Link 4-Melanin 95-97
In memory of Giovanna Misuraca
not arrive at ideas, they reach us. The courage to think comes down from the
urgent desire to be, then destiny blooms.
(MARTI N HEIDEGGER)
substances and black substances are very common in the lithosphere, the hydrosphere, the atmosphere and the
biosphere, and if one considers the black matter found in interstellar spaces
also in the cosmos ( Link 7 and
Link 8 ). The natural and synthetic black substances ( BCM and BSM ) of the
biosphere are called melanins (Link
of the black material is conductivity / superconductivity binding of organic
and inorganic products, storage of liquids and gases,assembling cellular
factor. All the natural and synthetic black substances which are cited in the
paper are characterised by a vast chromatic variation which, however, always
goes through the colour range : black - vermillion - yellow.
substances which present these chromatic variations are:
of cadmium and other sulphurs (lithosphere) .
acids (hydrosphere, lithosphere)
and hair pigments (biosphere)
case of cadmium sulphur colour is linked to the threshold of conductibility.
The lower the threshold the darker the colour. Pyrrole –black and
acetylene-black are the
most studied organic semiconductors. The idea that natural melanin is also a
semiconductor is not completely new . The works of the 1960s seem to have been
neglected by the contemporary scientific community. S. T. Allen and D. J. E.
Ingram say : ... In conclusion,
the free-radical property and the radiation properties of pigmented materials
may be understood if it is supposed that the melanin
acts as a one dimensional semiconductor with bound protons producing traps in
the system .... The study of conducibility of the biological melanins will be,
we are certain, one of the next objectives of world scientific research.
Besides, it should be stressed that the various melanogenesis in vitro and
in vivo are fluctuating chemical systems, in the sense predicted and
studied by Piccardi (Florence)
sensitive to variables of a terrestrial, solar and cosmic nature. Both the
structure of the molecule and the colloidal structure is important in a
radical process like that of melanin. In the text the term eumelanin ,
pheomelanin , allomelanin
are used to designate the black or red-brown substances of biological
or not .Whereas natural pigments are called BCM ( black cell matter)
the synthetic is indicated with the monogram BSM
( black synthetic matter ). It is hoped that in the future the
scientific community finds new terms to indicate "blacks" of all
origins in a single context. A brief aside before beginning the story. In the
Museum of Fine Arts in Basel there are some tables of the altar of
Heilospeigel by K. Wits, these are chromatically very different from one
another and where they appear in full light, among the different colours are
those of the semiconductors. The expressive meaning of the artist’s
operative processes and his capacity of distributing colours are shown by fact
that the more one thinks of the expressive value of the colours, the more they
seem mysterious. An analyis of the expressive meaning of the colours of the
semiconductors should be illustrated, in the future. In the mind of a painter
the black (a dark grey colour) is obtained also from the mixing of a set of
varnishes of different types and colours. For the painter the dark colours
symbolise the strong negative of life while the light colours represent the
positive side of life. Mourning is black, even though it is white and luminous
in other populations. The black cat which crosses the road of a latino is an
ill omen but in anglo-saxon populations it is a sign of good luck. The study
of chemists and physicists on melanins in this century have not always lead to
clarifications, but rather to taking up positions or points of view which are
not only discordant among themselves but also in disagreement with the
classical philosophy of the chemical science of natural organic substances.
are essentially two types of mechanism which transform the black substances,
starting from very simple composites of carbon, subjected to natural forces
like temperature, electrical discharges, radiation; into
complex structures. These
are part of a highly specialised chemistry called the chemistry of evolution
.One mechanism for increasing the concentration of the organic reagents of the
primitive soup predicts the absorption of these composites by inorganic
particles and clays. In particular the absorption by minerals would have also
had the task of impeding or diminishing photolythic and pyrolythic action
favouring stereospecific catalysm. A proof of all this is the synthesis of the
polypeptides of the glycocolla starting from aminoacetonitrile absorbed by
kaolin. Melanin must have played and important role in preenzymatic chemistry.
This black substance continues to be synthesised by the living organisms of
the Earth today, and is present in every Phyla. It is possible that,
hundreds of millions of years ago, there were two solid phases on Earth, one
inorganic and one organic. The melanin is thought to be the organic solid
state formed by a radical process catalysed by light and by temperature. This
process is still observable in our environment which is subject to radiation
and continuous electrical charges. Melanin must be considered not only as a
"lattice" but also as a semiconductor. In our opinion in the
presence of an atmosphere which was both reducing and oxidising, with
electrical discharges, solar radiation at short wavelengths and sudden thermal
changes atomic collision, melanin was the birthplace of aromaticity. Melanin,
through its large surface, its porosity and its internal molecular sites
offers a complex but satisfactory situation for stereo-specific or even
metalorganic synthesis. The radical property of melanin is important for the
chemical evolution on Earth. Uniformally distributed unpaired electrons in
melanin contribute to the creation of organic-metal semiconductors which
interfere in organic synthesis. It is important that water can reach the
unpaired electrons and condition the relaxation time. In the chemistry of
evolution it is always a risk to say which, among all the molecules, is the
first, the most primitive. Up to
now it seems clear that the role of the semiconductors in a biological context
must also to be considered. Although light has been thrown on the subject
recently, there are still several doubts on the biogenesis, the structure and
the function of melanins. We hope that this work is not only a testimony, but
can contribute to improving our knowledge. While the study of crystalline
substances has achieved important results for molecular structure the organic
chemist finds himself at a disadvantage in front of dark, amorphous,
insoluble, non crystallizable substances which are fluctuating and
Allomelanins ) ( Link 15 )
melanin (a limited number of species and genus Bacillus, Pseudomonas,
Azotobacter) are seen as black, dark red or yellow substances with
different tones and rarely are even green. They are insoluble and amorhphous
with non-specific spectral characteristics, but, as always, with a constant
EPR signal. The micro-organisms which produce melanin belong to aerobic forms
. The formation of melanins in micro-organisms is an oxidative process of
phenolic substances, influenced by radiation, temperature and the presence of
metals. In the future the cellular and extracellular melanins of the
micro-organisms could represent a very interesting material to study for
molecular structures and organic synthesis.
DOPA and cysteinyldopa ( Link 14 ) , other polyphenols including non-nitrogenated
forms are responsible for the formation of black pigments in micro-organisms.
Typical melanogens of microrganisms are, for example, pyrocatechin, 1-8
dioxynapthalene and (+)-scitalone isolated in the culture of the brm-1-mutant
of Verticillium Dahliae. A characteristic of some micro-organisms is
that the formation of the pigments appears as a disintoxication reaction of
the phenols present in the old culture, perhaps because of a mutated
metabolism inside of the cell. Micro-organisms (Azotobacter chroococcum) which
contributes to the formation of the humic acids and the humus of the ground
and participate in the general life of living nature. Ample and in depth
studies on Aspergilline, the black pigment of Aspergillis niger, have
been made starting from Quilico (
Milan ) and continued by his school: The tyrosinase enzyme was isolated from
fungi for the first time and today this is still considered the main enzyme in
the melanogenesis of all the living species. Tyrosinase has been given this
name because it is able to catalyse the transformation of tyrosine into DOPA.
For many fungi though, for example in Neurospora crassa, the enzyme
tyrosinase does not belong to the category of the enzymes necessary for
development. The synthesis of tyrosinase can be induced in such fungi, as for
example in Glomerella cingulata. Among the biological functions of the
melanin there are those of defence of the cells from different types of
radiation (which acts as a rapid ecological selection factor), and defensive
lysis for survival in pigmented fungi surrounded by a microflora in
biologically active terrain. The melanogenesis of the tuberculosis bacillus is
unclear as is that of the Mycobacerium nigrum. The Mycobacterium
leprae does not produce melanin in situ but provokes a pigmentation of the
skin of lepers. The melanin isolated by the Bacillus salmonicida is of
a red-brown "colour". The melanin produced by micro-organisms may be
either extracellular or intraccellular. Intracellular melanin is the most
common and is firmly linked to the cell walls. The combination of the
environment and, as always occurs in radical processes, light and temperature,
influences the production of the pigment. An antibiotic activity has been
attributed to some of these pigments (blacks, browns). The brown melanins
produced by these organisms are similar to the humic acids for a series of
chemical and physical properties. Many microscopic fungi with brown and dark
structures (hyphe, spore, conidio, peritecio etc.) are known even if they have
not always been shown to be melanin. Among the fungi producers of melanin are
believed to be: Pullularia plullulans, Cladosporium mansonii, Phialanphora
joanselmii, Nadsoniella nigra var. besuelica, Neurospora crassa,
Aspergillus nidulans, Daldinia concentrica, Aspargillus niger, Cephalosporium
sp, Mollisia caesia, Ustilago maydis DC, etc. Tyrosinase is very common in
micro-organisms, but its presence does not always mean that the fungus
produces melanin. It seems that it is also possible to produce melanin in an
formation of brown, red-brown and black products is a phenomenon which is
often observed on petals and leaves. The melanogens of plants are often non-nitrogenated
substances . The non-nitrogenated melanins of plants are called allomelanins.
There are also pigments which form because of damage to the tissue (potatoes,
apples, banana etc.). It is known that on contact with atmospheric O2 cellular phenols and polyphenols produce complex dark
and brown products, in a non-enzymatic reaction
Compositae and fungi contain acetylenic compounds which may go black
under the action of light . To date, the melanins of plants have not been
given serious chemico-physical examination. A plant rich in melanogenes is the
broom Sarothamnus scoparius. From legumes and from fruit it is possible
to isolate tyrosine, DOPA, tyramine, DOPAamine, epinine (N-methyldopamine).
The blackening which is seen in the course of maturation and conservation of
bananas seems to be due to the neurologic melanogene DOPAamine. The typical
blackening of slices of tubers (potatoes) and fruit (apples, pears, etc.) and
plants (in the Vicia faba one finds large quantities of DOPA) seems to
be a process of melanogenesis from tyrosinase or DOPA. In all the plants the
polyphenoloxidases are very common but this does not always mean the formation
of melanin. Besides, while the melanin is localised, the enzymes are much more
dispersed in the various parts of the plant.
in Animal kingdom.
animal world melanin is always present in various forms and coloured from
black to vermillion and to yellow. There are innumerable shades of colour:
brown, red-brown and yellow which depend on various factors . The black animal
melanins have been given the name eumelanins and those of lighter colours
pheomelanins (Link 14) . The
various shades of colour which we observe in nature depend on the gap ( Lin9 )
but also on the purity, on the state of oxidation of the aggregations, on
polymerisation and on copolymerisation of the various melanogenes or other
substances. Some species of pigmented animals contain black granular pigments
in the endoderm while a brown pigment is quite common in the ectoderm.
