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ChemistryЧA Central Pillar of Human Culture.

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Essays
Popularization of Chemistry
Chemistry—A Central Pillar of Human Culture**
Sason Shaik*
Keywords:
chemistry didactic · history of science ·
popularization of chemistry
Dedicated to my students of the “second culture”
who taught me that what is useful is not
necessarily also enchanting!
L
This Essay shares with the readers
ittle seems to have changed in the
public image of chemistry and chemists, my own experience of popularizing
since Gabriel-Franois Venel depicted, chemistry by delivering the following
in 1753, in Diderot's Encyclopedia, the universal message of our science, that:
“miserable state of the chemical com- * Chemistry is the window given to
munity” as being “isolated in the midst
Mankind to glimpse into its material
of the greater people hardly curious of
essence.
its business”.[1] We are all painfully It is through its relation to human
aware of the public image of chemis- characteristics such as love, addiction,
try,[2] and its status, in the media, as “the sex, dream, and pleasure, that chemistry
forgotten science”.[2a] Nevertheless, pop- can be appreciated in its above universal
ularization of chemistry[3] remains scant, sense. It is this universality that makes
and chemists themselves regard such chemical knowledge a dictum and an
attempts with ambivalence, if not dis- enchanting story for the layman. Once
dain, as if admitting the verdict that this point is made, it paves the way to the
there is little in their science that can introduction of concepts associated with
“chemical matter” and
enchant the layman.
how structure and interWhile there may be
actions trigger human
difficulties to enchant
traits. Subsequently, a
the
layman
with Chemistry is the winchemistry, popularize dow given to Mankind connection is made between the universal
we must! We just have
to glimpse into its
message of chemistry,
to find new ways to tell
and the system of
the story of “the chem- material essence
thought of alchemists
ical universe” and prowho considered that evject the position of
ery material entity had
chemistry as a central
also a spiritual manifespillar of human culture.
tation and vice versa. The Essay is constructed along these lines, and its con[*] Prof. S. Shaik
tent can serve as an example either for
Department of Organic Chemistry and
The Lise Meitner-Minerva Center for
an introductory lecture in freshmen
Computational Quantum Chemistry
chemistry or a popular-science
Hebrew University
talk to the general public.
91904, Jerusalem (Israel)
Fax: (+ 972) 2-658-4680
E-mail: sason@yfaat.ch.huji.ac.il
[**] This Essay is based on a course given to
students of the humanities & social sciences, and follows the outline of a public
lecture given for the first time in “The
Chemistry Year” (1999). Subsequently, it
has been given each year to freshmen
chemistry students and to audiences of
chemists and other scientists. It is an
example of a successful experience at
popularizing chemistry and is a proposal
for a teaching strategy, and a philosophy.
3208
though the chemical details of the emotional map are not yet worked out, it has
become gradually evident that emotional life is written in an alphabet of
genetically determined patterns and
coded by specific brain chemicals. For
example, a recent discovery[5] reveals
that individuals with different forms
(alleles) of the gene, which encodes the
transporter protein of the brain-chemical serotonin, exhibit different patterns
of activity in the brain's emotional
center, the amygdala. A hyperactive
amygdala is associated with permanent
anxiety even in nonthreatening situations.[5] Indeed, our brains are chemically wired.[6] Some of these neurochemicals are neurotransmitters, others are
neuromdulators that regulate the action
of neurotransmitters, and others include
hormones. These neurochemicals act
sometimes on their own, other times
with neuromodulators and other neurotransmitters, and sometimes by a cascade that leads to secondary molecules,
which transduce the signal to the final
trigger.[6]
Research suggests that the brainchemical
2-phenylethylamine
(1;
PEA;[7, 8] Scheme 1), is a neurotransmitter and neuromodulator of libido and
interpersonal energy;[7a] its administra-
Love, Addiction, Psychological Balance, and More
Pheromones are molecules
that control the “love life” and
all communicative aspects of
insects.[4a] This is true also for
higher organisms, such as mammals;[4b] humans do not seem to
be an exception. Thus, even
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Scheme 1. Molecules of emotion.
DOI: 10.1002/anie.200330038
Angew. Chem. Int. Ed. 2003, 42, 3208 – 3215
Angewandte
Chemie
tion increases emotional warmth, affection, sexuality, and the feeling of physical energy. It was even implicated in the
“runner's high”, which is the feeling of
well-being that accompanies physical
exertion.[9] While PEA may function
together with neurotransmitters (e.g.,
dopamine (2) and serotonin (3),
Scheme 1), its action in the emotional
domain is unique.[7] Recently, it was
discovered[8] that PEA has indeed a
specific receptor located mainly in the
amygdala, the brain's emotional command center. Unique also are the facts
that PEA has a very short lifetime
(minutes), and is degraded by a specific
isoform of the enzyme MAO (monoamine oxygenase), the MAOB isozyme.
