Stability of coordination compounds of dicarboxylic acid derivatives complexons. Advances of modern natural science

Dicarboxylic acids form two series of functional derivatives - one and two carboxyl groups.

Acidic properties. With the accumulation of acidic groups, the acidic properties of compounds increase. Dicarboxylic acids are more acidic than monocarboxylic acids. Thus, oxalic acid (pK a 1.23) is much stronger than acetic acid (pK a 4.76), which is associated with the -/- effect of the COOH group, and due to this, more complete delocalization of the negative charge in the conjugate base.

The influence of the substituent is most clearly manifested when it is located close to the acid center.

Decarboxylation. When heated with sulfuric acid, oxalic acid is decarboxylated, and the resulting formic acid decomposes further.

Malonic acid is easily decarboxylated when heated above 100°C.

Formation of cyclic anhydrides. In dicarboxylic acids, which contain four or five carbon atoms in the chain and are therefore capable of being in a claw-shaped conformation, functional groups converge in space. As a result of an intramolecular attack by one carboxyl group (nucleophile) on the electrophilic center of another carboxyl group, a stable five- or six-membered cyclic anhydride is formed (when heated), as shown in the examples of succinic and glutaric acids. In other words, dicarboxylic acid anhydrides are products intramolecular cyclization.

Maleic and fumaric acids exhibit similar chemical properties: they enter into reactions characteristic of compounds with a double bond (discoloration of bromine water, an aqueous solution of potassium permanganate) and compounds with carboxyl groups (form two series of derivatives - acidic and moderate salts, ethers, etc. ). However, only one of the acids, namely maleic, under relatively mild conditions undergoes intramolecular cyclization to form a cyclic anhydride. In fumaric acid, due to the spatial distance of the carboxyl groups from each other, the formation of cyclic anhydride is impossible.

Oxidation of succinic acid in vivo. The dehydrogenation (oxidation) of succinic acid into fumaric acid, catalyzed in the body by an enzyme, is carried out with the participation of the coenzyme FAD. The reaction proceeds stereospecifically with the formation of fumaric acid (in ionic form - fumarate).

3.1.4. Tautomerismβ -dicarbonyl compounds

A certain proton mobility of the hydrogen atom at the α-carbon atom in carbonyl compounds (weak CH-acid center) is manifested in their ability to undergo condensation reactions. If the mobility of such a hydrogen atom increases so much that it can be split off in the form of a proton, this will lead to the formation of a mesomeric ion (I), the negative charge of which is dispersed between the carbon and oxygen atoms. Reverse addition of a proton to this ion, according to its boundary structures, can result in either the parent carbonyl compound or an enol.

In accordance with this, the carbonyl compound can exist in equilibrium with the isomer - enol form. This type of isomerism is called tautomerism, and isomers in a mobile state
balance, - tautomers.

Tautomerism is equilibrium dynamic isomerism. Its essence lies in the mutual conversion of isomers with the transfer of any mobile group and the corresponding redistribution of electron density.

In the case under consideration, a proton transfer occurs between the ketone and enol forms, therefore this equilibrium is called prototropic tautomerism, in particular, keto-enol tautomerism.

In monocarbonyl compounds (aldehydes, ketones, esters), the equilibrium is almost completely shifted towards the ketone form. For example, the content of the enol form in acetone is only 0.0002%. In the presence of a second electron-withdrawing group at the α-carbon atom (for example, a second carbonyl group), the content of the enol form increases. Thus, in the 1,3-dicarbonyl compound acetylacetone (pentanedione-2,4), the enol form predominates.

General chemistry: textbook / A. V. Zholnin; edited by V. A. Popkova, A. V. Zholnina. - 2012. - 400 pp.: ill.

Chapter 7. COMPLEX CONNECTIONS

Chapter 7. COMPLEX CONNECTIONS

Complex-forming elements are the organizers of life.

K. B. Yatsimirsky

Complex compounds are the most extensive and diverse class of compounds. Living organisms contain complex compounds of biogenic metals with proteins, amino acids, porphyrins, nucleic acids, carbohydrates, and macrocyclic compounds. The most important life processes occur with the participation of complex compounds. Some of them (hemoglobin, chlorophyll, hemocyanin, vitamin B 12, etc.) play a significant role in biochemical processes. Many drugs contain metal complexes. For example, insulin (zinc complex), vitamin B 12 (cobalt complex), platinol (platinum complex), etc.

7.1. COORDINATION THEORY OF A. WERNER

Structure of complex compounds

When particles interact, mutual coordination of particles is observed, which can be defined as the process of complex formation. For example, the process of hydration of ions ends with the formation of aqua complexes. Complexation reactions are accompanied by the transfer of electron pairs and lead to the formation or destruction of higher order compounds, the so-called complex (coordination) compounds. A peculiarity of complex compounds is the presence in them of a coordination bond that arises according to the donor-acceptor mechanism:

Complex compounds are compounds that exist both in the crystalline state and in solution, a feature

which is the presence of a central atom surrounded by ligands. Complex compounds can be considered as complex compounds of a higher order, consisting of simple molecules capable of independent existence in solution.

According to Werner's coordination theory, a complex compound is divided into internal And outer sphere. The central atom with its surrounding ligands form the inner sphere of the complex. It is usually enclosed in square brackets. Everything else in the complex compound constitutes the outer sphere and is written outside square brackets. A certain number of ligands will be placed around the central atom, which is determined coordination number(kch). The number of coordinated ligands is most often 6 or 4. The ligand occupies a coordination site near the central atom. Coordination changes the properties of both the ligands and the central atom. Often coordinated ligands cannot be detected using chemical reactions characteristic of them in the free state. The more tightly bound particles of the inner sphere are called complex (complex ion). There are attractive forces between the central atom and the ligands (a covalent bond is formed by an exchange and (or) donor-acceptor mechanism), and repulsive forces between the ligands. If the charge of the inner sphere is 0, then there is no outer coordination sphere.

Central atom (complexing agent)- an atom or ion that occupies a central position in a complex compound. The role of a complexing agent is most often performed by particles that have free orbitals and a sufficiently large positive nuclear charge, and therefore can be electron acceptors. These are cations of transition elements. The most powerful complexing agents are elements of groups IB and VIIIB. Rarely as a complexing agent

The main agents are neutral atoms of d-elements and atoms of non-metals in varying degrees of oxidation - . The number of free atomic orbitals provided by the complexing agent determines its coordination number. The value of the coordination number depends on many factors, but usually it is equal to twice the charge of the complexing ion:

Ligands- ions or molecules that are directly associated with the complexing agent and are donors of electron pairs. These electron-rich systems, having free and mobile electron pairs, can be electron donors, for example:

Compounds of p-elements exhibit complex-forming properties and act as ligands in the complex compound. Ligands can be atoms and molecules (protein, amino acids, nucleic acids, carbohydrates). Based on the number of bonds formed by the ligands with the complexing agent, ligands are divided into mono-, di- and polydentate ligands. The above ligands (molecules and anions) are monodentate, since they are donors of one electron pair. Bidentate ligands include molecules or ions containing two functional groups capable of donating two electron pairs:

Polydentate ligands include the 6-dentate ethylenediaminetetraacetic acid ligand:

The number of sites occupied by each ligand in the inner sphere of a complex compound is called coordination capacity (dentate) of the ligand. It is determined by the number of electron pairs of the ligand that participate in the formation of a coordination bond with the central atom.

In addition to complex compounds, coordination chemistry covers double salts, crystalline hydrates, which decompose in an aqueous solution into component parts, which in the solid state are in many cases constructed similarly to complex ones, but are unstable.

