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Innovations and challenges in Modern Physical Chemistry

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ADVANCES IN APPLIED SCIENCE AND ENGINEERING
INNOVATIONS AND CHALLENGES
IN MODERN
PHYSICAL CHEMISTRY
RESEARCH AND PRACTICES
Nova Science Publishers, Inc.
ADVANCES IN APPLIED SCIENCE
AND ENGINEERING
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ADVANCES IN APPLIED SCIENCE AND ENGINEERING
INNOVATIONS AND CHALLENGES
IN MODERN
PHYSICAL CHEMISTRY
RESEARCH AND PRACTICES
A. K. HAGHI
EDITOR
Nova Science Publishers, Inc.
Copyright © 2020 by Nova Science Publishers, Inc.
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Library of Congress Cataloging-in-Publication Data
Names: Haghi, A. K., editor.
Title: Innovations and challenges in modern physical chemistry: research and practices / A.K. Haghi
(editor), Professor Emeritus of Engineering Sciences, University of Guilan, Iran.
Identifiers: LCCN 2020027181 (print) | LCCN 2020027182 (ebook) | ISBN
9781536181814 (hardcover) | ISBN 9781536182354 (adobe pdf)
Subjects: LCSH: Chemistry, Physical and theoretical.
Classification: LCC QD453.3 .I56 2020 (print) | LCC QD453.3 (ebook) | DDC 541--dc23
LC record available at https://lccn.loc.gov/2020027181
LC ebook record available at https://lccn.loc.gov/2020027182
Published by Nova Science Publishers, Inc. † New York
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CONTENTS
Preface vii
Chapter 1 Pain Face, Science and Ethics, Hot, Spicy, Fresh,
Aspirin, Opioids and Laws 1
Francisco Torrens and Gloria Castellano
Chapter 2 Antitumour, Pancracine, Patchouli, Antifungal
and Caryophyllene 39
Francisco Torrens and Gloria Castellano
Chapter 3 Review: Possible Fields of Metal Carbon
Mesoscopic Composites Application 57
V. I. Kodolov, V. V. Kodolova-Chukhontseva,
I. N. Shabanova, N. S. Terebova, Yu. V. Pershin,
R. V. Mustakimov and A. Yu. Bondar
Chapter 4 Antibiotic Sensitivity of Staphylococcus Aureus
from Prosopis Juliflora, Cassia Occidentalis
and Tephrosia Purpurea 123
Aishwarya A. Andhare and Ravindra S. Shinde
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Contents
vi
Chapter 5 Effect of Liquid Formulation of Azotobacter
vinelandii on Germination of Vigna radiate
(Mung Beans) 143
Aishwarya A. Andhare and Ravindra S. Shinde
Chapter 6 Microwave in Pharmaceutical Processes 165
Hitesh V. Shahare and Gokul S. Talele
About the Editor 191
Index 193
Nova Science Publishers, Inc.
PREFACE
This new volume, introduces readers to some of the latest research
applications of physical chemistry. The compilation of this volume was
motived by the tremendous increase of useful research work in the field of
physical chemistry and related subjects in recent years, and the need for
communication between physical chemists, physicists, and biophysicists.
This volume reflects the huge breadth and diversity in research and the
applications in physical chemistry and physical chemistry techniques,
providing case studies that are tailored to particular research interests. It
examines the industrial processes for emerging materials, determines
practical use under a wide range of conditions, and establishes what is
needed to produce a new generation of materials.
A. K. Haghi, PhD
Professor Emeritus of Engineering Sciences
University of Guilan, Iran
Nova Science Publishers, Inc.
Nova Science Publishers, Inc.
In: Innovations and Challenges in Modern ISBN: 978-1-53618-181-4
Editor: A. K. Haghi © 2020 Nova Science Publishers, Inc.
Chapter 1
PAIN FACE, SCIENCE AND ETHICS, HOT,
SPICY, FRESH, ASPIRIN, OPIOIDS AND LAWS
Francisco Torrens1,
and Gloria Castellano2
1Institut Universitari de Ciència Molecular, Universitat de València,
Edifici d’Instituts de Paterna, València, Spain
2Departamento de Ciencias Experimentales y Matemáticas,
Facultad de Veterinaria y Ciencias Experimentales,
Universidad Católica de Valencia San Vicente Mártir, València, Spain
ABSTRACT
Pain is an unpleasant sensory and emotional experience associated
with actual or potential tissue damage, or described in terms of such
damage (International Association for the Study of Pain). Four types of
pain exist: cognitive, physiological (opiate related), social and emotional
ones. Three types of receptors exist: -, - and -ones. Therapeutics: opioid
rotation. Watching: Analgesic, Activity, Aberrant behaviour and Adverse
effects (the four As). Pain is avoidable: Chronic pain has no age in the 21st
century. The predominant pain in the elderly is chronic pain. Change of
paradigm in pain treatment. Mesenchymal stromal cells are advanced
Corresponding Author’s Email: torrens@uv.es.
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2
drugs. Drug-checking services and European Union’s early-warning
system play an important role in reducing the harm associated with
adulteration in the drug illegal market. It is basic to be at street level
preventing. One should adapt himself to leisure and black market. Gender
is important. Some drugs are legal and others, not for economic-political
and cultural reasons.
Keywords: new psychoactive substance, adulteration, controlled drug,
illegal market, pain pharmacological treatment, opioid analgesic, pain
avoidability
1. INTRODUCTION
Setting the scene: the face of pain, science, ethics of a universal
symptom, hot, spicy, fresh, salicylic acid (SA), acetylsalicylic acid (ASA),
aspirin, N-acetyl-p-aminophenol (paracetamol), diazepam, morphine,
diacetylmorphine, stimulants, adrenaline, amphetamine, caffeine (Caff),
tetrahydrocannabinol (THC), dopamine, 3,4-dihydroxytyrosine, cocaine,
nicotine, serotonin (5-HT), fluoxetin, methylenedioxymethamphetamine
(MDMA), advances in pain pharmacological treatment with opioid
analgesics, chronic pain having no age in the 21st century, drugs in Society
4.0, this being what it is, laws and drugs.
The International Association for the Study of Pain (IASP) defined pain:
Pain is an unpleasant sensory and emotional experience associated with
actual or potential tissue damage, or described in terms of such damage.
There are four types of pain: cognitive, physiological, social and emotional
pains: In particular, physiological pain results opiate related. There are three
types of pain receptors: -, - and -receptors. Some treatments are based
on opioid rotation. The four As of watching: Analgesic, Activity, Aberrant
behaviour and Adverse effects (AEs). Pain results avoidable: Chronic pain
has no age in the 21st century. The predominant pain in the elderly is chronic
pain. Change of paradigm in pain treatment. Multipotent mesenchymal
stromal cells (MMSCs) are advanced therapy medicines. Drug-checking
services and EU’s early-warning system can play an important role in
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reducing the harm associated with adulteration in the drug illegal market. It
is essential to be at street level doing prevention. One should adapt himself
to leisure and black market. The importance of gender. Some drugs are legal
and some others are not for economic-political and cultural reasons. Journal
Mètode published a special issue on pain entitled The face of pain: Science
and ethics of a universal symptom (cf. Figure 1).
Figure 1. Mètode 2011 (71) special issue: The face of pain: Science and ethics of a
universal symptom.
Earlier publications in Nereis, etc. classified yams [1], lactic acid
bacteria [2], fruits [3], spices [4] and oil legumes [5] by principal component,
cluster and meta-analysis. The molecular classifications of phenolic
compounds derived from the cinnamic and benzoic acids from Posidonia
oceanica [6], flavonoids [7], stilbenoids [8], triterpenoids, steroids from
Ganoderma [9], isoflavonoids from Dalbergia parviflora [10],
sesquiterpene lactones [11, 12] and artemisinin derivatives [13] were
informed. A tool for interrogation of macromolecular structure was reported
[14]. Mucoadhesive polymer hyaluronan favours transdermal penetration
absorption of Caff [15, 16]. Polyphenolic phytochemicals in cancer
prevention, therapy, bioavailability and bioefficacy were reviewed [17]. The
natural product antioxidants from herbs and spices improved the oxidative
stability (OS) of vegetable oils (VOs) [18]. The VO compositionOS
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relationship was revealed via a multifactorial approach [19]. It was informed
chemical and biological screening approaches to phytopharmaceuticals [20],
cultural interbreeding in indigenous and scientific ethnopharmacology [21],
medicinal plants (MPs) ethnobotanical studies, underutilized wild edible
plants, food, medicine [22], biodiversity as a source of drugs, Cordia,
Echinacea, Tabernaemontana, Aloe [23], immunomodulatory molecules
from Himalayan MPs [24], antimicrobial, antioxidant, composition of
Verbena carolina, Mentha [25], phylogenesis by information entropy, avian
birds, influenza [26], pain, pleasure [27], ethnoscience, alternative medicine,
inflammation and pain models [28]. The purpose of the present work is to
review the face of pain, science, ethics of a universal symptom, hot,
spicy, fresh, SA, ASA, aspirin, paracetamol, diazepam, morphine,
diacetylmorphine, stimulants, adrenaline, amphetamine, Caff, THC,
dopamine, 3,4-dihydroxytyrosine, cocaine, nicotine, 5-HT, fluoxetin,
MDMA, advances in pain pharmacological treatment with opioid
analgesics, chronic pain having no age in the 21st century, drugs in Society
4.0, this being what it is, laws and drugs. The aim of this study is to initiate
a debate by suggesting a number of questions (Qs) that can arise when
addressing subjects of pain, pleasure, the historical development of opioid
analgesic agents, pharmacological aspects of opioid analgesics, the clinical
use of opioid analgesics, pain avoidability, drugs in society and laws, in
different fields and providing, when possible, answers (As), facts (Fs) and
hypotheses (Hs) on pain, pleasure, advances in pain pharmacological
treatment with opioid analgesics, drugs, society and laws.
2. HOT, SPICY AND FRESH
Hot, spicy and fresh flavours are chemical stimulations of pain [29].
Two types of nerves for pain exist: Class A are thin fibres that carry the
signal quickly (20m·s1); class C are thicker and carry the signals more
slowly (1m·s1), which signals are called fast and slow pain, respectively.
The former are the response to injuries and are usually acute and localized.
The latter are usually painful and delocalized sensations. Both types enter
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the spine along with the nerves responsible for the sensation of temperature:
They stimulate the neurones that reach the brain and their signals undergo
some local process. A characteristic of pain nerves is their interaction in a
gelatinous part of the spinal cord called the substantia gelatinosa (SG). The
signals that arrive along A fibres excite SG cells but those via C fibres inhibit
them. The net effect may be the inhibition of the cells responsible for
transmitting signals A/C to the brain-processing centre (thalamus). A
complex interconnection exists between the signals that initially arrive as
fast and slow pain. In response to pain signals, the brain secretes its own
pain relievers (endorphins, enkephalins). Both are polypeptides but
endorphins present longer chains than enkephalins, which affect the
transmission of nerve signals, and both are mimicked by opiates. The pain
receptors that initiate the complex cascade present nerve endings that are
branched: No specifically innervated pain receptors exist. However,
receptors exist that respond to thermal stimulation. They are of two types:
Some respond to heat and others, to cold; the latter are 10 times more
numerous. Fibres A/C transmit their signals, e.g., the painful ones, to the
thalamus, so that an intense thermal stimulation can be interpreted as pain.
Most spices used in curries and other foods stimulate nerve endings that
detect pain in the mouth (and elsewhere), but molecular structureresponse
relationship is unknown. Harmful heat (above 52ºC) stimulates one receptor,
moderate heat (42ºC) and capsaicin, another, and the cold or freshness
(below 22ºC), and menthol, other different. The missing receptor in 2224ºC
is in the skin, tongue, brain and nerve tissue. Its wide distribution may be
because of its role in the response to injury and inflammation.
3. SALICYLIC ACID C7H6O3 AND ACETYLSALICYLIC
ACID C9H8O4
Some of the softest analgesics, which are not addictive, which are in the
market, are type aspirin [29]. They are derived from acetylsalicylic acid (cf.
Figure 2), which name comes from Latin Salix alba or white willow.
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Figure 2. Molecular structure of acetylsalicylic acid (ASA, aspirin).
Salicylic acid (cf. Figure 3) is in white-willow bark, combined with a
sugar molecule forming glycoside salicin, which was used to relieve pain in
traditional medicinal (TM) preparations [29]. Leaves and bark extracts from
a number of trees and shrubs, e.g., tea tree, present similar medicinal
properties and contain alike substances.
Figure 3. Molecular structure of salicylic acid (SA).