The short lifetime suggests that PEA has
a special biodynamic role, possibly associated with excitory effects triggered in a
short space of time. By contrast, other
neuroamines (serotonin (3), noradrenaline (5), and dopamine (2)) have long
lifetimes (hours) and are degraded by
the other isozyme, MAOA.
The effects of PEA on human behavior have led to the hypothesis
(henceforth the “psychochemical hypothesis”) that PEA is associated with
the event of “falling in love”.[10] Even
though this connection is speculative, it
is nevertheless interesting to learn of the
psychochemical hypothesis, since it
might contain some truth considering
the role of PEA in regulating affect.
Walsh[10a] gives a vivid description of the
action of PEA: When we meet someone
who attracts us “the whistle blows at the
PEA factory”. Unlike other mammals
where “falling in love” is triggered by
scent or touch, in humans the main
trigger is sight. A mere glimpse is
required to activate the sensation of
romantic love. This is how the biblical
story of David and Bathsheba begins:
“From the roof he saw a woman bathing.
The woman was very beautiful…”. The
synthesis of PEA, in the brain, and its
relay into the entire nervous system are
implicated in the generation of excitement at the sight of the subject of love,
and the great longing when the lover is
not around.[10a, 11] PEA is also present in
chocolate, Nutrasweet (for which the
main ingredient is aspartame), and diet
soft drinks, and its concentration rises
with smoking of marijuana.[10d] However, all these sources of PEA do not
Angew. Chem. Int. Ed. 2003, 42, 3208 – 3215
produce the kick of the brain-PEA.
They fail to do so, in part because of
their fast degradation by the enzyme
MAOB. Thus, even though PEA can
cross the blood–brain barrier, most of it
would by degraded without the addition
of MAOB blockers.[7] Externally administered love potions may exist in Shakespeare's Midsummer-Night's Dream,
while in reality our chemical system
jealously safeguards the exclusivity of
emotional response.
The psychochemical hypothesis[10]
assigns roles to other neurotransmitters,
which figure in our psychobiological
energy. One such family of neurotransmitters is the endorphins produced in
the hypothalamus, the brain stem, and
the pituitary gland.[12] Endorphins are
neuropeptides (b-endorphin, the most
potent of the known endorphins, contains 31 residues) that serve as natural
painkillers in the body. They act on
specific opiate receptors,[12] to produce
analgesia and create a sense of wellbeing. However, according to the psychochemical hypothesis[10d] they also
play a major role in maintaining durable
relationships. Thus, in the course of time
after falling in love, the body requires
larger doses of PEA to maintain the
same initial kick, and we gradually “fall
out of love”.[10a–c] Had this been the
entire story, love would have consisted
of romance alone. Fortunately, the brain
being a versatile chemist, also makes
endorphins that fix us with durable
partnerships. Thus, whenever we see
our partner, the brain squirts a dose of
endorphin that permeates the entire
body,[10d] which in turn gets imbued by
a sense of security, calm, and well-being.
The sharp, almost physical pain that
accompanies the loss of a loved-one is
thought to be caused by the sudden
arrest of the endorphin mechanism.
PEA is only one of a few neuroamines that act as molecules of the
emotions, which are shown in Scheme 1.
The molecule dopamine (2) is manufactured from tyrosine in the Ventral
tegmental area of the brain and is
released in the frontal cortex. This
molecule is involved in reward-seeking
behavior, learning, drug addiction, and
development of dependencies, including
trained conditioning and willed control.[6c] According to the psychochemical
hypothesis,[10] dopamine regulates the
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desire to pursue pleasure, to seek danger, and is the motivator to achieve and
to desire. With too little dopamine there
is little joy of life, little sense of adventure and experience,[10, 13] while too large
quantities or enhanced dopamine absorption by nerve cells lead to addictive
behavior. It appears now that addictive
behavior is associated with long-term
potentiation (changes) in the synapses
between the neurons, much like in
memory and learning.[6c]
Serotonin (3) is formed (from tryptophan) in the raphe nuclei, deep in the
brain stem,[5] and is then transported to
the nerve endings. It is the “mood
molecule”,[10d] responsible for the psychological balance, and is the innate
antidepressant. Problems in the serotonin cycle are associated with ailments,
such as chronic pain, depression, Alzheimer's diseases, strokes, and Parkinson's disease. Serotonin deficiency is
associated with aggression (including
sexual), depression, schizophrenia, craving for carbohydrates and sweets. Normal levels cause a balanced personality,
while excess is associated with anxiety.