Particular interest has been seen in the case of melanogenesis of the cuticola
of the insects (sclerotisation process). In some studies, carried out in the
past and neglected in the present, on the cuticola of the desert locust, Schistocerca
gregaria, well known for the economic damage which it provokes in poor
populations, it was shown that the melanogeneses and sclerotisation are two
distinct processes. The melanins of vertebrates and invertebrates can be
observed in the skin, in fur, in hair, in feathers, in scales, in the choroid,
in the peritoneum, in the pia mater, in the brain, and in melanomas (malign
tumours of an intense black colour). One cannot yet confirm that the various
melanins coming from different sources are the same, even though they have the
presence of a free radical and the potential capacity to conduct electrical
current in common. Sometimes animal melanin has the function of protecting the
skin from radiation (short wavelengths), of controlling temperature, of
mimetisation. Little or nothing is known of the structure and the functions of
neuromelanins (eg. substantia nigra) expecially with respect to the
elecrical properties of this pigment (Link
Obviously the melanin associated with tumours has been studied more, by
of Substantia nigra from normal individual stained with toluidine blue.
cells of the Substantia nigra stained with toluidine blue
melanins of mammals are deposited under the form of granules in specialised
cells called melanocytes, rich in iron, copper and zinc. The granules have an
ovoid form (0.1 x 0.4 m
- 0.18 x 0.6 m) or spherical form (0.2 x 2.2 m), of proteins covered by melanin. The protein can be
"discovered" with a bland attack using H2O2
which "dissolves" the melanin (1, c). It is not easy to recognise a
melanin and it is almost impossible to do so when the melanins are formed by
copolymerisation from different precursors. The way in which the melanin is
seen in the animals is fascinating, with geometric figures of rare beauty. The
way in which they produce blue and green colourations is another fascinating
argument (Link 9, 11). One need only think of the alternation of colouration,
the lively tints, the shades, the tones which, with the exception of man, make
the animals so pleasant to see. The mutable colours which many animals use to
hide from predators are surprising; in these colourations the conductor
melanin has always played an important role. The melanins are responsinle for
the different "structural" colours like the Tyndall blue which is
seen in the skin of fish, amphibians, reptiles and birds. Through differing
mechanisms and the Tyndall effect melanin produces the blue, which in the
presence of a yellow pigment (for example a carotenoid) gives a beautiful
green colour. In English schools the teacher tells the students to treat a
green feather from a bird (e.g. a parrot) with CS2,
leave it over night, remove the intensely yellow coloured CS2,
wash it with H2O,
dry it, and you have a beautiful blue colour.
arrived in Australia from South America via Antartica. Almost all the species
have a red-orange fur (Megaleia rufa) or grey fur (Trichosurus
vulpecula) ( Link 14 ). In these animals there should be a double
melanogenesis, one from cysteinyldopa and one from tryptophane via kynurenine,
with the formation of cinnabaric acid. A double melanogenesis is also present
in the cephalopods and in some insects. A substance with a structure similar
to cinnabaric acid has been isolated from the eyes and from the skin of the
cephalopods and from the eyes of Musca domestica. In the extraction
mixture this substance transforms into various composites, among which
dihydroxantomatine has been idientified which could be a key intermediate of
melanogenesis and pheomelanogenesis from kynurenine .The characteristic
melanins of the hydrosphere and the lithosphere belong to humic substances.
They form from various precursors, like phenols, sugars, aminoacids,
glycerides, through the combined effects of radiation, heat, and
micro-organisms. Considering the variability and complexity of their origins,
the structure of the humic acids is one of the most complex problems in
chemistry. For the humic acids present in the lithosphere and for those in the
hydrosphere composition and structure depend on the place where they are found
and how they form. The humic acids play a role in the biogeochemical cycle of
carbon, though it is not clear how . Melanins are normally present in
organisms which live in the acquatic environment: both in animals and in
vegetation. Often melanins are the dark background which highlight the silvery
colour of many fish.
though it has not yet been recognised as a biopolymer pyrrole black is of
great interest for structural studies and for the chemico-physical behaviour
of natural melanins. Pyrrol black can be prepared by chemical, electrolytic or
ultrasound oxidation. If one examines the polymerisation process of pyrrole in
peracetic solution (Angeli) following the evolution of the solution over time,
the EPR signal can be observed from the beginning and becomes more evident at
lower temperatures. After a certain fluctuating and non-reproducible time one
obtains a black precipitate characterised by an intense EPR signal but wihout
any hyperfine interaction. The presence of unpaired electrons is necessary for
the formation of conduction bands and for the presence of the fundamental
colours of the semiconductors, black, vermillion and yellow. Another necessary
situation is that the radicalic species are stable and permanent, as happens
in the natural melanins. Important structural information for the history of
natural black systems is the fact that electrical conductivity in an organic
material is linked to the existence of a polyenic or a congugated polyarenic
system . It has been demonstrated that the polypyrrol contains cation centres;
it is a polycation with spectator counteranions. The conductivity of these
systems depends on the method of preparation, on the type of counteranion and
on the extension of the planarity. In the preparation of pyrrol black the
counteranion, also called the spectator ion, is also taken from the medium of
the process. The black produced varies in conductibility, and in the number of
cation centres present . The anions ClO4-,
give good conductors. Acetylene black is also a polymer semiconductor and
presents cation centres with spectator counteranions . Since there is no
reason to believe that natural melanin does not belong to the category of the
polyarenes and polycationic polyenes, like pyrrol black and acetylene black,
it is necessary to review all the chemical and biological analytic data
gathered to date in the study of natural melanins (eumelanins, pheomelanins,
allomelanins). Besides it is highly probable that the natural melanins are
artefacts with counteranions provided by the medium in which the
"purification" has been made. If one considers the black from
5,6-dioxyindole one finds interesting data. 5,6-dioxyindole is among the most
important melanogens and is a continuous reference for the chemistry,
biochemistry, and biophysics of the eumelanins. The oxidation product ,
generally a black or vermillion precipitate, is isolated through acidification
The analytic results which are obtained worry authors, in that they do not
agree with the theory which predicts that the blacks or vermillions are
polymers of the 5,6-dioxyindolequinone of its derivatives. They claim that a
certain number of molecules of H2O are linked to the polymer, in an "ad libitum"
or random quantity and in such a way as to close the gap between the analytic
data and the theoretical calculations for a polyindolquinonic ‘’
other blacks like the analin- black, catechol- black, 3-aminopyrocatechine-
black and tryptophane- black are in the same class as these composites.
Polyphenols composites, as is known, play and important role in the
melanogenesis of humic acids.
and Chemistry of Melanins.
peculiar characteristics of the melanins are always the colour and their free
radical nature (6). Scarse results have also been found with the most
sophisticated apparatus (X-rays, MS, NMR, Laser) (Link
are three fundamental theories on the chromophores of melanins. The first is
that which proposes that melanin is a mixture of chromophores which resonate
in different parts of the spectrum. A mixture of red, blue, green etc.
chromophores absorb the radiation of all the wave lengths of visible light and
appear black. Another theory predicts that a highly conjugated system produces
black, brown and red-brown depending to the gap value of the semiconductors.
What is the extension of the conjugation that allows a body to appear black?
Many natural substances possess extended systems of conjugated orbitals (for
example the carotinoids) but none of these compounds appears black. The study
of the electronic structure of an ordered and ideal polymer of
5,6-indolquinone which is a common component of the eumelanins (hair, eyes,
skin, etc.), conducted using the theory of Hückel, predicts that the black
colour appears in a polymeric unit with a number of monomers higher than 10
and up to a infinite polymer and that, besides, it is an amorphous
semiconductor and a good conductor of electricity (3) . The theoretical model
is not supported by few experimental data. The only experimental data which
currently exist for polyarene and polyene structures are those relative to
pyrrole- black and acetylene -black which, as has been said, are radical-polarone
system. ( Link 9, 12, 21, 22 ) In the study of the melanins it has often been
claimed that the different colours, yellow, orange, red, red-brown, black are
due to the type and the size of the granules of the pigment and to the
distribution of the granules in the tissue. A third theory proposes that the
melanins are schemochromes, that is that the colour depends on particular
particle structure. The melanins could be a sort of black body in which
the light which penetrates is reflected and diffused until it is completely
absorbed. The cause which produces the "black" must be studied using
solid state theory and band model of semiconductors.
as stable free radical .
the fact that every chemical and physical study of melanin must be interpreted
with more care compared to what would usually be the case in the study of pure
and crystaline substances, the black melanins (eumelanins), brown, red-brown,
and yellow melanins (pheomelanin), the allomelanins and the humic acids
present a characteristic EPR signal, sometimes with some hint of a hyperfine
The origin of the paramagnetism is still a controversial problem. Several
efforts, (nothing is ever clear and definitive in scientific research on the
black substances), have been made to correlate the free radical nature of the
melanin with certain biological functions, like the physiology of vision,
photoprotection, threshold switching, the electret effect etc. Studies have
been carried out on all the melanins in acqueous suspensions and almost always
give an EPR signal at about 4-6 G. The spin concentration is around the value
4-10 x 1017
In the "polymer" there would be one free radical every 200-1,000
"monomers". It would seem that there are two radicalic centres in
the black products that originate from the o.phenols: one being essential
(intrinsic), highly stable, generated in the course of melanogenesis and
"trapped" in the product and the another being extrinsic, transient
and reactive which can form in the melanin by the action of the different
chemico-physical agents. Passing from black melanins to brown and red-brown
products (pheomelanins) it is possible to observe radicals with better defined
structures, at different pH, like those of semiquinonamine and semiquinone.