The most stable and diverse complexes in composition and functions are formed by d-elements. Particularly important are complex compounds of transition elements: iron, manganese, titanium, cobalt, copper, zinc and molybdenum. Biogenic s-elements (Na, K, Mg, Ca) form complex compounds only with ligands of a certain cyclic structure, also acting as a complexing agent. Main part R-elements (N, P, S, O) is the active active part of complexing particles (ligands), including bioligands. This is their biological significance.

Consequently, the ability to form complexes is a general property of the chemical elements of the periodic table; this ability decreases in the following order: f> d> p> s.

7.2. DETERMINATION OF THE CHARGE OF THE MAIN PARTICLES OF A COMPLEX COMPOUND

The charge of the inner sphere of a complex compound is the algebraic sum of the charges of the particles that form it. For example, the magnitude and sign of the charge of a complex are determined as follows. The charge of the aluminum ion is +3, the total charge of the six hydroxide ions is -6. Therefore, the charge of the complex is (+3) + (-6) = -3 and the formula of the complex is 3-. The charge of the complex ion is numerically equal to the total charge of the outer sphere and is opposite in sign. For example, the charge of the outer sphere K 3 is +3. Therefore, the charge of the complex ion is -3. The charge of the complexing agent is equal in magnitude and opposite in sign to the algebraic sum of the charges of all other particles of the complex compound. Hence, in K 3 the charge of the iron ion is +3, since the total charge of all other particles of the complex compound is (+3) + (-6) = -3.

7.3. NOMENCLATURE OF COMPLEX CONNECTIONS

The basics of nomenclature were developed in the classical works of Werner. In accordance with them, in a complex compound the cation is first called, and then the anion. If the compound is of a non-electrolyte type, then it is called in one word. The name of a complex ion is written in one word.

The neutral ligand is named the same as the molecule, and an “o” is added to the anion ligands. For a coordinated water molecule, the designation “aqua-” is used. To indicate the number of identical ligands in the internal sphere of the complex, the Greek numerals di-, tri-, tetra-, penta-, hexa-, etc. are used as a prefix before the name of the ligands. The prefix monone is used. Ligands are listed in alphabetical order. The name of the ligand is considered as a single whole. The name of the ligand is followed by the name of the central atom with an indication of the oxidation state, which is indicated by Roman numerals in parentheses. The word ammin (with two "m") is written in relation to ammonia. For all other amines, only one “m” is used.

C1 3 - hexammine cobalt (III) chloride.

C1 3 - aquapentammine cobalt (III) chloride.

Cl 2 - pentamethylammine chlorocobalt (III) chloride.

Diamminedibromoplatinum (II).

If the complex ion is an anion, then its Latin name has the ending “am”.

(NH 4) 2 - ammonium tetrachloropalladate (II).

K - potassium pentabromoammine platinate (IV).

K 2 - potassium tetrarodanocobaltate (II).

The name of the complex ligand is usually enclosed in parentheses.

NO 3 - dichloro-di-(ethylenediamine) cobalt (III) nitrate.

Br - bromo-tris-(triphenylphosphine) platinum (II) bromide.

In cases where a ligand binds two central ions, a Greek letter is used before its nameμ.

Such ligands are called bridge and are listed last.

7.4. CHEMICAL BONDING AND STRUCTURE OF COMPLEX COMPOUNDS

In the formation of complex compounds, donor-acceptor interactions between the ligand and the central atom play an important role. The electron pair donor is usually a ligand. An acceptor is a central atom that has free orbitals. This bond is strong and does not break when the complex is dissolved (nonionic), and it is called coordination.

Along with o-bonds, π-bonds are formed according to the donor-acceptor mechanism. In this case, the donor is a metal ion, which donates its paired d-electrons to a ligand that has energetically favorable vacant orbitals. Such connections are called dative. They are formed:

a) due to the overlap of vacant p-orbitals of the metal with the d-orbital of the metal, which contains electrons that have not entered into a σ bond;

b) when vacant d-orbitals of the ligand overlap with filled d-orbitals of the metal.

A measure of its strength is the degree of overlap of the orbitals of the ligand and the central atom. The direction of the bonds of the central atom determines the geometry of the complex. To explain the direction of bonds, ideas about the hybridization of atomic orbitals of the central atom are used. Hybrid orbitals of the central atom are the result of mixing unequal atomic orbitals, as a result the shape and energy of the orbitals mutually change, and orbitals of a new identical shape and energy are formed. The number of hybrid orbitals is always equal to the number of original ones. Hybrid clouds are located in the atom at the maximum distance from each other (Table 7.1).

Table 7.1. Types of hybridization of atomic orbitals of a complexing agent and the geometry of some complex compounds

The spatial structure of the complex is determined by the type of hybridization of valence orbitals and the number of lone electron pairs contained in its valence energy level.

The efficiency of the donor-acceptor interaction between the ligand and the complexing agent, and, consequently, the strength of the bond between them (stability of the complex) is determined by their polarizability, i.e. the ability to transform their electronic shells under external influence. Based on this criterion, reagents are divided into "hard" or low polarizable, and "soft" - easily polarizable. The polarity of an atom, molecule or ion depends on its size and the number of electron layers. The smaller the radius and electrons of a particle, the less polarized it is. The smaller the radius and the fewer electrons a particle has, the worse it is polarized.

Hard acids form strong (hard) complexes with the electronegative O, N, F atoms of ligands (hard bases), and soft acids form strong (soft) complexes with the donor P, S and I atoms of ligands that have low electronegativity and high polarizability. We see here a manifestation of the general principle of “like with like.”

Sodium and potassium ions, due to their rigidity, practically do not form stable complexes with biosubstrates and are found in physiological environments in the form of aquatic complexes. Ca 2 + and Mg 2 + ions form fairly stable complexes with proteins and therefore are found in physiological environments in both ionic and bound states.

Ions of d-elements form strong complexes with biosubstrates (proteins). And soft acids Cd, Pb, Hg are highly toxic. They form strong complexes with proteins containing R-SH sulfhydryl groups:

Cyanide ion is toxic. The soft ligand actively interacts with d-metals in complexes with biosubstrates, activating the latter.

7.5. DISSOCIATION OF COMPLEX COMPOUNDS. STABILITY OF COMPLEXES. LABILE AND INERT COMPLEXES

When complex compounds are dissolved in water, they usually disintegrate into ions of the outer and inner spheres, like strong electrolytes, since these ions are bound ionogenically, mainly by electrostatic forces. This is assessed as the primary dissociation of complex compounds.

Secondary dissociation of a complex compound is the disintegration of the inner sphere into its constituent components. This process occurs like weak electrolytes, since the particles of the inner sphere are connected nonionically (by covalent bonds). Dissociation is of a stepwise nature:

To qualitatively characterize the stability of the internal sphere of a complex compound, an equilibrium constant is used that describes its complete dissociation, called instability constant of the complex(Kn). For a complex anion, the expression of the instability constant has the form:

The lower the value of Kn, the more stable the inner sphere of the complex compound is, i.e. the less it dissociates in an aqueous solution. Recently, instead of Kn, the value of the stability constant (Ku) is used - the reciprocal of Kn. The higher the Ku value, the more stable the complex.

Stability constants make it possible to predict the direction of ligand exchange processes.

In an aqueous solution, the metal ion exists in the form of aqua complexes: 2 + - hexaquatic iron (II), 2 + - tetraaqua copper (II). When writing formulas for hydrated ions, we do not indicate the coordinated water molecules of the hydration shell, but we mean them. The formation of a complex between a metal ion and any ligand is considered as a reaction of replacement of a water molecule in the internal coordination sphere by this ligand.

Ligand exchange reactions proceed according to the mechanism of S N -Type reactions. For example:

The values ​​of the stability constants given in Table 7.2 indicate that due to the process of complexation, strong binding of ions in aqueous solutions occurs, which indicates the effectiveness of using this type of reaction for binding ions, especially with polydentate ligands.

