Kaplaushenko A.G., Iurchenko I.A.,
Varinskiy B.A., Shcherbak M.A., Kucheryavyi Yu.N., Samelyuk Yu.G.
BIOGENIC S, P, D-BLOCK ELEMENTS, BIOLOGICAL ROLE, APPLICATION IN
MEDICINE
Teaching and methodical manual
for foreign students of Zaporozhye State Medical University
Zaporozhye, 2015
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Kaplaushenko A.G., Iurchenko I.A.,
Varinskiy B.A., Shcherbak M.A., Kucheryavyi Yu.N., Samelyuk Yu.G.
BIOGENIC S, P, D-BLOCK ELEMENTS, BIOLOGICAL ROLE, APPLICATION IN
MEDICINE
Teaching and methodical manual
for foreign students of Zaporozhye State Medical University
Zaporozhye, 2015
3
UDC 541.1(075.8) B 60
It is recommended by Methodic commission on chemical sciences as a textbook for students of medical faculty (Minutes №3, 27.11.2014).
Reviewers:
Aleksandrova E.V. PhD, Professor, head department of biochemistry and laboratory diagnostics of Zaporozhye State Medical University;
Priymenko B.A. PhD, Professor of organic and bioorganic chemistry department of Zaporozhye State Medical University.
Biogenic s, p, d-block elements, biological role, application in medicine: Educational and methodical recommendations / A.G. Kaplaushenko, I.A. Iurchenko, B.A. Varinskiy, M.A. Shcherbak, Yu. N.
Kucheryavyi, Yu.G. Samelyuk. - Zaporozhye : [ZSMU], 2015.-78 p.
UDC 541.1 (075.8)
© Zaporozhye State Medical University
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CONTENTS
1. Preface………..…..………..………...…5
2. Introduction………..…..………..………...…7
3. Concise theoretical material……..………….………..….…………..8
4. Questions for self-training……….…….…..………..38
5. Tasks………..……….…….….……...39
6. The standard answers…………..….………...……...…40
7. Experimental part……….…...…...41
8. Tests………...46
9. References………..…….…....……....76
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PREFACE
Medicinal Chemistry is one of the most rapidly developing areas within the discipline of Chemistry, both globally and locally. It is the study of the design, biochemical effects, regulatory and ethical aspects of drugs for the treatment of disease.
The aim of this discipline is to produce graduates with an appropriate background in biology and pharmacology, built upon a strong chemistry foundation.
Methodical recommendation of Medicinal Chemistry is designed to equip students with strong grounding in biological and chemical technique which is relevant to the pharmaceutical world.
The discipline gives an in-depth coverage of the chemical techniques required and relates these to the relevant pharmacology, anatomy, biochemistry and molecular biology.
The whole course of Medical chemistry which consists of ten topics is studied by students-physicians during the first year. Lecturer staff of department has prepared an educational and methodical recommendation in which the theoretical material is stated in the concise and available form.
The distribution of material on each of ten topics that are studied is set according to training program, the thematic plan of lectures and practical training.
The material of each topic is stated in such way that performance of practical work and the solution of situational tasks are preceded by theoretical part in which questions of medicine and biological value and also connection with other disciplines (biological chemistry, normal physiology, pathophysiology and others) are included.
Offered laboratory works and situational tasks will give students the chance to understand theoretical material fully and to use this knowledge in practice.
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The experience of teaching medical chemistry shows that it is not always possible to coordinate an order of laboratory works realization with sequence of lecture course statement. That is why students usually have to prepare for practical work performance independently before the lesson. Therefore the theoretical part (in which the necessary volume of knowledge for conscious performance of experiment is given) precedes to each section of these Methodical recommendations.
Increasing of level of seminar and laboratory works is reached by use of such forms of occupations which open and consolidate theoretical knowledge, train scientific thinking, develop creative initiative and impart skills of handling devices and chemicals, chemical ware.
The structures, figures and schemes are clear and easy to follow and color is used well, highlighting main points without being distracting.
Chapters are helpfully signposted throughout, informing the reader how topics are related, which is especially important in such a multidisciplinary subject.
Topics are also presented clearly and with a logical progression culminating in the main points, questions and reading sections at the beginning of each chapter.
An assortment of case studies is provided and the authors work through each one in great detail, giving an overall perspective on the science.
Finally, very useful and informative appendices and a glossary are provided together with a comprehensive index that is good enough to rival any search engine!
There are many books that describe medicinal chemistry and its uses, but these methodological recommendations present medicinal chemistry and its related topics in a clear, informative and interesting way that really demonstrates the application and impact of this fundamental subject in society.
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INTRODUCTION
Purpose: to form the system of students’ knowledge about physical- chemical and biological properties of s-, p-, d-block elements, their most important compounds which are used in medicine, as well as to develop logic and depth of thinking, ability to work with literature, chemical glassware and reagents.
Targets:
- To learn general characterization of s-, p-, d-block elements.
- To get an idea about atoms’ structure and main properties of s-, p-, d- block elements and their connections.
- To learn biological role and application of most important connections of s-, p-, d-elements in medicine.
- To get practical skills in experimental work on the definition of biogenic elements.
- To learn test material The student should know:
-Basic theoretical issues about biogenic s-, p-, d-block elements, namely atom structure, position in the Mendeleev's periodic table;
-biological properties of these elements and their compounds;
-the basic analytical methods of determination for biogenic elements;
The student should be able to do:
- to use the chemical glassware correctly;
- to use analytical reagents for qualitative analysis;
-to determine the cations of biogenic metals and anions of salts;
-to assess the received analytical results correctly.
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CONCISE THEORETICAL MATERIAL 1 s-Elements. Biological role, application in medicine.
Elements of IA-group Li, Na, K, Rb, Cs, Fr, elements of IIA-group, Be, Mg, Ca, Sr, Ba, Ra as well as hydrogen and helium belong to the block of s- elements. The electronic formula of the external shell of IA-group elements and hydrogen is ns1 and of the elements of IIA group and helium - ns2, where “n” is the number of the period.
Chemical properties of s-elements of IA and IIA-groups are similar. s- Block elements easily give their valences-electrons, which means that they are strong reducers. Stable ions with an external electronic shell of the previous inert gas are formed by losing their s-electrons.
Radiuses of the ions increase in groups by growth of the atomic number of an element and decrease at transition from IA to IIA-group. The closeness of ionic radiuses of Li+, K+, Ba2+ plays an important role in the biochemistry of these metals.
S-Block elements are characterized by small ionization energy at big radiuses of atoms and ions. Mainly s-elements form compounds with ionic bonds, except of hydrogen, whose connections even with the elements with the greatest electronegavity is characterized by a covalent bond.
Hydrogen is the first element of the periodic table of elements. Fraction of total mass of Hydrogen in the Earth's crust is 1%-this is the 10th most prevalent element. However, its role in nature is not determined by the weight, but by the number of atoms, which amount among other elements is 17% (second place after oxygen-52%).So the importance of hydrogen in chemical processes occurring on the Earth is as great as the importance of Oxygen. Almost all hydrogen on Earth exists in the form of compounds and only very small number of hydrogen is contained in atmosphere in form of a simple substance (0.00005% in volume).