Serotonin can be found in bananas,
tomatoes, and pasta. But again, this
does not mean that eating any one of
these foods increases serotonin levels in
the brain, because of its fast degradation
by the enzyme MAOA.
Adrenaline (4) and noradrenaline
(5) also known as epinephrine and
norepinephrine are shown in Scheme 1).
These are the stress hormones, which
prepare the body for strenuous activity.
Adrenaline, released from the adrenal
medulla, acts to raise the level of glucose
in the blood and thereby provides the
surge of energy needed for performing
demanding tasks or facing dangers.
Noradrenaline is a neurotransmitter,
which is also activated in stressful situations along with adrenaline. However,
it is implicated (in conjunction with
PEA and dopamine) in maintaining
the sensation of vitality and focus. The
molecule 6 (Scheme 1) is a hallucinogenic drug known as mescaline. The
structural similarity of mescaline to the
innate drugs is apparent. It raises
thoughts about the “reality” of emotions, independent of their unique chemical motors.
A neuropeptide that figures in the
psychochemical hypothesis.[10, 14] is oxy-
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Essays
Scheme 2. Molecules of pleasure and well-being.
tocin (7, Scheme 2), a nonapeptide
formed in the pituitary gland. Oxytocin
was one of the first natural peptides to
be synthesized in the laboratory and
thereby demonstrated the chemical origins of psychobiological energy flow. In
humans, oxytocin induces labor near the
end of pregnancy, controls contraction
of the uterine muscles, and stimulates
the flow of milk during suckling. In
laboratory animals, it was established
that oxytocin promotes sexual behavior
and pair bonding. By extrapolation, it
has been proposed[10, 14] that oxytocin is
one of the molecules responsible for
“pair bonding”,[14] and is behind the
human urge to touch, caress, and assure.
One can simply rub the back of one's
neck to feel the pleasing sensation
caused by oxytocin secretion. The sensation gets much stronger when your
partner does it for you, since this is an
evolutionary chemical mechanism of
seeking and getting addicted to “togetherness”. In women, oxytocin is thought
to play additional important roles. During nursing, the surge of oxytocin causes
pleasure and relaxation and thereby
reinforces the mother–child bond. During lovemaking the surge of oxytocin
causes the female's orgasm. Oxytocin
thus regulates our “chemical commitment” and its consequential well-being.
Male's orgasm is geared towards
ejaculation that was recently demonstrated[15] to be chemically triggered and
controlled by a population of spinal
neurons (lumbar spinothalamic (LSt))
and located in the two segments (L3 and
L4) of the lumbar region. These neurons
form part of the spino-thalamic tract
that relay sensory information from the
body to the thalamus area of the brain,
which in turn uses a chemical relay that
results in ejaculation. However ejaculation requires an initial erection, which is
also chemically triggered, by the natural
3210
Viagra, nitric oxide (8; Scheme 2) which
is an important neurotransmitter responsible for the regulation of blood
flow.[16] It is so essential, that a special
enzyme, called nitric oxide synthase
(NOS), exists for the sole purpose of
degrading l-arginine amino acid to
generate NO in the endothelial cells.[16]
The diffusion of NO (and its binding to
the heme of the guanylate cyclase) to
the smooth muscle cells, in the walls of
the penile arteries of the erectable
tissue, causes a cascade of chemical
events, by the end of which the muscle
cells are depleted from Ca2+ ions, the
muscles then relax and thereby enable a
blood flow into the penis and its eventual erection.
Nitric oxide is also involved in the
mechanism of long-term memory (longterm potentiation-LTP) in the hippocampus.[6, 17] In memory, NO acts as a
neuromodulator that helps the l-glutamate receptor, NMDA (N-methyl daspartate), increase the concentration of
Ca2+ ions within the cells. This results in
repetitive firing patterns of the cell,
which is the essence of LTP. One cannot
avoid smiling at the recognition that
erection and memory require opposite
mechanisms of Ca2+ ion flow, outwards
versus inwards.
The artificial compound sildenafil
(9) better known under the trade name
Viagra (Scheme 2), is simple enough to
synthesize that a 2nd year undergraduate student who had completed a laboratory course of chemical synthesis may
be able to produce homemade quantities of this molecule. The molecule
interferes with the mechanism of the
NO-induced Ca2+ ion depletion described above. The excitement caused by
Viagra has barely subsided, and chemists are already utilizing their understanding of the mechanism of the erection-based NO mechanism to synthesize
drugs that are “more than Viagra.”[18]
The love elixir may well be within the
reach of chemistry.