Table 7.2. Stability of zirconium complexes

Unlike ion exchange reactions, the formation of complex compounds is often not a quasi-instantaneous process. For example, when iron (III) reacts with nitrilotrimethylenephosphonic acid, equilibrium is established after 4 days. For the kinetic characteristics of complexes, the following concepts are used: labile(quickly reacting) and inert(slow to react). Labile complexes, according to the proposal of G. Taube, are considered to be those that completely exchange ligands within 1 min at room temperature and a solution concentration of 0.1 M. It is necessary to clearly distinguish between thermodynamic concepts [strong (stable)/fragile (unstable)] and kinetic [ inert and labile] complexes.

In labile complexes, ligand substitution occurs quickly and equilibrium is quickly established. In inert complexes, ligand substitution occurs slowly.

Thus, the inert complex 2+ in an acidic environment is thermodynamically unstable: the instability constant is 10 -6, and the labile complex 2- is very stable: the stability constant is 10 -30. Taube associates the lability of complexes with the electronic structure of the central atom. The inertness of the complexes is characteristic mainly of ions with an incomplete d-shell. The inert complexes include Co and Cr complexes. Cyanide complexes of many cations with an external s 2 p 6 level are labile.

7.6. CHEMICAL PROPERTIES OF COMPLEXES

Complexation processes affect practically the properties of all particles forming the complex. The higher the strength of the bonds between the ligand and the complexing agent, the less the properties of the central atom and ligands appear in the solution and the more noticeable the features of the complex are.

Complex compounds exhibit chemical and biological activity as a result of the coordination unsaturation of the central atom (there are free orbitals) and the presence of free electron pairs of the ligands. In this case, the complex has electrophilic and nucleophilic properties that differ from the properties of the central atom and ligands.

It is necessary to take into account the influence of the structure of the hydration shell of the complex on the chemical and biological activity. The process of education

The formation of complexes affects the acid-base properties of the complex compound. The formation of complex acids is accompanied by an increase in the strength of the acid or base, respectively. Thus, when complex acids are formed from simple ones, the binding energy with H + ions decreases and the strength of the acid increases accordingly. If the OH - ion is located in the outer sphere, then the bond between the complex cation and the hydroxide ion of the outer sphere decreases, and the basic properties of the complex increase. For example, copper hydroxide Cu(OH) 2 is a weak, sparingly soluble base. When exposed to ammonia, copper ammonia (OH) 2 is formed. The charge density of 2+ compared to Cu 2+ decreases, the bond with OH - ions is weakened and (OH) 2 behaves as a strong base. The acid-base properties of ligands bound to a complexing agent are usually more pronounced than their acid-base properties in the free state. For example, hemoglobin (Hb) or oxyhemoglobin (HbO 2) exhibit acidic properties due to the free carboxyl groups of the globin protein, which is the ligand HHb ↔ H + + Hb -. At the same time, the hemoglobin anion, due to the amino groups of the globin protein, exhibits basic properties and therefore binds the acidic oxide CO 2 to form the carbaminohemoglobin anion (HbCO 2 -): CO 2 + Hb - ↔ HbCO 2 - .

The complexes exhibit redox properties due to the redox transformations of the complexing agent, which forms stable oxidation states. The process of complexation strongly influences the reduction potentials of d-elements. If the reduced form of cations forms a more stable complex with a given ligand than its oxidized form, then the potential increases. A decrease in the potential occurs when the oxidized form forms a more stable complex. For example, under the influence of oxidizing agents: nitrites, nitrates, NO 2, H 2 O 2, hemoglobin is converted into methemoglobin as a result of oxidation of the central atom.

The sixth orbital is used in the formation of oxyhemoglobin. The same orbital is involved in the formation of bonds with carbon monoxide. As a result, a macrocyclic complex with iron is formed - carboxyhemoglobin. This complex is 200 times more stable than the iron-oxygen complex in heme.

Rice. 7.1. Chemical transformations of hemoglobin in the human body. Scheme from the book: Slesarev V.I. Fundamentals of living chemistry, 2000

The formation of complex ions affects the catalytic activity of complexing ions. In some cases, activity increases. This is due to the formation of large structural systems in solution that can participate in the creation of intermediate products and reduce the activation energy of the reaction. For example, if Cu 2+ or NH 3 is added to H 2 O 2, the decomposition process does not accelerate. In the presence of the 2+ complex, which is formed in an alkaline environment, the decomposition of hydrogen peroxide is accelerated by 40 million times.

So, on hemoglobin we can consider the properties of complex compounds: acid-base, complexation and redox.

7.7. CLASSIFICATION OF COMPLEX CONNECTIONS

There are several systems for classifying complex compounds, which are based on different principles.

1. According to the complex compound’s belonging to a certain class of compounds:

Complex acids H 2;

Complex bases OH;

Complex salts K4.

2. By the nature of the ligand: aqua complexes, ammonia, acido complexes (anions of various acids, K 4 act as ligands; hydroxo complexes (hydroxyl groups, K 3 act as ligands); complexes with macrocyclic ligands, within which the central atom.

3.According to the sign of the charge of the complex: cationic - complex cation in the complex compound Cl 3; anionic - complex anion in complex compound K; neutral - the charge of the complex is 0. The complex compound does not have an outer sphere, for example. This is an anticancer drug formula.

4.According to the internal structure of the complex:

a) depending on the number of atoms of the complexing agent: mononuclear- the complex particle contains one atom of a complexing agent, for example Cl 3 ; multi-core- the complex particle contains several atoms of a complexing agent - an iron-protein complex:

b) depending on the number of types of ligands, complexes are distinguished: homogeneous (single-ligand), containing one type of ligand, for example 2+, and dissimilar (multi-ligand)- two types of ligands or more, for example Pt(NH 3) 2 Cl 2. The complex includes ligands NH 3 and Cl - . Complex compounds containing different ligands in the inner sphere are characterized by geometric isomerism, when, with the same composition of the inner sphere, the ligands in it are located differently relative to each other.

Geometric isomers of complex compounds differ not only in physical and chemical properties, but also in biological activity. The cis isomer of Pt(NH 3) 2 Cl 2 has a pronounced antitumor activity, but the trans isomer does not;

c) depending on the denticity of the ligands forming mononuclear complexes, groups can be distinguished:

Mononuclear complexes with monodentate ligands, for example 3+;

Mononuclear complexes with polydentate ligands. Complex compounds with polydentate ligands are called chelate compounds;

d) cyclic and acyclic forms of complex compounds.

7.8. CHELATE COMPLEXES. COMPLEXONS. COMPLEXONATES

Cyclic structures that are formed as a result of the addition of a metal ion to two or more donor atoms belonging to one molecule of the chelating agent are called chelate compounds. For example, copper glycinate:

In them, the complexing agent, as it were, leads into the ligand, is covered by bonds, like claws, therefore, other things being equal, they have higher stability than compounds that do not contain rings. The most stable cycles are those consisting of five or six links. This rule was first formulated by L.A. Chugaev. Difference

the stability of the chelate complex and the stability of its non-cyclic analogue is called chelation effect.

Polydentate ligands, which contain 2 types of groups, act as chelating agents:

1) groups capable of forming covalent polar bonds due to exchange reactions (proton donors, electron pair acceptors) -CH 2 COOH, -CH 2 PO(OH) 2, -CH 2 SO 2 OH, - acid groups (centers);

2) electron pair donor groups: ≡N, >NH, >C=O, -S-, -OH, - main groups (centers).

If such ligands saturate the internal coordination sphere of the complex and completely neutralize the charge of the metal ion, then the compounds are called within the complex. For example, copper glycinate. There is no external sphere in this complex.