The SA, in its Na salt form, presents AEs in the stomach [29]. An
improvement with regard to its tolerance was discovered by Hoffmann
(1897), who worked for Bayer and was searching for a treatment for his
father, who suffered from rheumatoid arthritis. The compound was marketed
(1899) under the trademark Aspirin, which is protected in countries, e.g.,
Germany, but is generic in many others. Its way of action remained unknown
for much time. It interferes with the synthesis of compounds [prostaglandins
(PGs)], inhibiting the action of PG cyclooxygenase (COX) enzyme. The PGs
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are hormones that act locally and participate in many processes that happen
in the body; e.g., the modification of the signals transmitted via synapse
(connection between neurones), particularly pain signals. They intervene in
blood-vessels dilation, which causes headache (if vessels are intracranial) or
migraines (if vessels are outer cranium), in which cases, aspirin and other
local analgesics act inhibiting the synthesis of PGs, which are those causing
and transmitting pain. The zigzag lines, which persons suffering for
migraine see, are caused by the constriction of the blood vessels of the brain
region responsible for vision. As this presents a different cause from
headache, it can be treated independently with small doses of substances,
e.g., amyl nitrite, which dilate blood vessels. Aspirin applications seem to
present no end. It reduces the risk of heart attacks and strokes recurrence,
because it reduces the trend of platelets to gather and blood flows more
freely, which was explained by Kafka to his fiancée Bauer in a not much
romantic way: Aspirin is one of the few things that relieve the unbearable
pain of being. Trademark Alka-Seltzer, popular since a number of decades,
consists of aspirin, anhydrous citric acid (cf. Figure 4) and NaHCO3.
Figure 4. Molecular structure of citric acid.
When the mixture above is added to water, aspirin (an acid) becomes
converted into its Na salt that is more soluble, and citric acid releases carbon
dioxide CO2 (cf. Figure 5) from HCO3 ions, producing effervescence and a
more pleasant taste than aspirin [29].
Figure 5. Molecular structure of carbon dioxide CO2.
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4. N-ACETYL-
para
-AMINOPHENOL C8H9O2N
Analgesic properties of medicines, as those seen above, were discovered
by accident when a certain amount of acetanilide (like molecule in Figure 6
but without OH group) was added to the compound prescribed to a patient
[29]. Acetanilide can, in many cases, be toxic, so that lesser harmful
components were searched; e.g., N-acetyl-p-aminophenol (marketed as
Tylenol). In fact, it becomes converted into paracetamol in the body, which
generates its analgesic properties; however, part of it is converted into
aniline, a benzene molecule with an H-atom replaced by NH2 group, which
is toxic.
Figure 6. Molecular structure of N-acetyl-p-aminophenol (paracetamol, Tylenol).
Notice the similarity between acetanilide molecule and ASA (Figure 2)
[29]. Although they form from different atoms, they present a similar
conformation, so the same enzyme, that responsible for PGs synthesis so that
paracetamol acts inhibiting their synthesis, recognizes both.
5. DIAZEPAM C16H13ON2CL
Sleeplessness is almost always because of anxiety, which is associated
with a frenetic activity of neurones in the limbic system (LS), the brain
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region associated with emotions, which activity can be irradiated to brain
stem, the most primitive part of the brain, and keep a state of constant and
aggravated anxiety and alert [29]. Molecules called benzodiazepines, e.g.,
diazepam (cf. Figure 7), bind to proteins in zones where nerves link up
(synapse zones), and favour the capacity that GABA (cf. Figure 8)
neurotransmitter join neighbouring sites in the same molecule.
Figure 7. Molecular structure of diazepam (Valium).
The GABA inhibits nerve transmission, so that benzodiazepines
promote the inhibition [29]. The sites to which benzodiazepines join are
abundant in LS, so that on ingesting the compounds, the abnormal neurone
activity that take people to experiment the generalized worry and fear
(anxiety) is suppressed; i.e., benzodiazepines are medicines specific to treat
anxiety that act indirectly like tranqullizers. They are used in alcohol-
detoxification processes to avoid or mitigate the abstinence syndrome.
Figure 8. Molecular structure of -aminobutyric acid (GABA).
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Benzodiazepines are slightly addictive but not lethal [29]. However,
alcohol and benzodiazepines join in neighbouring sites of the same protein.
Both together can change the conformation of such protein, so that GABA
present a high inclination to bind it. If this happens, a massive inhibition of
the nervous-system (NS) activity occurs and death can happen.
Benzodiazepines include diazepam molecule (Valium), which is used as
muscular relaxing and tranquillizer. If Cl atom on the left side is substituted
by NO2, and >NCH3 by >NH, one obtains nitrazepam, which trademark is
Modagon. Another widely used tranquillizer is chlordiazepoxide (Librium).
6. MORPHINE C17H19O3N AND
DIACETYLMORPHINE C21H23O5N
Morphine (cf. Figure 9) is the main component of opium (from Greek
opion, meaning poppy juice), which is obtained as a milky liquid exuded
from the immature capsules of poppy Papaver somniferum [29]. It was
isolated by Sertürner (18031805). Unlike aspirin, morphine and related
compounds act on central NS (CNS) and induce addiction. The specific
action of the compounds is related with the capacity of a molecule of fitting
and blocking a specific receptor placed on the neurones.
Figure 9. Molecular structure of morphine.
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Figure 10. Tentative conformation for the protein acting as morphine and related-
molecules receptor.
The proposed receptor conformation is shown in Figure 10 [29]. The
benzene group of the morphine molecule fits tightly on the flat side, and the
neighbouring group of C-atoms is at the correct distance and orientation to
fit in the groove. Behind such groove, an anionic group exists, which attracts
cationic N-atom. On fitting with receptor shape and binding it, morphine
molecule removes its action: Morphine imitates body natural analgesics,
enkephalins.
Morphine acts on deep or slow pain but it presents no effect on fast pain
[29]. Substantia gelatinosa (SG), the spine region when pain signals are first
processed, is filled with morphine receptors: There morphine acts increasing
the threshold to which people feel slow pain. Morphine receptors abound in
the medium part of thalamus, the brain part that acts as entry of slow-pain
signals. High concentrations of the receptors exist in LS, region associated
with emotion. A close relative of morphine is codeine, which is obtained
when OH group (Figure 9, left) is substituted by OCH3. In the body,
OCH3 is replaced by OH, so that codeine becomes converted into
morphine. Diacethylmorphine (diamorphine, heroin, cf. Figure 11) is a
morphine molecule in which H-atoms of both OH groups were replaced by
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two acetyl COCH3 groups. It was synthesized by Wright (1874). The
substitution of H that bonds OH groups makes heroin lesser water soluble
than morphine, but more soluble among the hydrocarbon (HC) chains of fats.
Although it must be injected directly into blood, it passes much faster the
bloodbrain barrier (BBB, which prevents that big and water-solved
molecules pass to brain). The result is that it is more powerful than morphine
(more heroic) but its effect does not last so much. Once heroin became
absorbed, acetyl groups are removed, which transforms it into morphine,
causing an analgesic and euphoric action.
Figure 11. Molecular structure of diacethylmorphine (diamorphine, heroin).
7. STIMULANTS
Many drugs are not used for medical purposes, which has to do with the
degree of social acceptance [29]. Some are used providing a euphoria
feeling, e.g., ethanol CH3CH2OH (cf. Figure 12, a depressant).
Figure 12. Molecular structure of ethanol.
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The brain region associated with emotions is LS: Stimulation of LS
neurones, if neurotransmitters capacity to make them communicate with
each other via synapse is enhanced, and the capacity of inhibitory
neurotransmitter GABA (Figure 8) to join them is lowered, can generate
exaggerated responses of emotional activity [29]. Many connections in LS
include branched neurones that originate in a small blue region of the
encephalic trunk [locus coeruleus (LC)], which neurones characteristic is
that the neurotransmitter that causes synapse is a molecule {noradrenaline
[NA, norepinephrine (NE) in US]}, which is abundant in LS itself, which
neurones significant neurophysiological characteristic is their branching,
which result is the establishment of multiple synapses with other
(polysynaptic) neurones in LS and other brain regions. So much branching
and synapses may be connected to emotion, whereas lesser-branched and
monosynaptic neurones would be to rational functions, which, if sure, any
modification in the response of the branched neurones groups can produce
modifications in emotional responses. The key for such modification must
be neurotransmitter NA.
8. ADRENALINE C9H13O3N AND AMPHETAMINE C9H13N
Not all stimulants need to be administered from outside: Some, e.g.,
adrenaline (cf. Figure 13), are synthesized in the body itself and participate
in the signal transmission from one neurone to another [29]. Adrenaline
[epinephrine in US, from Greek (ren is kidney in Latin, nephros, in Greek)]
is produced in the kidney glands. It circulates via blood and affects the
autonomous NS (ANS, nerves on which one has not voluntary control,
which are different from CNS). It acts on heart muscles to increase the
contraction force, dilates the pupils and stimulates sweat and saliva
secretion. However, H-bonds between OH and >NH groups in the molecule
cause that it do not pass BBB.
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Figure 13. Molecular structure of adrenaline (epinephrine).
Figure 14. Molecular structure of (L)-tyrosine (Tyr, Y).
However, the brain synthesizes adrenaline and similar compounds, e.g.,
NA [29]. Its precursor is amino acid (AA) tyrosine (Tyr, Y, cf. Figure, 14),
with the same structural planning than adrenaline, and becomes converted
into NA by different enzymes. The conversion occurs abundantly in LC and
LS neurones and, in any way, feeds people’s emotions.
Amphetamine (cf. Figure 15) molecule was marketed under trademark
Benzedrine as a stimulant [29]. Conformational similarity with NA suggests
that it can act similarly, stimulating LS in LC.
Figure 15. Molecular structure of amphetamine.
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As LC is connected to upper centres (mainly brain cortex), amphetamine
can stimulate cognitive functions, causing a state of higher alert and
euphoria feeling [29]. Amphetamine action is not simply to play NA role as
neurotransmitter. Their molecules can imitate so perfectly NA ones that they
can occupy their place in storage areas of presynaptic (front) neurones,
which results in NA being displaced from its storage site, entering the space
between the pre and postsynaptic (posterior) neurones. On rising their
concentration in the place, NA molecules join proteins on the wall of the
postsynaptic neurone, changing their conformation and shooting a signal.
Neuronal activity is enhanced and a euphoria, alert and power sensation
occurs. Amphetamine molecules exist in two forms, one is the mirror image
of the other [they are chiral compounds, e.g., lactic acid (cf. Figure 16)]. The
form that rotates polarized-light plane to the right (Dexedrine) is much more
potent than its mirror image. The two differ in shape, e.g., hands, and only
one of them will fit in the glove that is the protein.
Methamphetamine differs from amphetamine molecule in that it
presents a CH3 group instead of one H-atom of NH2 group [29]. The
stimulant molecule is marketed as Methedrine (speed).
Figure 16. Molecular structure of lactic acid: (a) (L)-lactic acid and (b) (D)-lactic acid.
9. CAFFEINE C8H10O2N4
Caffeine (cf. Figure 17) is the component of coffee and tea that
stimulates brain cortex, inhibiting the phosphodiesterase enzyme that, in
turn, degrades a 2nd messenger from the same family as adenosine
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triphosphate (ATP, cf. Figure 18) [cyclic adenosine momophosphate
(cAMP)] [29].
Figure 17. Molecular structure of caffeine (Caff).
Figure 18. Molecular structure of adenosine triphosphate (ATP).
Molecule of Caff could be taken for ATP: A comparison of the
structures of both molecules shows that they include two fused heterocyclic
rings [29].
Typically, a cup of coffee or tea contains 1/10 of Caff [29]. Coffee is
obtained from roasting the seeds of tree Coffea arabica, and tea, from the
fermented leaves of Camellia thea. Caffeine occurs in the seeds of cola plant
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Cola acuminata and C. nitida, which grows in East Africa and South
America. The plants extracts are used to spice (and by their stimulant action)
cola drinks instead of cocaine, which is what they originally contained.
Theobromine is a Caff close relative, which molecule differs in that it
presents an >NCH3 group substituted by >NH. It is the stimulant that occurs
in chocolate. Black chocolate is cacao and sugar. Milk chocolate contains
additional ingredients, e.g., vanilla cream, etc. Theobromine provides a
stimulating effect lesser than Caff.
10. TETRAHYDROCANNABINOL C21H30O2
Tetrahydrocannabinol (cf. Figure 19) is the active component of
cannabis, which is obtained from plant Cannabis sativa, from the same
family as hop, plant used to make beer [29]. Cannabis was cultivated for its
fibres (hemp), which are used in industry to make sailcloth, clothes and
ropes, which derives from Latin cannabis. The female plant exudes a resin
that covers near flowers and leaves, and such resin is added to preparations
that humans consume in different forms. Marijuana is obtained from dried
and ground leaves and flowers; hashish is the treated resin of cannabis. The
way of action of the high-structural-complexity molecule was not
determined.
Figure 19. Molecular structure of tetrahydrocannabinol (THC).
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11. DOPAMINE C8H11O2N AND 3,4-DIHYDROXYTYROSINE
C9H11O4N
Dopamine (cf. Figure 20) is an important neurotransmitter [29]. Its
distribution in brain is not at all uniform as it usually concentrated in corpus
striatum, which is the brain region involved in movement co-ordination, and
LS. A dopamine-production deficit is responsible for causing Parkinson’s
disease (PD), whose main symptoms are rigidity, trembling and hypokinesia
(slow to start movements). A dopamine excess in the brain is related to the
beginning of Huntington’s disease (HD, chorea), genetic upset, which
symptoms are marked involuntary movements. It is involved, as
neurotransmitter, in the brain routes that control reinforcement and pleasure,
and addictive processes (e.g., cocaine, nicotine).
