontaniana Vol. L, 2001. Pontaniana.unina.it firstname.lastname@example.org
Melanins obtained either enzymatically or by autoxidation of DOPA or
Dopamine largely retain the hydrogen atoms
of the methylene groups of the original side chains.
G.A.Swan, Ann.New York, Acad.Sciences, 100, 1005-1016, 1963
NMR spectra show always the presence of an aliphatic part. In BCM or BSM
) BCM (
Black Cell Matter ) and BSM ( Black
Synthetic Matter ) have one oxygen
more than their precursors.
37) ...... tyrosinase is the only enzyme of melanogenesis...... www.tightrope.it/nicolaus/index.htm
38 ) During the extractive process melanins (BCM) are
oxidized by H2O2 contained in melanosomes or formed from
39) The red solution is called dopachrome. The solution
is a mixture of quinones and phenols. Any substance or material which
decolorizes the red solution is believed to be an enzyme.
40)………melanogenesis universal model for earth and
space……… The WEB. Link 7
41) …optically active tetrameric melanin intermediates are discovered……
A.Pezzella et al. Tetrahedron Asymmetry 14,1133-1140, (2003)
42) Melanin particle ( L.Zeise, B.L.Murr, M.R.Chedekek, Pigment Cell
Research, 5, 132-142, 1992 ) is formed by mixture of oligomers species with
molecular weight in the range of 500-1500 Da
A.Napolitano et al.,
Rapid Comm. Mass
Spectrom., 10,204-208, 1996 ; 10,468-472, 1996 ; A.Pezzella et al. Tetrahedron,
53, 8281-8286, 1997.
43 ) The
black pigment from Ustilago maydis spores has been studied. Analytical data and
degradation experiments show it to be a catechol-melanin.
et al., Tetrahedron, 21, 1229-1236,
Melanin is not a
polymer. Melanin is a particle ( L.Zeise
et al., 5, 132-142, 1992 ) formed by radical-polarones of polyene systems the most
simple one being acetylene-black.
is not a biological garbage as commonly believed.Melanin is one of the most
important substance of
peculiar properties known until now are:
c. Binding of ions and
Conducting melanins ( BCM, BSM ) and
control of adherent
All chemical and physical data may change with form and size of the particle,
preparation and purification methods, binding
45 ) Melanin standard method : particle description.
L.Zeisel et al. Pigment
Cell Research, 5, 132-142, 1992.
….. the effect of preparation procedures on particle morphology of
et al., Pigment Cell Research, 16,
and 15N NMR of
sepiomelanin and sepiomelanic acid------------ B.Bhavin et al.,
Magn.Reson.Chem., 41, 466-474, 2003
conductivity of DOPA-melanin.
et al. J.Biomater.Sci.Polym., 7, 577-586, 1995 ; G.M.R.Robinson at al.,
conductivity and related papers.Research of pigment conductivity
in the area of Biology is strongly recommended.Tecnique of conductivity
determination in tissues are to be
et al., in ‘’Free Radicals in biological systems ‘’ ,211,AP,NewYork,1961.
‘’ Amorphous semiconductors ‘’ Springer,Berlin,1979 ; R.Bibang,et
al.,Pigment Cell Res.,2,395-400,1989 ; 387-394 ; A.Berlin et al.
Mat. Res. Soc. Symp. Proc. Vol.413 (Materials Research Society) ,1996 ;
A.Berlin,et al.,Synthetic Metals ,
84, 451,1997 ; A.Berlin et al . ,Tetrahedron, 52,7947, 1996 ; B.Commoner et al.,
Nature, 174, 689, 1954 ; F.W.Cope et al., Arch. Biochem. Biophys. , 100, 71,
1963 ; K.K.Darrow, Endeavour XIII N. 50 pp. 101- 106 ,1954 ; C.C.Felix, J. Am.
Chem. Soc. 100, 3922-3926 ,1978 ; J.Filatovs
et al . , Biopolymers 15, 2309, 1976 ; D.S.Galvao et al., J.Chem.Phys.
93, 2848- 2853,1990 ; E.P.Goodings, Endeavour XXXIV,
123- 130, 1975 ; S.K.Kurtz et al., Pigment Cell Res. 1, 261- 262,1987 ;
Scientific Seminar of the Society of Cosmetic Chemists, Orlando,Florida USA ;
Little et al. ‘’ Organic
Superconductivity ‘’ pp.1-386,1990,PP,New York ; Scientific American 212,
21-27, 1965 ; H.C.Longuet-Higgins, Arch.Biochem.Biophys., 86, 231, 1960
; McGinness et al., Pigment Cell Res.,2, 316, 1960 ; J.Theor.Biol., 39,
677-678, 1973 ; A.Menon et al.,
Can.J.Biochem., 55, 783-787, 1977 ; M.Okasaki, Arch.Biochem.Biophys.123,
197-205, 1985 ; A.Rabenau, Endeavour, XXV, 158-165, 1966 ; G.A.Pagani,
Heterocycles, Vol.37, n° 3, 1994 ;
D.Slawinska et al., Physiol.Chem.Phys., 14, 363-374, 1982
; J.E.Simmons, Endeavour, XXVII, 138-143, 1968 ; L.J.Wolfram et al.,
J.Invest. Dermatol., 87s, 396, 1986 ; G.W.Zajac
et al., J.Vac.Sci.Technol., 12, 1512, 1994.