Hydrogen is a part of almost all organic substances and is present in all living cells. In living cells the number of atoms of hydrogen is nearly 50%.
Hydrogen is used in such industries as: chemical industry (production of ammonia, methanol, soap and plastic), food industry (registered as a food additive E949), and aviation industry.
Electron configuration of atoms of hydrogen is 1s1. Hydrogen similar to alkaline metals is univalent and has reducing properties. Hydrogen has three isotopes: protium11Н , deuterium21Н and tritium13Н .
Hydrogen concentration in the human body is approximately 10%, that comparing to its content in the Earth's crust (1%) demonstrates its exceptional role in the human body. In human organism hydrogen exists in the form of different compounds, for example water.
Sodium, potassium.
Na+ and K+ ions are always togetherin the geosphere and their separation is a difficult process, on the contrary in the biosphere these ions are distributed on different sides of the cell membrane as they relate to the extracellular (sodium) and intracellular (potassium) cations.
These ions continuously move on ion channels in both directions, down a concentration gradient. This is the movement from a region of high substance density (prevalence) to a region of low density (prevalence).Such process can't proceed spontaneously, that is why the energy for it is reported by reaction of ATP hydrolysis. K+penetrates into cells thanks to affinity to the protein membrane - phosphoprotein. ATP hydrolysis takes place in a cell with the formation of ADF (adenosine diphosphate acid), the released РО43--group phosphorylate phosphoprotein, and it "releases" K+ ion into intracellular space.
As a resultphosphorylated phosphoprotein has an increased affinity for Na+ ion, it captures the ion and "goes" with it outside, where "releases" the ion into the extracellular space. This is one of the simplified work schemesof sodium- potassium pump, whose main task is to maintain the balance of potassium and sodium in all systems of the body. Firstly, this balance provides the maintenance of required osmotic pressure in bioliquids, which is the driving force of all absorption and excretion processes; Secondly, this balance keeps pH
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values of each organ and tissue. Thirdly, sodium and potassium play a very important role in the transmission of nerve impulses.
By "ionophore" mechanism the K+ ions fall into the central cavity of the lipid membrane, which is about 1 nm in diameter and contains hydrated K+ ion.
Polypeptide spiral, which forms this cavity, has an electrostatic charge which is able to keep suchnumber of K+ ions, that corresponds to approximately 2 mol/l concentration. Then the central cavity is compressed and turns into a narrow channel-filter, which omits only already dehydrated K+ ions. This filter has 4 places to link K+thanks to peptide groups C=O, and the coordination number of K+ is equal to 8.In the same conditions the Na+ions are not associated, that provides the selectivity of cavity to K+in 104 times.
It should be noted that the ions of Rb+ and Cs+can be linked by carbonyl groups in a membrane cavity that allows to use them as probes in the study of cell membrane channels. Whenlinking K+ the internal charge of the cavity changes and it lets in and lets out K+ ions from a cell.
It is possible to explain the action of sodium-potassium pump differently, considering ability of cellular membranes "to be turned inside out" at a change of an electrostatic charge on its surface.
Magnesium, calcium
Inside the cell the amount of Mg2+ is many times more, than in the extracellular space, whenСа2+ is predominantly extracellular cation. Mg2+ion is a stronger complex former than Са2+ ion. It serves as the center of some metal- enzymes, for example, catalyzes animportant hydrolysis of ATP. Magnesium complex with ATP is a part of substrate kinase enzyme responsible for the transfer of phosphate groups. Kinases are controlled by calmodulin and other proteins and are the basis of the signal system in higher organisms.
In the plant world Mg2+ is the part of coordination centre of two main enzymes that control such global process as photosynthesis, which is to make Н2О and СО2 into carbohydrates and О2 by the influence of light energy. In photosynthesis, which can occur in the dark (so-called "dark phase"),
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magnesium is the center of the enzyme containing ribulose-1,5-diphosphate- carboxylate, which is called rubisko. This enzyme is very common in biosphere and controls the binding of atmospheric СО2 (~ 1011 tons per year!). In the original form of enzyme the Mg2+ion (with coordination number equal to 6)coordinates carboxyl groups of glutamic and aspartic acids, 3 molecules of water and the residue of lysine carbamate.
By the way carbamate is formed by the reaction of the original СО2 portion with the terminal amino group of lysine, so already present СО2 "runs" the mechanism of photosynthesis.
The content of Ca2+ in the body is ~1%, calcium- is the fifth element on prevalence after C, H, O, N. In mammals organism 95% of calcium is placed in solid tissues: bones and teeth, where it exists in the form of fluorapatite Ca5(PO4)3F and hydroxyapatite Са5(РО4)3ОН; in birds and shellfish organisms it exists in the form of СаСО3. In the blood vessels and arteries, calcium is present in the form of СаСО3 or the complex with cholesterol.
Ca2+ ions form not very strong coordination compounds, have low values of formation constants and variable coordination number (6 and 8), have moving coordination sphere, as well as the high speed exchange of ligands.
Therefore, calcium complexes are suitable for signal systems, regulate the reduction of muscle fibers, activate many enzymes, and define the process of blood clotting.
The concentration of Ca2+ in the body is regulated by parathyroid hormone - kalcitocin and its absorption is determined by the content of vitamin D in the body. The lack of this vitamin decreases the absorption of Ca and manifests itself in the form of the rickets disease. Ca is an extracellular element; its concentration in the cell is small: ~ 10-7 mol/l, and outside the cell~ 10-3 mol/l, a concentration gradient is maintained thanks to Ca-pump.
The most studied Ca-containing enzyme is calmodulin. It activates a protein kinase, catalyzes the protein phosphorylation, activates Fe-containing enzyme NO-synthase. In calmodulin Ca2+ ion has a coordination number equal
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to 6 and is surrounded by three monodentate carboxyls of asparagin acid, a bidentate fragment of glutamin acid and a water molecule.
2. P-block elements. Biological role, application in medicine.
30 elements of IIIA-VIIIA group of the periodic system belong top- elements; the p-elements enter into (II) and (III) short periods, as well as in the V-VI big periods. Elements of III-A group have one electron on the p-orbital. In other groups IVA-VIIIA there is a consecutive filling of the p-sublevel to 6 electrons.
Among p-elements there are elements that can be both cations and anions (A1, Ca, Ti, Se, Pb, PB, Sb, Bi) or only anions (В, С, Sі, N, Р, Аs, О, Те, Р, СІ, Вг, І, Аt). All cations, except A13+(1s22s22p6)have a structure of external electronic shell (n-1)d10ns2, where n is the number of period. Increased stability characterizes external electronic shell of elements of VI period because 6s2electrons are preceded by4fІ45d10electrons, which shield the nucleus.