Figure 20. Molecular structure of dopamine.
Figure 21 shows (L)-3,4-dihydroxyphenylalanine [levodopa,
(L)-DOPA, 3-hydroxytyrosine] molecule: L comes from the chiral form
(levo, left) in which it occurs [29].
Figure 21. (L)-3,4-dihydroxyphenylalanine [levodopa, (L)-DOPA,
(L)-3-hydroxytyrosine].
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Dopamine is synthesized via (L)-DOPA from Tyr (Figure 14) in
substantia nigra (SN), which colour is because of melanin (cf. Figure 22)
accumulation, which is made up of Tyr [29]. As SN cells die, dopamine
production decays and symptoms intensify. An HD-symptoms temporal
relief is gotten administering (L)-DOPA but cells continue dying. Dopamine
itself does not pass BBB so it is ineffective when it is administered
intravenous (i.v.), but 1% of (L)-DOPA opens pass to the brain when it is
ingested and, once there, it becomes converted into dopamine by COOH-
group loss. As amount is small, high and frequent doses are needed but its
effectiveness decays as HD advances.
Figure 22. Molecular structure of melanin.
Symptoms of PD can be caused by illegal-heroin consumption,
sometimes contaminated with compounds that kill SN cells and cause PD
[29].
12. COCAINE C17H21O4N
Cocaine (coke, cf. Figure 23) is an alkaloid that is obtained from the
leaves of plant coca Erythroxylon coca, endemic in the hills of East Andes
and widely cultivated in Bolivia, Peru, Ecuador and Colombia [29].
Niemann isolated it (1860). Coca developed cocaine production as pesticide,
as it inhibits neurotransmitter-octopamine reuptake, specific of insects. In
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humans, it inhibits dopamine, NA and serotonin reuptake in the brain. Such
neurotransmitters are in the synaptic zone for a longer time: Cocaine
stimulates the release of more dopamine. The immediate effect is euphoria,
verbosity and motor activity but the effects pass at once and are succeeded
by a depression and anguish feeling, which only calms down consuming
more.
Figure 23. Molecular structure of cocaine (coke).
The habitual form of administering cocaine is as its chloride (salt formed
on combining cocaine with HCl) by nasal inhalation; however, the result
makes that the nose capillary vessels constrict, which can cause that the nasal
septum necrose [29]. Crack is cocaine to which HCl was removed, heating
the compound in a NaHCO3 solution until water evaporate. The free base
that is obtained makes a sound like crack when heated because of CO2
release from HCO3 (here the name). As the free base is more molecular than
ionic (not so in Cl), it evaporates at low temperature and can be inhaled via
a heated tube. It was used for eye and mouth operations [later, it was
substituted by local anaesthetics (e.g., lidocaine, novocaine)], and oral and
throat pains. It has no medical uses but as soft anaesthetic in ophthalmology.
13. NICOTINE C10H14N2
Nicotine (cf. Figure 24) is found in the leaves of plant tobacco Nicotiana
tabacum (called by one of the first tobacco importers, French ambassador in
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Portugal Nicot) in combination with citric (Figure 4) and malic (cf. Figure
25) acids [29].
Figure 24. Molecular structure of nicotine.
Alkaloids occur frequently in plants to defend themselves vs. predators,
because of its unpleasant taste [29]. When tobacco is harvested, leaves dry,
which causes that proteins, carbohydrates (CH2O) and alkaloids composition
change. For cigarettes tobacco, leaves are hung in a room with ventilation
and a heat source. After a week, green leaves turn yellow as carotenes are
made dominant. Leaves present greater sugars and nicotine concentration.
Cigars tobacco is cured in the air, hanging them for a number of weeks. The
resultant product is low in sugars and variable in nicotine. Tobacco curing
at fire causes that leaves green be exposed to wood smoke and heat, and is
used to smoke a pipe: It is low in sugars and nicotine. After curing, leaves
are fermented storing them in a humid place: Taste changes on rehydrating,
which makes them lesser fragile.
Figure 25. Molecular structure of malic acid.
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A typical cigarette contains 10mg nicotine, 1mg of which is absorbed
by the smoker, mainly via the lungs, where it arrives transported by tar
molecules [29]. Pipe and cigar tobacco smoke is lesser acidic than cigarettes,
in such a way that nicotine in both is more similar to its basic form. The
result is that more nicotine becomes absorbed in the mouth and nasal cavity.
Cigarettes cause that nicotine concentration in blood rise faster than with
cigars or pipe consumption, which causes a slower but lasting concentration.
Nicotine presents complex and numerous pharmacological effects, some of
which are identical to cocaine (Figure 23), and final result depends on dose.
Smokers experience sometimes alert feeling and, others, relaxation.
Nicotine, like cocaine, heroin and marijuana, increases dopamine (Figure
20) level, which affects the routes by which brain controls pleasure. As it
causes an adrenaline unloading from the adrenal cortex, its ingestion causes
an immediate kick. Adrenaline, via the endocrine system, stimulates glucose
release and alert feeling, which stimulation is followed by depression and
fatigue. Hormone corticosterone, which is released in a stress episode,
reduces nicotine effects, which causes that more amount be required to get
the same effect. Nicotine is addictive and smokers use to reject the cigarettes
that do not present it. Cigarettes with low tar content present a low substance
in nicotine but with these, smokers inhale more strongly and smoke with
more frequency: As a result, the net effect of passing to low-tar cigarettes is
a rise in CO enter rate, with the underlying risk of suffering cardiovascular
(CV) accidents. Menthol cigarettes increase nicotine addiction. In some
countries, e.g., Pakistan, clove is added to cigarettes.
14. SEROTONIN C10H12ON2 AND FLUOXETIN C17H18ONF3
Serotonin (5-hydroxytryptamine, cf. Figure 26) is a neurotransmitter
and a slightly modified version of essential AA tryptophan (Trp, W) used in
proteins manufacturing [29]. Although food contains 5-HT, most part forms
in the body by enzyme action on Trp. The 5-HT participates in a wide
number of activities, especially in CNS, modulating courage, emotion, sleep
and appetite. The cerebrospinal fluid of the persons that suffer for depression
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contains lower concentrations of substances derived from 5-HT, and the
same happens in suicidal cases, which low concentrations can be because of
an abnormally slow Trp transport via BBB.
Figure 26. Molecular structure of serotonin (5-hydroxytryptamine, 5-HT).
The 5-HT is a powerful vasoconstrictor [29]. When it acts on veins
smooth musculature, it hinders capillaries blood flow and causes blush.
Certain hallucinogen drugs affect its mechanism of action. The most famous
is lysergic acid diethylamide (LSD, trippy) but its precise (probably
multifaceted) action mode remains unknown. Melatonin is closely related
with 5-HT: benzene OH group is substituted by OCH3, and side-chain
NH2 becomes converted into NHCOCH3. Melatonin is produced in the
pineal gland, a structure remembering a 3rd eye that Descartes thought that
it was where the soul rested, in the vascular side of BBB. It is believed that
melatonin controls hormones amounts during the day and it has to do with
jet lag. Sun stimulates the pineal gland to free 5-HT and melatonin, although
an excess of the latter causes dullness, lethargy and sleepiness. Seasonal
affective disorder (SAD) or winter depression occurs when persons are
exposed to too low levels of sunlight for long periods, e.g., in countries of
high latitudes. Nobody really knows SAD cause but a number of hypotheses
exist. A possible cause results that low light levels be not enough to produce
melatonin or 5-HT suitable amounts. Fluoxetine (cf. Figure 27) combining
with HCl forms the fluorinated salt marketed as Prozac (Sarafem), an
antidepressant. In a depression, a 5-HT disequilibrium exists in synapse;
e.g., not much 5-HT is present to stimulate synapse. Prozak inhibits 5-HT
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reuptake, i.e., avoids that 5-HT molecules that exist in synapse return to the
presynaptic neurone. The result is that 5-HT is at greater concentration more
time in the synapse site and could join the postsynaptic neurone, which
replies sending the signal, e.g., in a non-depressed individual. Prozac is
specific for 5-HT receptors and presents lesser secondary effects than the
drugs that interact more generally.
Figure 27. Molecular structure of fluoxetine (Prozac, Sarafem).
15. METHYLENEDIOXYMETHAMPHETAMINE C12H17O2N
The little monster methylenedioxymethamphetamine (Figure 28) exists
in the street as ecstasy (E, to be out of oneself, molly) [29]. It was synthesized
by Merck Laboratories (1912) searching for drugs for the treatment of nasal
haemorrhages. Its chemical structure is similar to methamphetamine,
methylenedioxyamphetamine (MDA) and mescaline, all causing brain
damage. It affects the neurones that use 5-HT and influences courage,
aggressiveness, sexual activity, sleep and pain sensitivity. It developed as
treatment vs. obesity. When it is taken for a long period (67 years), 5-HT
receptors become exhausted. Concentration and cognitive sense are lost. In
high doses, it produces a rise in body temperature, which causes that
muscles, kidneys and CV system fail. At the point, one is permanently
outside of him. It was used for the treatment of post-traumatic stress, e.g.,
cases of women that were raped.
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Figure 28. Molecular structure of methylenedioxymethamphetamine [MDMA, ecstasy
(E), molly].
16. ADVANCES IN PAIN PHARMACOLOGICAL TREATMENT
WITH OPIOID ANALGESICS
Academy of Pharmacy of Comunitat ValencianaAristo organized a
colloquium on advances in pain pharmacological treatment with opioid
analgesiscs. López Muñoz proposed Q/A/F/H on victo dolore and historical
development of opioid analgesic agents [30].
Q1. Pain?
A1. Pain is a symptom as old as humanity itself.
F1. Sertürner (1805) discovered morphine.
F2. Wright (1874) synthesized diamorphine (heroin).
H1. (IASP). Pain: an unpleasant sensory/emotional experience
associated with actual/potential tissue damage, or described in terms of such
damage.
Selva Otaolaurruchi proposed H/Q/A on opioid-analgesic
pharmacological aspects from pharmacist’s perspective [31].
H2. Four types of pain exist: cognitive, physiological (opiate related),
social and emotional pains.
Q2. How to choose the opioid?
Q3. What is the action they have?
A3. Analgesic action.
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H3. Three types of pain receptors: -, - and -receptors.
H4. Treatment: opioid rotation.
López Alarcón proposed Q/A considering opioid-analgesic clinical
use/responsible management [32].
Q4. Electronic (e)-prescription, how do we prescribe?
Q5. How do we prescribe at home?
Q6. What to watch?
A6. The four As of watching: Analgesic, Activity, Aberrant behaviour
and AEs.
17. CHRONIC PAIN HAS NO AGE IN THE 21ST CENTURY
Grisolía and de Andrés organized Day Chronic Pain Has No Age in 21st
Century [33]. Borrás Blasco proposed H/Q on ageing and changes in pain
perception [34].
H1. Ageing: process during which structural/functional changes
accumulate in an organism as a result of passing of time.
Q1. How does the perception of pain change with ageing?
H2. Ageing leads to decay in adaptive capacity.
H3. Pain door theory.
H4. Referred pain.
H5. Pain Fragility Disability.
She provided a conclusion (C).
C1. The predominant pain in the elderly is chronic pain.
Mínguez Martí proposed H on polypharmacy, interactions and
limitations for pharmacological prescription in chronic pain [35].
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H6. Serotonin syndrome: Tramadol/Meperidine/Fentanyl increase 5-HT
levels if co-administered with others modulating 5-HT route.
H7. Keep paracetamol as opioids saving.
De Andrés proposed H on alternatives in supervising treatment,
endoscopic and minimally invasive techniques [36].
H8. (Grisolía). Pain is avoidable.
H9. Pain is avoidable because pain is treatable.
H10. Myofascial pain syndrome: Pressure on sensitive points in your
muscles causes pain in muscle and sometimes in seemingly unrelated parts
of your body.
He provided a conclusion.
C2. Change of paradigm in pain treatment.
Raya raised Q on illuminating confusion, stem cells (SCs)’ riot,
scientific/terminological clarification on altars of its correct application in
present/future medicine [37].
Q2. The SCs: cancer predisposition?
Blanquer raised the following questions on MMSCs [38].
Q3. The MMSCs, where are they obtained?
Q4. The MMSCs, which are their applications?
Q5. Pain related to exercise: The new fashions: running, fitness… What
exercise to do?
Q6. Pain related to exercise: The new fashions: running, fitness… How
to prepare oneself?
Q7. Where do people talk when talking about fat?
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He provided a conclusion.
C3. The MMSCs are advanced therapy drugs.
Moraleda proposed H/Q on blood as regenerative-therapies origin and
applications in body improvement/pain control [39].
H11. Change of paradigm: We do not work with medicines but cells.
Q8. Relapse: antitumour immunotherapy?
Q9. Chimeric antigen receptor (CAR)-T cells: How do they work?
H12. (TerCel, 2019). White Book of Cell Therapy in Spain [40].
18. DRUGS IN SOCIETY 4.0
Group SOLINDRUGS organized Workshop Drugs in Society 4.0 [41].