EPR studies carried out on the hair and skin of several bovine races and on
albinoes have mainly been used by geneticists and pathologists. Albino
subjects, with the same phenotype character, have hair with differing
electronic characteristics. In some albino subjects there is a weak EPR signal
which is completely absent in others. There are, that is, true albinoes and
false albinoes (6, l).
chemistry of free radicals, which has almost always been associated to the
processes of polymerisation and oxidation, has developed in isolation from the
context of organic chemistry. The chemistry and biochemistry of natural
substances have always considered the free radicals with diffidence because of
their reactivity which makes them difficult to control. It is probable that
different radicalic reactions intervene in melanogenesis. Melanogenesis has
never been considered as an essentiallly radicalic process. The EPR signal,
present in all the melanins, has been attributed to a system like the cyaninic
colourants (merocyanines) which give, as is known, EPR signals similar to
those of the melanins even though they do not have unpaired electrons. This
explanation of the meaning of the EPR signal by the merocyanines seems
strange? The hypothesis that the signal comes from an inert radical of the
copolymerisation material of the melanin cannot be accepted. A somewhat
surprising observation is that the radical is little present in the melaninin
granule and therefore of little significance , while it is highly probable
that the important properties of the melanin (solubility, colour, reactivity,
conductivity) are linked to this electron which lives alone in a gap of the
granule. When the melanin lightens from black it becomes brown, red-brown,
yellow, that is one passes to pheomelaninic granules (hair, fur, feathers,
eyes), not only is the EPR signal always present but it appears in a more and
more structured form, to the point that it is possible to distinguish the
black (melanin) from the red-brown (pheomelanin). The EPR signal is present
both in melanins prepared in the laboratory under most varied conditions and
in pheomelanins of very varied origins. For the humic acids
of the hydrosphere and of the lithosphere, so important for life, one
has a very similar general picture even if the heterogeneousness of the
material makes the granules of the humic acid much more difficult to study.
The results obtained with IR, NMR, X-rays and MS cannot be believed
significant. The various spectra which often present absorption
characteristics, may not be due to the humic acid but to incorporated
substances (which can be used for the qualitative and quantitative analysis of
terrains and of waters). The EPR signal is pure, clear and very similar to
that of the melanins. In general one obtains the EPR signal of two types of
stable radical which must be attributed either to the pyrocatechine-resorcine
type or the quinhydrone type. In general one has signals of various intensity
according to the origin of the humic acid (humic acids from micro-organisms,
soluble humic acids, black carbon humic acids, grey humic acids, brown humic
acids, marshland, manure, peat). Notable paramagnetism is present in the
fungal humic acid (Cephalosporium gordoni) which is also darker: the
blacker the composite the more intense the EPR signal. It is calculated that
for a concentration of 1017
spin/g in a "composite" of molecular weight 10,000 there is 1
radical for every 600 monomers. It is plausible that, from a structuralis
chemical point of view, the part of the "macromolecule", perhaps the
chromatic part (acetylene-black), responsible for the paramagnetic phenomenon
is assimilable to that of the more typical melanins present in the animals or
produced by micro-organisms. Therefore the history of the EPR signal is
identical for all the melanins regardless of their origins. As often happens
in research the failure of an objective (identification, for example, of the
structure responsible for paramagnetism in the melanin) produces new and
useful knowledge. The discovery that the humic acids of various origins and
natures are free radicals has given useful information on all the existing
relationships between the EPR signal and the properties of these substances.
In the soil there are all the conditions for the genesis of free radicals:
water, light, heat, organic and inorganic catalysts (Fenton reactive types).
The soil is all a melting pot of radicals; in the soil the primordeal matrix
can operate with ease .
hypothetical radical melanogenes of the soil can form through the action of
oxygen and light on products deriving from micro-organisms, from the oxidative
demolition of the lignin, and from other biological polymers. In the
physiology of plants humic acids act both as growth factors and as activators
of cellular respiration. The semiquinonic radicals of the humic acids
influence germination and, linking to atmospheric oxygen, transport active
oxygen in the soil. The humic acids as polycations fix and transfer precious
counteranions to the life of the soil and the waters.They can be good
conductors when opportunely prepared and doped. In conclusion, polymers like
melanin from DOPA, melanin from sepia, humic acids, melanin from phenols, like
pyrocatechine and pyrrole blacks, etc. , apparently differing among
themselves, exhibit an identical signal at EPR which can be reinforced up to
even 100 times if the measurement is made on sodium salts. The melanins of the
soil (humic acids) form by a fluctuating and non-reproducible mechanism where
time must be considered as an intrinsic parameter of the dynamic of the
natural process and where the activation of water is a fundamental parameter
(also cellular liquid). The concept of time is a problem of fundamental
importance for the biologist of melanin, in that in its genesis this is not
free from environmental and cosmic forces and influences or from the
activation of the water under the action of electromagnetic fields or from
solar phenomena in general. To show that some reactions cannot be located in
the current logic of science, Piccardi stressed
that accepting time as a coordinate negates the fundamental dogma according to
which only reproducible experiments are valid. In the case of melanin, in
fact, it is not possible to control the conditions in which an experiment is
conducted without taking into account the time coordinate, because during its
course the conditions in which an experiment, a chemical or biochemical
reaction, is conducted change. In experiments on melanin the time may not be
considered an isotrope in every direction in space, nor homogeneous for every
successive instant. Melanin cannot be represented by a formula, with a
complete melanogenetic scheme in that it is not representable in terms of
linear equations because it is not possible to hypothesise a correspondence
between cause and effect in the temporal succession of the relationships. A
negligible reaction in a fixed instant can become a determining reaction in a
melanogenesis many classical concepts, definitions, chemical dogmas are
obsolete, they are lost in the past. If the experimentor looks at the
scientific explanation of the natural processes and is not content with the
measurements of the immediately measurable quantities then he understands that
he is working in an imperfect way. The analysis (combustion) of the melanins
coming from the sack of the sepia are non-reproducible even with the same
method of preparation of samples coming from the same source. To the chemist
the synthesis of black content in the sack of the sepia must seem a
non-reproducible process and is perhaps fluctuating because of the
interference of magnetic activity and radiation of the sun on the sea, of the
atmospheric electrical potential, of the variations in the Earth’s magnetic
spirit of research in the field of the melanins must be renewed, accepting the
hypotheses works some researchers, sometimes students, most of the time young
emarginated researchers, would like to introduce into the world of research.
chemical processes which produce black substances in vitro, either in
the presence or the absence of enzymes are considered as chemical
melanogeneses. Three parameters dominate the scene of mealanogenesis: colour,
conductibility, EPR. Michaelis was the author of one of the most important and
general theories on two-step oxidations in organic chemistry (1932).
Oxidations and reductions of organic composites (in vivo and in
vitro) are bivalent (bivalent reactions) and these reactions procede necessarily
through two successive univalent steps. A radical process must be at the basis
of the synthesis of the melanins (6, n). In the case of a quinoid substratum
Michaelis, applied the term "semiquinone" to an intermediate
electronic form called "free radical " . The existence of these
electronic forms was proved through the accurate study of free radicals which
are formed during oxidation. After the death of Michaelis a not indifferent
advance was made in the semiquinonic free radicals which became better
identified and classified by EPR studies. In the study on oxidation of
hydroquinone it was shown that the formation of the semiquinones is a
reversible reaction at neutral pH, while a black precipitate is formed at
alkali pH. The black precipitate which is thereby obtained has an EPR signal
similar to that of the natural melanins. The black precipitate which is
obtained, for example, by the oxidation of DOPA is the result of the
polymerisarion between quinones and phenols. A question which can certainly be
asked is: How come the radicalic mechanism which Michaelis has predicted in
oxidation does not occur in the case of the melanins? However, everyone who
has studied the formation of the melanins with EPR, starting from the
diphenols like pyrocatechin, has registered EPR signals which transform in the
course of melanogenesis over time. This suggests that different chemical
species, also coming from oxidative and bioxidative degradation, are produced
in the formation of melanin. An observation which successive studies have made
in the fundamental equation of DOPA-melanin, which is considered the
fundamental melanogenesis of superior organisms, is that in effect there is
more oxygen in the black than that which the theory can predict and that
besides the composition is variable and fluctuating. These results are the
same whether the oxidation of the DOPA is made with or without enzymes.
should also be noted that often the experiment has been carried out with the
use of tyrosinase from pathological sources like melanomas.
the DOPA with or without enzymes forms different intermediaries like
dopaquinone and dopachrome, 5,6-dioxyindole (DHI), 5,6-dioxyindole-2-carbonic
acid (DHICA) which can be
oxidation is followed by UV one sees the formation of a species which absorbs
at 280 nm to which the structure of the dopaquinone has been attributed, and
which, with a kinetic of the first order, transforms into a species absorbing
at 480nm normally identified with the dopachrome. This reaction is strongly
dependent on the pH. Oxidising the 5,6-dioxyindole even with simple
atmospheric oxygen forms a red substance in solution (540 nm) to which the
formula of 5,6-indolequinone or one of its dimers or trimers has been
attributed. Anyway the reaction is rapid and leads to a black even in the
absence of the enzyme. The first stages of melanogenesis seem typical
radicalic reactions deriving from a semiquinonic radical of the DOPA. The
formation of phenoxonic radicals is well known in living organisms and
explains the formation of metabolites of plants like the alkaloids, the lignin
in the course of pheomelanogenesis a
series of cysteinyldopas ,6-cysteinyldopa (yield 2%), 5-cysteinyldopa (yield
70%), 2-cysteinyldopa (yield 15%), 2,5-dicysteinyldopa (yield 6%) form by
reaction between DOPA and cystein. The genesis of these substances is well
explained with the possible reactivity which the mesomeric radicals of the
DOPA. The dopasemiquinone which is formed in the first stages of melanogenesis
by oxidation of the DOPA also provides the explanation of the formation of
different tricochromes (pheochromes) (1, d) from the various cysteinyldopas.
Recently it has been shown that the oxidation of the 3-oxy-kynurenine also
procedes through the formation of free radicals . An examination or a
reexamination, with EPR, or radical sequestrators which lead to establishing
the participation of the free radicals in the course of melanogenesis both in
an autooxidative process and in an enzymatic process would be welcome; in this
future research it is necessaty that the enzyme is compared only with its
natural substrate. Melanin forms by a radical process, but surprisingly it can
degrade with a radical process, by the action of light, of atmospheric oxygen
and of the H2O2
which is formed. Like in soil the radicals play a very important role for the
biology of the skin. The light , the environmental factors, the fluctuating
factors of the cellular water are very important. The periodic influence of
the nuclear explosions of the sun make the melanogenetic system of the skin
one of the most interesting biological phenomena not studied on the Earth.
conclusion a short comment on melanogenesis in mammals. It seems that recently
our knowledge in the field of physiological and pathological melanogenesis in
mammals has progressed . Unfortunately no distinction has been made between
the melanogenesis under strict enzymatic control, as claimed by the authors of melanoma and of neuromelanin isolated from every
environmental conditioning, and the radical fluctuating and non-reproducible
melanogenesis of the skin. The formation of black products in the cells is
illustrated by one scheme denominated melanogenesis which is based mainly on
work started in 1924 by the physiologist Henry Stanley Raper of Manchester .