A large group of organic substances containing basic and acidic centers in the molecule are called complexons. These are polybasic acids. Chelate compounds formed by complexones when interacting with metal ions are called complexonates, for example magnesium complexonate with ethylenediaminetetraacetic acid:

In aqueous solution, the complex exists in anionic form.

Complexons and complexonates are a simple model of more complex compounds of living organisms: amino acids, polypeptides, proteins, nucleic acids, enzymes, vitamins and many other endogenous compounds.

Currently, a huge range of synthetic complexones with various functional groups is produced. The formulas of the main complexones are presented below:

Complexons, under certain conditions, can provide lone pairs of electrons (several) to form a coordination bond with a metal ion (s-, p- or d-element). As a result, stable chelate-type compounds with 4-, 5-, 6- or 8-membered rings are formed. The reaction occurs over a wide pH range. Depending on the pH, the nature of the complexing agent, and its ratio with the ligand, complexonates of varying strength and solubility are formed. The chemistry of the formation of complexonates can be represented by equations using the example of sodium salt EDTA (Na 2 H 2 Y), which dissociates in an aqueous solution: Na 2 H 2 Y → 2Na + + H 2 Y 2-, and the H 2 Y 2- ion interacts with the ions metals, regardless of the degree of oxidation of the metal cation, most often one metal ion interacts with one complexone molecule (1:1). The reaction proceeds quantitatively (Kp >10 9).

Complexones and complexonates exhibit amphoteric properties over a wide pH range, the ability to participate in oxidation-reduction reactions, complex formation, form compounds with various properties depending on the degree of oxidation of the metal, its coordination saturation, and have electrophilic and nucleophilic properties. All this determines the ability to bind a huge number of particles, which allows a small amount of reagent to solve large and varied problems.

Another undeniable advantage of complexones and complexonates is their low toxicity and ability to convert toxic particles

into low-toxic or even biologically active. The products of the destruction of complexonates do not accumulate in the body and are harmless. The third feature of complexonates is the possibility of using them as a source of microelements.

Increased digestibility is due to the fact that the microelement is introduced in a biologically active form and has high membrane permeability.

7.9. PHOSPHORUS-CONTAINING METAL COMPLEXONATES - AN EFFECTIVE FORM OF CONVERSION OF MICRO-AND MACROELEMENTS INTO A BIOLOGICALLY ACTIVE STATE AND A MODEL FOR STUDYING THE BIOLOGICAL ACTION OF CHEMICAL ELEMENTS

Concept biological activity covers a wide range of phenomena. From the point of view of chemical effects, biologically active substances (BAS) are generally understood as substances that can act on biological systems, regulating their vital functions.

The ability to have such an effect is interpreted as the ability to exhibit biological activity. Regulation can manifest itself in the effects of stimulation, inhibition, development of certain effects. The extreme manifestation of biological activity is biocidal action, when, as a result of the influence of a biocide substance on the body, the latter dies. At lower concentrations, in most cases, biocides have a stimulating rather than lethal effect on living organisms.

A large number of such substances are currently known. However, in many cases, the use of known biologically active substances is insufficiently used, often with an effectiveness far from maximum, and the use often leads to side effects that can be eliminated by introducing modifiers into the biologically active substances.

Phosphorus-containing complexonates form compounds with various properties depending on the nature, degree of oxidation of the metal, coordination saturation, composition and structure of the hydration shell. All this determines the polyfunctionality of complexonates, their unique ability of substoichiometric action,

the common ion effect and provides wide application in medicine, biology, ecology and in various sectors of the national economy.

When a complexone is coordinated by a metal ion, a redistribution of electron density occurs. Due to the participation of a lone electron pair in the donor-acceptor interaction, the electron density of the ligand (complexon) shifts to the central atom. A decrease in the relative negative charge on the ligand helps to reduce the Coulomb repulsion of the reactants. Therefore, the coordinated ligand becomes more accessible to attack by a nucleophilic reagent having an excess electron density at the reaction center. The shift in electron density from the complexone to the metal ion leads to a relative increase in the positive charge of the carbon atom, and therefore to an easier attack by the nucleophilic reagent, the hydroxyl ion. The hydroxylated complex, among the enzymes that catalyze metabolic processes in biological systems, occupies one of the central places in the mechanism of enzymatic action and detoxification of the body. As a result of the multipoint interaction of the enzyme with the substrate, an orientation occurs that ensures the convergence of the active groups in the active center and the transfer of the reaction to the intramolecular mode, before the reaction begins and the transition state is formed, which ensures the enzymatic function of the FCM. Conformational changes can occur in enzyme molecules. Coordination creates additional conditions for redox interaction between the central ion and the ligand, since a direct connection is established between the oxidizing agent and the reducing agent, ensuring the transfer of electrons. FCM transition metal complexes may be characterized by electron transitions of the L-M, M-L, M-L-M types, which involve the orbitals of both the metal (M) and ligands (L), which are respectively linked in the complex by donor-acceptor bonds. Complexons can serve as a bridge along which the electrons of multinuclear complexes oscillate between the central atoms of the same or different elements in different oxidation states (electron and proton transfer complexes). Complexons determine the reducing properties of metal complexonates, which allows them to exhibit high antioxidant, adaptogenic properties, and homeostatic functions.

So, complexons convert microelements into a biologically active form accessible to the body. They form stable

more coordinately saturated particles, unable to destroy biocomplexes, and therefore low-toxic forms. Complexonates have a beneficial effect in cases of disruption of microelement homeostasis in the body. Ions of transition elements in complexonate form act in the body as a factor determining the high sensitivity of cells to trace elements through their participation in the creation of a high concentration gradient and membrane potential. Transition metal complexonates FCM have bioregulatory properties.

The presence of acidic and basic centers in the FCM composition ensures amphoteric properties and their participation in maintaining acid-base equilibrium (isohydric state).

With an increase in the number of phosphonic groups in the complexone, the composition and conditions for the formation of soluble and poorly soluble complexes change. An increase in the number of phosphonic groups favors the formation of poorly soluble complexes in a wider pH range and shifts the region of their existence to the acidic region. The decomposition of complexes occurs at pH above 9.

The study of complex formation processes with complexones made it possible to develop methods for the synthesis of bioregulators:

Long-acting growth stimulants in colloidal chemical form are polynuclear homo- and heterocomplex compounds of titanium and iron;

Growth stimulants in water-soluble form. These are multi-ligand titanium complexonates based on complexones and an inorganic ligand;

Growth inhibitors are phosphorus-containing complexonates of s-elements.

The biological effect of the synthesized drugs on growth and development was studied in chronic experiments on plants, animals and humans.

Bioregulation- this is a new scientific direction that allows you to regulate the direction and intensity of biochemical processes, which can be widely used in medicine, animal husbandry and crop production. It is associated with the development of methods for restoring the physiological function of the body in order to prevent and treat diseases and age-related pathologies. Complexons and complex compounds based on them can be classified as promising biologically active compounds. The study of their biological action in a chronic experiment showed that chemistry gave into the hands of doctors,

livestock breeders, agronomists and biologists have a new promising tool that allows them to actively influence a living cell, regulate nutritional conditions, growth and development of living organisms.

A study of the toxicity of the used complexones and complexonates showed a complete lack of influence of the drugs on the hematopoietic organs, blood pressure, excitability, respiratory rate: no changes in liver function were noted, no toxicological effect on the morphology of tissues and organs was detected. The potassium salt of HEDP is not toxic at a dose 5-10 times higher than the therapeutic dose (10-20 mg/kg) when studied for 181 days. Consequently, complexones are low-toxic compounds. They are used as medicines to combat viral diseases, poisoning with heavy metals and radioactive elements, calcium metabolism disorders, endemic diseases and microelement imbalance in the body. Phosphorus-containing complexons and complexonates are not subject to photolysis.