Semiconductor properties of natural melanins.
Physiol.Chem.Phys,14, 223-231, 1982.
) Melanogenesis in the ink gland of Sepia.
Pigment Cell Research, 16, 517-522,
color loci of mice……
et al., Pigment Cell Research, 16, 333-344, 2003
Melanins,melanocytes, melanogenesis : an illustrated history of the past half
Pigment Cell Research, 13, 283-293, 2000 .
) For the first time the
sepiomelanin particle was described . Chemical
, physical, biological properties of
units and subunits would be of
interest .Simon 2003 see text.
Electric and acoustic conductivity, electric switch, photoelectric
conductivity, conductivity depending to preparation methods and doping .Melanins
are biological material with striking large conductivity.
The semiconductor band model ( Link 9,17,21,22 ) parameters are :
EG = Optical band gap (
colours band , condudctor or insulating state) The same model has been
qualitatively suggested for amorphous semiconductors.
BW= band width
of valence band.
EA = electron affinità.High value indicated easy reducible
IP = ionization potential
. Low value indicated easy oxidable
Melanins are considered material with a little gap.
can be made from a poorly conducting to a highly conducting state at fairly low
electric state i.e., from 10 K ohm –cm to 100 ohm ar a field of 300
V cm-1 . ( McGinness et
al., Science, 183, 853-856, 1974 ). The gap and
conductivity of dopa-melanin and
natural melanins was measured ( T. Strzelecka, Physiol.,Chem.,Physi.,
14,219-222, 1982 ; 14, 223-231, 1982 ; 14, 233-237, 1982 ;
M. Jastrzebska et al., Stud. Biophys., 122, 39-43, 1987 ;
M.Jastrzebska et al., J. Biomater. Sci.Polym.Ed. 7, 781, 1996 ; 7,
577,1995 ; 33, 4023-4028, 1998 ;
M.Jastrzebska et al., Gen.Physiol.Biophys., 9, 373-383, 1990 ; L.Zeise
1992 ; L.Hanyz et al., Cryst.Res.Technol.,
38, 325-330, 2003 ; K.B.Stark et
al., J.Phys.Chem.B., 107, 11558-11562 , 2003
; V.Horak et al., Biorganic
Chemistry, 21, 24-33, 1993.
switching in hydrated melanin was first reported by McGinness et al.
in 1984.The American researchers opened a new area for switching studies
by showing that low electric field switching occurs in organic semiconductors
and in living system.This discovery was not taken in the right consideration by
‘’expert biologists ‘’. See
the recent paper R.J.R.Nicolaus “
Neuromelanin “ Atti della
Accademia Pontaniana, Vol. LIII,2004. and www.brunonic.org
current-vs-voltage curves show that the time to traverse the negative -
differential-resistance (NDR) segment is much slower than would be expected
from electronic switching mechanism.Double-pulse measurements add to the
evidence that thermal effects dominate electronic effects in melanin.A
pseudomemory was found in melanin (
C.H.Culp et al. J.Appl.Phys. 46,3658-3660 ,1975 )
) Particle binding
power for organic and
inorganic materials, ions and
B. Larsson et al.,Biochem.Pharmacol., 28, 1181-1187, 1978 ; Pigment Cell
Research, 6, 127-135, 1993 ; U.
Mars, PHD Thesis, University of Uppsala 1998. ) a typical behaviour of the
) Ability of store
liquids and gases ( meteorites, humic
acids, cellular oxygen, active charcoal ) . Cosmochemistry.
) Active culture substratum controlling
cell growth and form.
(J.Y.Wong et al., Proc.Natl.Acad.Sci.USA, 91, 3201, 1994 ; D.E. Ingber,
J.Cell Sci., 116, 1397-1408, 2003 )
) explosive fragmentation by exposure to LASER
( S.L.Jacques et al.,Photochem. Photobiol. 53, 769, 1991.) occurs with
spectra show complex pyrrole acids of obscure origin.
) Behaviour as innovative sensor and energy generator with the capacity
to grow and shrink significantly in length and volume when subjected to electric
stimulation .Biosensors..( A. Berlin et al.,Chem.Mater.6, 1742-1748, 1994 ;
A.Berlin et al., Tetrahedron 23, 7947-7960 , 1996 )
) Chemical and physical data may
change with form and size of the particle, methods of synthesis,
purification and doping.