The chemical intuitions of the researcher not common for a physiologist were
certainly influenced by Sir Robert Robinson then professor at Manchester. The
history of melanin can also be seen in the history of schemes of melanogenesis
but that would take us too far afield.
1964, based on BCS calculus (Barden, Cooper, Schrieffer theory of
superconductivity) W.A. Little proposed a chemical structure for a consistent
ideal organic superconductor, composed by a polyunsaturated chain, called
“spine”, substituted in some points by heterocyclic structures (often
resonance hybrids) having cation centres and counteranion. Even if the hope
finding a room temperature superconductor has not been realized, Little’s
hypothesis had been very profitable, making possible the synthesis of numerous
compounds or organic materials which proved to be conductors. Because of their
technical properties these compounds were given the exotic name “organic
metals” You can therefore confirm, from experimental data that
polyunsaturated polymers (the “spines”) with cation and counteranion
centres (and vice versa) are conductors or candidates for conduction.
Many of these materials, for example pyrrole black , were considered for long
time as insulators but experience has shown that the conductivity of Little
compounds is influenced by various factors such as the way the polymer film
forms, the doping, type and concentration of the counteranions, the pH,
temperature of reaction, etc. The significance of the colour of these products
or materials and their possible correlation with EPR and electroactivity have
never, to our knowledge, been looked into by organic chemistry. The present
paper attempts to find this correlation and to create a bridge between
physics, chemistry and biology. In this connection, it should be stressed that
conductivity also plays an important role in various biological mechanisms and
sites, where these polymers are present. It is well known that a pure
semiconductor can occur in
coloured forms originating from the transition of electrons into materials
with band structures, whereas most synthetic and natural colours are
attributed to the transition from one molecular orbit to another.
pure semiconductor may appear black red yellow depending on the amplitude of
the prohibited band: the colours of the band have generally been attributed to
inorganic compound with different. eV expressed values (E.g. CdS 2.6 eV
yellow, HgS 2.1 eV vermilion, CdSe 1.6 eV black). The sequence of the colours
of the prohibited band in increasing order of this amplitude is black-redyellow-colourless,
the rarer green. Some of these pigments, with different chromatic shades,
occur in nature and are called biochromes . Furthermore formation of a
light-induced charge-transfer complex was observed by measuring the increase
in the conductivity after mixing solutions of chlorpromazine and sepiomelanin
[23 page 22].
polyarenic structure with cation and counteranion centres, is a structure
containing all the structural elements necessary to obtain a Little conductor
or a polymer candidate for superconduction. The polyarenic spine present in
sepiomelanin and in other natural compounds is that of acetylene black . We
found that numerous families o[ polymer conductors, some of biological
interest, descend from three well-known systems, namely, indole, pyrrole (desbutenylindole),
and benzene (desaminovinylindole).
chemical formulas of the precursors of the product or the electroactive
material are reported, together with the polymer colour as it appears in
nature or in the laboratory. Moreover, one can find the relationship between
these compounds (materials) and natural pigments, the observed electroactivity,
(with the term “positive” and the theoretical electroactivity with the
term “candidate”), and the presence of an EPR signal common to all the
pigments. The polymer material with electrical activity indicates an intrinsic
or extrinsic conduction (doped or undoped).
In the most polymerized phase the derivatives of pirrole , indole ,
benzene , are amorphous black products. The derivatives of indole are
predicted from calculus to be amorphous semiconductors . The derivatives of
pyrrole, like pyrroleblack , bile pigments
and porphyrins are
conductors. Among the derivatives of benzene there are various good
conductors, with electrical properties whith can be improved they are doped such as aniline-black [, poly(p.phenylene), fullereneblack
and graphite. Fullerenes and graphite, which do not seem to be
Little’s structures, are been regarded as arbitrary polymers of benzene
based upon their colour, EPR, electrical activity. Both calculus and
Little’s theorem indicate that all the melanins (derivatives of pyrrole,
indole and benzene polymers), BCM or BSM are amorphous semiconductors. With
increasing the number of rings, the aromatic character decreases, whereas the
radicalic behaviour, the reactivity towards oxydants and other chemicals, the
electron paramagnetism(EPR) and the electric conductivity increase. At the
same time there is a colour shift from colourless (benzene) to green-black (heptacene).
The EPR signal can not correlate to a specific structure. The properties of
the polynuclear compounds gradually approach those of graphite, with the
fullerenes being found in the middle of the series. This also applies to
electrical conductivity. Aromatic polynuclear hydrocarbons are semiconductors
and exhibit photoconductivity, a strong increase of conductivity also being
recorded under the influence of irradiation. Consequently, a photocurrent is
produced, which is caused by a conduction band, as in graphite.
The close structural relationship between the aromatic polynuclear fullerenes
and graphite is well expressed by the colour, the EPR signal, the electrical
conductivity, and the sensitivity to oxygen. As a matter of fact graphite can
be considered the most highly condensed aromatic system, or the prototype of
aromatic compounds and this
justifies its position as a
“polymer” of benzene. From an electrical point of view, the differences
between conducting polymers and graphite like compounds are to be ascertained.
The relation between colour, molecular weight, and conducibility is not known.
A new class of carbon compounds obtainable from laser vaporization of graphite
can be listed: fullerenes  (from C60 to C158 so far
obtained) are good conductors in a doped state. C60 has a beautiful
magenta colour whereas C580 is, from a theoretical point of view,
expected to be black.
It is of interest to note that: «it was shown that some of the black dust
clouds of the Milky Way Galaxy were full of long carbon chain molecules (the
polyynes). Not only was HC5N detected but subsequently, the even
longer chains HC7N and HC9N were discovered. The
discovery of fullerenes was an
important breakthrough in our knowlege of the carbon content of space. The
fullerenes come from the Giant Red Stars which produce large quantities of
“carbon molecules” and carbon dust. The prototype C60, the most
studied of the fullerenes is a polyhedral cage with pentagonal and hexagonal
faces. The well studied poly (p.phenylene)
which shows different colours, shades of black, good conducibility in a
doped state presenting all the structural features of Little’s model.
Pyrroleblack is a good semiconductor in the doped state [2, 4], for which a
linear and planar chain structure, linked through the 2,5-positions of the
heterocyclic ring, is generally accepted. This structure was confirmed by the
isolation of pyrrole acids (during oxydation with KMn O4 )like
other blacks, pyrrole black gives a strong EPR signal and contains cationic
centres with counteranions. Is after melanin, according to Pullman , is one
other similar case of a “bonding empty orbital” the biliverdin, a
metabolic degradation product of hemoglobin, Bile pigments
must be considered, for their structure and properties, candidates for
conductivity and superconductivity. The inverse, namely the transformation of
a bile pigment into a porphyrin, was accomplished treating the bis-iminoether
of bilirubin diethylester with cobalt or nickel salts, yielding the cyclic
the purple ink of the sea-hare Aplysia the biline
derivative aplysioviolin is present. The uroporphynin I was found in
the integument , whereas the giant neurons of Aplysia are coloured by
biline derivatives. Some of those pigments are expected to be conductors or
candidates for conduction.
It would be obvious at this point to think of fish producing electrical
current (torpedo, electrophoros, astroscopus, malapterus etc.): but no
knowledge of conducting polymers is found in the literature . The melanins are
often considered macromolecules made up by the crosslinked skeleton of the
monomeric melanogens with a variable number of non-localized free electrons
and positive charges, diluted along the surface of the polymer and balanced by
counteranion spectators. This structure has some structural and functional
analogies with acetylene-black , which can be considered a simple
unsubstituted melanin. All indole polymers and derivatives are Little’s
structures and therefore must be considered as conductors or candidates for
Neuromelanin has been recorded to be originated from dopamine and
cysteinyldopamine, through a mixed enzymatic and non enzymatic oxidative
process, catalyzed by Fe and other redox metal ions present in substantia
nigra. Neuromelanin appears to be associated with the bioelectrical
activity of neurons, with the degeneration of the substantia nigra and
conducted on the melanins have, to date, not given satisfactory results (Link
This state has been reached for two main reasons: the first is that Biology,
Chemistry and Physics have developed in unidirectional and unidisciplinary
ways; the second is the ignorance of the fact that almost all natural black
pigments are amorphous semiconductors which in nature are formed by
fluctuating radical processes and
not by enzymatic processes.
a previous work on biochromes we hypothesised, on the basis of experimental
data and theories expressed in the literature, that many natural pigments owe
their colour to electronic transitions in band materials (www.organicsemiconductors.com).
Our working hypothesis is that all black pigments, both synthetic and natural
(melanin), belong to the organic solid state. The pigments are characterised
by the colours black, blue black, matt black, pitch black, brown black, copper
black, bronze black, gold black, metallic black being those of the pure
semiconductor. While the colours of the pure semiconductors are well defined
in terms of the amplitude of the gap the situation is not as clear for the
amorphous semiconductors where the “colours” black, brown, brown-red
predominate. The colours of the amorphous semiconductors are often seen in
hair and body hair of various mammals . These pigments although not pure have
characteristic properties of the amorphous semiconductors:
weak electrical activity(10-11 – 10-7 W-1cm-1)
at the limit of the insulating state. The conductivity is increased by doping,
by the type of counteranion, by the formation of charge transfer complexes,
methods of synthesis and purification used, by light and temperature.
A stable EPR signal
The phenomenon of threshold switching
The photovoltaic effect
can the electroactive material be ‘a priori’ synthesised? In order to plan
the synthesis, especially concerning the superconductor material at high TC
(critical temperature of transition from semiconductor to superconductor) the
following characteristics must be considered:
stable free radical
obtain band overlaps; small HOMO-LUMO gap, large band widths
delocalized molecular orbitals
not homogeneous charge and spin distribution.
segregated stacks or sheets of radical species.
no periodic distortion which yields a gas in the density of states
across the entire Fermi surface
molecular components of appropriate size
fractional charge transfer
strong interchain coupling
polarization species to help to reduce U.
conductivity of melanin in its natural state is rather poor but what can
influence the electrical conductivity may be the presence of foreign
substances or metals (doping effect ) or
a proteic part which is difficult to dislodge from the complex. It is also to
remember that heating modifies planarity of the system (hydrogen bonds and
conductivity). In melanins iron is always found as well as other metals such
as Zn and Cu; the latter is part of the tyrosinase but it is found in the
premelanosome and in the melanosome in much smaller quantitles than Fe. The
presence of iron suggests that the radical process is triggered by a
peroxidase/H202 system or by a Fenton reactive system.