In the period from left to right atomic radiuses of p-elements decrease with the increase of nuclear charge andincrease with the increase of ionization energy(ЕІ) and electron affinity (Еa); electronegativity (EN) increases and oxidative activity of simple substances and non-metallic properties become stronger. In groups with the increase of sequence number the radius of atoms and ions also increases. Ionization energy in transition from 2p-elements to 6p- elements decreases. With an increase of number of p-element in the group the non-metallic properties become weaker, and metal properties become stronger.
The properties of p-elements and their compounds are influenced both by the appearance of new sublevels in the external electronic shell and by the filling of sublevels of internal electronic shells. Properties of p-elements of the second period B, C, N, O, P differ from the properties of elements of other periods. So, starting with the p-elements of the third period, we receive free p-sublevel, on which electrons from 5s-sublevels can move to (when atoms are excited). Fully
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filled 3p-sublevel of p-elements of the fourth period makes them distinctive from elements of the third period.
In the period from the left to the right the ability of p-elements to form positive ions with charge, corresponding to the number reduces, and ability to form negatively charged ions with a charge equal to the difference (8-group number)increases. Some p-elements form diatomic molecules Е2with varying resistance. The most stable diatomic molecules are molecules of the elements of the second period. When we move from IVA to IIIA and VA-groups the resistance of molecules increases, and then when we move to the VIIA-group the resistance decreases. In groups from top-to-bottom the strength of E-Ebond decreases.
P-elements of II period, namely nitrogen, oxygen and fluorine have shown a strong ability to participate in the formation of hydrogen bonds.
The elements of II and following periods loose this property. The similarity between p-elements of III period and p-elements of following periods consists mostly only of the outer shells structure and of valence states that appear from unpaired electrons in excited atoms. Boron, carbon and nitrogen in particular are very different from the rest of elements in its subgroups. When moving from p-elements of the II to III and following periods all link types, that characterize elements of the II period are saved and also more diverse types of chemical bonds appear. This increases both the ability of cells to form complex compounds and the value of coordination number. So if p-elements of the second period have the coordination number equal to 2, 3, 4, the p-elements of following periods may have coordination number equal to 5, 6, 7, 8 or even 12.In the group down wards the resistance of maximum positive oxidation states for p-elements increases and the resistance of lower degrees of oxidation decreases. So, for example, for carbon oxidation resistant is +4, +2 for the lead, +3 for aluminium, and -1 for thallium.
Physical properties of simple substances of p-elements differ significantly, in groups and periods the difference is not monotonic. The nature of these
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changes is not always easy to associate with the structure of electronic shells of atoms, a type of chemical bond, coordination number.
So, the differences of the properties of p-elements both within the group and period are significantly bigger than of the s-elements. All p-elements and especially p-elements of II and III periods form numerous connections between s-, d-and f-elements. Most of known on earth connections are connections of p- elements.
Boron is an impurity microelement. It is known that boron is a part of teeth and bones, probably in the form of poorly soluble salts of boric acid. Excess of boron is harmful for the human. There are some facts that large excess of boron inhibits amylase, proteinase, reduces the activity of adrenaline. The decline of adrenalin activity, which is a derivative of polyphenol, is connected with its interaction with boric acid.
It was known long time ago that higher plants need boron, but data on its biological role is controversial. Studies in recent years have shown that boron is an essential element for some animals. It was found that boron is involved in carbohydrate-phosphate exchange and works with a number of biologically active compounds (carbohydrates, proteins, vitamins, hormones). However, consumption of foods with high content of boron violates the exchange of carbohydrates and proteins, which leads to endemic enteric diseases-enteritis.
Aluminium, same as boron, belongs to impurity microelements. Daily intake of aluminum for an adult is 47 mg. Aluminum affects the development of epithelial and connective tissues, bone regeneration, exchange of phosphorus, enzymatic processes. Al3+mostly replaces the E2+ions, which are enzyme- activators, such as Mg2+ and Ca2+.
Such substitution is possible because of some properties similarity of Mg2+
and A13+, Ca2+ ions. For example, Mg2+and A13+ ions have equal radii and similar coordination number equal to 6. The A13+ and Ca2+ ions have equal ionization energy (IE = 12.2 kJ/mol) and similar coordination number equal to 6.
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An excess of aluminium in the body inhibits the synthesis of hemoglobin, because due to relatively high complexing ability aluminium blocks the active centers of enzymes involved in blood formation. There are reports that aluminum can catalyze the reaction of transamination. Aluminum salts of oxygen-containing acids are water-soluble, except aluminium phosphate А1РО4.
The formation of slightly soluble phosphate plays an important role in the life of organisms. Assimilation of phosphorus becomes weaker in the presence of Al3+cations due to slightly soluble aluminium phosphate formation in the gut.
In living organisms aluminum forms chelate complex compounds with bioligands, such as hydroxy acids, polyphenols, carbohydrates, lipids. Usually links with organic ligands occur via oxygen atoms.
Carbonhas a tendency to long homochain creation. Molecules containing links between two carbon atoms can have linear, branched and cyclic structure.
Various organic molecules, that contain connected carbon atoms with various radicals, form a huge number of biomolecules. Having intermediate electronegativity, carbon forms less-polar connections with such vital elements as hydrogen, oxygen, nitrogen, sulfur, etc. Other elements of this group form links predominantly through the oxygen atom, and the lead links through sulfur.
The ability of lead to form links with sulfur determines its toxic effect (blocking protein sulfhydryl groups).
Carbon monoxide (CO)-carbon monoxide is a product of incomplete oxidation of carbon. Human is one of the main sources of CO, as the body produces and releases carbon monoxide into environment approximately 10 ml per day. This is the so-called endogenous carbon (II) oxide, which is formed in the process of hematopoiesis.
Penetrating into lungs with air, CO quickly passes alveolar-capillary membrane, dissolves in blood plasma, diffuses into red blood cells and interacts in the opposite chemical reaction with both oxyhemoglobin НbО2 and hemoglobin Hb:
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HbO2+CO=HbCO+O2
Hb+CO=HbCO.
Formed carboxyhemoglobinis not able to attach oxygen;as a result transport of oxygen from the lungs to the tissues becomes unable. High chemical affinity of carbon (II) oxide with bivalence iron is a major reason of hemoglobin interaction with CO. It should be assumed that other bio-organic compounds containing Fe2+ions must react with CO.
Since the reaction of carbon monoxide with oxyhemoglobin is partially reversed, so the increase of partial O2 pressure will accelerate the dissociation of carboxyhemoglobin and CO excretion from the body (the equilibrium is shifted to the left by Le Chatelier's principle).
At the moment there are drugs that are used as antidotes in poisoning the body with CO. For example, the introduction of reduced iron shortly accelerates the CO removal from the body in the form of a carbonyl iron. The action of this drug is based on the ability to act as a ligand in complexes.
Carbon dioxide (CO2) is constantly formed in the tissues of the body during metabolism and plays an important role in the regulation of respiration and blood circulation. CO2 is a physiological stimulator of respiratory centre.