) Sepiomelanin composition change
with time in vivo and in vitro
( Link 5,6,9,12,19,21,22 )
) Communication between tissues
and between tissues and brain. ( Link ,2122, )
) Presence of organic black
matter in interstellar spaces
( Link 7,8 )
) Primordial soupe
( S.W. Fox ‘’ The origins of Prebiological Systems and their
molecular matrices ‘’ AP , New York, 1965 )
Melanin contribute to the blue,green,jellow
physical colours formation in Nature ( Link
Some kinds of biological tissues generate fast electrical responses to
intense light and both stable and unstable responses have been detected.The
unstable response is known to be associated with visual pigments.The possibility
that melanin may be responsible for the photostable electrical response of the
eye ( no large photostable response in albino )
is supported by a study of electrical photoresponse from various tissues.
T.G.Ebrey et al. Nature,
January 28, 360-362, 1967 .
The ink gland of the cuttlefish Sepia officinalis has been shown to
contain a variety of melanogenic enzymes as tyrosinase, dopachcrome tautomerase,
al. Biochem.J., 323, 749-756, 1997
Sepiomelanin radical-polarone oligomers are formed from cyclodopa.
melanins ( BCM and BSM ) are
hydrate-quinones..That is melanins have one oxygen more in respect of the
theory of quinone hydrate is published also on ATTI ACCADEMIA PONTANIANA
Quantitative determination of PDCA, PTCA, specific degradation products,
carboxylic content, rate of ferricyanid comsumption,absorption spectra, MALDI
experiments revealed that sepiomelanin consist of a mixture of oligomers
incorporating over 75% of
DHICA and 20% of DHI units
occurring for the most part in the
degraded pyrrole form.A.Pezzella et
al., Tetrahedron 53, 8281-8286,1997
such a pigment would be colourless
we are induced to suppose that new and strange oligomers bluilt up the black particle and a new melanogenesis
must be suggest.
70 ) Polymerization of monomers
into melanin indicate that uncyclised and carboxylated derivatives are not
incorporated into the polymer in vitro.The paper clash with the above mentioned
Hearing et al., BBA 611, 251-268,
there are often relation between
laboratory findins and biological data we conclude that
no carboxylated units are present in BCM
71 ) It was found that about 96%
of the CO2 evolved in
the reaction DOPA-----Melanin arise
from the breakdown of the benzene nucleous.
al., J.Chem.Soc.381-384, 1954.
interesting to know if such a degradation process which remember that of
Parkinson disease occurs also in the cell.
72 ) Composition of melanin samples depends on centrifuge speed
73 ) Binding property ( solid, liquid and gases ) of the black material is of
interest for humic acids
74 ) MALDI spectra of
DHI-melanin, DHICA-melanin, sepiomelanin are reported.
contrast to the commonly held
notion of melanins as high molecular weight polymers all the pigment analysed
are mixtures of oligomers species with
molecular weight in the range of 400-1500.A.Napolitano et al., Rapid Comm. Mass
Spectrom., 10, 204-208, 1996 ; A.Napolitano
et al., Rapid Comm. Mass Spectrom.,
10, 465-472, 1996 ;
A.Pezzella et al.,
Rapid Comm. Mass Spectrom., 11, 368-372, 1977
MALDI spectra interpretations were a great surprise to the pigment cell
the peaks of the spectra do not correspond to oligomers but to
degradation products of obscure origin it seems possible that the oligomers of
low molecular weight are necessary to built up the particle.
While dopachrome and
leucodopachrome can be ruled out merely on the basis of their reactivity there
is now fresh evidence that DHI and DHICA when allowed to co-oxidize under
suitable biomimetic conditions give mainly mixtures of the corresponding
homopolymers,in keeping with their markedly different redox pontential.Thus,
eumelanins would show now more as mixtures of oligomers of DHI and/or DHICA,
partially oxidized,rather than as intimate copolymers of various precursors. In
conclusion , though many structural details of eumelanins are uncertain, new
evidence is rapidly accumulating that is expected to lead to
a fairly realistic picture of such unfathomable materials.Verification of
this preview is expected in the very near future.
Melanins and melanogenesis ‘’ , pag
118, AP, San Diego 1992
conclusions about the structure of BCM ( eumelanin ) in 1992.
noted that dopachrome and leucodopachrome are very reactive substances and no
evidence was given about the oligomers structure.
Pheomelanin and Pheochrome ( other names trichosiderin,trichochrome ) derive
from the new aminoacid 5-S-cysteinil-dopa
( Cysdopa ) .Chromophores are dibenzothiazine and dibenzo thiazinone.The
structure of the pigment of red haior was established
‘’ Melanins ‘’ pag 190-199,
in Methodicum Chimicum, Vol. 11, Part 3, Eds.
F.Korte and M.Goto. AP Tokyo 1978
Ringraziamo il personale della Biblioteca della Stazione Zoologica di Napoli per la assistenza data.
Various teaching tools (
school, journals, books,
encyclopedias, Internet, etc. ) still
of black matter ( BCM and
BSM ) and melanogenesisi which are
not up to date and do not comply with those reported by here..