Progressive pollution of the environment with heavy metals - products of human economic activity - is a constantly operating environmental factor. They can accumulate in the body. Excess and deficiency of them cause intoxication of the body.

Metal complexonates retain a chelating effect on the ligand (complexone) in the body and are indispensable for maintaining metal ligand homeostasis. Incorporated heavy metals are neutralized to a certain extent in the body, and low resorption capacity prevents the transfer of metals along trophic chains, as a result, this leads to a certain “biominimization” of their toxic effect, which is especially important for the Ural region. For example, free lead ion is a thiol poison, and strong lead complexonate with ethylenediaminetetraacetic acid is low-toxic. Therefore, detoxification of plants and animals involves the use of metal complexonates. It is based on two thermodynamic principles: their ability to form strong bonds with toxic particles, turning them into compounds that are poorly soluble or stable in an aqueous solution; their inability to destroy endogenous biocomplexes. In this regard, we consider complex therapy of plants and animals an important direction in the fight against eco-poisoning and obtaining environmentally friendly products.

A study was carried out of the effect of treating plants with complexonates of various metals under intensive cultivation technology

potatoes on the microelement composition of potato tubers. Tuber samples contained 105-116 mg/kg iron, 16-20 mg/kg manganese, 13-18 mg/kg copper and 11-15 mg/kg zinc. The ratio and content of microelements are typical for plant tissues. Tubers grown with and without the use of metal complexonates have almost the same elemental composition. The use of chelates does not create conditions for the accumulation of heavy metals in tubers. Complexonates, to a lesser extent than metal ions, are sorbed by soil and are resistant to its microbiological effects, which allows them to remain in the soil solution for a long time. The aftereffect is 3-4 years. They combine well with various pesticides. The metal in the complex has lower toxicity. Phosphorus-containing metal complexonates do not irritate the mucous membrane of the eyes and do not damage the skin. Sensitizing properties have not been identified, the cumulative properties of titanium complexonates are not expressed, and in some cases they are very weakly expressed. The cumulation coefficient is 0.9-3.0, which indicates a low potential danger of chronic drug poisoning.

Phosphorus-containing complexes are based on the phosphorus-carbon bond (C-P), which is also found in biological systems. It is part of phosphonolipids, phosphonoglycans and phosphoproteins of cell membranes. Lipids containing aminophosphonic compounds are resistant to enzymatic hydrolysis and ensure stability and, consequently, normal functioning of outer cell membranes. Synthetic analogues of pyrophosphates - diphosphonates (P-S-P) or (P-C-S-P) in large doses disrupt calcium metabolism, and in small doses they normalize it. Diphosphonates are effective against hyperlipemia and are promising from a pharmacological standpoint.

Diphosphonates containing P-C-P bonds are structural elements of biosystems. They are biologically effective and are analogues of pyrophosphates. Diphosphonates have been shown to be effective treatments for various diseases. Diphosphonates are active inhibitors of bone mineralization and resorption. Complexons convert microelements into a biologically active form accessible to the body, form stable, more coordination-saturated particles that are unable to destroy biocomplexes, and therefore low-toxic forms. They determine the high sensitivity of cells to trace elements, participating in the formation of a high concentration gradient. Capable of participating in the formation of multinuclear compounds of titanium heteronuclei-

of a new type - electron and proton transfer complexes, participate in the bioregulation of metabolic processes, body resistance, the ability to form bonds with toxic particles, turning them into slightly soluble or soluble, stable, non-destructive endogenous complexes. Therefore, their use for detoxification, elimination from the body, obtaining environmentally friendly products (complex therapy), as well as in industry for the regeneration and disposal of industrial waste of inorganic acids and transition metal salts is very promising.

7.10. LIGAND EXCHANGE AND METAL EXCHANGE

EQUILIBRIUM. CHELATOTHERAPY

If the system has several ligands with one metal ion or several metal ions with one ligand capable of forming complex compounds, then competing processes are observed: in the first case, ligand exchange equilibrium is competition between ligands for the metal ion, in the second case, metal exchange equilibrium is competition between ions metal per ligand. The process of formation of the most durable complex will prevail. For example, the solution contains ions: magnesium, zinc, iron (III), copper, chromium (II), iron (II) and manganese (II). When a small amount of ethylenediaminetetraacetic acid (EDTA) is introduced into this solution, competition between metal ions and binding of iron (III) into a complex occurs, since it forms the most durable complex with EDTA.

In the body, the interaction of biometals (Mb) and bioligands (Lb), the formation and destruction of vital biocomplexes (MbLb) constantly occur:

In the human body, animals and plants there are various mechanisms for protecting and maintaining this balance from various xenobiotics (foreign substances), including heavy metal ions. Heavy metal ions that are not complexed and their hydroxo complexes are toxic particles (Mt). In these cases, along with the natural metal-ligand equilibrium, a new equilibrium may arise, with the formation of more durable foreign complexes containing toxicant metals (MtLb) or toxicant ligands (MbLt), which do not perform

necessary biological functions. When exogenous toxic particles enter the body, combined equilibria arise and, as a result, competition of processes occurs. The predominant process will be the one that leads to the formation of the most durable complex compound:

Disturbances in metal ligand homeostasis cause metabolic disturbances, inhibit enzyme activity, destroy important metabolites such as ATP, cell membranes, and disrupt the ion concentration gradient in cells. Therefore, artificial defense systems are created. Chelation therapy (complex therapy) takes its rightful place in this method.

Chelation therapy is the removal of toxic particles from the body, based on chelation of them with s-element complexonates. Drugs used to remove toxic particles incorporated in the body are called detoxifiers.(Lg). Chelation of toxic particles with metal complexonates (Lg) converts toxic metal ions (Mt) into non-toxic (MtLg) bound forms suitable for sequestration and membrane penetration, transport and excretion from the body. They retain a chelating effect in the body for both the ligand (complexone) and the metal ion. This ensures the metal ligand homeostasis of the body. Therefore, the use of complexonates in medicine, animal husbandry, and crop production ensures detoxification of the body.

The basic thermodynamic principles of chelation therapy can be formulated in two positions.

I. The detoxicant (Lg) must effectively bind toxicant ions (Mt, Lt), the newly formed compounds (MtLg) must be stronger than those that existed in the body:

II. The detoxifier should not destroy vital complex compounds (MbLb); compounds that can be formed during the interaction of a detoxicant and biometal ions (MbLg) must be less durable than those existing in the body:

7.11. APPLICATION OF COMPLEXONES AND COMPLEXONATES IN MEDICINE

Complexon molecules practically do not undergo cleavage or any changes in the biological environment, which is their important pharmacological feature. Complexons are insoluble in lipids and highly soluble in water, so they do not penetrate or penetrate poorly through cell membranes, and therefore: 1) are not excreted by the intestines; 2) absorption of complexing agents occurs only when they are injected (only penicillamine is taken orally); 3) in the body, complexones circulate mainly in the extracellular space; 4) excretion from the body is carried out mainly through the kidneys. This process happens quickly.

Substances that eliminate the effects of poisons on biological structures and inactivate poisons through chemical reactions are called antidotes.

One of the first antidotes used in chelation therapy was British anti-lewisite (BAL). Unithiol is currently used:

This drug effectively removes arsenic, mercury, chromium and bismuth from the body. The most widely used for poisoning with zinc, cadmium, lead and mercury are complexones and complexonates. Their use is based on the formation of stronger complexes with metal ions than complexes of the same ions with sulfur-containing groups of proteins, amino acids and carbohydrates. To remove lead, EDTA-based preparations are used. Introducing drugs into the body in large doses is dangerous, as they bind calcium ions, which leads to disruption of many functions. Therefore they use tetacin(CaNa 2 EDTA), which is used to remove lead, cadmium, mercury, yttrium, cerium and other rare earth metals and cobalt.