Ventura proposed H/Q on substances analysis as tool to monitor drug
recreational market, use patterns/detected trends [42].
H1. Attractors of false ecstasy.
H2. (Giné et al., 2013). New psychoactive substances (NPSs)
adulterating controlled drugs [43].
Q1. The NPSs as adulterants of controlled drugs: A worrying
phenomenon?
Q2. What have they found?
Q3. What are the implications of these findings?
Pérez proposed questions/answers on current challenges in drug control
labratories [44].
Q4. How to monitor the drug recreational market?
Q5. How does people know the appearance of NPSs?
Q6. When do NPSs begin to be detected?
Q7. Economic responsibilities?
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Q8. What do people know about their origin?
A8. China and in bulk.
Q9. How have European countries reacted?
Q10. What do people know about synthetic cannabinoid agonists?
Q11. When are they detected in the illegal drug market?
Q12. How are they called?
Q13. How do people differentiate the new ones?
A13. Method European Monitoring Centre for Drugs and Drug
Addiction (EMCDDA).
Q14. What is its toxicity?
Q15. Synthetic catinones, when are they first detected?
De San Román provided conclusions on Ai Laket!!, a story for risk
reduction [45].
C1. It is essential to be at street level doing prevention.
C2. One should adapt himself to leisure and black market.
C3. The importance of gender.
Bravo proposed H on controlling drug precursors [46].
H3. (Untrue H). Oversight bodies invent stories.
Hernández proposed H on drug use from a global analytical chemistry
perspective/wastewater-analysis contributions [47].
H4. Wastewater-based epidemiology.
Gallart proposed the following hypothesis on contributions to drug
analysis [48].
H5. Ion mobility spectrometry (IMS).
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Costero proposed hypothesis on drugs, colours and protection vs.
chemical submission [49].
H6. -Hydroxybutyric (GHB) acid (cf. Figure 29).
Figure 29. Molecular structure of -hydroxybutyric (GHB) acid.
Sorribes proposed a hypothesis on drug analysis in biological fluids via
IMS [50].
H7. IMS problem: low sensibility in complex samples. e.g., saliva.
19. THIS IS WHAT IT IS: LAWS AND DRUGS
Consumo-ConCiencia proposed questions and answers on this being
what it is, laws and drugs [51].
Q1. Why is it a crime to sell drugs?
A1. Drugs are harmful to health and trafficking with them means
endangering the health of others.
Q2. Are alcohol, coffee, tobacco or psychoactive drugs not harmful to
health or are they not drugs?
A2.Yes, of course they are drugs and can be harmful to health.
Q3. In addition, why are they not prohibited like the others?
A3. Some drugs are legal and some others are not for economic-political
and cultural reasons.
Q4. What drugs are illegal?
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A4. Cannabis, MDMA (ecstasy), cocaine, heroin, LSD (trippy),
psilocybin (magic mushroom), 2,5-dimethoxy-4-bromophenethylamine
(2C-B, nexus), etc.
Q5. Is using illegal drugs a crime?
A5. Consuming any substance in a private space is not a crime, but any
other situation, yes.
Q6. What if one is a minor?
A6. If one is a minor Criminal Code would not apply but a specific law
regulating minors.
Q7. Is it legal to grow marijuana at home?
A7. One can have a crop for self-consumption in his own home if it is
not visible from outside.
Q8. What is the drugtest?
A8. A device used in traffic controls that detects via saliva if drugs were
consumed in last hours.
Q9. What happens if one tests positive for non-alcoholic drug traffic
control?
A9. If one is positive, a second test will be performed of saliva but in a
laboratory chromatograph.
Q10. If I refuse to take the test?
A10. If one refuses, the criminal code will apply.
20. FINAL REMARKS
From the present results and discussion, the following final remarks can
be drawn.
1) (International Association for the Study of Pain). Pain: an
unpleasant sensory and emotional experience associated with actual
or potential tissue damage, or described in terms of such damage.
2) Four types of pain: cognitive, physiological (opiate related), social
and emotional pains.
3) There are three types of pain receptors: -, - and -receptors.
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4) Treatment: opioid rotation.
5) The four As of watching: Analgesic, Activity, Aberrant behaviour
and Adverse effects.
6) Pain is avoidable: Chronic pain has no age in the 21st century.
7) The predominant pain in the elderly is chronic pain.
8) Change of paradigm in pain treatment.
9) Multipotent mesenchymal stromal cells are advanced therapy drugs.
10) Drug-checking services and European Union’s early-warning
system can play an important role in reducing the harm associated
with adulteration in the drug illegal market.
11) It is essential to be at street level doing prevention.
12) One should adapt himself to leisure and black market.
13) The importance of gender.
14) Some drugs are legal and some others are not for economic-political
and cultural reasons.
ACKNOWLEDGMENTS
The authors thank support from Fundación Universidad Católica de
Valencia San Vicente Mártir (Project No. 2019-217-001UCV).
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[33] Grisolía, S.; de Andrés, J. Book of Abstracts, El Dolor Crónico No
Tiene Edad en el Siglo XXI [Chronic Pain Is Ageless in the 21st
Century], València, Spain, Novenber, 21, 2019, Fundación Valenciana
de Estudios Avanzados: València, Spain, 2019.
[34] Borrás Blasco, C. Book of Abstracts, El Dolor Crónico No Tiene Edad
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València, Spain, Novenber, 21, 2019, Fundación Valenciana de
Estudios Avanzados: València, Spain, 2019; O-1.
[35] Mínguez Martí, A. Book of Abstracts, El Dolor Crónico No Tiene
Edad en el Siglo XXI [Chronic Pain Is Ageless in the 21st Century],
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Estudios Avanzados: València, Spain, 2019; O-2.
[36] De Andrés, J. Book of Abstracts, El Dolor Crónico No Tiene Edad en
el Siglo XXI [Chronic Pain Is Ageless in the 21st Century], València,
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[37] Raya, Á. Book of Abstracts, El Dolor Crónico No Tiene Edad en el
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[38] Blanquer, M. Book of Abstracts, El Dolor Crónico No Tiene Edad en
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Spain, Novenber, 21-22, 2019, Universitat de València: València,
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[42] Ventura, M. Book of Abstracts, Drogas en la Sociedad 4.0 [Drugs in
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Nova Science Publishers, Inc.
In: Innovations and Challenges in Modern ISBN: 978-1-53618-181-4
Editor: A. K. Haghi © 2020 Nova Science Publishers, Inc.
Chapter 2
ANTITUMOUR, PANCRACINE, PATCHOULI,
ANTIFUNGAL AND CARYOPHYLLENE
Francisco Torrens1,
and Gloria Castellano2
1Institut Universitari de Ciència Molecular,
Universitat de València, València, Spain
2Departamento de Ciencias Experimentales y Matemáticas,
Facultad de Veterinaria y Ciencias Experimentales,
Universidad Católica de Valencia San Vicente Mártir, València, Spain
ABSTRACT
Chinese-Herbal-Formula-CHF03 protective effect on non-alcoholic
fatty liver disease in mice is related to its ability to regulate the
inflammatory response and lipogenic response controlled by sterol
regulatory element binding transcription factor 1. Formula CHF03 is a mix
of natural compounds that could be used for the treatment of non-alcoholic
fatty liver disease. Patchouli oil, alcohol, pogostone and -patchoulene
possess prebiotic-like effect in C57BL/6J mouse model. The herbal
treatments improve the gut epithelial barrier, reinstating the expressions of
epithelial and neural cadherin, upregulating p-lysozyme and Muc 2 genes
Corresponding Author’s Email: torrens@uv.es.
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Francisco Torrens and Gloria Castellano
40
expression, and suppressing the pro-inflammatory cytokine expressions.
Sequencing data of 16S show that the herbal treatments positively
modulate gut microbiota composition, in which the relative abundance of
short-chain fatty- and lactic-acid-producing bacteria are enhanced, while
certain pathogenic bacteria are reduced. Essential oils are used in a number
of fields. Numerous studies highlight the action of these oils. In light of the
facts that the current rise in invasive fungal infections because of the rise
in immunosuppressive therapies is a real concern, and the emergence of
resistant strains induces therapeutic failures, classes of antifungals are
anticipated. The plant kingdom represents an immense potential of natural
resources to exploit for the purposes.
Keywords: patchouli essential oil, patchouli alcohol, pogostone,
-patchoulene, gut microbiota, antifungal, invasive fungal infection
1. INTRODUCTION
Setting the scene: the bioprocess and metabolic engineering of
Cheiloclinum cognatum roots for the production of antitumour
quinonemethide triterpenes, pancracine as a novel candidate lead-structure
in the therapy of oncological diseases, patchouli essential oil (EO) and its
derived compounds revealing prebiotic-like effects in C57 black
(C57BL)/6J mice, EOs and their natural active compounds presenting
antifungal properties, caryophyllene in EO from Chrysanthemum boreale
inducing G1 phase cell cycle arrest in human lung cancer cells, natural
products (NPs) in neurodegenerative diseases as a great promise but an
ethical challenge, factors responsible for the risen use of NPs, a review of
limonin pharmacology, toxicity and pharmacokinetics.
As an alternative therapeutic source, EOs extracted from plants are
qualified as a biotechnological product to be explored for pharmaceuticals
and food companies. The EOs are constituted by volatile organic products
of classes synthesized by a secondary metabolism from different plants
parts. Studies documented EOs to be effective antimicrobial agents vs.
pathogens. Effect of EO is closely related to the capability of permeabilizing
and/or destroying membrane integrity, leading to the leakage of intracellular
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substances. The antibiofilm activity of EOs was reported. Eighty percent of
the world population uses traditional medicine (TM), and medicinal plants
(MPs) represent a large bioactive-compounds source. Traditional Chinese
medicine (TCM) compiled thousands of herbs and formulae used for disease
treatment and dietary supplements. Emerging evidences showed that the
certain active constituencies from TCMs possess distinct prebiotic-like
effects, to which the inflammation and cancer progress were alleviated. It
was speculated that TCMs might exert their medicinal functions via the
modulation of gut microbiota (GM), and the gut epithelial environment to
host benefit. -Cell regenerative potential of selected herbal extracts was
informed in alloxan-induced diabetic rats [1]. Efficacy and safety of TCM
for primary intracerebral haemorrhage were reviewed [2]. Bicyclo-[6.3.0]-
undecane-sesquiterpenoids structures, bioactivities and syntheses were
revised [3].
Earlier publications in Nereis, etc. classified yams [4], lactic acid
bacteria [5], fruits [6], food spices [7] and oil legumes [8] by principal
component (PCA), cluster (CA) and meta-analysis (MA). The molecular
classifications of 33 phenolic compounds derived from the cinnamic and
benzoic acids from Posidonia oceanica [9], 74 flavonoids [10], 66
stilbenoids [11], 71 triterpenoids and steroids from Ganoderma [12], 17
isoflavonoids from Dalbergia parviflora [13], 31 sesquiterpene lactones
(STLs) [14, 15] and STL artemisinin derivatives [16] were informed. A tool
for interrogation of macromolecular structure was reported [17].
Mucoadhesive polymer hyaluronan favours transdermal penetration
absorption of caffeine [18, 19]. Polyphenolic phytochemicals in cancer
prevention and therapy, bioavailability and bioefficacy were reviewed [20].
From Asia to Mediterranean, soya bean, Spanish legumes and commercial
soya bean PCA, CA and MA were published [21]. Antioxidants (AOs) of
NPs from herbs and spices improved the oxidative stability and frying
performance of vegetable oils [22]. The relationship between vegetable oil
composition and oxidative stability was revealed via a multifactorial
approach [23]. It was informed chemical and biological screening
approaches to phytopharmaceuticals [24], cultural interbreeding in
indigenous and scientific ethnopharmacology [25], ethnobotanical studies of
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Francisco Torrens and Gloria Castellano
42
MPs, underutilized wild edible plants, food, medicine [26], biodiversity as a
source of drugs, Cordia, Echinacea, Tabernaemontana, Aloe [27],
immunomodulatory molecules from Himalayan MPs [28], antimicrobial,
AO, composition of Verbena carolina and Mentha [29], phylogenesis by
information entropy, avian birds and 1918 influenza virus [30]. The aim of
the present work is to review bioprocess and metabolic engineering of C.
cognatum roots for production of antitumour quinonemethide triterpenes,
pancracine as a novel candidate lead-structure in therapy of oncological
diseases, patchouli EO, its derived compounds revealing prebiotic-like
effects in C57BL/6J mice, EOs, their natural active compounds presenting
antifungal properties, caryophyllene in C. boreale EO inducing G1 phase cell
cycle arrest in human lung cancer cells, NPs in neurodegenerative diseases
as a great promise but an ethical challenge, factors responsible for risen NPs
use, limonin pharmacology, toxicity and pharmacokinetics.