The discovery of the chemical neurotransmission in the late 1950s has led
to a paradigm shift from an “electrical
brain” to a “chemical brain”.[6c,d] Thus, it
is the neurotransmitters that carry the
information flow between nerve cells,
and serve as the means by which the
brain commands and receives information from the body and reacts to exter-
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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nal stimuli. At any given time 100 billion
(100 I 109) nerve cells may be engaged
in this “conversation”, which is conducted by two prototypical mechanisms—
fast ion “firing” and the slow biochemical cascade—and combinations thereof.[6b] Cell communication is an exceedingly rich and fast developing topic that
cannot be elaborated in this popularizing essay.[6, 19] Perhaps the easiest to
illustrate, albeit very briefly, is the mode
of cell communication that is triggered
by a neurotansmitter molecule and
mediated by an electrical impulse (“firing”).
At rest, the nerve cells are segregated by gaps, known as synapses.[19] The
synaptic gap is the “off” position while
the neurotransmitter is responsible for
the “on” position by bridging this gap
and enabling the transmission of the
signal into the cell. The neurotransmitter molecules are stored in sacs in the
nerve endings of a pre-synaptic cell.
When an electrical signal (for example,
a flux of Ca2+ ions) reaches the cell, it
swells and its sacs release the neurotransmitter molecules that cross the gap
and attach themselves to receptors of
the next cell, the post-synaptic cell. The
receptor is an ion channel, made from a
bundle of a few proteins (for example,
NMDA, the receptor of l-glutamate
contains five proteins,[17] while the receptors of the amine neurotransmitters,
in Scheme 1, belong to a special family
of
G-protein
coupled
receptors
(GPCRs) which include seven helices[20]). The attached neurotransmitter
opens the channel by causing a conformational change in the receptor. The
opened channel then allows an ion flux
that causes another neurotransmitter to
cross the synaptic gap, leading another
cell to fire (this may also activate intracellular biochemical pathways, e.g., as in
LTP where persistent changes are induced in the post synaptic cell).
The neurotransmitter molecules,
which completed their job, must then
return to their nerve endings (the transporter cells) by recrossing the synaptic
gap. Otherwise they generate radicals,
by inhibition of superoxide dismutase,
that lead to the death of the cell owing to
its chemical degradation. In the case of
neuroamines, the enzymes MAOA,B degrade any stray neurotransmitter, not on
a receptor or inside a sac in a transporter
Angew. Chem. Int. Ed. 2003, 42, 3208 – 3215
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cell (neurotransmitters are replenished
in the brain by specific biochemical
pathways). A recent exciting discovery
is associated with the mechanisms of
return of serotonin molecules to their
pre-synaptic cells.[5] Serotonin is assisted
to recross the synaptic gap by transporter proteins, which in turn are encoded by a gene that has two forms
(alleles). One of these alleles produces
only about half as much of the transporter protein as the other allele, thus
resulting in a more frequent neurotransmission by the serotonin molecules.[5]
This higher frequency manifests in the
brain as a hyperactive amygdala, and is
associated with the psychological state
of permanent anxiety and fearfulness.
This is a striking connection between
isoforms of a single gene, transportation
efficiency of a single brain chemical, and
different patterns of human response to
emotion-laden stimuli.
The understanding of the chemical
essence of neurotransmission enabled
the synthesis of drugs that function by
homing in on the neurotransmitter. For
example, Prozac (an antidepressant)
homes in on serotonin by blocking the
transporter cell and causing the small
amount of serotonin to go back to the
receptor and induce refiring. Redux (an
anti-obesity drug that has been recently
taken off the market owing to its
undesirable side effects) on the other
hand, homes in on the sacs of the
transporter cell and causes enhanced
transportation of the serotonin. lDOPA can cross the blood–brain barrier
and be converted into dopamine, and is
used for treatment of Parkinson's patients with dopamine deficiency. Recent
results from chemists show that, for
example, acetyl choline and serotonin
attach their positive ends to the receptor
by making a type of a p complex with
the aromatic rings of the amino acids,
Tyr and Trp.[21] Thus, the interaction of
the neurotransmitter with the ion channel of the receptor turns out to be
chemically very specific. Eventually we
may find that these interactions, and
hence also the “emotional” domains of a
given neurotransmitter, are coded in a
manner akin to DNA or to protein
synthesis, though not through hydrogen-bonding interactions.
The above examples, the unfolding
universality of the neurotransmission
Angew. Chem. Int. Ed. 2003, 42, 3208 – 3215
mechanisms in nature, and the recent
establishment of a trinity: gene, neurotransmission and brain patterns, personality traits,[5] indicate that despite the
biocomplexity, in the basis of the most
wondrous human characteristics there
lies fundamental simplicity. An information flow between the unconscious (the
body) and the conscious (the brain)
domains of the biosystem is carried out
by molecular triggers through weak
interactions
and
conformational
changes. Even learning and behavioral
changes in one's own lifetime are the
result of chemical reactions.[6a,c] In short,
the whole emotional-sensory-intellectual system,[19, 22] which we term “human”,
has a molecular basis. This highlights the
following central position of chemistry
for the human race:
* Mankind is made of chemical matter, the same matter that constitutes
all substances. Mankind is indeed
the “salt of the earth”.