The process of melanogenesis is a fluctuating process which transforms a
colourless insulating compound into a black conducting material or into an
amorphous semiconducting material. In the course of the process there is a
dramatic moment of transformation of the orbital transition colour into
colours of the electronic transitions of band materials, the transformation of
the molecular state into the solid state, the transformation of the molecular
biology into the biology of the solid state. Theoretically based on the
existing relationship between conductivity and the number of double bonds, on
the limiting number of indole units seen with MALDI-TOF-MS the transformation
could occur when there are about 30—40 linked double bonds of the polymer
present. These compounds for polymerization yield black products which are
electronic conductors, especially when doped. This was also the first attempt
to represent the organlc amorphous solid state. The electronic structure of
the amorphous solids can be written in terms of bands of energy and prohibited
intervals as for the crystals, microcristalline structures, and highly
repetitive and stereospecific polymers. The electronic, magnetic, optical,
structural properties which interest the organic state are not molecular
properties but are, rather, associated with intermolecular interactions.
Blacks such as graphite, aspergillin and Daldinia-melanin belong, as
shall be shown later, to polycondensed benzene systems which when doped, are
electrical conductors. The fullerenes (or melanins from space) also belong to
polycondensed systems. There is a relationship between colour, the number of
double bonds (length of the Little spine) and electrical conductivity
Our knowledye of the organic polymers were, until a short time ago,
considered to be insulators. The relation between the structure of a polymer
and its ability to transport electrical charge is still today limited by
technological interests, and therefore is based on data which are not
altogether satisfactory for the study of structure. In a previous work (Nicolaus,
B.J.R., et al., 1997) we tried to find a relationship between the structure of
a natural organic compound and its conductivity. The use of the theory of
orbitals is often mixed up with band theory without major errors. In a
polyenic chain the n-electrons are delocalized and this tends to make all the
-C-C- links of equal length. This is seen in the polymers of type:
where the conductivity
increases wlth the increase in the number of double bonds. Melanin-like
polymers with conjugated double bonds (melanins) are, in general, poor
conductors unless appropriately doped. Melanin-like polymers with
conjugated double bonds are, in general, poor conductors unless appropriately
doped. The crystalline ® amorphous transformation is observable with UV, IR, EPR
spectra which, with the increase in polymer length, tend to become broad
spectra. The conductivity is seen to vary between the crystalline oligomers to
the amorphous oligomers. The electronic structure of the amorphous
semiconductors is still describable in terms of bands of energy and prohibited
rare series of black cristalline products of the charge transfer
complex class derived from ethylenedioxyethylenedlthiotetrathiafulvalene (EDOEDTTTF),
ethylenedloxymethylenedithlotetrathiafulvalene (EDOMDTTTF) , ethylenedioxyvinylenedithiotetrathlafulvalene
(EDOVLITTTF), methylenedlthlotetra-thiafulvalene (MDTTTF). These complex salts
present interesting crystallographic properties and electrlcal activity as
semiconductors, conductors and superconductors.
In the pyrrole series
the homologues yield blacks which conduct electrical current. The indole and
the methylindole yield blacks which conduct electrical current. Several
homologous polymers obtained from DHI are reported in the literature. Direct
measurement of the electrical conductivity of the natural melanins has been
undertaken from 1982. Even though the number of the melanins examined is
small, the conductivity of all the “black polymers” is rather low, in the
sense that they are at the limit of the isolators. Besides, it is seen that
there is not a great diference between the synthetic melanins and the natural
melanins. The polymers, if doped, can give materials which conduct electrical
current well, while for the melanins the same operation of doping has not been
made. It remains, however, to consider that the low values for conductivity of
the melanins may be found in the non-optimal methods of preparation and
methods of purification used. It was also observed that melanins modify slowly
in alkali giving rise to two parts which are optically different. The research
on the electrical activity has shown properties new to the melanins or perhaps
discovered new properties of biological interest for the pigment, until now
considered, among other things, biological garbage. Conductivity measurements
have been carried out on skin pigment, the electrical properties of amorphous
semiconductor melanosome have been studied throughout melanogenesis. The
presence of long-lasting current was observed in the study of catechol-melanin
in the temperature range -200C and 350C (Ozak, W., et
al., 1987). Natural and synthetic melanins have been studied with optical
absorption and their photoconductivity measured in the interval 200-700 nm.
Both the photoconductivity and the optical absorption increase in the
ultraviolet region while a negative photoconduction is observed with a maximum
at about 500 nm. These results are in agreement with the band theory for
Charge Transfer Complexes
complexes, already recognised in the l9th century, have obtained new notoriety
with the discovery of the complex obtained between tetra-cyanoquinodimethane
TCNQ and tetrathiofulvalene which has a metallic type conductivity
comparable or better than graphite . From a theoretical point of view, melanin
would be an optimal partner of the charge transfer complex. DOPA-melanln
oxidises NADH and also in part NADPH, reduces potassium ferricyanide, 2,
6-dichlorophenol, indolephenol (DCPIP), the
cytochrome C . Melanins from different sources and neuromelanins
possess the same properties of “electron transfer complexes” as does the
dopa-melanin. This would seem to indicate that the melanin can be reversibly
oxidised by ferricyanide and reduced by NADH. Sepia and hair melanin are used
to form charge transfer complexes between chlorpromazine (electron donor) and
melanin (electron acceptor). Testing of the complex can be undertaken by
forming pills from the components (the conductivity must be higher than that
of the single parts), or in solution by conductimetric titration . The
formation of the charge transfer complexes observable in solvents can be
carried out, before or after.
irradiation. EPR, UV, IR spectrometry and NMR can be used to establish the
occurrence of formation of charge transfer complexes. Although there is a well
known affinity between the melanins for organic molecules and ions
the results of the study of the charge transfer complexes, electrical
and bioelectrical measurements have, been scarse, so far. For some time it has
been known that melanin is a “threshold switching” amorphous
semiconductor. Until recently it had been thought that these properties were
only common to inorganic materials. “Threshold switching measurements of
synthetic melanin show that the organic semiconductor switches to a
low-resistance state in low electric fields”.
Isolation of pyrrole acids from oxidation products of sepiomelanin:
of pyrrolic acids from the oxidation products of sepiomelanin (10 g) was
carried out using 36 % hydrogen peroxide (250 ml) in acetic acid (250 ml) as
the oxidizing agent (Piattelli, Fattorusso Magno, 1962) . After the
reduction of excess oxidant, the solution was concentrated in vacuo to
350 ml, filtered and continuosly extracted with ether (40 hours). The solvent
was removed and the residue dissolved in water (20 ml); the fIltered solution,
after addition of conc. H2SO4 (1 ml), was subjected to
countercurrent distribution (150 stages) between water and ether. Analysis of
the contents of each tube by paper chromatography (ethanol - 33 % NH3 -
water 80: 4: 16) gave the following results:
2-10: one spot Rf = 0.1
13-16: one spot Rf = 0.21
17-22: two spots Rf = 0.21 and 0.51
23-31: one spot Rf = 0.51
35 42: one spot Rf = 0.75
evaporation of the contents of tubes 2-10 left a brown tarry residue (2.25 g),
which was purified by paper chromatography (n-propanol - 33 ~ NH3 -
water 60: 30: 10). The band with Rf = 0.7 thus obtained was eluted with water,
and the eluate evaporated to dryness, giving a brown, partially crystalline
residue (0.68 g). This was again chromatographed in n-butanol - acetic acid-
water 60: 15:25, and the band with Rf = 0.56 eluted with water; paper
electrophoresis (electrolytes: 005 M pyridinium formate and 0.03 M potassium
dihydrogen phosphate) of this solution showed that a small amount of
pyrrole-2,3-dicarboxylic acid and a larger quantity of pyrrole- 2, 3, 4,
5-tetracarboxylic acid were present. The failure to separate these acids in
the preparative chromatograms, run in nbutanol - acetic acid - water
60 :15: 25 (in which their Rf values are different, but rather close), was
probably due to the presence of large amounts of other oxidation
products(sepiomelanic acids). 10% KCL solution (0.5 ml) was added to
the remainder of the eluate (12 ml) containing the two acids; the crystalline
precipitate was collected and recrystallized from water (yield: 37 mg). Ion
exchange on a strongly acidic resin (Dowex 50 W) gave the free acid (31 mg),
which crystallized from dioxan in colourless prisms. This compound decomposes
at high temp. without a sharp m.p.; its identity with pyrrole-2, 3, 4,
5-tetracarboxylic acid was shown by its infrared spectrum, by paper
chromatography (ethanol - 33 % NH3 - water 80: 4 :16:
= 0.1; n-propanol - 33 % NH3 - water 60: 30 :10: Rf = 0.07; n-butanol
- acetic acid - water 60 :15: 25: Rf = 0.57) and by paper
electrophoresis (0.05 M pyridinium formate and 0.03 M potassium dihydrogen
phosphate). The combined mother liquors, obtained after precipitation and
crystallization of the salt of pyrrole- 2, 3, 4, 5-tetracarboxylic acid
, were passed through a column of cation exchange resin; 58 mg of residue were
obtained after evaporation to dryness. This material was further purified by
paper chromatography in n-butanol - acetic acid - water 60 :15: 25. Two
bands of rather close Rf values were obtained from the upper band (Rf = 0.68),
an additional 30 mg of pyrrole-2, 3, 4, 5-tetra- carboxylic acid (identified
as above) was isolated (total yield of pyrroie-2, 3, 4, 5-tetracarboxylic acid
= 61 mg). For analysis, a sample was recrystallized from water (Found: C,
18.15 %; N, 4.69 %. C8H3O2N.3H2O
requires C, 18.18 % N, 4.71 %) . A
crystalline material (18 mg) was eluted from the lower band (Rf = 0.62). Paper
electrophoresis showed that it was a mixture of pyrrole-2, 3, 4-tricarboxylic
acid and pyrrole-2, 3, 4, 5-tetracarboxylic acid . Colourless crystals (3.2
mg) were finally isolated by electrophoresis on SS 470 paper (0.05 M
pyridinium formate); this product was identified with pyrrole-2, 3,
4-tricarboxylic acid (8mg) by infrared spectroscopy, chromatography (ethanol -
33 ~ NH3 - water 80: 4 :16: Rf = 0.1; n-propanol - 33 % NH3 - water
60: 30 :10: Rf = 0.07; n-butanol - acetic acid - water 60: 15: 25:Rf =
0.5) and paper electrophoresis (migrational aptitude relative to that of acid
in 0.05 M pyridinium formate: 0.59; in 0.03 M potassium dihydrogen phosphate:
0.48). The residue (450 mg) from tubes 17-31 of the countercurrent
distribution was chromatographed in ethanol - 33 % NH3 -water 80: 4: 16. Two
bands were obtained, the upper of which had a Rf value (0.5) identical with
that of pyrrole2, 3, 5-tricarboxylic acid . From this band, 230 mg of crude
acid were isolated; crystallization from acetic acid gave 200 mg of pure
pyrrole-2, 3, 5-tricarboxylic acid (yield: 2.9%). The second band yielded a
small amount of another unknown product. Pyrrole-2, 3-dicarboxylic acid,
present in tubes 35-42, was further purified by countercurrent distribution
(50 stages) between water and ether and it was estimated that there were 100
the melanins sepiomelaninic acid , the most widely studied, occurs as a Ca and
Mg sal in the ink gland of Sepia officinalis The polymeric material
belongs probably to the cyclodopa-melanin group
and is considered an amorphous semiconductor. Already in ancient times,
the ink gland of cephalopods was recognized as being an excellent source of
melanin, as well as a good tool of investigating its natural process, called
melanogenesis. Several studies were made on this interesting issue some years
ago: accordingly, the ink resulted to be composed of melanin granules,
further cellular constituents and degraded oligomers.( See Link 12
allomelanins must include Daldinia-melanin, Ustilago-melanin , humic
acids , aspergillin . This latter is particularly interesting because
oxidative degradation produces the same acid which can be obtained from
graphite: mellitic acid. In other words it may be the case that aspergillin is
a “graphite” synthesized by a living organism. Aspergillin is a pigment
which gives Aspergillus niger its characteristic dark colour. The
typical coloration of the conida constitutes the fundamental distinctive
character of numerous species. The appearance of the pigment in the spores is
at first yellow-ish, becoming green-yellow, green-grey, brown-black. These
“colours” are typical of the amorphous semiconductors. The oxygen in this
synthesis plays a special role next to the iron in that the quantization of
the chemical elements can lead to a gold—yellow pigment. The IR spectrum in
the molecular phase is very similar to that of humic acids. The band theory
may be extended to these amorphous semiconductors with polycondensed nuclei.