2. CHEILOCLINUM COGNATUM ROOTS
FOR ANTITUMOUR QUINONEMETHIDE TRITERPENES
Biochemical and genetic manipulation of in vitro root cultures are
exploited to increase target-bioactives production. Roots from Celastraceae
species accumulate quinonemethide triterpenoids (QTs) of interest because
of their range of bioactivity, especially their notable and selective cytotoxic
activity vs. myeloma cell proliferation, hepatocellular carcinoma, prostate
cancer, glioblastoma and pancreatic cancer cells. Franca group established
in vitro culture of Cheiloclinum cognatum roots, able to produce and excrete
QTs, as an alternative for continuous production under monitored conditions
of QTs [31]. Biochemical and genetic manipulations and strategies, e.g.,
exogenous addition of isotopically labelled precursors were performed to
increase the yield of active metabolites, and obtain metabolic intermediates
of interest for elucidation of the biosynthetic path, driving the production of
C. cognatum QTs. Metabolomic and transcriptomic studies conducted to
investigate the enzymatic regulation by oxidoreductases cytochrome P
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(CYP)450, key enzymes that catalyze oxidative reactions responsible for the
diversity of QTs biosynthesized in C. cognatum roots, allowed the
identification of expressed sequences related to three CYP450 types:
quinone oxidoreductase (NQO1), laccase and cytochrome C oxidoreductase.
They performed analyses for sequence categorization by similarity search
with sequences deposited in Genbank database (NCBI), and multiple
alignments with Clustal software. Cheiloclinum cognatum expressed
sequences related to NQO1 gene showed high similarity, more than 96%,
with sequences of 12 other Celastraceae species. Enzymes of NQO1 play a
role in the excretion of compounds for detoxification of cells and may be
related to the excretion of QTs into C. cognatum root culture medium.
Overall results contribute for the elucidation of key redox steps of the
biosynthetic pathway of QTs, and validation of the established bioprocess
as a viable alternative for the continuous production of QTs to be used in the
development of innovative medicines.
3. PANCRACINE: A NOVEL CANDIDATE
LEAD-STRUCTURE IN ONCOLOGICAL THERAPY
Cancer is one of the most dangerous worldwide diseases with lethal
impacts. Thanks to a huge effort of many scientists from the whole world,
the understanding of oncological diseases is considerable. Current treatment
of oncological diseases includes surgical treatment, radiotherapy (RT),
chemotherapy [CT, e.g., hormonal therapy (HT)], in cases immunotherapy
(IT) and appropriate combination of all of them. According to National
Cancer Institute (NCI), plant program is the most promising source of
anticancer agents of natural origin. The NPs are a source of not only
cytotoxic compounds but also substances capable of overcoming apoptosis
resistance together with the anti-invasive and anti-metastatic activity.
Peterova group evaluated the mechanism of anticancer action of potential
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Francisco Torrens and Gloria Castellano
44
therapeutics based on selected promising montanine-type isoquinoline
alkaloid, pancracine, which was isolated from plant of Amaryllidaceae
family at the department of Pharmaceutical Botany, Faculty of
Pharmacy in Hradec Králové, and its molecule is characterized by a
5,11-methanomorphanthridine ring system [32].
4. PATCHOULI AND ITS DERIVED COMPOUNDS
REVEALED PREBIOTIC-LIKE EFFECTS
Pogostemon cablin (PC) is a medicinal herb (MH) commonly used for
treating gastrointestinal (GI) symptoms (e.g., colds, headaches, nausea,
vomiting, abdominal pain, diarrhoea, ulcerative colitis, dyspepsia, poor
appetite). Patchouli EO (PEO) extracted from PC leaves is the main active
component and a well-known EO for a number of medicinal purposes.
Patchouli alcohol (PA, C15H26O, cf. Figure 1a) is a tricyclic sesquiterpene
[33]. It is the major component of PC and contributes to EO pungent smell.
Pogostone (PO, C12H16O4, Figure 1b) is a 2H-pyranone derived from PEO.
-Patchoulene (-PAE, C15H24, Figure 1c), which derived from PEO, is
another PEO representative hydrocarbon (HC) sesquiterpenoid.
5. OILS AND NATURAL ACTIVE COMPOUNDS
PRESENTING ANTIFUNGAL PROPERTIES
The composition of an EO varies not only from one species to another,
but also from one organ to another (e.g., root, aerial organs) and according
to the season. It can contain tens to hundreds of different compounds. Three
or four main compounds represent more than 60% of the mass and determine
the bioproperties of EOs. The major components are displayed in Figure 2
[34].
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Figure 1. The chemical structure of (a) PA, (b) PO and (c) -PAE.
Figure 2. Major compounds of EOs: (a) thymol; (b) carvacrol; (c) geraniol; (d) (E)-
cinnamaldehyde.
6. CARYOPHYLLENE IN C. BOREALE EO INDUCES
G1 PHASE CELL CYCLE ARREST
Chrysanthemum boreale (Asteraceae) is a plant widespread in East Asia,
used in folk medicine to treat a number of disorders (e.g., pneumonia, colitis,
stomatitis, carbuncle). Whether C. boreale (ECB) EO and its active
constituents present anti-proliferative activities in lung cancer (LC) is
unknown. The cytotoxic effects of ECB in A549 and National Cancer
Institute (NCI)-H358 human LC cells were investigated [35]. Culture of
A549/H358 cells with ECB induced apoptotic cell death, as revealed by a
rise in annexin V staining. The ECB treatment reduced mitochondrial
membrane potential (MMP), disrupted pro-anti-apoptotic Bcl-2 proteins
balance and activated caspase-8/9/3, as assessed by western blot analysis.
Pretreatment with a broad-spectrum caspase inhibitor (z-VAD-fmk)
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attenuated ECB-induced apoptosis. Gas chromatography-mass spectrometry
(GC/MS) analysis of ECB identified six compounds. Among them,
caryophyllene exhibited an anti-proliferative effect and was identified as the
major active compound. Caryophyllene induced G1 cell cycle arrest by
downregulating cyclin D1/E, cyclin-dependent protein kinase (CDK)-2/4/6
and retinoblastoma (RB) phosphorylation, and upregulating p21CIP1/WAF1 and
p27KIP1, which results indicate that caryophyllene exerts cytotoxic activity
in LC cells via induction of cell cycle arrest. Analysis of GC/MS of ECB
revealed six major constituents (cf. Figure 3), and their cytotoxicity was
determined in A549/H358 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-
diphenyltetrazolium bromide (MTT) assay. Caryophyllene showed the
strongest cytotoxicity among the compounds.
7. DEGENERATIVES: FACTORS RESPONSIBLE
FOR RISEN USE OF NATURAL PRODUCTS
Despite remarkable breakthroughs in people’s understanding of
neurodegenerative diseases (NDs), little success existed in developing
effective therapies. The therapies currently available seem to be inadequate
for NDs, as they only act to alleviate symptoms but cannot stop the progress
of the disease. The use of NPs grows, probably because of several factors:
1) dissatisfaction with the results from traditional drugs; 2) claims on the
efficacy of plant medicines; 3) rising propensity of consumers for natural
therapies and alternative medicines; 4) diffuse misconception that herbal
products are safer than traditional ones; 5) high cost of many traditional
drugs; 6) improvements in the quality, efficacy and safety of herbal
medicines with the development of science and technology; 7) risen patient
decision-making autonomy regarding therapeutic options and alternatives;
8) a movement towards self-medication [36].
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Figure 3. a) 1,8-cineole; b) thujone; c) caryophyllene; d) camphor; e) borneol; f) 2-
isopropyl-5-methyl-3-cyclohexen-1-one.
8. LIMONIN: A REVIEW OF ITS PHARMACOLOGY,
TOXICITY AND PHARMACOKINETICS
Double -lactone limonin is a natural tetracyclic triterpenoid compound,
which widely exists in Euodia rutaecarpa (Juss.) Benth., Phellodendron
chinense Schneid. and Coptis chinensis Franch. Its extensive
pharmacological effects attracted attention. A review provided the latest
information on the pharmacology, toxicity and pharmacokinetics of limonin,
exploring the therapeutic potential of the compound and looking for ways to
improve efficacy and bioavailability [37]. It presents a wide spectrum of
pharmacological effects [e.g., anti-cancer, anti-inflammatory (AI) and
analgesic, anti-bacterial and anti-virus, AO, liver protection properties].
However, it led to hepatotoxicity, renal toxicity and genetic damage. It
presents complex impacts on hepatic metabolic enzyme. Pharmacokinetic
studies showed that it presents poor bioavailability, and the reduction,
hydrolysis and methylation are its main metabolic pathways. The position
and group of its substituents are key in affecting pharmacological activity
and bioavailability. However, issues exist, e.g., its mechanism of AO
activity not being clear. Few studies exist on its toxicity mechanism, and the
effects of its concentration on pharmacological effects and toxicity are not
clear, and no researchers reported ways in which to reduce its toxicity. It
(obaculactone, evodin, cf. Figure 4) belongs to the tetracyclic triterpenoids
and is a secondary metabolite with high bioactivity in plants.
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Francisco Torrens and Gloria Castellano
48
Figure 4. Molecular structure of limonin.
9. DISCUSSION
The TCM alleviates chronic liver disease, reducing lipidosis, regulating
immunity, improving liver function and protecting hepatocytes. Via 10
MHs, Chinese Herbal Formula (CHF03) was formulated to test the
hypothesis that exerts protective effects vs. non-alcoholic fatty liver disease
in vivo in mice [38]. Its main components were identified via liquid
chromatography-MS analysis (amino acids, organic acids, fatty acids,
nucleosides, flavones). Substances with the highest concentration were citric
acid and L-arginine. Oral CFH03 reduced in vivo/vitro high-fat diet-induced
lipid accumulation, chronic liver injury and protected hepatocytes. Patchouli
is a TCM for the treatment of GI symptoms. The PEO and derived
compounds are its main active ingredients that possess AI, AO, anti-
microbial, anti-allergy and anti-cancer effects based on cellular and animal
studies. Ten drugs are available in antifungal arsenal for the treatment of
invasive fungal infections. Five classes exist, each with a different mode of
action. 1) Polyenes, e.g., amphotericin B, target the plasma membrane and,
in particular, ergosterol, a major component of the fungal membrane that
increases membrane fluidity and causes cell death. 2) Echinocandins, e.g.,
caspofungin, target -(1-3)-glucan in the fungal cell wall. 3) Azole
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derivatives (e.g., fluconazole, voriconazole) act on the biosynthetic pathway
of ergosterol, increasing membrane fluidity and accumulation of a toxic
sterol. 4) Allylamines, e.g., terbinafine, target the plasma membrane and, in
particular, the first steps of ergosterol synthesis. 5) Pyrimidines, e.g., 5-
fluorocytosine, act on the nucleus and, in particular, on deoxyribonucleic
acid (DNA) synthesis. Mechanisms are involved in the synergistic effect of
antifungals: 1) inhibition of different stages in the fungal intracellular
pathways that are essential for cell survival; 2) action of another antifungal
agent on the fungal cell membrane; 3) inhibition of carrier proteins; 4)
simultaneous inhibition of different cell targets.
Botanical medicines were used in developing countries as the major
source of treatment. Anti-cancer NPs or derivatives included 49% of 175
FDA-approved small molecules; e.g., vinca alkaloids, isolated from
Catharanthus roseus, cause microtubule disruption and induce cell cycle
arrest at metaphase, resulting in cancer-cells apoptosis. The SB365, a
saponin D extracted from Pulsatilla koreana roots, exhibits anti-
proliferative effects in cancer cell lines. In pancreatic cancer, it induces
apoptosis and inhibits angiogenesis, contributing to a rise in patient survival
rate to 54% without adverse effects. The efficacy of its intravenous treatment
is investigated in clinical trials. Chrysanthemum boreale is distributed along
the Korean Peninsula and spread to the Manchuria region. It and similar
species (C. indicum, C. lavandulaefolium) were used in conventional
Eastern treatments for stomatitis, pneumonia, carbuncle, fever and vertigo.
Guaianolide derivative 8-acetoxy-4,10-dihydroxy-2,11(13)-guaiadiene-
12,6-olide, isolated from C. boreale, presented cytotoxic activity vs. human
cancer cell lines. However, ECB underlying mechanisms were not reported.
Compounds were isolated from ECB: monoterpenes camphor, thujone, cis-
chrysanthenol, 1,8 cineole, -pinene and sesquiterpene caryophyllene,
which induces cell cycle arrest at G1 phase in human LC cell lines, based on
the observation that caryophyllene promoted downregulation of G1 cell
cycle positive and upregulation of G1 cell cycle negative regulators.
As an alternative therapeutic source, EOs extracted from plants are
qualified as an important biotechnological product to be explored for
pharmaceuticals and food companies [39]. The EOs are constituted by
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Francisco Torrens and Gloria Castellano
50
volatile organic products of classes (e.g., aldehydes, terpenes, phenolic
compounds) synthesized by a secondary metabolism from different plants
parts. Studies documented EOs to be effective antimicrobial agents vs.
pathogens. Effect of EO is closely related to the capability of permeabilizing
and/or destroying membrane integrity, leading to the leakage of intracellular
substances. Antibiofilm activity of EOs was published. The growing threat
of antimicrobial drug resistance to conventional antimicrobial drugs
stimulated the search for therapeutic alternatives (e.g., extracts of MPs,
EOs), which are recognized for potential antimicrobial role vs.
microorganisms [40]. Eighty percent of the world population uses TM, and
MPs represent a large bioactive-compounds source. Frankincense and
myrrha represent a clinically typical herbal pairing found in Ruxiang Zhitong
San, with effects of invigorating circulation, reducing stasis, astringing
wounds and generating muscle [41].