Big concentrations of CO2(more than 10%) cause severe acidosis (the lowering of blood pH), choking and paralysis of the respiratory centre. CO2solution is the carbonic acid.Salts solutions of it are the result of hydrolysis and have alkaline medium (pH>7), for example:
Na2CO3+HOH=NaHCO3+NaOH CO32-+HOH=HCO3-+OH-
Carbonate buffer system (Н2СО3 + HCO3-) is the main buffer system of blood plasma, which provides support for acid-base homeostasis.
Silicon (silicium) is an impurity microelement. As natural silicum (IV) oxide is poorly soluble in water, so silicon falls into the human body not through the digestive tract, but with air through the lungs in the form of powdered SìO2. The inhalation of dust containing SìO2 leads to silicosis. The
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metabolic disorder of silicon leads to hypertension, rheumatism, ulcers and anemia. It was found that silicium is located in the skin, cartilage, mucopolysaccharides, where it strongly connected with essential hydroxide groups of carbohydrates.
Unlike carbon, silicon in the composition of biomolecules is only connected with the oxygen atoms (bond Sì—О), because the energy of this bond is significantly higher than the energy of bonds Sі—Н, Sі—С, Sі—S etc.
Metabolism of silicon and germanium in living organisms has mutual influence, due to the similarity of chemical properties of these elements.
Germanium is present in soy beans, tea, aloe, ginseng. It also contains in some medicinal plants, especially those that have been used in the East folk medicine for a long time. Therefore, it was assumed that there is a link between the content of germanium in plants and their pharmacological properties. A wide range of biological actions (such as neurotropic, anesthetic, hypotensive, bactericidal, antifungal, antiviral, antiradiacion and antitumorial) of compounds, that contain Germanium has been noted.
On content in the human body (10-4 %) tin (stannum) belongs to microelements. Information about its biological role is inconsistent. Stannum is ingested from acidic foods preserved in the can, covered with a layer of tin.
Stannum dissolves in acidic environment and enters the bloodstream providing toxic effect:
Sn+2HA=SnA2+Н2.
However, in experiments on rats it was found that in small quantities stannum provides stimulating effect on their growth. This suggests the need of this element for a human. Certainly, the biological role of this microelement requires further study.
Lead (plumbum) and its compounds, especially organic one, are very toxic. Plumbum ions form gelatinous albuminates reacting with cytoplasm of microbial cells and tissues. In small doses plumbum salts show astringent effect, causing jellification of proteins. Formation of jelly prevents the penetration of
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germs into the cells and reduces the inflammatory response. The effect of stannum washes is based on this action. With an increase of Pb2+ ions concentration the formation of albuminates becomes irreversible, albuminates of proteins accumulate in superficial tissues:
Рb2+ + 2R-СООН = Рb(R-СОО)2 + 2Н+.
Therefore, medicines of plumbum (II) are designated exclusively for external use, in case of being absorbed in the gastrointestinal tract or the respiratory tract, they exhibit high toxicity. Compounds of plumbum affect the protein synthesis, the energy balance of cells and its genetic apparatus. It was found that plumbum is one of those elements whose presence in food affects the development of caries.
There are numerous evidences that accumulation of plumbum in plants, in the tissues of animals and humans body is a result of environmental plumbum pollution. With food, water, air man daily absorbs up to 100 micrograms of plumbum. Plumbum deposited in skeleton (up to 90%) in the form of hard dissoluble phosphate Rb3(RO4)2.
Mass fraction of plumbum in human body is 10-6%. It’s safe to intake 0.2 - 2 mg per a day.
Ions of Pb2+ are more active complexants comparing to other cations of 4th A group. They form stable complexes with bioligands. Pb2+ ions are able to interact with sulfideSН-groups of protein molecules of enzymes and block them:
R-SH + Pb2+ + SH-R = RS-Pb-SR + 2H+
Ions of Pb2+ are involved in the synthesis of Porphyrins which control hemoglobin synthesis, and other biomolecules. Ions of Pb2+ may displace other cations Me2+, inhibiting the metal-enzymes.
So, p-elements of the 4th group considerably differ from each other both on content in the human body and biological effect. Macroelement carbon plays central role in the life of organisms; microelement silicon, probably, is vital;
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microelement germanium may perform physiological role in the body, while the stannum and, especially, plumbum are toxic elements.
Nitrogen belongs to macroelements. However, few organisms are able to absorb gaseous nitrogen.
Plants can use soluble nitrates as a source of nitrogen and animals need ammonia and amino acids. With the absorption of nitrogen by plants, soil depletion becomes a problem. Therefore, already at the beginning of the 20th century due to the need to amend the soil with nitrogenous fertilizers, measures have been taken to use air for nitrogen compounds, called nitrogen fixation.
The synthesis of ammonia from nitrogen and hydrogen is the main way to link atmospheric nitrogen. However, this method of nitrogen fixation is quite energy-intensive, therefore, it’s expensive. That is why many scientists explore the possibility to link atmospheric nitrogen by using a variety of complex compounds.
It’s interesting in the biological aspect, that one essential property of nitrogen is it’s solubility in water, which is similar to oxygen. The presence of excess nitrogen in blood can cause the development of decompression sickness.
With the rapid rise of divers a rapid drop of blood pressure happens – so it decreases the solubility of nitrogen in blood (Henry's law), and the bubbles of nitrogen coming out of blood, occlude small blood vessels. This can lead to paralysis and death.
Together with oxygen, hydrogen, and carbon nitrogen forms a vital link - amino acids, which are bio-organic substances that serve as building blocks for the formation of proteins - the basics of life.
Ammonia itself in human body is one of the metabolism products of amino acids and proteins that income with food, or present in cells as a storage material. The reason of ammonia toxicity on the brain has not been already determined. In blood at pH = 7.4 ammonia is almost entirely present in form of ammonium ions. Ammonium ions, despite the fact that they are present in blood
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in great excess, cannot pass through the cell membrane, while the neutral NH3
molecules easily pass through the membranes and can affect the brain.
Some nitrogen compounds with oxygen are toxic. The production of nitric acid and some other substances produces nitrous gases which are a mixture of nitrogen oxides: NO, NO2, N2O4, N2O3. These gases contacting with wet surface of lungs form nitrous and nitric acids that affect the lungs, leading to edema and other disorders. Nitrogenous poisoning of blood by gases also forms nitrates and nitrites.
Nitrites were recently added as conservants in sausages and other meat products. Although conservants are added in small amounts, there is a perception that they are dangerous for human. One of the reasons of poisonous properties of nitrous acid and nitrites is that they are deaminating agents, promoting the oxidation of amino groups of nucleic bases. Particularly strong impact is made by nitrous acid, which is formed from organic precursors, for example, nitrosamines and nitro compounds. This changes the structure of the nucleic DNA bases and their ability to form hydrogen bonds, so DNA damage is occurred.