* Mankind has learnt, and is still
learning, the secrets of manipulating
and shaping chemical matter. This
gnosis is chemistry.
* Chemistry is hence the window that
Mankind uses to probe his own
material being and come to terms
with its limitations.
* It is the ultimate fate and quest of
Mankind to widen the window.
Philosophy tends to characterize selfcognition and free choice as human
characteristics that form the great divide
from the rest of the animal world. I
recently read that rats dream about
themselves and their whereabouts during the day (running around their laboratory mazes).[23] In this sense, a rat
certainly has a form of self-cognition
and awareness. In fact, the chemistry of
emotions, memory, learning, is universal, much as are the genetic code and the
synthesis of proteins. Thus, the great
divide between humans and the animal
world is not any form of self-cognition
and free choice. It is rather the selfcognition gained as Mankind has journeyed through chemical matter in the
unconscious process of selfintrospection, we call chemistry. Thus, whereas
the details of the above story are
certainly simplistic and new facts will
replace quite a few of them, the above
lesson is with us to stay.
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The Chemical Matter
Since Mankind is made of chemical
matter, this is a good point to discuss
some key features of the chemical
matter that may pertain to this identity.
The central paradigms of chemistry
are that:
* There exist atoms, which can form
chemical bonds.
* The bonds are directed in space and
determine the molecular architecture, the reactivity, and interactivity
potentials of molecules.
* This in turn holds all the properties
of inanimate and animate matter.
The atom is a neutral entity composed
of electrons and protons, which are
charged particles, and neutrons, which
are neutral particles. The electron mass
is 1/2000 of those of the proton and
neutron. Scheme 3 shows dimensions of
Scheme 3. Dimensions of the atom and the
nucleus - All that “matters” resides in a minute space and the electrons “hover over the
surface of the deep”.
an average atom as a sphere (defined by
a 99 % probability of locating the electrons), which is occupied in its center by
a nucleus that packs together all the
massive particles. The radius (R) of the
atom is 1 M. However, the radius of the
nucleus is 105-times smaller. If we represent the atom as a football field, the
nucleus will not even be the football, but
rather a speck of dust on a shoe of the
player standing in the center of the field.
The chemical matter is empty and we,
made from it, are sculpted voids.
Why doesn't the void collapse unto
itself ? The architecture of the void is
shaped by the behavior of this tiny,
particle/not-particle, entity called the
electron. In general, all chemical matter
and its various interaction modes abide
by the rules of the electron. In this sense,
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Essays
chemical matter is unique because the
electron is already an elementary particle and hence, chemical patterns cannot be further reduced or constructed
from the bottom up (that is, from more
elementary constituents). As an elementary particle, a few “laws” govern the
electron behavior. The Heisenberg uncertainty principle forbids the electron
to be located and have, at the same time,
a definite energy (velocity). Therefore
the electron is delocalized in space and
“hovers” over the nucleus. In brief, the
uncertainty principle gauges the size of
the void in the atomic entity.
Accepting that atoms do not collapse, why then they do not all combine
into a single giant molecule, making all
of us pieces of the same material continuum (a material nirvana)? Here
comes to play the Pauli exclusion principle, which when applied to electrons,
imposes upon all atoms a specific connectivity that chemists discovered as
early as the 19th Century and called it
“valency”. It is the exclusion principle
that underlies the division of matter into
discrete molecules, and this is also the
creator of the molecular diversity of the
chemical matter.
The outcome of these two laws is
that chemistry is a game of Lego with
atoms and fragments, which have specified connectivities. The patterns of connecting two fragments form the archi-
tecture of the molecule, its electric and
magnetic properties, and its modes of
interaction, with other molecules and
with light, to form new information and
emergent properties. This, in a nutshell,
is chemical causality. The magnum opus
of the chemical matter and its emergent
qualities are manifestations of the architecture of the molecule and the movements of its atoms.
moral values and into poetry. This is a
demonstration how information stored
in the architecture of matter is mediated
by light through molecular processes of
the biosystem to evoke an emotional–
mental response. This is an emergent
property of the architecture of matter
through the information created by its
interaction with light, and through the
specific evocation mediated by the
chemical mechanisms of neurotransmitters and neuromodulators.