CONCLUSION
From the present results and discussion, the following final remarks can
be drawn.
1. Chinese-Herbal-Formula-CHF03 protective effect on non-alcoholic
fatty liver disease in mice is related to its ability to regulate the
inflammatory response and lipogenic response controlled by sterol
regulatory element binding transcription factor 1. Thus, Formula
CHF03 is a promising mix of natural compounds that could be used
for the treatment of non-alcoholic fatty liver disease.
2. Patchouli oil/alcohol/pogostone/-patchoulene possess prebiotic-
like effect in C57BL/6J mouse model. The herbal treatments
improved the gut epithelial barrier, reinstating the expressions of
epithelial and neural cadherin, upregulating p-lysozyme and Muc 2
genes expression, and suppressing the pro-inflammatory cytokine
expressions. Sequencing data of 16S showed that the herbal
treatments positively modulated gut microbiota composition, in
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51
which the relative abundance of short-chain fatty- and lactic-acid-
producing bacteria were enhanced, while certain pathogenic
bacteria were reduced.
3. Essential oils are widely used in a number of fields, e.g.,
cosmetology or the food industry. Numerous studies highlighted the
action of these oils on various physiological effects in humans. In
addition, their antimicrobial effects were recognized.
4. The antifungal effects of these oils, alone or in combination with
pre-existing antifungals, would be an interesting solution for
improving therapeutic failures related to emergence of resistant
strains and an increase in immunosuppressive treatments in
medicine.
5. Although the studies are promising, people must not forget to
consider the toxicity of these products. In fact, essential oils are
already known to pose a high risk of allergy and irritation.
6. Oil from Chrysanthemum boreale exerts its anti-proliferative effect
via caspase activation and mitochondria-dependent apoptosis in
human lung cancer cells. Its active constituent is caryophyllene,
which promotes G1 cell cycle arrest in the cell types. The oil is a
potential chemotherapeutic agent for the treatment of non-small cell
lung cancer.
ACKNOWLEDGMENTS
The authors thank support from Fundación Universidad Católica de
Valencia San Vicente Mártir (Project No. 2019-217-001UCV).
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Francisco Torrens and Gloria Castellano
52
in alloxan induced diabetic rats. Curr. Drug Discov. Technol. 2019,
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[2] Wang, H. L.; Zeng, H.; Xu, M. B.; Zhou, X. L.; Rong, P. Q.; Jin, T.
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In: Innovations and Challenges in Modern ISBN: 978-1-53618-181-4
Editor: A. K. Haghi © 2020 Nova Science Publishers, Inc.
Chapter 3
REVIEW:
POSSIBLE FIELDS OF METAL CARBON
MESOSCOPIC COMPOSITES APPLICATION
V. I. Kodolov1,2,
, V. V. Kodolova-Chukhontseva1,3,
I. N. Shabanova1,3, N. S. Terebova1,3, Yu. V. Pershin1,2,
R. V. Mustakimov1,2 and A. Yu. Bondar2
1Basic Research High Educational Centre of Chemical Physics
and Mesoscopics, UD, RAS, Izhevsk, Russia
2M. T. Kalashnikov Izhevsk State University, Izhevsk, Russia
3Udmurt Federal Research Centre, Izhevsk, Russia
ABSTRACT
This chapter is dedicated to the consideration of the metal carbon
mesocomposites application possibilities for the different practical trends.
Each from these trends is determined by correspondent peculiarities of
content and structure of mesoscopic composites. The main peculiarities of
these nanosized particles are following: a) the presence of unpaired
Corresponding Author’s Email: vkodol.av@mail.ru.
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electrons on the carbon shell; b) the structure of carbon shell from poly
acetylene and carbine fragments; c) the atomic magnetic moment of inner
metal is equaled to more than 1–3 μB. The creation of reactive mesoscopic
materials with regulated magnetic characteristics which can find the
application as modifiers of materials properties, catalysts for different
processes, effective inhibitors of oxidation processes including corrosion
processes, sorbents, stimulators of plant growth and also as medicine
magnetic transport within organisms, is very topical. The present
investigation has fundamental character. It’s based on the ideas concerning
to the change of metal carbon mesocomposites reactivity. The using is
possible as metal carbon mesocomposites both and their modified
analogous. The application examples are presented for the properties
improvement of concretes, polymer compounds, plastics as well as for the
increasing of positive qualities of such substances as glues, corrosion
inhibitors, fire retardants, stimulators of plants growth and medicine
magnetic transport.
Keywords: metal carbon mesoscopic composites (mesocomposites), phase
coherency, charge quantization, interference, annihilation, self
organization, red ox synthesis, catalysts, reagents, modifiers, adhesives,
glues, inorganic and organic polymeric materials, corrosion inhibitors,
fire retardants, magnetic transport of medicines in organism, stimulators
of plants growth
1. INTRODUCTION
The manuscript is presented as the review of series of papers,
manuscripts and patents on the obtaining, investigations and applications of
uncials magnetic mesoparticles which are mesoscopic metal carbon
composites [141]. The correspondent structure and content of these
mesocomposites are caused by the special conditions of their production. In
as much as the application of mesoparticles is determined by the properties
of these particles which are defined by their structure and content. At the
beginning let us consider the initial metal carbon mesocomposite electron
structure and correspondent magnetic characteristics (metal atomic
magnetic moments, and the spin quantities on carbon shell). The activity of
metal-carbon mesoscopic composites are caused by the structure and
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composition of correspond mesocomposites, which contain the delocalized
electrons and double bonds on the surface of carbon shell. Therefore the
initial mesoscopic composites are early participated in reactions, especially
radial processes and reduction oxidation processes. This activity may be
used in modification processes mesocomposites accompanied by the
magnetic characteristics changes in modified mesoscopic composites. That
development of possibilities processes opens new era for further
investigations and development of metal carbon mesoscopic composites
application fields. The expansion of metal carbon mesocomposites
application chances takes place.
2. COMPOSITIONS AND STRUCTURES OF METAL
CARBON MESOCOMPOSITES INCLUDING
MODIFIED MESOCOMPOSITES
The representation about metal carbon mesocomposites is based on the
results of the following investigations: IR or Raman spectroscopy, x-ray
photoelectron spectroscopy (XRPES), electron paramagnetic resonance
(EPR), transition electron microscopy (TEM), atomic force microscopy
(AFM). The images of Copper Carbon and Nickel Carbon mesocomposites
structures show on Figure 1a, b [33, 41].
According to the investigation results the Copper Carbon
mesocomposite includes Copper containing clusters linked with Carbon
shell which consists from 3-4 layers of carbon fibers. These fibers contain
the carbine and poly acetylene fragments on the joints which the unpaired
electrons are found. These fragments are defined by means of x-ray
photoelectron spectra (Figure 2a, b) as well as metals atomic magnetic
moments.
The atomic magnetic moment of Copper is equaled to 1,3 μB. The
mesocomposite obtained is tested as materials modifier.(in minute
quantities, less than 0,01%), as additives to corrosion inhibitors, fire
retardants, thermal retardants, antistatic as well as catalysts or reagents at
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radical or reductionoxidation processes, stimulators of plant growth,
magnetic transport of medicine in organism. Further the examples of Copper
Carbon mesocomposite application are presented.
a
b
Figure 1. TEM microphotographs for Copper Carbon (a) and Nickel Carbon
(b) mesocomposites.
a b
Figure 2. C1s spectra for Copper Carbon (a) and Nickel Carbon mesocomposites.
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Nickel Carbon mesocomposite has similar structure to previous Copper
Carbon mesoscopic composite only with the increased quantity of joints
between carbine and poly acetylene fragments and consequently more
number of unpaired electrons. This mesocomposite may be ascribed to
ferromagnetic substances. Atomic magnetic moment of mesocomposite is
equaled to 1,8 μB.
According to the XPS spectra (Figure 2), the carbon fibers can contain
fragments of carbine and poly acetylene; the component at 281-282 eV is
ascribed to carbine, and the peak at 285 eV is attributed to the C-H bond. It
can be assumed that at the junction of the two fragments the formation of
unpaired electrons is possible. The coordination interaction of metal with
double bonds of corresponding fragments, mainly carbine fragments, can be
a stabilizing factor for such carbon shell. From the C1s spectra for the Cu-C
and Ni-C mesocomposites it can be seen that the peak corresponding to C-
H bonds is 30% higher for the Ni-C mesocomposite than that for the Cu-C
mesocomposite. This fact can be connected with the decrease (shortening)
of carbine fragments in the Ni-C mesocomposite. The obtained result can be
explained by the incomplete reduction of nickel oxide during the Ni-C
mesocomposite formation (Table 1).
Table 1 presents the ratio of metal-containing phases in the metal carbon
mesocomposite calculated with the use of the X-ray diffraction patterns [31].
Table 1. The metal containing phases content in Cu-C
and Ni-C mesocomposites
Phase
Cu-C mesocomposite
Ni-C mesocomposite
CuO
1.17%
-
Cu2O
5.19%
-
Cu
93.64%
-
NiO
-
32.15%
Ni
-
67.85%
From the previous it is following that the Ni-C mesocomposite has more
junctions between the carbine and poly acetylene fragments and,
consequently, a larger number of unpaired electrons that is confirmed by the
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EPR spectra: for the Ni-C mesocomposite 2.46·1023 spin/g, and for the
Cu/C mesocomposite 1.2·1017. The presence of unpaired electrons on the
fibers of carbon shell of the studied particles indicates the possibility of their
activity in the reactions with chemical substances. The results of TEM and
x-ray photoelectron spectroscopy investigations are very well confirmed to
EPR spectra (Table 2). EPR spectrum of Copper Carbon mesocomposite is
presented as a singlet spectrum in which the distance between points of
incline maximum ΔHpp = 6,8 Hz, g-factor equals to g-factor of biphenyl
picryl hydrazyl (g = 2,0036), and the unpaired electrons number corresponds
to value 1,2·1017 spin/g. In the comparison with this spectrum, the EPR
spectrum for Nickel/Carbon mesocomposite has ΔHpp corresponding to
2400 Hz, g 2,46 and the unpaired electrons number 1022 spin/g.
Table 2. Data of EPR spectra for Copper Carbon
and Nickel Carbon Mesocomposites
Type of metal carbon
mesocomposite
g-factor
Number of unpaired electrons, spin/g
Copper Carbon mesomposite
2,0036
1,2•1017 spin/g
Nickel Carbon mesocomposite
2,46
10²3 spin/g
The difference in EPR spectra is in all probability explained by the
Carbon shell difference of these mesocomposites.
Cobalt Carbon mesoscopic composite is obtained with following
characteristics: the density 1,9 g/cm3, the Cobalt atomic magnetic moment
is equaled to 1,6 μB, and also this mesocomposite has the high chemical
activity at concentration less than 0,01% in polar media.
Iron Carbon mesocomposite has the following characteristics: the
density 2,1 g/cm3, the Iron atomic magnetic moment 2,5 μB, the high
chemical activity in polar media at concentration equaled to 0,001%.
Both these composites have analogous structures similar to structures of
previous Ni-C and Cu-C mesocomposites. These substances may be
classified as stable radicals with the migration of unpaired electrons from
metal to carbon shell and back. These mesoparticles can stimulate the
transport of electrons within media. The correspondent structures and
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properties of mesocomposites cause their application as catalysts and active
reagents or additives in the different reactions.
3. CATALYSTS AND REAGENTS
FOR DIFFERENT PROCESSES
3.1. Reagents for Reduction-Oxidation Processes
The investigation of Copper- and Nickel Carbon mesocomposites (Cu-
C and Ni-C MC) interactions with such reagents as ammonium
polyphosphate (APPh), silica (SiO2), aluminium oxide, iron oxide, nickel
oxide and copper oxide is carried out. In correspondent reactions the element
reduction for reagents and Nickel or Copper atomic magnetic moments
growth in mesoparticles take place. Below in Tables 3 and 4 the examples
of metal atomic magnetic moments changes (in Boron magnetons) and
quantities of unpaired electrons (in spin/g) for mesoparticles modified by
APPh or silica after the mechanochemical modification processes
proceeding are given.
The metal atomic magnetic moment growth proceeds owing to the redox
processes with above chemical compounds. In papers [32, 33] it’s shown
that the reduction reactions of Phosphorus and Silicon from correspondent
substances at the interaction on the interphase boundary with mesoparticles
are realized (Figure 3, 5).