Toxic effect of nitrite is manifested in the fact of transforming hemoglobin into methemoglobin, which is unable to bind and transport oxygen:
НbFе2+ + NO2- + 2Н+ = НbFе3+ + NO + Н2O
Methemoglobin is formed under the action of oxidants: oxides of nitrogen, nitrite, and aniline. Blood methemoglobin can also increase when some hemoglobinopathies associated with hereditary lack of reductase enzyme, which restores the methemoglobin to hemoglobin. In addition, methemoglobin is formed if to take high doses of certain drugs, for example, sulfonamides.
Up to the norm a small amount of methemoglobin can spontaneously form in erythrocytes, but the action of reductase restores it. Blood plasma and urine become brown in case of toxic methemoglobinemia.
Methemoglobinemia is treated by methylene blue or ascorbic acid that restore it into hemoglobin.
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You can prevent death from lack of oxygen by the timely increasing of partial oxygen pressure that means inhalation of pure oxygen.
So, getting into the bloodstream, nitrites cause oxygen deficiency.
However, in very small quantities, some inorganic nitrites (connection type R—
O—N=O) and organic nitrates (R—O—NO2) improve coronary circulation and are used to prevent coronary heart disease and to stop the strokes (glycerol trinitrate, etc.).
On content in human body phosphorus as nitrogen refers to macroelements and plays an important role in metabolism. Living organisms cannot live without phosphorus. The value of phosphorus is that monosaccharides and glycerol cannot be used by cells as a source of energy without prior phosphorylation.
Exchange of phosphorus in the body is closely linked to the exchange of calcium. This is confirmed by the decrease of inorganic phosphorus while the increase of calcium content in blood (antagonism). Human daily need for phosphorus is 1.3 g. Phosphorus is so common in food that its apparent failure (phosphate starvation) is virtually unknown. However, not all phosphorus contained in foods can be assimilated, as it depends on many factors: pH, the ratio of calcium and phosphorus in the diet, the content of fatty acids in food, but primarily from the vitamin D content.
From the biological point of view bioinorganic diphosphorus acid derivatives H4P2O7 and uncommitted in a free form triphosphoric acid H5P3O10 are extremely important. These are adenosine diphosphate acid (ADP) and adenosine triphosphate acid (ATP). At pH 7.4 ATP and ADP exist almost as ATF4- and ADP3-anions, which means that their phosphate groups are fully ionized. Many biosynthesis reactions occur due to the transfer of phosphate groups from high-energy to a low-energy acceptor.
Similar to polyphosphoric acids anions ATP 4- and ADP3- can be hydrolyzed. As a result of interaction with one water molecule ATP4-anion hydrolyses into ADP3- and hydrophosphate HPO42-ion. ADP and ATP form
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complex salts with cations of metals. Thus, in intracellular fluid ADP and ATP are present mainly in the form of magnesium complexes: MgATP2- and MgADP. In enzymatic reactions of phosphorylation, in which ATF participates as a donor of phosphate group, the complex of MgATF2- is an ATP active form.
Phosphate buffer system is one of the main buffer systems of the blood (HPO42-+ H2PO4-). It should be noted, that certain organophosphorus compounds containing the C-P bond, are strong poisons, that comprise into chemical warfare agents. Used as pesticides. White phosphorus is toxic due to its high solubility in fats, and thus the ability to penetrate through the cell membrane, as well as its highly reactive activity. The rest of the allotropic modifications of phosphorus due to their insolubility are non-toxic.
Arsenic is toxic in the extent of oxidation +5, unlike the phosphorus, which is toxic only in phosphorus (III) compounds. This is caused by the fact that human body easily recovers arsenic (V) to arsenic (III). Mechanism of arsenic toxic effects is explained by its ability to block sulfhydryl groups of enzymes and other biologically active compounds.
In addition, arsenic replaces iodine, selenium, phosphorus. Breaking the biochemical processes of metabolism in the body, it is the antimetabolite of these elements. The lethal dose for human is about 0.1-0.3g of arsenic. In the acute poisoning by arsenic (III) oxideAs2O3 death occurs in approximately 70 hours.
Arsenic is accumulated in bones and hair for several years and doesn’t output to the end. This feature is used in forensics to determine the issue of poisoning by arsenic compounds. Determination of arsenic in biological material is carried out by the Marsh’s reaction. Marsh’s reaction is very sensitive and allows to define 7×10-7g of arsenic.
Arsenic compounds not only kill, but also help. As2O3 is used externally to treat skin diseases. In dental practice As2O3is applied for necrosis of soft tissues of the tooth. In addition, this drug is prescribed in microdoses (0.001g per reception) for the treatment ofanemia, exhaustion, nervousness. It’s an
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interesting fact that, the body can get used to As2O3 if its introduced gradually, increasing the dose. In clinical practice, other arsenic compounds, such as Na2HAsO4 are also used.
The physiological role of antimony (stibium), obviously, is similar to arsenic. Arsenic As3+ ions, antimony Sb3+ions, and in lesser extent Bì3+ions are synergistic. So, it is known that in biogeochemical provinces with the excess of arsenic, there is an increase of not only arsenic, but also antimony in the organism. While both elements are accumulated in the thyroid gland, they inhibit its function and cause goiter.
Synergism of arsenic and antimony is determined by their ability to form compounds with sulfur ligands. Water-soluble compounds of antimony, falling into the body, show toxic effect, which is similar to the action of arsenic compounds. Bismuth reacts more with ligands, thatcontain NH2 group. Thus, bismuth compounds inhibit enzymes of amino- and carboxypolipeptidaze.
Water-soluble compounds of bismuth are toxic. For example, for dogs lethal dose is 6 mg per 1 kg of mass. However, getting into digestive tract, most compounds of antimony and bismuth practically do not show toxic actions. The reason of this is the fact that Sb(III) and Bi (III) salts in the digestive tract are subjected to hydrolysis with the creation of soluble products which are not absorbed through the tunicof gastrointestinal tract.
Comparing biochemical properties of elements of VA group, we can make following conclusions. Nitrogen compounds with carbon and hydrogen in biomolecules; phosphorus is linked via oxygen; arsenic, antimony and bismuth- through oxygen and sulfur. This leads to the lack of mutual substitution of nitrogen and phosphorus, as well as the lack these elements substitution of by arsenic, antimony and bismuth. Nitrogen and phosphorus are essential elements for all living organisms. Perhaps arsenic can be an indispensable element, at the same time the necessity ofantimony and bismuth for living organisms is unknown. Arsenic, antimony and bismuth are synergistic, they block sulfhydryl groups of bioligands, and in large doses they are very toxic. At the same time
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positive biological role of arsenic micro amount suggests that antimony and bismuth may be in one or another way useful for living organisms.
Oxygen refers to macroelements. It is an indispensable element and is one of the most important elements that form the basis of living systems. Oxygen is a part of all vital organic substances: proteins, fats, carbohydrates. Many essential life processes are impossible without oxygen, for example, respiration, the oxidation of amino acids, fats, carbohydrates. Only few microorganisms, called anaerobic, can live without oxygen. In the organism of higher animals, oxygen enters the bloodstream, connects with hemoglobin, forming oxyhemoglobin, which is easily dissociated. With the blood, this compound goes into the capillaries of various organs. Here oxygen rifts from hemoglobin and diffuses into tissues through tunicas capillaries. The link between hemoglobin and oxygen is unstable and is carried out by donor-acceptor interaction with Fe2+ ion.