The pigment is purified dissolving in NH4OH 5% (solubility 1g per
1000 cc) and reprecipitated with HC1 2N, washing with H2O,
dissolved again in NH4OH 5% reprecipitated with H2S04.
The dissolving in NH4OH and the precipitation with H2SO4
are carried out several times. The insoluble fractions are discarded. The
final product is washed with H20, alcol, acetone, H2O.
The wet product is dissolved in water . The solution is used for measuring the
conductivity (difference between conductivity of the solution and of distilled
water) both in solution and in the solid state. The mass spectrometry (MALDI-TOF-MS)
was not used.
of aspergillin gives C%=52.7 H%4,0 N%=3.4 0%=36.0 . Nitrogen may be
part of a protein. Aspergillin oxidised with H2O2 10%
yields mellitic acid (1 g from 4 g of pigment) and oxalic acid; reduced with
N. Raney it yields perylene next to hydroderivatives, phenanthrene and
napthalene derivatives. These degradation products are precious elements for
MALDI—TOF-MS and, in general, in mass spectrometry studies. Asperglliln can
be dissolved both for measurement of the electrical conductivity (perylene
itself is a good conductor if doped) and for mass spectrometry studies.
spectrometry has only recently become a precious weapon in the study of some
polymers. It allows the establishment of the structure of proteins,
polysaccarids and biopolymers in general. The determination of terminal
groups, molecular weight, of the oligomers, direct determination of the
sequence and distribution of the copolymers are performed by MS. No
results on “ melanin
molecular weight “were obtained in our BCM and BSM studies (unpublished
results),Melanin do not have a ionic
or molecular mass. It also seems that MALDI-TOF-MS (Matrix Assisted Laser
Desorption Ionization - Time of flight Mass Spectrometry) or other
variants of mass spectrometry together with chemical degradation products can
reach a correct analysis of some polymers, a fact not easy until today. A
systematic study of the natural and synthetic melanins, applying mass
spectrometry, has been underway at Padova since 1985. The possibility that in
conducting polymers besides stable unpaired electrons there are positive
centres associated with counteranions has not been considered For the first
time it has been possible to identify the o.quinone of the dopamine, the
aminochrome, the semiquinone, classical intermediates in melanogenesis.
structural study of tryptophane- melanins allows identification of degradation
products such as toluene, ethylbenzene, styrene, indole, methylindole, phenol,
cresol, methylpyrrole, indolin-2-one. These demolition products are precious
elements for further structural and analytical investigation but more complexe
intermediates were not seen The MALDI method has also been used for
determination of the molecular weight of the melanins which appears to be very
much lower that expected. The determined masses oscillate between 500 —
1,500 (sometimes with a 35,000 peak) showing that they concern mainly mixtures
of oligomers, proteic materials, oxidative fission and photolysis products,
simple and complex salts and clatrates. The melanogenesis of
5,6-dihydroxytryptamine (5,6-DHT) and 5,7-dihydroxytryptamine (5,7-DHT) , one of the most important neurotoxins derived from the
metabolism of serotonine, has
A system with
many conjugated double bonds (Little spine), in different experimental
conditions, tends to transform into black products. The chain of conjugated
double bonds may be part of linear or polycondensed benzene or heterocyclic
systems. The black material belongs to the organic solid state and gives a
broad EPR signal in the region of 2,0005 G, being an electrical conductor if
doped. It shows the phenomenon of threshold switching, good conductivity as
charge transfer complexes. The colour of these materials is due to electronic
transitions in materials with band structure. Interesting amorphous
semiconductors ( BSM ) are pyrrole-black, acetylene-black, aniline-black All
these blacks are good conductors, especially when doped. For benzene black we
know linear polymers, polymers with condensed nuclei and mixed polymers. The
grade of polymerization, both linear and condensed, which precedes the
transformation of the molecular state to
solid state is defined at about 30-40 double bonds.
produce,like other black particle an explosion. The fragments so obtained are
useful in the study of oligomers structure .
( Link 12 ) (
Link 21) ( Link
22) . Peculiar is the binding capacity for gases,liquids,solids,
Collection of papers to put into the text
Works on melanins,
melanogenesis and fluctuating systems
A.Quilico, I pigmenti neri animali e vegetali, Ed. Fusi, Pavia 1937.
R.H.Thomson, Melanins, Comparative Biochemistry, Ed. M.Florkin, H.S.Mason,
AP. 727 (1962)
R.A.Nicolaus, Melanins, Hermann, Paris 1968.
G.Prota, Melanins and melanogenesis, AP, (1992).
P.Manzelli, M.G.Costa, Il tempo
come coordinata: gli studi di Giorgio Piccardi (1895-1972). Congress Nazionale
di Storia e Fondamenti della Chimica, Perugia 27 Nov. 1993. This
work should be read with some criticism.
G.A.Swan, Structure, chemistry and biosynthesis of the Melanins. In
Fortschritte der chemie Organische Naturstoffe, Eds. W.Hertz, H.Grisenbach,
G.W.Kirby. Vol. XXXI 522-582, Springer Verlag, Wein (1974).
D.L.Fox, Animal Biochromes, University Californiana Press (1976), Berkely.
R.A.Nicolaus, Melanine, Quaderni Accademia Pontaniana n. 4, Ed.
Giannini, Napoli, 1984.
1). M. Thomas (1955), Modern Methods of Plant Analysis, Vol.4, pag
661-675. Eds K. Paech, M.V.Tracey, Springen Ferlag Berlin.
2). H.S. Mason (1955) "Melanins" Advances in Enzymology,
3). H.S. Mason, (1957) "Melanins" Advances in Enzymology
4). R.H. Thomson (1957) "Naturally Occuring Quinones"
5). H.S. Mason (1959) "Structure of Melanins" in Pigment
cell Biology, Ed. M. Gordon AP New York Pag. 563-583.
6). R.H. Thomson (1962) "Melanins" 727-754, Comparative
Biochemistry Vol. III, AP, New York and London.
7). R.H. Thomson (1962) "Some Naturally occurring black pigments"
in Chemistry of natural and synthetic colouring matters and related fields AP,
New York 99-113.
8). G.A. Swan (1963) "Chemical Structure of Melanins"
1005-1016, Annals of the New York Academy of Sciences Vol. 100.
9). G.A. Swan (1964) "Some Studies on the formation and Structure
of Melanins" 1-20, Rend.Acc.Sci.Fis.Mat. XXXI. Napoli.
10). G.A. Swan (1974) "Structure, Chemistry and biosynthesis of
the melanins", 522-528 in Fortschritte der Chemie Organischer
Naturstoffe Vol. 31 Springer-Verlag, Wien.
10a). R:A.Nicolaus ‘’
The chromatographic study of pyrrolic acids arising from oxidative degradation
of natural pigments ‘’
Rassegna di medicina sperimentale VII, 1-23, 1960.
10b). R.A.Nicolaus ‘’
Biogenesis of melanin ‘’
Rassegna di medicina sperimentale IX,Suppl.1,1-32, 1962
10c). M.Rolland ‘’
Oxidation des restes de tyrosine des proteines par la polyphenolxidase
‘’ These 30/XI/1962 n° 108,
Facultè des Sciences, Universitè D’Aix-Marseille.
10d). R.A.Nicolaus,M.Piattelli, ‘’
Progress in the chemistry of natural black pigments ‘’
Rend.Acc.Sci.Fis.Mat., XXXII, 1-17, 1965.
‘’ Chimica delle
melanine naturali ‘’
( Conferenza alla Sezione Lombarda della Società Chimica Italiana,
Milano 27 Ottobre,1965 ) , Chimica ed Industria, 48, 341-347, 1966.
Recent reviews on melanin
11). G. Prota (1988) "Progress in the Chemistry of Melanins and
related metabolites" Medicinal Research Reviews 8, 525-556.