Table 3. The values of Copper (Nickel) atomic magnetic moments in
the interaction products for systems: Cu-C MC APPh (or SiO2)
and Ni-C MC APPh (or SiO2)
Systems Cu-C MC substances
μcu
Systems Ni-C MC - substance
μNi
Cu-C MC silica
3,0
Ni-C MC silica
4,0
Сu-C MC APPh
2,0
Ni-C MC APPh
3,0
Cu-C MC - APPh, relation 1:0,5
4,2
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Table 4. The unpaired electron values (from EPR spectra) for systems
“Cu-C MC silica” and “Cu-C MC APPh” (relation 1:1)
in comparison with initial mesoparticle Cu-C MC
Substance
Quantity of unpaired electrons, spin/g
Cu-C mesocomposite
1,2 × 1017
system «Cu-C MC SiO2»
3,4×1019
system «Cu-C MC APPh»
2,8×1018
The increase of the metal atomic magnetic moment during the mixing
of the Cu-C mesocomposite with chemical compounds and the change of the
number of delocalized electrons on carbon structures is connected with the
interaction of a nanosized particle with the environment. The assumed
mechanism of the increase of the metal atomic magnetic moment is the
electron exchange at the phase boundary similar to heterogeneous catalysis
in multi cells. For a large particle, the relation of the surface to mass is so
small that the metal surrounding cannot influence the electron density of its
d-zone; in this case, the magnetic moment of a small particle can noticeably
change. It is shown in [33] that as a result of mechanochemical mixing, in
the obtained systems “Cu-C ammonium polyphosphate” and “Cu-C
silica,” phosphorus or silicon of the compound are reduced; this fact
confirms the interaction presence of mesocomposite with reagents on the
phase boundary.
The XPS P2p spectra for phosphorus-containing mesocomposites
prepared at the ratio of presents the reagents Cu-C: ammonium
polyphosphate = 1 and Cu-C: ammonium polyphosphate = 2 show in
Figure 3.
The phosphorus reduction at the ratio of 2 is almost 50% more complete
[32, 33] and from the comparison Figure 3a and Figure 3b.
Such result can be explained by the rate of the electron quantization at
the increase in the thickness of the ammonium polyphosphate layer.
In this case the structure Phosphorus containing Copper Carbon
mesocomposite is similar to the initial mesocomposite (Figure 4), only the
increasing of carbon fibers thickness is noted because of the possible
disposition of phosphorus reduced between carbon atoms of carbon fibers.
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The Phosphorus disposition between carbon fibers can be explained by
the interaction of Phosphorus electrons with the carbine double bonds
electrons that is confirmed by further studies on the reactions of
mesocomposite obtained with different reagents.
Figure 3. The XPS P2p spectra: a) Cu/C + APP 1:1; b) Cu/C + APP 1:0.5 [8].
Figure 4. TEM microphotograph for Phosphorus containing Copper Carbon
mesoocomposite.
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Figure 5. The XPS Si2p spectrum for the sample Cu/C + SiO2 at the ratio 1:1
(E(SiO) = 100.7 eV; E(Si) = 99 eV).
Figure 6. x Ray photoelectron spectra of Copper-Carbon mesocomposites modified by
p element containing substances.
In the case, when ammonium polyphosphate is replaced by aerosol (or
silicon), the reduction of silicon from silicon oxide takes place by 50%
independent of the used amount of the reagents (Figure 5); this can be
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explained by the decrease of the rate of the electron quantization in the layer
containing Si-O bonds.
The early created method [2, 7] on the base of the x-ray photoelectron
spectra is used for the Copper Carbon mesocomposite modification
mechanism investigation. The inner levels spectra for C1s, O1s, Si2p, P2p,
S2p Cu3s are studied to investigate the mechanism of chemical bonds
formation between metal or carbon atoms and silicon or phosphorus atoms.
It’s noted the presence of changes in the Cu3s spectra in mesocomposites
modified in comparison with initial mesocomposite.
Cu3s spectra of mesoparticles modified by Si, P and S containing
compounds are presented below (Figure 6).
Below the results of investigations by means of x-ray electron
spectscopy for Nickel Carbon nanocomposite interactions with oxides of
such metals as Aluminium, Iron, Nickel and Copper are given in Tables 5-7
and in Figures 7, 8.
The relations of nanocomposites (mesoparticles) to above oxides are
changed from 1:1 to 1:0,2 depending on the qualitive spectra obtaining, For
example, the relations of 1:1 and 1:0,5 for system “Ni-C MC Al2O3” leads
to full mask of mesoparticle. Therefore the quantity of aluminium oxide is
decreased to the relation 1 : 0,2. In accordence with Al3s spectra Aluminum
is completely reduced during the modification process, and Nickel atomic
magnetic moment is increased to 4,8μB (Table 5).
Table 5. Parameters of multiple splintering Me3s spectra
in system Ni-C + Al2O3
Sample
I2/I1 (Ni)
Ni, eV
μNi
μБ
Ni/C
0.3
3.0
1.8
Ni/C + Al2O3=1:0.2
0.9
1.0
4.8
I2/I1 the relation of multiple splintering lines maximums intensities;
- Energetic distance between the multiple splintering maximums in Me3s spectra.
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Table 6. Parameters of multiple splintering Me3s spectra in systems
Ni-C MC Fe2O3 and Ni-C MC CuO
Sample
I2/I1
(Ni)
Ni,
eV
μNi μБ
(I2/I1) Fe
Fe, eV
μFeБ
Ni-C MC + (Fe2O3)
0.5
2.4
2.5
0.6
2.0
3.0
Ni-C MC + CuO
0.5
3.0
2.5
0.4
3.0
2.0
I2/I1 the relation of multiple splintering lines maximums intensities;
- Energetic distance between the multiple splintering maximums in Me3s spectra.
In this case the reduction process is related to not only Aluminum oxide
but also to Nickel oxide from metal cluster of mesoparticle (Ni-C MC).
Therefore the reduction processes are stipulated by the electron transport
from carbon shell of mesoparticle in direction to Al+3 and Ni+2 of atoms in
correspondent oxides.
The next researches with using of x-ray photoelectron spectroscopy are
carried out for the following systems: Ni-C MC Fe2O3 and Ni-C MC
CuO (Table 6).
It’s necessary to note, that the iron oxide is sufficient easily transformed
in Fe3O4 (magnetite). At the heating the farther reduction of iron with its
implantation within the carbon shell is observed.
When Copper oxide (CuO) is added to Ni-C mesocomposite in the
relation 1:1 at the grinding, the relative intensity of multiple maximum for
Ni3s and Cu3s spectra is correlated with the atomic magnetic moments
values (Table 6).
C1s spectrum for system “Ni-C MC–CuO” consists from 3 components:
CC (sp2 hybridization) 284 eV; CH bond 285 eV; CC (sp3 hybridization)
286 eV. The results of multiple splintering in Ni3s spectra for systems “Ni-
C MC –CuO” and “Ni-C MC NiO” are closed (Tables 6, 7).
X ray photoelectron spectroscopy investigations of Ni/C mesoparticles
modified by Nickel oxide are carried out for the following systems: a) Ni-C
MC NiO, relation 1:1; b) Ni-C MC NiO, relation 1:0,5. The researches
proceed without the sample heating and with the heating (300ºC) of samples.
When the studies are realized without heating the intensity of maximum
Ni2p line corresponds to binding energy equaled to 855 eV (NiO). However
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at the heating to 300ºC the intensity maximum for this line is attributed on
binding energy to 852 eV (Ni). Below the Ni3s spectra for a) and b) systems
without heating are shown (Figure 7).
Figure 7. Ni3s spectra for systems: a) Ni C MC NiO (1:0,5);
b) Ni-C MC NiO (1:1).
Figure 8. C1s spectra: a) surface without heating; b) Ni/CNiO, 1:1 (300ºC);
c) Ni/CNiO, 1:0,5 (300º).
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Table 7. Parameters of multiple splintering Me3s spectra in Ni/C
nanocomposite (Ni/C NC) and in systems, containing Ni-C MC NiO
Sample
I2/I1Ni
Ni, eV
μNiБ
Ni-C MC .
0.32
3,0
1.8
Ni-C MC+ NiO= 1:0,5
0.6
2.6
3.0
Ni-C MC+ NiO= 1:1
0.8
2.2
4.0
I2/I1 the relation of multiple splintering lines maximums intensities;
- Energetic distance between the multiple splintering maximums in Me3s spectra.
The Oxygen content is more much decreased at the sample heating. The
C1s spectra (Figure 8) consist from three components which take place [2]
in Carbon nanostructures: 285 eV(CH bond); 284 eV (sp2 hybridization);
286 eV (sp3 hybridization).
According to C1s spectra for system “Ni-C MC NiO” (relation 1:1)
the maximum intensity of sp2 hybridization peak is only remained at the
sample heating to 300ºC (Figure 7b), and the CH component intensity for
the sample with relation 1:0,5 is decreased as well as the correspondent
intensity at the relation 1:1 becomes equaled to zero. These changes are
accompanied by changes of Nickel atomic magnetic moments:
for system of content 1 Ni-C MC0,5 NiO the Ni atomic magnetic
moment increasing corresponds to 1,2 μB;
for content system 1 Ni-C MC1NiO analogous increasing value
equals to 2,2 μB (Table 7).
It’s possible that the increasing of Nickel atomic magnetic moments
proceeds because of the growth of atomic magnetic moments both
mesoparticle cluster metal and modifier (NiO) metal.
The distance decrease between the maximums of multiple spintering
in Ni3s spectra for systems shows on the increase the hybridization of
d electrons in Nickel atomsthat is the reason of Nickel atomic magnetic
moment growth.
Thus, when the mesoparticles modification reactions with the using
APP, SiO2, metal oxides are carried out, the redox processes are realized. In
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these cases the modifiers reduction reactions takes place. These processes
are accompanied by the metal atomic magnetic moments growth, that is
explained by the electron shift on high energetic levels because of the
annihilation phenomenon. The energy which is evolved at this can be used
in chemical rections including connection to mesoparticle. On the base of
studies results the hypothesis of possibility of two phenomena (interference
and annihilation) in redox processes is proposed. The correspondence of
results obtained by the methods of x-ray photoelectron spectroscopy and
electron paramagnetic resonance (EPR) is given. The of changes for metal
atomic magnetic moments in dependence on the number of electrons which
participated in redox process is observed.
3.2. Reagents and Catalysts in Radical Processes
According to [40] in the presence of chemical particles containing
unpaired electrons (or radicals) and double bonds the addition reactions flow
on the radical mechanism. Below the reactions between Copper Carbon
mesoscopic composite and organic amines or halides are considered. The
explanation of these reactions mechanism concludes the notions of negative
charges quantization and interference. The quants from unpaired electrons
are active agents interacted with reagents across the formation radical
particles which are recombining. The examples of these reactions with the
participating of polyethylene polyamine (PEPA) and ammonium iodide
(AmI) are presented below.
The interaction of Copper Carbon mesocomposite with polyethylene
polyamine (PEPA) and also ammonium iodide (AmI) is studied by IR and
x-ray photoelectron spectroscopy. In these cases according to spectra the
nitrogen and iodine addition to carbon shell without change of oxidation
states as well as the absence of metal atomic magnetic moment changes in
mesoparticles is observed.
The modification processes of Copper Carbon mesocomposite is carried
out by means of the grinding of mesoparticles with reagents (PEPA or AmI)
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in mechanical mortar with the duration equaled to 3 minutes (the energy
used corresponds to 220 kJ/mol, approximately).
It’s possible to suppose the following stages:
Mechanical action on the mixture of mesoparticle and reagent
initiates unpaired electrons on mesoparticle carbon shell and
negative charge quants begin to move in side to positive charged
atom of reagent.
Then the increasing of reagent polarization with the negative charge
quants flow formation proceeds, and farther the negative charge
quants move to opposite flow of mesoparticle negative charge flow.
These processes lead to the interference and the formation of such
chemical bonds as CN and CI bonds.
In parallels the Hydrogen from reagent (for instance, PEPA) is
added to carbine bonds. Therefore, at the amine group interaction
with mesoparticle carbon shell the formation of C=N bond is
possible.
The proposed scheme is confirmed by the results of C1s and N1s spectra
(Figure 9, 10). In C1s spectrum of Cu/C nanocomposite modified by PEPA
the following components as CH (285 eV), CN (286,4 eV) and C=N (289
eV) are found. It’s necessary to note that the peak at 289 eV has the small
intesity. This fact is explained by the small quantity of NH2 groups in PEPA
because these groups are the ultimate groups in olygomer.
In N1s spectrum of Cu-C mesocomposite (Figure 10) the presence of C
N (398,8 eV) and NH (397 eV) bonds is observed.
The results of C1s and N1s spectra are confirmed the data of IR
spectroscopy for samples modified by PEPA.
In IR spectra the additional peaks at 1075 and 1268 cm-1 are appeared.
These peaks can be relevant to CN bonds in Nitrogen containing
compounds including bonds in the adsorbed PEPA on the surface of Copper
Carbon mesocomposite.
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Figure 9. C1s spectra of Cu/C nanocomposite moified by PEPA (a) and by AmI (b).
Figure 10. N1s spectra of Cu/C mesocomposite modified by PEPA.
Thus, in the case, when in the reactions with mesocomposite such
reagents as polyethylene polyamine and ammonium iodide are applied, the
connection reactions takes place. As the main method in the investigations
x-ray photoelectron spectroscopy is applied. Owing to this method the
chemical bonds formation between mesoparticles carbon shells and
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Nitrogen or Iodine is found because of the interference of negative charge
quants during the interaction processes of polyethylene polyamine or
ammonium iodide with mesocomposite. At the interactions of PEPA with
mesoparticles the CN bond formation is explained by the interference of
negative charges quants.