Molecular Architecture
Figure 1 shows a demonstration of
the transcendental function of architecture using diamond and graphite. Diamond and graphite are both made of
carbon atoms. However, they differ in
their architecture that is nascent from
the degree of freedom in the fourconnectivity of carbon. Diamond is hard
and translucent, while graphite is opaque and brittle. The different architecture determines the outcome of the
interaction of the two compounds with
light. But much more than that: Diamond is “beautiful” and expensive while
graphite “ugly” and cheap. Some people
will murder for diamonds and scheme
daring robberies, others will simply
eulogize its beauty. No one will devote
a single such thought to graphite. The
architectural differences of diamond
and graphite transcend into social and
“Let there be light”
Indeed, our inner-visual world is
shaped by the interaction of a molecule
with light and by the ability of one
molecule to exist in two definite states.
The visual pigment is the rhodopsin
receptor, a G-protein coupled receptor
(GPCR),[20, 24] that contains a chromophore called retinal. The retinal, in
Scheme 4, has a cis configuration that
gives the molecule a shape of a short
curve. Upon light absorption, the molecule is isomerized to the trans configuration and thereby attains the shape of
a lengthened chain. This architectural
change modifies the structure of the
membrane and activates a G-protein.[20]
This event triggers an amplification of
the initial signal, which is transmitted as
a neural signal and onward to imag-
Scheme 4. The light sensitive chromophore of rhodopsin in its resting state, the double bond with cis configuration is shown in bold.
Figure 1. Molecular architecture transcends to social values and poetry. On top, structures of
graphite (left) and diamond (right). At the bottom, the real materials, a piece of graphite (left)
and the Topkapi diamond (right).
3212
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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ing.[24] Subsequently, another event of
neurotransmission, yet to be elucidated,
takes over and evokes an emotional
response (oh diamonds are beautiful!).
Our cognition of shape and the innate
sense of beauty are outcomes of the
interaction of matter with light and of
the motions of the atoms of matter. This
is reminiscent of the emotional–sensory
system that is activated by the chemical
mechanisms of the neurotransmitters
and neuromodulators.
Angew. Chem. Int. Ed. 2003, 42, 3208 – 3215
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Chemistry and Its Emergent Expressions
Again and again one witnesses the
same truism, that in the basis of the
human attributes there lies chemical
mediation. Molecules, weak molecular
interactions and conformational energies harbor information that make us
tick. This algorithm is everywhere; from
the way “matter recognizes matter” by
chirality recognition,[25] or lock-and-key
fits, to the genetic code and protein
synthesis that are based on the hydrogen-bonding templates. Chemistry provides infinite ways by which a few
fundamental mechanisms and the power
of numerous combinations can lead to a
great variety of emergent qualities. This
chemical machinery, its genetic origins,
and its emergent emotional-sensory expressions[5] form the “psychophysical
connection” (body = chemistry; spirit =
thinking, emotions, motivation) that is
gradually unfolding.[6c, f, 19, 26, 27]
Dawn and Future
In the dawn of chemistry there was
alchemy. The first alchemist was
Hermes Trismegistus, shown in Figure 2.[28a, 29] This legendary figure gave
Mankind the “Hermetic Knowledge of
the Divine Art”. The phrase Hermetic
Knowledge evokes the sense of mysticism and magic, which is brushed off by
modern chemists. However, we must
recognize that alchemists were trying to
do precisely what modern chemists are
doing to day. The alchemists investigated matter in order to formulate a world
viewpoint–as system of philosophy and
cognition. In their system, spirit and
matter were entangled;[28b] every material entity had a spiritual manifestation
and vice versa.
Alchemists also practiced the manipulation of matter and left behind
chemical tools, which are still in contemporary use.[28b] Maria the Jewess is
considered to be the first alchemist in
the Western world. The tools she invented for gentle warming and separation of matter serve chemistry to this
day, and she may thus be credited as
being the first to investigate the behavior of matter, something that chemists
do to this day. The accumulation of
chemical knowledge has taught us, howAngew. Chem. Int. Ed. 2003, 42, 3208 – 3215
and our chemistry has
yet to fulfill the biblical dictum.
Bringing chemistry closer to the public is the duty of
chemists, especially
in these times when
some of the world's
major problems are
chemistry-laden.