Thanks to donor-acceptor interaction with ions of Fe2+, Cu2+ oxygen forms such complexes as Нb(Fе2+)О2, Не(Сu2+)О2, where Нb -hemoglobin, Не - hemocyanin. Having two unseparated pairs of electrons, oxygen acts in these coordination compounds as a donor.
At rest person inhales roughly 0.5m3 of air per hour, but only 1/5 of inhaled oxygen is contained in the body. However, the excess of oxygen (4/5) is required to create high concentrations in blood, which provides sufficient oxygen diffusion rate through the tunic of capillaries. Thus, a person actually takes about 0.1m3 of oxygen per a day. Oxygen is used for oxidation of various substances in the tissues. These reactions eventually lead to the formation of the main products of metabolism: carbon (IV) dioxide, water and energy (-2888 kJ/mol).
Phagocytic (protective) functions of the body are also associated with the presence of oxygen. The reduction of oxygen content in the body decreases its protective properties. In phagocytes (cells that can capture and digest foreign particles) O2 is restored to superoxide anion radical O2-:
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О2+е-= О2-.
O2 initiates the radical-chain oxidation processes of foreign organic substances RH, captured by phagocytes:
О2- +HOH=HO2 + OH- HО2- + RH=R-O-O* +H2
With a lack of oxygen, these processes are slowed down; as a resulted resistance of organism to infections is decreased.
Oxygen is used for inhalation in conditions involving oxygen deficiency (hypoxia), diseases of respiratory system, cardiovascular system, carbon (II) monoxide and hydrocyanic acid poisoning.
Ozone O3 is an allotropic modification of oxygen. A small impurity of it in the air creates a feeling of pleasant freshness and beneficial effect on human, particularly pulmonary patients. Applying oxygen O2 and ozone O3we should take into account their toxicity due to the intensification of oxidation processes in the body.
Oxidative effect of ozone on organic substances is associated with the formation of radicals:
RН + О3 =RO2 +НО*
RO2radicals and НО initiate radical-chain reactions with bioorganic molecules, such as lipids, proteins, and DNA. Such reactions lead to the damage and cell death. Ozone kills microorganisms in air and water. This is the base of ozone usage in sterilizing drinking water and water of swimming pools.
The most common oxide on the Earth is oxide of hydrogen (water). Over 70 years of life a person drinks about 25000 kg of water. Thanks to the unique structure of molecules water has its own properties. It is the solvent of organic and inorganic compounds involved in the ionization of molecules of dissolved substances in a living organism. Water is not only the environment for biochemical reactions, but it is also intensely involved in hydrolytic processes.
Sulfur is a macroelement. It is vital element, like oxygen. A daily requirement of sulfur for an adult is 4-5g. Sulfur is included in many
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biomolecules: proteins, amino acids (cysteine, cystine, methionine, etc.), hormones (insulin), vitamins (B). A lot of Sulfur is contained in hair, bones, nervous tissue.
A number of proteins containing cysteine and an important coenzyme A (which includes the p-aminoetanol) have sulfide (thiol) group-SH and behave like bioorganic derivatives of hydrogen sulfide. Some photosynthetic bacteria, for example green sulfur bacteria, use hydrogen sulfide as a source of hydrogen donor:
2H2S+CO2 = CH2O + HOH + 2S
(This reaction is occurred in the light with the help of enzymes)
These bacteria emit sulfur, which is the oxidation product of H2S.
Hydrogen sulfide is a toxic substance, because it is an inhibitor of the enzyme cytochrome oxidase, which transfers electrons to the respiratory chain. H2S inhibits the transfer of electrons with cytochrome oxidase on oxygen.
Sulfur oxides (IV, VI) also apply to toxic substances.
Oxide SO2 primarily effect on the higher animals as an irritant of mucous membrane of the respiratory tract. This gas is toxic for plants. SO2 compounds in the atmosphere in the industrial areas, where coal containing large amounts of sulfur is burned. Dissolving in water, which is on the leaves of plants, SO2
forms a solution of sulphurous acid, which in it turn is oxidized to sulfuric acid H2SO4.
Atmospheric moisture with dissolved SO2 and H2SO4 falls as acid rain, leading to the death of plants.
Selenium is a microelement. Selenium deficiency causes a decrease in the concentration of the Glutathione peroxidase enzyme which causes the oxidation of lipids and sulfur-containing amino acids. The active centre of Glutathione peroxidase contains the remainder of amino acids selencysteine. This enzyme together with the glutathione tripeptide protects cells from the ravages of organic peroxides ROOH and hydrogen peroxide H2O2. There is evidence that
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selenium deficiency in the body prevent tissue necrosis by adding sodium gypsum Na2SeO3to the diet of rats.
On the content of human body chlorine (0.15%) refers to micronutrients and the other halogens are microelements (content 10-5%). Halogens in various forms of compounds are included in the human and animal tissue.
In human body fluoride weight is about 7 mg (5-10%). The shortage of fluoride in the organism causes tooth's decay. Mineral base of dental tissues - dentin – consists of hydroxylapatite Са5(РО4)3(ОН), chlorapatite Са5(РО4)3С1 and fluorapatite Са5(РО4)3Р. Formation of hydroxylapatite can be expressed by scheme:
5Са2+ + ЗНРО2-+ НОН = Са5(ОН)(РО4)3 + 4Н+.
Fluoride-ion replaces hydroxide-ion easily in hydroxylapatite, forming a protective layer of enamel of more solid fluorapatite:
Са5 (РО4)3(ОН) + F = Са5(РО4)3F + О-.
Moreover, fluoride ions facilitate the deposition of calcium phosphate, expediting the process of remineralization (crystal formation):
10Са2+ + 6РО43- +2F- =ЗСа3(РО4)2 + СаF2.
Caries begins with the formation of damaged area of enamel on tooth surface in the form of the spot. Under the action of the acids produced by bacterias, hydroxylapatite component of enamel dissolves:
Са5(РО4)3(ОН) + 7Н+ = 5Са2+ + ЗН2РО4- + Н2О.
Enrichment of drinking water with fluoride (water fluoridation) in order to transmit fluoride content to normal (1 mg/l), results in a significant decrease of the caries incidence, but an excess of fluoride is also harmful.
With increased content of fluoride in water tooth enamel becomes fragile and destroyed. A disease that occurs in this case is called fluorosis. In many biochemical processes fluoride act as inhibitor, blocking active centers of enzymes that contain Са2+, Мg2+ and other metal ions.