12). G. Prota (1988) "Some new aspects of melanin chemistry"
Advances in pigment Cell Research, (J.T. Bagnara Ed), 101-124, A. Liss, New
13). G. Prota (1989) "Melanins and pigmentation Coenzymes and
cofactors" (D. Dolphin R.Paulson, O. Abramovic eds) Vol 3, 441-466,
J. Wiley, New York.
14). G. Prota (1992) "Melanins and Melanogenesis" AP,
San Diego pp.1-290
15). G. Prota (1993) "Melanins and related metabolites"
in Black Skin, W. Montagna, G. Prota, J.Kenney, pp. 73-99
16). G. Prota (1995) "The Chemistry of melanins and Melanogenesis"
Org. Nat. Prod. Eds. W. Herz, G.W. Kirby, R.E. Moore, W. Steglich, Ch. Tamm.
pp 94-148 Springer- Verlag, Wien and New York.
17). R.A. Nicolaus, G.
Scherillo (1995) "La Melanina un riesame su struttura, propietà e
sistemi" Atti Accademia Pontaniana Vol. XLIV
18). B.J. Nicolaus, R.A. Nicolaus (1996) "Speculating on the Band
Colours in Nature" Atti Accademia Pontaniana Vol. XLV pp. 365-385
19). R.A. Nicolaus (1997) "Coloured organic semiconductors:
melanins" Rend.Acc.Sci. Fis. Napoli LXIV, 325-360
20). P.A. Riley (1997) "Melanin" Int.J.Biochem, Cell
Biol. 29, 1235-1239.
21). P.A. Riley (1997) "Epidermal melanin: Sun screen or waste
disposal ?" Biologist 44, 408-4.
22). G. Nicolaus, R. A. Nicolaus (1999) "Melanins, Cosmoids,
Fullerenes" Rend. Acc. Sci. Fis. Mat. Napoli Vol. LXVI, 131- 158.
23). G. Prota (2000) "Melanins, Melanogenesis and melanocytes:
Looking at their functional significance from the Chemist's viewpoint"
Pigment Cell Res. 13 283-293
A social event of melanin Chemistry.
24). R.A. Nicolaus, G.
Parisi (2000) "The Nature of Animal Blacks" Atti Accademia
Pontaniana, Napoli Vol. XLIX, 197-233.
25). A. Bolognese, R.A.
Nicolaus (2001) "Natural Black Conductors" Atti Accademia
Pontaniana, Vol. L, 210- 224.
28). R.A.Nicolaus ‘’
Le melanine del cosmo ‘’
Rend.Acc.Sci.Fis. LXIV, 1-2, 1999
B.J.R.Nicolaus, R.A.Nicolaus, M.Olivieri
‘’ Riflessioni sulla
materia nera interstellare ‘’ Rend.Acc.Sci.Fis.Mat. LXVI,110-129, 1999.
B.J.R.Nicolaus, R.A.Nicolaus ‘’
Lo scrigno oscuro della vita ‘’
Atti Accademia Pontaniana , XLVIII, 355-380, 2000.
‘’ Divagazioni sulla
struttura a bande del colore in natura :
il nero ‘’
32). R.A.Nicolaus ‘’ Maldi mass spectrometry and melanins ‘’ Rend.Acc.Sci.Fis.Mat.
LXIV, 315-324, 1997.
‘’ Melanogenesis as
the basis for melanoma targeting ‘’
1-48, AUU,,Uppsala 1998.
34). R.A.Nicolaus ‘’ The
chemistry of interstellar black matter ‘’
Atti Accademia Pontaniana, CB, XLVIII, 486-42000
‘’ Le melanine.Soluzione dell’enigma chimico : prospettive in biologia’’
Atti Accademia Pontaniana CB, XLIX, 304-306, 2001.
A.Bolognese, R.A.Nicolaus ‘’
About the structure of sepiomelanin
‘’ Atti Accademia
Pontaniana CB, 309-312 , 2001.
A.Bolognese,R.A.Nicolaus ‘’ Nero
di Adrenalina ‘’ Atti Accademia Pontaniana CB, L, 391-393, 2002.
Conduttori biologici neri ‘’
Atti Accademia Pontaniana CB,
39). R.A.Nicolaus,A.Bolognese, B.Nicolaus
‘’ The pigment cell
and its biogenesis ‘’
Atti Accademia Pontaniana, L,
Chemical studies on natural melanins and in particular on sepiomelanin.
L.Panizzi, R.Nicolaus - Ricerche sulle melanine. I. Sulla melanina
di seppia. Report of Scienze Fisiche, Matematiche e Naturali della
Accademia dei Lincei, Serie VIII, Vol. XII, 420 (1952)
R.Nicolaus - Ricerche sulle melanine. Nota I. Sulla melanina di seppia.
Chem. Ital., 82, 435 (1952);
R.A.Nicolaus - The structure of melanins and melanogenesis. I. The
structure of melanin in Sepia. Tetrahedron, 15, 66 (1961);
E.Fattorusso, S.Magno, R.A.Nicolaus - The structure of melanins and
melanogenesis. II. Sepiomelanin and synthetic pigments. Tetrahedron, Vol.
18, 941 (1962);
E.Fattorusso, S.Magno, R.A.Nicolaus - The structure of melanins and
melanogenesis. III. The structure of sepiomelanin. Tetrahedron, Vol. 19,
f) M.Piattelli, E.Fattorusso, S.Magno,
R.A.Nicolaus - The structure of melanins and melanogenesis. IV. On some
natural melanins. Ibidem, Vol. 20, 1136 (1964).
g) E.Fattorusso, M.Piattelli, R.A.Nicolaus,
S.Magno - The structure of melanins and melanogenesis. V. Ustilago-melanin.
Tetrahedron, Vol. 21, 3229 (1965);
R.A.Nicolaus - Biogenesis of melanins. Rassegna di Medicina Sperimentale, Anno IX, Supplemento N°1, Ed.
V.Idelson, Napoli (1962).
- Contribution à l’analyse quantitative des mèlanines. Application
comparée de mètodes de caractérisation et de degradaation oxidative à la
melanine de l’encre de seiche, à la melanine de l’iris de boeuf et à la
dopa-melanine. PhD thesis presented to the Faculté des Sciences de
l’Université de Lausanne, Thesis supervisor Prof. H.Wyler, Imprivite S.A.,
A.Dall’Olio, G.D’Ascola, V.Varacca, V.Bocchi, Resonance
paramagnetique electronique et conductivité d’un noir d’oxypyrrole électrolytique,
presentée par M. René Lucas, Comptes Rendues Academie Scientifique, Paris, 267
S.Jasne in Encyclopedia of Polymer Science and Engineering, II Edition,
Vol. 13 Polypyrroles 42 (1985).
G.P.Gardini, A.Berlin, I polimeri conduttori, Chimica e
Industria 73 764 (1991).
A.Pullman, B.Pullman, The Band structure of Melanins, Biochim.
Biophys. Acta 54 384 (1961).
Humic acids and melanins produced by microrganisms
a). M.M.Kononova, Soil Organic Matter,
Permagon Press 1961.
b). M.H.B.Hayes, P.MacCarty, R.L.MacColm,
R.S.Swift, Humic Substances, Wiley 1989.
c). S.P.Liach, E.L.Ruban, Microbnye Melaniny,
SSSR, Institut Mikzobiologii, Izd. Nauka 1-86, Moskova 1972.
d). A.A.Bell et al., Tetrahedron 32 1353
e). Ciny Lee et al., Organic Matter in Sea
Water Biogeochemical Processes, Chemical Oceanographiic, V. 9 1-49 (1989),
Ed. Riley, Accademic Press.
Substances able to give black or brown composites
by chemical or enzymatic oxidation are called melanogens. A melanogen can
produces red-brown, red, orange, yellow and rarely green "pigment".
The pigments have an EPR signal and are all potential electrical and sound
S.Roy, A.K.Chakraborty, .D.P.Chakraborty, Melanin formation and
breakdown of Indole under Underfriend conditions, J. Chem. Soc. 58
G.Cimino, S.De Rosa, S.De Stefano, A.Spinella, G.Sodano, The Zoochrome
of the Sponge Verongia Aerophoba (Uranidine), Tetrahedron Letters 25
G.Natta, G.Mazzanti, P.Corradini,
Polimerizzazione stereospecifica dell’acetilene, Rendiconti Accademia
dei Lincei, XXV (1958); J.D.Bu’Lock, Quart. Revs.
(London), 10 371 (1956).
L.Horner, K.Sturm, Modellreaktion zur Melaninbildung, Liebigs Ann.
Chem. 608 128 (1957).
B.Schmidli, Über Melanine, die dunklen Haut und Haarpigmente, Helv. Chim.
Acta XXXVIII 1078 (1955). (prepares melanin from hystidine, hystamine,
carnpsine, DOPA; tyrosine, phenol, phenylalanine, pyrrol, tyramine and melanin
from hair. Spearation by column chromatography)
P.A.Wehrli, F.Pigott, U.Fischer, A.Kaiser, Oxidations produkte von
6-hydroxy-dopamine, Helv. Chim. Acta LV 3057 (1972); R.J.S.Beer,
T.Broadhurst, A.Robertson, The Chemistry of Melanins. Part V. The
autoxidation of 5,6-dihydroxyindoles, J. Chem. Soc. 1947 (1954).
The melanogenetic properties of tryptophane and its derivatives have been
the object of extensive studies by L.Musajo and his School of Padova. Some
works which concern this partial literature are presented here.
E.M.Nicholls, K.Rienits, Marsupial pigpents, in Pigment Cell,
Mechanism in Pigmentation, Vol. 1, pag. 142. Ed. McGovern, Russel, Riley
S.Karger Basel 1973; A.Bolognese, C.Piscitelli,
G.Scherillo, Formation of
dihydro and dihydroisotriphenodioxazines by acidic treatment of some
substituted 3H-phenoxazin-3-ones: isolation and characterization. A new
perspective in the chemistrry of ommochromes. J. Org. Chem., 48, 3649
(1983); A.Bolognese, R.Liberatore, G.Riente, G.Schirillo, Oxidation of
3-hydroxykynurenine. A reexamination. J.
Heterocyclic Chem., 25, 1247 (1988).
m) T.Uemura, T.Shimazu, R.Miura, T.Yamano, NADPH dependent melanin
pigment formation from 5-hydroxyindolealkalamines by hepatic and cerebral
microsomes, Biochem. Biophys. Res. Comm. 93 1074 (1980).
n) F.Celentano, Luce, colore e materia, Le Scienze n. 21, Feb 1985, Milano 1985.