Since the first therapeutic use of thetacine in 1952, this drug has found wide use in the clinic of occupational diseases and continues to be an indispensable antidote. The mechanism of action of thetacin is very interesting. Toxic ions displace the coordinated calcium ion from thetacin due to the formation of stronger bonds with oxygen and EDTA. The calcium ion, in turn, displaces the two remaining sodium ions:

Thetacin is administered into the body in the form of a 5-10% solution, the basis of which is saline solution. So, already 1.5 hours after intraperitoneal injection, 15% of the administered dose of thetacine remains in the body, after 6 hours - 3%, and after 2 days - only 0.5%. The drug acts effectively and quickly when using the inhalation method of administering tetacin. It is quickly absorbed and circulates in the blood for a long time. In addition, thetacin is used to protect against gas gangrene. It inhibits the action of zinc and cobalt ions, which are activators of the lecithinase enzyme, which is a gas gangrene toxin.

The binding of toxicants by thetacin into a low-toxic and more durable chelate complex, which is not destroyed and is easily excreted from the body through the kidneys, provides detoxification and balanced mineral nutrition. Close in structure and composition to pre-

paratam EDTA is the sodium calcium salt of diethylenetriamine-pentaacetic acid (CaNa 3 DTPA) - pentacin and sodium salt of dacid (Na 6 DTPP) - trimefa-cin. Pentacine is used primarily for poisoning with compounds of iron, cadmium and lead, as well as for the removal of radionuclides (technetium, plutonium, uranium).

Sodium salt of ethyacid (CaNa 2 EDTP) phosphicine successfully used to remove mercury, lead, beryllium, manganese, actinides and other metals from the body. Complexonates are very effective in removing some toxic anions. For example, cobalt(II) ethylenediaminetetraacetate, which forms a mixed-ligand complex with CN -, can be recommended as an antidote for cyanide poisoning. A similar principle underlies methods for removing toxic organic substances, including pesticides containing functional groups with donor atoms capable of interacting with the complexonate metal.

An effective drug is succimer(dimercaptosuccinic acid, dimercaptosuccinic acid, chemet). It firmly binds almost all toxicants (Hg, As, Pb, Cd), but removes ions of biogenic elements (Cu, Fe, Zn, Co) from the body, so it is almost never used.

Phosphorus-containing complexonates are powerful inhibitors of crystal formation of phosphates and calcium oxalates. Xidifon, a potassium-sodium salt of HEDP, has been proposed as an anti-calcifying drug in the treatment of urolithiasis. Diphosphonates, in addition, in minimal doses, increase the incorporation of calcium into bone tissue and prevent its pathological release from the bones. HEDP and other diphosphonates prevent various types of osteoporosis, including renal osteodystrophy, periodontal

destruction, as well as destruction of transplanted bone in animals. The antiatherosclerotic effect of HEDP has also been described.

In the USA, a number of diphosphonates, in particular HEDP, have been proposed as pharmaceuticals for the treatment of humans and animals suffering from metastatic bone cancer. By regulating membrane permeability, bisphosphonates promote the transport of antitumor drugs into the cell, and hence the effective treatment of various oncological diseases.

One of the pressing problems of modern medicine is the task of rapid diagnosis of various diseases. In this aspect, of undoubted interest is a new class of drugs containing cations that can perform the functions of a probe - radioactive magnetorelaxation and fluorescent labels. Radioisotopes of certain metals are used as the main components of radiopharmaceuticals. Chelation of cations of these isotopes with complexons makes it possible to increase their toxicological acceptability for the body, facilitate their transportation and ensure, within certain limits, selectivity of concentration in certain organs.

The given examples by no means exhaust the variety of forms of application of complexonates in medicine. Thus, the dipotassium salt of magnesium ethylenediaminetetraacetate is used to regulate fluid content in tissues during pathology. EDTA is used in the composition of anticoagulant suspensions used in the separation of blood plasma, as a stabilizer of adenosine triphosphate in determining blood glucose, and in the bleaching and storage of contact lenses. Bisphosphonates are widely used in the treatment of rheumatoid diseases. They are especially effective as anti-arthritis agents in combination with anti-inflammatory drugs.

7.12. COMPLEXES WITH MACROCYCLIC COMPOUNDS

Among natural complex compounds, a special place is occupied by macrocomplexes based on cyclic polypeptides containing internal cavities of certain sizes, in which there are several oxygen-containing groups capable of binding cations of those metals, including sodium and potassium, the dimensions of which correspond to the dimensions of the cavity. Such substances, being in biological

Rice. 7.2. Valinomycin complex with K+ ion

ical materials, ensure the transport of ions through membranes and are therefore called ionophores. For example, valinomycin transports potassium ion across the membrane (Figure 7.2).

Using another polypeptide - gramicidin A sodium cations are transported via a relay mechanism. This polypeptide is folded into a “tube”, the inner surface of which is lined with oxygen-containing groups. The result is

a sufficiently long hydrophilic channel with a certain cross section corresponding to the size of the sodium ion. The sodium ion, entering the hydrophilic channel from one side, is transferred from one oxygen group to another, like a relay race through an ion-conducting channel.

So, a cyclic polypeptide molecule has an intramolecular cavity into which a substrate of a certain size and geometry can enter, similar to the principle of a key and lock. The cavity of such internal receptors is bordered by active centers (endoreceptors). Depending on the nature of the metal ion, non-covalent interaction (electrostatic, formation of hydrogen bonds, van der Waals forces) with alkali metals and covalent interaction with alkaline earth metals can occur. As a result of this, supramolecules- complex associates consisting of two or more particles held together by intermolecular forces.

The most common tetradentate macrocycles in living nature are porphins and corrinoids similar in structure. Schematically, the tetradent cycle can be represented in the following form (Fig. 7.3), where the arcs represent carbon chains of the same type connecting donor nitrogen atoms into a closed cycle; R 1, R 2, R 3, P 4 are hydrocarbon radicals; Mn+ is a metal ion: in chlorophyll there is an Mg 2+ ion, in hemoglobin there is a Fe 2+ ion, in hemocyanin there is a Cu 2+ ion, in vitamin B 12 (cobalamin) there is a Co 3+ ion.

Donor nitrogen atoms are located at the corners of the square (indicated by dotted lines). They are strictly coordinated in space. That's why

porphyrins and corrinoids form stable complexes with cations of various elements and even alkaline earth metals. It is essential that Regardless of the denticity of the ligand, the chemical bond and structure of the complex are determined by the donor atoms. For example, copper complexes with NH 3, ethylenediamine and porphyrin have the same square structure and similar electronic configuration. But polydentate ligands bind to metal ions much more strongly than monodentate ligands

Rice. 7.3. Tetradentate macrocycle

with the same donor atoms. The strength of ethylenediamine complexes is 8-10 orders of magnitude greater than the strength of the same metals with ammonia.

Bioinorganic complexes of metal ions with proteins are called bioclusters - complexes of metal ions with macrocyclic compounds (Fig. 7.4).

Rice. 7.4. Schematic representation of the structure of bioclusters of certain sizes of protein complexes with ions of d-elements. Types of protein molecule interactions. M n+ - active center metal ion

There is a cavity inside the biocluster. It includes a metal that interacts with donor atoms of connecting groups: OH -, SH -, COO -, -NH 2, proteins, amino acids. The most famous metallofers are

enzymes (carbonic anhydrase, xanthine oxidase, cytochromes) are bioclusters, the cavities of which form enzyme centers containing Zn, Mo, Fe, respectively.

7.13. MULTICORE COMPLEXES

Heterovalent and heteronuclear complexes

Complexes that contain several central atoms of one or different elements are called multi-core. The possibility of forming multinuclear complexes is determined by the ability of some ligands to bind to two or three metal ions. Such ligands are called bridge Respectively bridge are also called complexes. Monatomic bridges are also possible in principle, for example:

They use lone pairs of electrons belonging to the same atom. The role of bridges can be played by polyatomic ligands. Such bridges use lone electron pairs belonging to different atoms polyatomic ligand.