The human body contains about 100g of chlorine (0.15%). Gaseous Сl2, which is a strong oxidant, is a poisonous substance which causes irritation of
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the mucous membranes of eyes, nose, larynx and lung affection. Maximum allowable concentration of chlorine gas in the air is 0.001 mg/l. As for the biological role of the chloride ions, they activate some enzymes that create an favorable conditions for the action of proteolytic enzymes of gastric juice, involve in maintaining osmotic balance.
Сl- is present in the body in macroscopic quantities. Hydrochloric acid is an essential component of the gastric juice; its mass fraction is about 0.3%. For derivation of hydrochloric acid in the stomach NaCl must be present (table salt).
Hydrochloric acid forms as follows:
Н2СО3 (blood) + Cl-= НСО3 (blood) + НС1 (stomach).
Hydrochloric acid of the gastric juice with pepsin is necessary for transfer of the inactive enzyme pepsinogen into the active form-pepsin. Pepsin provides digestion of proteins by hydrolytic cleavage of the peptide bonds.
Hypochloric acid is a strong oxidizing agent, germicidal and bleaching effects of chlorinated water are explained by its content. Atomic oxygen, which is produced by the decomposition of НС1О, discolors paints and kills germs.
Hypochloric acid reacts with organic compounds RH:
RH + HClO = ROH + HCl;
RH + HClO = RCl + H2O
E.g. as oxidizer and as chlorinating substance HClO breaks down proteins, which are micro-organisms.
Mass of bromine in the human body is about 7 mg (5-10%). There is evidence, that bromine connections inhibit thyroid function and increased adrenocortical activity.
Central nervous system is most sensitive to the action of Br ions. The insertion of bromide ions into the body restores the disturbed balance between the processes of excitation and inhibition. They are easily absorbed in the gastrointestinal tract. Their toxicity is low, however, due to the slow removal from the body (30-60 days) they can accumulate that leads to the development of chronically poisoning, which is called "bromism".
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Iodine is an essential element, and its compounds play an important role in the process of metabolism. Iodine affects the synthesis of some proteins, lipids, thyroid hormones and thyroxine. Iodine, in the same way as chlorine, replaces hydrogenous atoms at the nitrogen atoms in the proteins molecules of microorganisms, which leads to their death:
R-CO-NH-R1 + I2 = R-CO-NI-R1 + HI
The human body contains about 25 mg (4-10%) of iodine. More than half of it belongs to the thyroid gland secretes hormones - thyroxine and triiodothyronine. Decreased activity of the thyroid gland (hypothyroidism) can be due to reducing its ability to accumulate iodide ions, as well as the lack of iodine in foods (goiter).
Analysis of the biochemical properties of halogens shows that bromine and chlorine are usually found in the body in the form of hydrated ions Вг-, Сl- , fluorine and iodine in the related condition: iodine forms a connection with link С—І, and fluorine binds to metals (Ca, Mg, Fe).
On the physical-chemical characteristics and propensity for coordination with biogenic elements fluoride differs significantly from other halogens: it almost does not participate in replacement of ions of chloride, bromide and iodide. СІ, Вr, І are close in properties, and replace each other in the body, while exercising synergy and antagonism.
So, most of the elements of the p-block arenonmetals. They all can be a part of organic molecules and can participate in the creation of living tissue.
The six elements (C, K, O, P, S, Cl) are found in the organism in big quantities, five (P, Sì. As, Se, I) are vital for human beings, Borium is essential for higher plants.
Bromine value to human is not fully understood. Metals that block elements are vital. Bismuth compounds are applied in medicine. However, most p-block metals have excessive toxicity. The most dangerous for human are plumbum compounds which are common in industry; they disrupt the normal
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synthesis of porphyrin, which is necessary for further synthesis of hemoglobin and other hemoproteins.
3. d-Block elements. Biological role, application in medicine.
D-elements belong to the microelements. Metal microelements have certain common characteristics:
1) they are quite common, so are available for absorption from the soil;
2) they have high comprehensive ability in relation to various donor atoms, have different stable oxidation states and easily move from one stage of oxidation to other.
These macroelements are involved in the most important processes, that take place in cells:
1) enzymatic catalysis of reactions of synthesis and reactions of cellular energy;
2) transfer of electrons, ions, molecules and molecular enzymes;
3) regulate the activity of cell mechanisms and systems.
Free ions of d-metals don’t exist in the body, most commonly in biochemical reactions d-elements take part in the form of bioinorganic complexes of metals.
Essential elements Zn, Cu, Fe, Mn, Co, Mo are called vitals metals.
Copper is an essential macroelement of plant and animal organisms.
Currently, there are about 25 copper-containing proteins and enzymes.
The part of enzymes catalyzes oxygen interaction with the substrate. They are a part of a so-called oxygenase group.
There is a large group of copper-containing proteins catalyzing redox reactions with transfer of protons or electrons from the substance,which are oxidized to molecular oxygen (these are so-called oxidases). They are characterized by high affinity to oxygen, as well as the high value of redox potentials. Most important respiratory enzyme cytochrome oxidase (CHO), which catalyzes the final step of tissue respiration concerns to oxidases.
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Ceruloplasmin (CP) ("blue" oxidase) is a very important cooper containing plasma protein of the blood of mammals. Performing the transport function the CP controls the balance of copper and copper excess excretion from the body.
There are known copper-bearing proteins, for example, superoxide dismutase (SOD), which accelerates the decomposition reaction of superoxide О2- ion. This ion enters into interaction with organic components of cells and destroys it:
[SOD • Сu2+ ] + О2-= [SOD • Сu+] + О2;
[SOD • Сu+ ] + О2-+ 2Н+ = [SOD • Сu2+ ] + Н2O2.
Thus, the SOD translates the superoxide ion О2 to hydrogen peroxide, which is relatively mild oxidant and decomposes rapidly in the body under the action of the enzyme catalase.
Copper with ferrum takes part in blood formation. At copper deficiency in the body iron exchange between blood plasma and erythrocytes is disturbed that can lead to the destruction of red blood cells. In experiments on animals it is shown that copper deficiency leads to severe changes in metabolism: copper anemia, exotic ataxy, etc. The human need for copper (2-3 mg/day) is totally ensured by food.
Wilson-Konovalov disease is associated with excess content of copper in the body. It’s believed that cooper excess forms as a result of the violation of the synthesis of ceruloplasmin and excess excretion of copper is not supplied with food.
In high concentrations, soluble copper salts are toxic. Copper (II) sulfate up to 2 g causes severe poisoning with possible fatal consequences. This is because copper forms an insoluble bioinorganic chelate-albumins with the protein, e.g.
coagulate proteins.
Zinc is included in composition of more than 40 metal-enzymes, catalyzing the hydrolysis of peptides, proteins, certain esters and aldehydes.
Permanent oxidation state defines its role in the reactions of non-electron transport hydrolysis.
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One of the most studied is the zinc containing enzyme - carbonic anhydrase. This enzyme in erythrocytes and blood occurs in three forms, which differ in activity. The enzyme consists of about 260 amino acid residues and is a bioinorganic complex in which the coordination number of zinc is 4 (three coordinating places are taken by amino acid residues; the fourth one binds water (or OH group).