However, imparting
knowledge is easy only if the topic is fasciFigure 2. The “first” alchemist (left) and the unification of matter,
nating, which chemisspirit, and soul (right). Adapted with permission from refs. [28a]
try certainly is. In a
and [28b], respectively.
way, chemistry is a
practical form of inever slowly, that behind the spectrum of trospection—an unconscious introspechuman traits there lie chemical mecha- tive analysis that has taken place as
nisms of molecular motions and mutual Mankind journeyed through Matter.
interactions of molecules with each Chemistry brings to life Mankind's inother and with the surrounding photonic ternal experience of change, of betterfield. We come full circle, to close a ment, and the innate knowledge that
chasm between the old and modern changes are brought by the existence of
worlds of chemistry. Chemistry is the opposites with great affinity. All in all,
intellectual adventure of Mankind in his chemistry touches the human existence,
excursion through his own material well-being, and commitment to be a
being. As this journey unfolds, so Man- benevolent master of matter—our eskind discovers the complex connection sential constituent. All these features
between matter and its emergent spiri- make chemistry a central pillar of human culture.
tual manifestations.[27]
Closing Remarks
Clearly, chemistry is the manifestation of the personal and universal cognition of Mankind of his own material
being, and is also the intellectual matchmaker between this material being and
Mankind's rule over matter. On the one
hand, with knowledge of chemistry we
are Matter that possesses self-cognition
and gnosis, which have immense importance for progress and well being of
Mankind. On the other hand, practicing
our control over matter, we are constantly reminded of the warning to
Mankind (represented by Cain) in the
Old Testament, Genesis 4:7: “Sin is
crouching at your door; it desires to
have you, but you must master it.”
Chemistry defines the limitation of the
power over matter, and exemplifies this
limitation by, for example, pollution and
chemical warfare. Ruling over matter
means also mastering the right ways of
tinkering with it. We are still not there,
www.angewandte.org
The author is indebted to D. Avnir, R.
Fisch, R. Hoffmann, E. Keinan, D.
Milstein, A. D. Mosnaim, C. Nowerstein,
D. Porte, R. Rachamimoff, Z. Rappoport, H. Schwarz, A. Stanger, and H.
Vancik for helpful discussions and comments. Z. Naor is thanked for making
accessible his own material on “chemistry of Love”. H. Sabelli has kindly
provided ref. [7a] . My daughter Yif'at,
helped with the artwork of Figure 1,
and S. de Visser and D. Danovich with
the rest. Needless to say, none of them
should be held responsible for the content of the essay.
[1] “peux curieux de son commerce et
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[2] See for example, a) R. M. Baum, Chem.
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c) M. Jacobs, Chem. Eng. News 2001,
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77(15), 5; d) W. Berry, Life is a Miracle,
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3213
Essays
[3]
[4]
[5]
[6]
3214
Counterpoint Press, Boulder, CO, 2000
(chemistry is mentioned once on p. 20 in
association with pollution); e) see however, B. Werth, The Billion-Dollar Molecule, Simon and Schuster, New York,
1994 (the book creates however a wrong
impression that chemistry is only the
synthesis part, while the rest, even NMR
spectroscopy or molecular modeling, is
not).
See for example, a) R. Hoffmann, P.
Laszlo, Angew. Chem. 2001, 113, 1065;
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b) R. Hoffmann, The Same and Not the
Same, Columbia University Press, New
York, 1995; c) R. Hoffmann, S. Leibowitz-Schmidt, Old Wine New Flasks,
W. H. Freeman, New York, 1997; d) R.
Hoffmann, V. Torrence, Chemistry Imagined, Smithsonian, Washington, 1993;
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f) H. Vancik, Found. Chem., in press;
g) A. L. Buchachneko, Herald Russ.
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McClintock, B. Zelano, C. Ober, Nat.
Genet. 2002, 30, 175. Note that even in
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A. R. Hariri, V. S. Mattay, A. Tessitore,
B. Kolachana, F. Fera, D. Goldman,
M. F. Egan, D. R. Weinberger, Science
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a) See review and articles in a special
issue of Science 2001, 294 from the
groups of Greengard, Holden, Helmuth,
Carlsson, b) P. Greengard, Science 2001,
294, 1024. The mechanisms by which
nerve cells communicate involve fast
and slow synaptic transmissions. The fast
mode (1 ms) involves the excitory mechanism of neurotransmission. The slow
mode (100 ms to minutes) involves the
generation of secondary messengers and
a subsequent sequence of biochemical
steps. There is interplay between the
slow and fast mechanisms (The 2000
Nobel Prize for Medicine was awarded
for the investigation of the slow mechanism, see A. Carlsson, ChemBioChem
2001, 2, 484 – 493 c) On addictive behavior, see: C. Holden, Science 2001, 294,
980; L. Helmuth, Science 2001, 294,
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296, 1624; B. Brembs, F. D. Lorenzetti,
F. D. Reyes, D. A. Baxter, J. H. Byrne,
Science 2002, 296, 1706; d) A. Carlsson,
Science 2001, 294, 1021; e) For developments in the science of signal transduction, see the articles by L. B. Ray,
S. A. Kliewer et al., A. S. Cashmore
et al., C. A. Parent and P. Devreotes
and by S. Artavanis-Tsakonas et al. in
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[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
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Goeddel, and H. Wajant, et al. and R.
Iyengar, et al. G. A. Koretzky, et al. J. C.