A.A. Greenberg and F.M. Filinov studied bridging compounds of the composition, in which the ligand binds complex compounds of the same metal, but in different oxidation states. G. Taube called them electron transfer complexes. He studied electron transfer reactions between the central atoms of various metals. Systematic studies of the kinetics and mechanism of redox reactions led to the conclusion that electron transfer between two complexes

comes through the resulting ligand bridge. The exchange of electrons between 2 + and 2 + occurs through the formation of an intermediate bridging complex (Fig. 7.5). Electron transfer occurs through the chloride bridging ligand, ending in the formation of 2+ complexes; 2+.

Rice. 7.5. Electron transfer in an intermediate multinuclear complex

A wide variety of polynuclear complexes have been obtained through the use of organic ligands containing several donor groups. The condition for their formation is the arrangement of donor groups in the ligand, which does not allow the chelate cycles to close. There are often cases when a ligand has the ability to close the chelate cycle and at the same time act as a bridge.

The active principle of electron transfer is transition metals, which exhibit several stable oxidation states. This gives titanium, iron and copper ions ideal electron-carrying properties. A set of options for the formation of heterovalent (HVC) and heteronuclear complexes (HNC) based on Ti and Fe is presented in Fig. 7.6.

Reaction

Reaction (1) is called cross reaction. In exchange reactions, heterovalent complexes will be intermediates. All theoretically possible complexes actually form in solution under certain conditions, which has been proven by various physicochemical tests.

Rice. 7.6. Formation of heterovalent complexes and heteronuclear complexes containing Ti and Fe

methods. For electron transfer to occur, the reactants must be in states that are close in energy. This requirement is called the Franck-Condon principle. Electron transfer can occur between atoms of the same transition element, which are in different states of oxidation of HVA, or different elements of HCA, the nature of the metal centers of which is different. These compounds can be defined as electron transfer complexes. They are convenient carriers of electrons and protons in biological systems. The addition and donation of an electron causes changes only in the electronic configuration of the metal, without changing the structure of the organic component of the complex. All these elements have several stable oxidation states (Ti +3 and +4; Fe +2 and +3; Cu +1 and +2). In our opinion, these systems are given by nature a unique role of ensuring the reversibility of biochemical processes with minimal energy costs. Reversible reactions include reactions that have thermodynamic and thermochemical constants from 10 -3 to 10 3 and with a small value of ΔG o and E o processes. Under these conditions, the starting materials and reaction products can be present in comparable concentrations. When changing them in a certain range, it is easy to achieve reversibility of the process, therefore, in biological systems, many processes are oscillatory (wave) in nature. Redox systems containing the above pairs cover a wide range of potentials, which allows them to enter into interactions accompanied by moderate changes in Δ G o And E°, with many substrates.

The likelihood of HVA and GAC formation increases significantly when the solution contains potentially bridging ligands, i.e. molecules or ions (amino acids, hydroxy acids, complexones, etc.) that can bind two metal centers at once. The possibility of electron delocalization in the GVK contributes to a decrease in the total energy of the complex.

More realistically, the set of possible variants of the formation of HVC and HNC, in which the nature of the metal centers is different, is visible in Fig. 7.6. A detailed description of the formation of GVK and GYAK and their role in biochemical systems is considered in the works of A.N. Glebova (1997). Redox pairs must be structurally adjusted to each other for transfer to become possible. By selecting the components of the solution, you can “extend” the distance over which an electron is transferred from the reducing agent to the oxidizing agent. With coordinated movement of particles, electron transfer over long distances can occur via a wave mechanism. The “corridor” can be a hydrated protein chain, etc. There is a high probability of electron transfer over a distance of up to 100A. The length of the “corridor” can be increased by adding additives (alkali metal ions, background electrolytes). This opens up great opportunities in the field of controlling the composition and properties of HVA and HYA. In solutions they play the role of a kind of “black box” filled with electrons and protons. Depending on the circumstances, he can give them to other components or replenish his “reserves”. The reversibility of reactions involving them allows them to repeatedly participate in cyclic processes. Electrons move from one metal center to another and oscillate between them. The complex molecule remains asymmetrical and can take part in redox processes. GVA and GNA actively participate in oscillatory processes in biological media. This type of reaction is called oscillatory reactions. They are found in enzymatic catalysis, protein synthesis and other biochemical processes accompanying biological phenomena. These include periodic processes of cellular metabolism, waves of activity in cardiac tissue, in brain tissue, and processes occurring at the level of ecological systems. An important step in metabolism is the abstraction of hydrogen from nutrients. At the same time, hydrogen atoms transform into an ionic state, and the electrons separated from them enter the respiratory chain and give up their energy to the formation of ATP. As we have established, titanium complexonates are active carriers of not only electrons, but also protons. The ability of titanium ions to perform their role in the active center of enzymes such as catalases, peroxidases and cytochromes is determined by its high ability to form complexes, form the geometry of a coordinated ion, form multinuclear HVA and HNA of various compositions and properties as a function of pH, the concentration of the transition element Ti and the organic component of the complex, their molar ratio. This ability manifests itself in increased selectivity of the complex

in relation to substrates, products of metabolic processes, activation of bonds in the complex (enzyme) and substrate through coordination and changing the shape of the substrate in accordance with the steric requirements of the active center.

Electrochemical transformations in the body associated with electron transfer are accompanied by a change in the degree of oxidation of particles and the appearance of a redox potential in the solution. A major role in these transformations belongs to the multinuclear complexes GVK and GYAK. They are active regulators of free radical processes, a system for recycling reactive oxygen species, hydrogen peroxide, oxidants, radicals and are involved in the oxidation of substrates, as well as in maintaining antioxidant homeostasis and protecting the body from oxidative stress. Their enzymatic effect on biosystems is similar to enzymes (cytochromes, superoxide dismutase, catalase, peroxidase, glutathione reductase, dehydrogenases). All this indicates the high antioxidant properties of transition element complexonates.

7.14. QUESTIONS AND TASKS FOR SELF-CHECKING PREPARATION FOR CLASSES AND EXAMINATIONS

1.Give the concept of complex compounds. How are they different from double salts, and what do they have in common?

2. Make up formulas of complex compounds by their names: ammonium dihydroxotetrachloroplatinate (IV), triammintrinitrocobalt (III), give their characteristics; indicate internal and external coordination areas; central ion and its oxidation state: ligands, their number and dentity; nature of connections. Write the dissociation equation in aqueous solution and the expression for the stability constant.

3. General properties of complex compounds, dissociation, stability of complexes, chemical properties of complexes.

4.How is the reactivity of complexes characterized from thermodynamic and kinetic positions?

5.Which amino complexes will be more durable than tetraamino-copper (II), and which ones will be less durable?

6. Give examples of macrocyclic complexes formed by alkali metal ions; ions of d-elements.

7. On what basis are complexes classified as chelate? Give examples of chelated and non-chelated complex compounds.

8. Using copper glycinate as an example, give the concept of intracomplex compounds. Write the structural formula of magnesium complexonate with ethylenediaminetetraacetic acid in sodium form.

9. Give a schematic structural fragment of any polynuclear complex.

10. Define polynuclear, heteronuclear and heterovalent complexes. The role of transition metals in their formation. Biological role of these components.

11.What types of chemical bonds are found in complex compounds?

12.List the main types of hybridization of atomic orbitals that can occur at the central atom in the complex. What is the geometry of the complex depending on the type of hybridization?

13. Based on the electronic structure of the atoms of elements of s-, p- and d-blocks, compare the ability to form complexes and their place in the chemistry of complexes.