The availability of zinc in enzyme is a necessary condition of catalytic activity of carbonic anhydrase, which provides the hydration of СО2:
СО2 + Н2О = Н2СО3 = Н+ + НСО3-.
Consensus on the mechanism of action of enzyme is not present.
According to other sources zinc coordinates hydroxyl group, which is involved in the process of hydration (the mechanism of "zinc - hydroxide"):
ОН- +СО2=НСО3-
The other zinc containing enzyme - carboxypeptidase (CPD) exists in several forms, which vary in the number of amino-acid residues and molar mass. Carboxypeptidase is involved in reactions of peptide bonds hydrolysis.
The mechanism of action of the CPD has also not been elucidated yet.
There are zinc enzymes involved in the hydrolysis of dipeptide, they are called dispeptidase. Zinc is a part of the hormone insulin, which affects blood sugar. The richeston zinc are meat, liver, milk, eggs.
Manganese is necessary for normal processes in animal and plant organisms. In the body manganese make complexes with proteins, nucleic acids (RNA and DNA) and amino acids. These complexes are a part of metal- enzymes (arginase, cholinesterase, etc.).
It is proved, that participating in biochemical processes, manganese, as a rule, does not change its oxidation state. This is likely due to the fact that there are no strong oxidants in the body, and ligands (thanks to the expense of the chelate effect) and ligands fields, stabilize the status of manganese (II).
Manganese is a participant in the synthesis of vitamins C and B, the synthesis of chlorophyll. It is known that an agent and a battery of chemical
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energy in the body is a system of ATP-ADP. There are following enzyme reactions, in which MnATF2complex performs the role of the donor of phosphate groups. So, manganese is involved in such vital process as accumulation and transfer of energy in the body. The daily requirement of manganese is 5-7 mg, we get it by the food. A lot of manganese containsin tea, beets, carrots, liver, potatoes.
Permanganates are poisons for the body.
Big part of iron (ferrum) is concentrated in blood hemoglobin (70%). Iron is a part of many enzymes. In a related form iron is found in some proteins, which act as vectors of iron.
One of the most important chelate natural compounds of iron is hemoglobin. This is a complex protein that contains nonprotein (prosthetic) group - the gem, mass fraction of which is 4%. Prosthetic group is a bio- complex with iron (II) polycyclic organic matter - porfirin. This group is known as the gem (from Greek "Gemma"-blood). Gem has a flat structure. At gem ion of iron (II) forms the four nitrogen atoms of donor groups in the plane of the porphyrin rings. The fifth iron ion forms a link with the nitrogen atom of the imidazole group of histidine. Iron (II) ion in the gem also has the sixth orbital, which is used in the hemoglobin oxygen binding. This orbital is involved in bond formation with carbon monoxide (II). The physiological function of hemoglobin is the ability to bind oxygen back and transfer it from the lungs to the tissues. Hemoglobin, which attached oxygen, is called oxyhemoglobin and hemoglobin which gave his oxygen - dezoxyhemoglobin.
[Hb•Fe2+] + О2 = [НbFе2+ • О2].
Hemoglobin has a structure which is characterized by the lowest electron affinity, in its iron atoms protrude above the plane of the porphyrin ring. At the same time, oxyhemoglobin iron atoms are in the plane of the porphyrin ring.
The hemoglobin reacts with carbon monoxide and forms the macrocyclic complex - carbonylhemoglobin:
[Нb • Fе2+ ] + СО = [НbFе2+ • СО].
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When carbon monoxide (II) is inhaled most of the hemoglobin becomes carboxyhemoglobin, which disrupts the transport of oxygen from the lungs to the tissues and causes poisoning of the body.
There is a group of iron-containing enzymes that catalyze electron transfer process in the mitochondria, so-called cytochromes (CCh). In total more than 50 cytochromes are known. The most studied cytochrome is C. The transfer of electrons in a redox chain involving this enzyme is carried out by changing the state of iron:
CChFе3+ + е-=>CCh-Fе2+.
The enzyme peroxidase accelerates the oxidation of organic substances by hydrogen peroxide.
In organs and tissues so called deposited iron is placed, which is used in iron deficiency. It is deposited by the help of ferritin protein with a molecular weight of 460000, which is bioclaster. The lack of iron and cobalt in the body leads to the hemoglobin synthesis. This causes a disease of blood called anaemia.
The iron in the body can be transported in the form of amino acid complexes. Formation of bioinorganic complexes allows the passage of iron ions through the cell membrane.
Cobalt as a microelement performs a variety of functions, as it forms the catalytically active centers of enzymes necessary for DNA synthesis and the metabolism of amino acids. Some of its complexes with proteins are the trasfers of molecular oxygen.
Cobalt in the body exists in the form of vitamin B12. The composition of vitaminВ12(С63Н90N14О14РСо) - bioinorganic complex compound, in which complexing compound is Со3+. In a molecule of vitamin B12 cobalt has a coordination number equal to 6. There are enzymatic systems, in which vitamin B12 acts not in free state but in so-called B12—coenzymes. Cofactor is an active part of enzyme, which is easily separated. The inactive protein part that is left, is called aloenzyme. As aloenzyme B12 participates in two processes:
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1) transfers propellant CH3-groups (methylation reactions) 2) transfers hydrogen ions.
Cobalt affects carbohydrate, mineral, protein, lipid metabolism, and participates in the process of hematopoiesis. The radioactive cobalt isotope has found application in the treatment of malignant tumors, and the complex of cobalt with nicotinic acid (koamid) - in the treatment of anemia.
It is known that enzymes that contain molybdenum are involved in the reactions associated with the transition of oxygen groups. This is possible thanks to the ability of molybdenum to form solid oxygen complex.
Molybdenum does not form stable cations at low degrees of oxidation in biological systems. In the body it exists only in the form of complexes in which oxidation state of Mo is +5 and +6. In the complexes molybdenum is associated usually with an oxygen atom.
Molybdenum is a part of enzymes catalyzing redox reactions in plant and animal organisms. These include xanthine oxidase, xanthine dehydrogenase, aldehyde oxidase. These enzymes catalyze the reactions associated with transfer of oxygen. Xanthine oxidase catalyzes the oxidation of xanthine to uric acid by oxygen.
Molybdenum has an important role in the process of soft air nitrogen fixation. Enzymes that contain molybdenum catalyze processes of transformation of molecular nitrogen into ammonia and other products containing nitrogen. Therefore, molybdenum is important for plant organisms.
Vanadiumconsists of one of the most important enzymes of nitrogen- fixing microorganisms of the soil, which restores the molecular nitrogen to ammonia- vanadium nitrogenase.
A microelement chromium is not enough studied, but it has essential nutrient role in plant and animal organisms.It is a part of some enzymes involved in redox reactions in the cells. Chrome is also a part of pepsin, which splits proteins in the digestive tract of animals and involves in the regulation of glucose absorption. Chrome, which is contained in leaps and bounds as a