Cambier and D. P. McDonnell et al.,
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Farmer and J. Sheen et al., T. R. Parsons
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internet site www.stke.org); f) See the
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M. L. Dustin and D. R. Colman and by
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a) For a most recent review, see: H.
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the Treatment of Psychiatric Disorders
(Eds.: D. Michoulon, F. Rosenbaum),
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B. Borowsky, N. Adham, K. J. Jones, R.
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Leibowitz, The Chemistry of Love, Berkeley Book, New York, 1983; c) M. B.
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1996; e) H. E. Fisher, Anatomy of Love,
Norton, New York, 1992.
It was found in a study of medical
students that at the early stage of
“romantic love” they exhibited changes
in serotonin transporter similar to the
changes reported in obsessive–compulsive disorder. See: D. Marazziti, H. S.
Akiskal, A. Rossi, G. B. Cassano, Psychol. Med. 1999, 29, 741.
C. B. Pert, Molecules of Emotion, Simon
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p 43; b) T. Greenfeld, TIME, September
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a) C. S. Carter, Psychoneuroendocrinology 1998, 23, 779; b) L. J. Young, M. M.
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See the Nobel Lecture, R. F. Furchgott,
Angew. Chem. 1999, 111, 1990; Angew.
Chem. Int. Ed. 1999, 38, 1870.
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[17] a) L. R. Squire, E. R. Kandel, Memory:
From Mind to Molecules, Scientific
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[18] K. E. Wilson, Chem. Eng. News 1998,
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[19] J. LeDoux, Synaptic Self. How Brains
Become Who We Are?, Viking, New
York, 2002.
[20] These receptors activate guanine nucleotide binding proteins (G-proteins) in
the interior of the cells. The G proteins
are signaling molecules within the cell
and they stimulate ion channel, and
cause the synthesis of second messenger
molecules. See descriptions and discussions of G proteins in, a) C. A. Parent,
P. N. Devreotes, Science 1999, 284, 765;
b) S. P. Neves, P. T. Ram, R. Iyengar,
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[22] For a discussion of “taste” and “smell”,
see: C. L. Wilkinson, Chem. Eng. News
2000, 78(18), 1; P. Zurer, Chem. Eng.
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[23] TIME, February 5, 2001, p 51.
[24] a) K. Palczewski, T. Kumasaka, T. Hori,
C. A. Bhnke, H. Motoshima, B. A. Fox,
I. Le Trong, D. C. Teller, T. Okada, R. E.
Stenkamp, M. Yamamoto, M. Miyanao,
Science 2000, 289, 739; b) The neurons
of the visual system, which respond to
different parts of the same object become “fixed” by firing in synchronicity.
This synchronicity of neural firing tends
to prefer symmetric objects. See, S. H.
Lee, R. Blake, Science 1999, 284, 1165.
[25] A beautiful metaphor for chiral recognition is the “Handshakes in the Dark”,
described by Hoffmann on p. 40 in
ref [3b]. This can become very “handy”
in a public talk—shake hands with your
audience to illustrate chiral recognition.
[26] The drug “Ecstasy”(3,4-methylenedioxymethamphetamine) was recently shown
to cause huge amplification of serotonin
neurotransmission. The drain of serotonin causes depression, as well as permanent brain damage and profound dopaminergic toxocity (disruption of the
axon of neurons, and vulnerability to
Parkinson's desease). See Science 2002,
297, 2185.
[27] Unlike chemistry that uses a very precise language, neurochemistry has been
forced to use a much less precise language, because of the necessity to shift
from the level of chemical-mechanical
details (neurotransmission, brain reAngew. Chem. Int. Ed. 2003, 42, 3208 – 3215
Angewandte
Chemie
gions, etc) to the level of integrated
experience (depression, love, motivation). The chasm between these levels
can be likened to the relationship between the letters of alphabet and a
poem. The letters are certainly the only
constituents of the poem, but not every
pile of letters makes a poem. Bridging
this language gap in a manner that draws
the relation between the whole and its
parts is a great challenge that lies ahead.
See e.g., “Whole-istic Biology” in Science 2002, 295, 1661 – 1682.
[28] a) C. J. S. Thompson, The Lure and
Romance of Alchemy, Senate Press,
1990; b) R. Patai, The Jewish Alchemists,
Princeton University Press, Princeton,
1994, pp. 62, 63, 79, 254.
[29] H. W. SchUtt, Auf der Suche nach dem
Stein der Weisen – die Geschichte der
Alchemie, Beck, Munich, 2000.
In the printed version, the DOI is incorrect. The correct DOI is 10.1002/anie.200330038
Angew. Chem. Int. Ed. 2003, 42, 3208 – 3215
www.angewandte.org
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3215
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