J.Itten, Arte e colore, Il Saggiatore, Milano 1965.
o) Green is rarely represented. We may recall
emeraldine chlodhydrate (3, c) and biverdina (B.Pullman, M.Perault, Proc. Nat.
Acad. Sci. U.S. 45 1476 (1959).
Radicals and semiconductors
H.C.Longuet-Higgins, On the origin of the free radical properties of
melanins, Arch. Biochem. Biophys. 86 225 (1960);
P.R.Crippa, Electret state and hydrated structure of melanin, Biol.
Biochem. 8 555 (1981);
H.S.Mason, J. Biol. Chem. 172
J.E.McGinness, Mobility gaps: a mechanism for
band gaps in melanin, Science 177 896 (1972);
J.E.McGinness, P.Proctor, The importance of the fact that
melanin is black, J. Theor. Biol. 39 677 (1973); J.E.McGinness,
P.M.Corry, P.Proctor, Amorphous semiconductor switching in melanins,
Science 183 853 (1974)
et al., Biophys. J., 16 1165 (1976).
J. Chem. Soc. (B) 2026 (1971);
G.A.Swan, An Introduction
to the alkaloids, Blackwell Scientific Publications, Oxford and Edinburg
D.H.R.Barton, Proc. Chem.Soc.
293 (1963); R.H.I.Manske, The Alkaloids, AP, New York 1960.
M.R.Chedekel et al., J. Chem. Soc. Chem. Comm. 1170 (1984).
D.S.Galvano, M.J.Caldas, Polymerization
of 5,6-indolequinone: a view into the band structure of melanins, J. Chem.
Phys. 88 4088 (1988); J. Chem. Phys. 93 2848 (1990); J. Chem.
Phys. 92 2630 (1990).
P.H.Sidles, Threshold switching in melanin, J. Appl. Phys. 46
J.E.Wertz, D.C.Reitz, F.Dravnieks, Electron
Spin Resonances Studies of autoxidation of 3,4-dihydroxyphenyl alanine, in
M.S.Blois, H.W.Brown, R.M.Lemmo,, R.O.Lindblom, M.Weiss Bluth, Free Radicals
in Biological Systems, AP 1961.
T.J.Stone, W.A.Waters, J.
Chem. Soc. 213 (1964);
R.H.Thomson, Organic Chemistry of Stable Free Radicals, pp.280-405,AP,
London New York 1968.
M.Rizzotti, G.Succi - Misure di risonanza paramagnetica elettronica su peli
di bovini a diverso mantello. Ibidem, Vol. XIII, 1967 (Milano);
p). M.Rizzotti, R.Striani
Pannelli, G.Aureli, L.Zanotti, G.Succi - Ricerche morfologiche e
istochimiche sulla pelle e biofisiche sui peli di bovini albini. Ibidem,
Vol. XV, 1969 (Milano); H.U.Winzenreid, J.J.Lauvergne, Spontanes Suftreten
von Albinos in der Schweizerischen Braunviehrasse,
Schweizer Archiv. für Tierheilkunde, 112 581 (1970).
M.A.Pathak, in Advances in
Biology of skin, Vol. VII, Ed. W.Montagna, Permagon Press, Oxford and New York
R.A.Nicolaus, Biogenesis of melanins. Rassegna
di Medicina Sperimentale, Anno IX, Supplemento N°1, Ed. V.Idelson, Napoli
K.Nassau, in Le Scienze
quaderni n. 21 February 1985, 59, Milano, 1984.
B.T.Allen, D.J.E.Ingram, The Investigation of Unpaired Electron
Concentration produced in large Molecules by ultraviolet Irradiation, in
Free Radicals in Biological Systems 218, Ed. M.S.Blois, H.W.Brown, R.M.Lemmon,
R.O.Lindborn, M.Weissbluth, AP (1961).
A.Bolognese, R.Bonomi, R.Chillemi, S.Sciuto, Oxidation of
3-hydroxykynurenine. An EPR
investigation, J. Heterocyclic
Chem., 27, 2207 (1990).
G.Elli, A.Bertazzo, C.Costa, G.Allegri, Laser desorption ionization Mass
Spectrometry in the study of Natural and Synthetic Melanins. 1.
Tyrosine Melanins, Biol. Mass Spectrom. 22, 687 (1993).
W.A.Little, Possibility of synthesizing an organic superconductor,
Physical Review 134, A116 (1964).
Conductivity and related papers relevant for pigment cell research.
1) F. London, 1950 "Superfluids", vol. 1, J. Wiley, New
2) Darrow, K.K., (1954). "I semiconduttori". Endeavour XIII, N. 50, pp. 101-106.
3) Commoner, B., Townsend. J., Pake, G., (1954) "Free radicals in
biological materials" Nature 174,689.
4) W.G. Walter (1954) "The electrical activity of the brain"
Scientific American, Published by W.H. Freeman, 660 Market Street, San
Francisco 4, California, USA.
5) Mason, H.S., Fowlks, W.L., Peterson, E., (1995). "Oxygen
transfer and electron transport by the phenolase complex". J.
Am. Soc. 77, 2914-2915.
6) Keynes, R.D., (1956). "La
produzione di elettricità nei pesci". Endeavour
N. 60 pag.215-230.
7) N. Millott (1957)
"La fotosensibilità animale particolarmente nelle forme prive degli
occhi" Endeavour, Vol. XVI, 19-29.
8) J. Bardeen, L. N. Cooper, J. R. Schrieffer, (1957) Phys. Rev., 108,
9) A. Pullman, B. Pullman "The Band Structure of Melanins"
Biochim. Biophyis. Acta 54, 384 (1961); B. Pullman, A. M. Perault, Proc. Natl.
Acad. Sci., USA, 45, 1496/1497 (1959).
10) N.B. Hannay (1959) "Semiconductor" pag. 551,
Rheinold, New York.
11) K.Herzfeld, T.A Lictowitz (1959) "Absorption and dispersion
of ultrasonic waves" AP, New York.
12) P.George, J.S. Griffith (1960) "Electron trasfer and Enzyme
Catalysis" John Harrison Laboratory of Chemistry, University of
Pennsylvania, Philadelphia, and Department of Theoretical Chemistry, The
University of Cambridge, Cambridge, England.
13) Mason, H.S., Ingram, D.J.E; Allen, B., (1960). "The free
radical property of melanins". Arch. Biochem. Biophys. 83,
14) Longuet-Higgins, H.C., (1960). "On
the origin of the free radical properties of melanins". Arch.
Biochem. Biophys. 86,
15) R.O. Becker (1961) "Search for evidence of Axial Current Flow
in Peripheral Nerves of Salamander" Science, 134, 101-102.
16) E.P. Wigner, "The logic of personal knowledge", pag.
231, (Rouledge Routledge and Kegan Paul, London 1961).
17) Allen, B.T., Ingram, D.J.E., (1961) "The investigation of the
umpaired electron concentrations produced in large molecules by ultraviolet
irradiation" in Blois, Brown, Lemmon, Lindblom, Weinbluth "Free
Radicals in biological systems" 211, AP, New York.
19) R. Fujii, (1961) "Demonstration of the Andrenergic Nature of
Trasmission of the junction between Melanophore-concentrating nerve and
Melanophore in Bony Fish", J. Faculty of Science 9, 171-196.
University of Tokio.
20) E.A. Lynton (1962) "Supercondutivity" J. Wiley New
21) Cope, F.W., Sever, R.J., Polis, B.D., (1963) "Reversible free
radical generation in the melanin granules of the eye by visible light"
Arch. Biochem. Biophys. 100, 171-177.
22) B. Pullmann (1963) "Sur la biogenese des melanins"
BBA, 66, 164-165.
23) W.A. Little (1964) "Possibility of synthesing an organic superconductor" Phys. Rev. 134, A1417.
24) J.E.Kurler (1964) "I magneti superconduttori" Endeavour XXIII, 115-121.
25) P. Seybold, M. Gouterman (1964) "Radiation Transitions in
Gases and Liquids" 413-433, Conant Chemical Laboratory,
Harvard University, Cambridge Massachusetts 02138.
26) Parks, R.D., (1965). "Quantum effects in superconductors".
Scientific American, 1965 pp. 57-67.
27) Blois, M.S., (1965). "Random polymers as a matrix for
chemical evolution". In: The origins of Prebiological systems, ed.
Fox, S.W., AP, New York pp.19-39.
28) Bassett, C.A.L.,
(1965). "Electrical effects in bone". Scientific American, pp.
29) Bowen, E.J., (1965). "Recent progress in Photobiology".
30) Little, W.A., (1965) "Superconductivity at Room Temperature"
Scientific American 212, pp. 21-27.
31) G. Tollin, C. Steelink. (1966) "Biological Polymers Related
to catechol: electron paramagnetic resonance and infrared studies of melanin,
tannin, lignin humic acid and hydroxyquinone" BBA 112, 377-379.
32) Bolt, A.G., Forrest, I.S., (1966) "Charge-transfer reaction
between melanin and chloropromazine" Paper given at 152 nd ACS
Meetting, New York City.
33) Rabenau, A., (1966),
"I problemi chimici negli studi sui semiconduttori". Endeavour
XXV, pp. 158-165.
34) Pathak, M.A., (1967). "Photobiology of melanogenesis:
Biophysical aspects". In Advances in Biology of Skin (W. Montagna and
F. Hu, eds.), Vol. 8, pp. 397-420. Pergamon Press, Oxford.
35) Mulay, I.L., Mulay, L.N., (1967). "Magnetic susceptibility
and electron spin resonance absorption spectra of mouse melanomas S91and S91A".
J. Natn. Cancer Inst. 39, 735.
36) F.Gutman, L.E. Lyon (1967) "Organic Semiconductors"
Wiley, New York
37) Simmons, J.E., (1968) "Electrical conduction in thin
insulating films" Endeavour XXVII, N. 102, pp 138-143.
38) Pathak, M.A., Stratton, K., (1968). "Free radicals in human
skin before and after exposure to light" Archiv. Biochem. Biophys.
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The full italian version of this paper with figures, R.A.Nicolaus,G.Scherillo '' La Melanina.Un riesame su struttura,proprietà e sistemi '' Atti della Accademia Pontaniana,Vol.XLIV,265-287,Napoli 1995,is available on request.
BCM = black cell
BSM = black synthetic
melanosome whithout enzymatic or chemical activity
dopachrome = a red
solution obtained from tyrosine containing quinones and phenols
Revised September 2003