3.3. Reactivity of Metal Carbon Mesocomposites in
the Coordination Reactions and at the Metals Sorption
The metal carbon mesoscopic composites reactivity in the coordination
reactions is caused by the electron structure of these composites which also
determines the nanostructures forms and the peculiarities of its interactions
with media or reagents. It’s necessary to note that the metals of
mesocomposites are coordinated on carbine or on poly acetylene fragments
of these nanostructures carbon shells. The coordination reaction with the
carbine fragment of carbon shell is more probable because of great electron
density. The presence of metal cluster coordination to carbon shell secures
the electron transport from metal to carbon shell fragment. In this case the
possibility of reagents metals coordination is appeared.
For these cases the following coordination processes mechanism can be
proposed:
1. The negative charge quants stream is directed to the electron shell
of reagent atom (may be metal) and activates the electron shell
quants.
2. This activation can to initiate the positive charged quants
appearance and then the annihilation phenomenon.
3. In order to the annihilation stimulates the interference process
development which provides the metal sorption from correspondent
medium.
If the metal oxide is applied as modifier agent, it’s possible the
competition of metal reduction processes between modifier agent metal and
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mesocomposite (or mesoscopic granule) metal. For instance, at the Cu-C
MC modification by Nickel oxide it’s observed the atomic magnetic
moments growth for Copper (cluster metal within mesogranule) on 0,7 μB,
and for Nickel 0,5 μB (Table 8).
Table 8. Parameters of multiplet splitting of Ni3s and Cu3s spectra
for Cu-C mesocomposites modified by Nickel oxide, including atomic
magnetic moments of metals
Sample
I2/I1
Δ, eV
μmet, μB
Cu3s nano (Ni)
0,4Cu/0,4Ni
3Cu/2Ni
2Cu/2,3Ni
Figure 11. C1s spectrum of Nickel containing of Copper Carbon mesocomposite.
Table 9. Atomic magnetic moments of metals in modified
Nickel Carbon mesocomposite
Mesocomposite and Modifier (mass part)
μNi, μB
μCu, μB
μFe, μB
Ni-C MC NiO (0,5)
3,0
Ni-C MC NiO
4,5
Ni-C MC CuO
2,0
2,0
Ni-C MC Fe2O3
2,5
3,0
Ni-C MC Al2O3 (0,2)
4,8
Also the deformation of carbon shell takes place as well as the sp
hybridization appearance (carbine fragments) (Figure 11).
The metal atomic magnetic moment changes at Nickel Carbon
mesocomposite modification by the following metal oxides as CuO, NiO,
Fe2O3, Al2O3 are adduced in Table 9.
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On the base of results of Ni-C mesocomposite modification it’s possible
to conclude that the ability to polarization of metal oxide layer influences on
the Nickel atomic magnetic moment growth. For example, the significant
growth of Nickel magnetic moment takes place if the Aluminum Oxide is
used as modifier. During this process the Aluminum is completely reduced
(according to data of x-ray photoelectron spectroscopy).
At the beginning of processes during the joint grinding of components
the multiples (mesoscopic reactors) are formed and simultaneously the flows
of quants of negative and positive charges are appeared. In this case there is
phenomenon of annihilation with the formation of electromagnetic field
which stimulates the atomic magnetic moment growth.
4. METAL CARBON MESOCOMPOSITES APPLICATION
POSSIBILITIES AS MAGNETIC MESOSCOPIC MATERIALS
4.1. The Glues and Adhesives on the Base of Metal Carbon
Mesoscopic Composites
The presence of unpaired electrons and double bonds in carbon shell of
metal carbon mesocomposites guarantees the additional conditions for the
adhesion increasing especially at the metal materials connection. In these
cases the positive meaning has the presence of above mesocomposites
magnetic properties. For example, the introduction of Nickel Carbon
mesocomposite in the composition of Silver containing current conductive
a b
Figure 12. The adhesion durability on shift for Ag containing glue (pink) and paste
(blue), initial (a) and modified by Nickel Carbon mesocomposite.
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a b
Figure 13. The adhesion durability on separation for Ag containing glue (pink) and
paste (blue), initial (a) and modified by Nickel Carbon mesocomposite.
Table 10. The measuring results of the current conductive paste (glue)
electro resistance, modified by Nickel Carbon mesocomposite
Characteristics
Current conductive
paste
Current conductive
glue
Specific volume electro resistance,
Om∙cm (initial sample)
2,4∙10-4
3,6∙10-4
Specific volume electro resistance,
Om·cm (modified sample)
2,2∙10-5
3,3∙10-5
glue leads to the improvement of adhesion and electric conductivity (Figure
12, 13; Table 10).
Thus, the Metal Carbon mesocomposites can be applied for the
improvement of the current conductive materials characteristics.
Analogous results are obtained at the modification of cold hardened
epoxy resins by the Metal Carbon mesocomposites. According to the
investigation on the modification results of cold hardened epoxy resins the
following conclusion may be made:
The test for defining the adhesive strength and thermal stability
correlate with the data of quantum-chemical calculations and indicate the
formation of a new phase facilitating the growth of cross-links number in
polymer grid when the concentration of Cu-C mesocomposite goes up. The
optimal concentration for elevating the modified epoxy resin (ER)
adhesion equals 0.003% from ER weight. At this concentration the strength
growth is 26.8%. At the same time the optimal quantity of Cu-C
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mesocomposite for elevating the modified industrial epoxy materials
adhesion equals 0,005% that leads to the strength growth equals 60.7%.
From the concentration range studied, the concentration 0.05% from ER
weight is optimal to reach a high thermal stability. At this concentration
the temperature of thermal destruction beginning increases up to 195°С.
The modification of hot hardened epoxy resins by means of Copper
Carbon mesocomposites is carried out with the application of the finely
dispersed suspension based on iso methyl tetra phtalic anhydrate or based
on toluene. After testing the samples of four different schemes, the increase
in the strength at detachment σdet up to 50% and shear τsh up to 80% takes
place, the concentration of Copper Carbon mesocomposite introduced
corresponds to 0.0001-0.0003%.
The application of these materials as adhesives for the gluing of metals
and vulcanite is realized on the schemes “metal1 adhesive1 vulcanite
adhesive2 metal2.” To define the adhesive tear and shear strengths the
above proposed scheme was used (Figure 14, 15). The investigations carried
out revealed that the modification of the conventional recipe of the glue 51-
К-45 results not only in increasing the glue adhesive characteristics but also
in changing the decomposition character from adhesive-cohesive to
cohesive one.
The availability of metal compounds in mesocomposites can provide the
final material with additional characteristics, such as magnetic susceptibility
and electric conductivity.
Scheme 1 Scheme 2 Scheme 3 Scheme 4
Figure 14. Relative changes of adhesive tear strengths of epoxy glues modified by
Copper Carbon mesocomposites (content of MC 0,0001%).
Модификация клеевых систем тонкодисперсными
суспензиями на основе металл/углеродных
нанокомпозитов (содержание нанокомпозита 0,0001%)
(адгезионная прочность на отрыв)
0
1
2
3
4
5
6
схема 1 схема 2 схема 3 схема 4
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Scheme 1 Scheme 2 Scheme 3 Scheme 4
Figure 15. Relative changes of adhesive shear strengths of epoxy glues modified by
Copper Carbon mesocomposites (content of MC 0,0001%).
The modification of different materials by minute quantities of Metal
Carbon mesocomposite allows improving their technical characteristics,
decreasing material consumption and extending their application.
4.3. Magnetic Transport of Medicines within Organism
from Metal Carbon Mesocomposites
At last time the great attention is spared to the creation of medicine
remedies with address direction for the action on the organs which are
needed in correspondent healing. Usually the transport of therapeutically
active substances to the correspondent organ is carried out by means of the
magnetic mesoparticles containing the linker connected with medicine
substance. In other words, the remedies of medicine carriage in organisms
are constructed on the following scheme: transport magnetic mesoparticle
linker medicine [42]. In above patents the iron containing nanosized
particles, for example, Fe3O4, are used as magnetic mesoparticle, and the
organic substances connected with this mesoparticle by covalent or
coordinative bonds as linker. In this case it’s possible the certain difficulties
on the undoing of medicine because of the bio active substances big
interaction with the some functional groups. The medicine release from
magnetic mesoparticles with linker occurs at the variable magnetic fields.
The best linker can be phosphorus organic compounds which, as it’s known,
are easily destructed in water media. Therefore it’s proposed [34] to
Модификация клеевых систем
тонкодисперсными суспензиями на основе
металл/углеродных нанокомпозитов
(адгезионная прочность на сдвиг)
0
1
2
3
4
5
6
7
8
схема 1 схема 2 схема 3 схема 4
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accomplish the modification of metal containing magnetic mesoparticle by
ammonium polyphosphate. At the same time the copper carbon
mesocomposite [37] is proposed as magnetic mesoparticle since the Copper
has bactericidesand anti microbes’ properties and increases the organism
protective forces. For that reason the Copper Carbon mesoscopic composite
modified by ammonium polyphosphate chooses as the investigations object.
The modification process is carried out by mechanic chemical method in
processing which the Phosphorus reduction and the formation of linker
which consists phosphorus with the following oxidation states as 0, +3, +5
takes place.
The obtaining of remedy for medicine delivery to definite organ is
carried out on the following scheme:
The phosphorus containing copper carbon mesoscopic composites
(MC(P)) are applied as magnetic mesoparticles. Then the medicines (M) are
linked with MC(P) at the relation (MC(P) /M) correspondent to 1:(0,020,5)
by means of mechanic chemical method with the using the mechanical
mortar. The MC(P) applied are obtained by the interaction of copper carbon
mesocomposite (Cu-C MC) and ammonium polyphosphate (APP) at the
relation 1:0,5 for the obtaining of high atomic magnetic moment of Copper.
The therapeutically active substances such as adenosine tri phosphorus
acid (the relation MC(P) /M = 1:0,02), ascorbic acid (MC(P) /M = 1:0,2) and
Urotropine (MC(P) /M = 1:0,5) is linked with phosphorus containing
mesocomposite across the phosphorus containing liker.
The investigations of phosphorus containing Copper Carbon
mesocomposite and its analogous are realized with the application of
methods complex from which the basic methods are x-ray photoelectron
spectroscopy (RPES), transition electron microscopy of high solution
(permeation) (TEM), electron micro diffraction, electron paramagnetic
resonance (EPR), x-ray diffraction measuring.
According to these investigations the copper atomic magnetic moment
growth is established at the copper carbon mesocomposite modification by
ammonium polyphosphate and therapeutically active substances. The
atomic magnetic moment of Copper is obtained more (μ = 4,5μБ) in the
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comparison with iron containing nanostructures (μ = 2,5μБ). Hence the
proposed magnetic mesoparticles can be interested as the remedies of
medicine carriage in organisms by means of drive magnetic field.
The production of magnetic mesoscopic particles with connected
therapeutically active substances is realized by mechanic chemical method
on the next scheme:
The reduction-oxidation synthesis of copper carbon mesocomposite
from CuO and polyvinyl alcohol at the reagents relation equaled to
1 mol : 4 mol [31]
The copper carbon mesocomposite modification by ammonium
polyphosphate at the reagents relation [33, 39]
The phosphorus containing copper carbon mesocomposite
modification by therapeutically active substances, such, as
adenosine tri phosphoric acid (relation 1:0,02), ascorbic acid
(relation 1:0,2) and Urotropine (relation 1:0,5). (Pat.
2018143197).
The mechanic chemical synthesis is carried out with the using of
mechanical mortar by the joint grinding of reagents at the energetic expenses
approximately equaled to 260270 kJ/mol. After mechanic chemical process
the mesoscopic product obtained is dried in the closed crucible at 400ºC for
the first stage, and at 150ºC for second and third stages. Then the product
obtained is standee in vacuum at 100150ºC during 3 minutes.
The results of mechanic chemical process with thermo chemical
finishing are estimated with the application of following methods: x-ray
photoelectron spectroscopy, electron paramagnetic resonance, transition
electron microscopy with high permission.
The transition analytic electron microscope FET Tecnai G2F20 with
prefix EDAX is used for the investigation of copper carbon mesoscopic
composite structure and phase content. High permission corresponds to 2nm
in 1,5 cm.
X-ray photoelectron spectroscopic investigations are realized by x-ray
photoelectron magnetic spectrometer with the permission 10-4 at the
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activation AlKα line 1486 eV in vacuum 10-810-10 Torre. On the basis of
Van Fleck theory the model for metal atomic magnetic moments calculation
is proposed.
EPR investigations are carried out by means of EPR spectrometer Е–3
of firm «Varian».
Figure 16. C1s spectra phosphorus containing copper carbon mesocomposite (a) and its
analogous modified adenosine tri phosphorus acid (relation 1:0,02) (b), ascorbic acid
(relation 1:0,2) (c), Urotropine (relation 1:0,5) (d).
The peak correspondent to binding energy 132,5 eV is ascribed [43]
bond C=P that can be possible at the appearance of interference phenomenon
because of the direct electromagnetic field which