14. Define complexones and complexonates. Give examples of those most used in biology and medicine. Give the thermodynamic principles on which chelation therapy is based. The use of complexonates to neutralize and eliminate xenobiotics from the body.

15. Consider the main cases of disruption of metal ligand homeostasis in the human body.

16. Give examples of biocomplex compounds containing iron, cobalt, zinc.

17. Examples of competing processes involving hemoglobin.

18. The role of metal ions in enzymes.

19. Explain why for cobalt in complexes with complex ligands (polydentate) the oxidation state is +3, and in ordinary salts, such as halides, sulfates, nitrates, the oxidation state is +2?

20.Copper is characterized by oxidation states of +1 and +2. Can copper catalyze electron transfer reactions?

21.Can zinc catalyze redox reactions?

22.What is the mechanism of action of mercury as a poison?

23.Indicate the acid and base in the reaction:

AgNO 3 + 2NH 3 = NO 3.

24. Explain why the potassium-sodium salt of hydroxyethylidene diphosphonic acid is used as a drug, and not HEDP.

25.How is electron transport carried out in the body with the help of metal ions that are part of biocomplex compounds?

7.15. TEST TASKS

1. The oxidation state of the central atom in a complex ion is 2- is equal to:

a) -4;

b)+2;

at 2;

d)+4.

2. Most stable complex ion:

a) 2-, Kn = 8.5x10 -15;

b) 2-, Kn = 1.5x10 -30;

c) 2-, Kn = 4x10 -42;

d) 2-, Kn = 1x10 -21.

3. The solution contains 0.1 mol of the compound PtCl 4 4NH 3. Reacting with AgNO 3, it forms 0.2 mol of AgCl precipitate. Give the starting substance a coordination formula:

a)Cl;

b)Cl 3;

c)Cl 2;

d)Cl 4.

4. What shape do the complexes formed as a result of sp 3 d 2-gi- hybridization?

1) tetrahedron;

2) square;

4) trigonal bipyramid;

5) linear.

5. Select the formula for the compound pentaammine chlorocobalt (III) sulfate:

a) Na 3 ;

6)[CoCl 2 (NH 3) 4 ]Cl;

c) K 2 [Co(SCN) 4 ];

d)SO 4;

e)[Co(H 2 O) 6 ] C1 3 .

6. Which ligands are polydentate?

a) C1 - ;

b)H 2 O;

c) ethylenediamine;

d)NH 3;

e)SCN - .

7. Complexing agents are:

a) electron pair donor atoms;

c) atoms and ions that accept electron pairs;

d) atoms and ions that are donors of electron pairs.

8. The elements that have the least complex-forming ability are:

a)s; c) d;

b) p ; d)f

9. Ligands are:

a) electron pair donor molecules;

b) electron pair acceptor ions;

c) molecules and ions-donors of electron pairs;

d) molecules and ions that accept electron pairs.

10. Communication in the internal coordination sphere of the complex:

a) covalent exchange;

b) covalent donor-acceptor;

c) ionic;

d) hydrogen.

11. The best complexing agent would be:

To the class dicarboxylic acids These include compounds containing two carboxyl groups. Dicarboxylic acids are divided depending on the type of hydrocarbon radical:

saturated;

unsaturated;

aromatic.

Nomenclature of dicarboxylic acids similar to the nomenclature of monocarboxylic acids (part 2, chapter 6.2):

trivial;

radical-functional;

systematic.

Examples of dicarboxylic acid names are given in Table 25.

Table 25 – Nomenclature of dicarboxylic acids

Isomerism. The following types of isomerism are characteristic of dicarboxylic acids:

Structural:

skeletal.

Spatial :

optical.

Methods for obtaining dicarboxylic acids. Dicarboxylic acids are prepared using the same methods as for monocarboxylic acids, with the exception of a few special methods applicable to individual acids.

General methods for preparing dicarboxylic acids

Oxidation of diols and cyclic ketones:

Hydrolysis of nitriles:

Carbonylation of diols:

Preparation of oxalic acid from sodium formate by fusing it in the presence of a solid alkali:

Preparation of malonic acid:

Preparation of adipic acid. In industry, it is obtained by the oxidation of cyclohexanol with 50% nitric acid in the presence of a copper-vanadium catalyst:

Physical properties of dicarboxylic acids. Dicarboxylic acids are solids. The lower members of the series are highly soluble in water and only slightly soluble in organic solvents. When dissolved in water, they form intermolecular hydrogen bonds. The solubility limit in water lies at WITH 6 - WITH 7 . These properties seem quite natural, since the polar carboxyl group constitutes a significant part in each of the molecules.

Table 26 - Physical properties of dicarboxylic acids

Table 27 - Behavior of dicarboxylic acids when heated

The high melting points of acids compared to the melting and boiling points of alcohols and chlorides are apparently due to the strength of hydrogen bonds. When heated, dicarboxylic acids decompose to form various products.

Chemical properties. Dibasic acids retain all the properties common to carboxylic acids. Dicarboxylic acids turn into salts and form the same derivatives as monocarboxylic acids (acid halides, anhydrides, amides, esters), but reactions can occur on one (incomplete derivatives) or on both carboxyl groups. The reaction mechanism for the formation of derivatives is the same as for monocarboxylic acids.

Dibasic acids also exhibit a number of features due to the influence of two UNS-groups

Acidic properties. Dicarboxylic acids have increased acidic properties compared to saturated monobasic acids (average ionization constants, table 26). The reason for this is not only the additional dissociation at the second carboxyl group, since the ionization of the second carboxyl is much more difficult and the contribution of the second constant to the acidic properties is barely noticeable.

The electron-withdrawing group is known to cause an increase in the acidic properties of carboxylic acids, since an increase in the positive charge on the carboxyl carbon atom enhances the mesomeric effect p,π-conjugation, which, in turn, increases the polarization of the connection HE and facilitates its dissociation. This effect is more pronounced the closer the carboxyl groups are located to each other. The toxicity of oxalic acid is associated primarily with its high acidity, the value of which approaches that of mineral acids. Considering the inductive nature of the influence, it is clear that in the homologous series of dicarboxylic acids, the acidic properties sharply decrease as the carboxyl groups move away from each other.

Dicarboxylic acids behave like dibasics and form two series of salts - acidic (with one equivalent of base) and average (with two equivalents):

Nucleophilic substitution reactions . Dicarboxylic acids, like monocarboxylic acids, undergo nucleophilic substitution reactions with the participation of one or two functional groups and form functional derivatives - esters, amides, acid chlorides.

Due to the high acidity of oxalic acid itself, its esters are obtained without the use of acid catalysts.

3. Specific reactions of dicarboxylic acids. The relative arrangement of carboxyl groups in dicarboxylic acids significantly affects their chemical properties. The first homologues in which UNS-groups are close together - oxalic and malonic acids - are capable of splitting off carbon monoxide (IV) when heated, resulting in the removal of the carboxyl group. The ability to decarboxylate depends on the structure of the acid. Monocarboxylic acids lose the carboxyl group more difficult, only when their salts are heated with solid alkalis. When introduced into acid molecules EA substituents, their tendency to decarboxylate increases. In oxalic and malonic acids, the second carboxyl group acts as such EA and thereby facilitates decarboxylation.

3.1

3.2

Decarboxylation of oxalic acid is used as a laboratory method for the synthesis of formic acid. Decarboxylation of malonic acid derivatives is an important step in the synthesis of carboxylic acids. Decarboxylation of di- and tricarboxylic acids is characteristic of many biochemical processes.

As the carbon chain lengthens and functional groups are removed, their mutual influence weakens. Therefore, the next two members of the homologous series - succinic and glutaric acids - do not decarboxylate when heated, but lose a water molecule and form cyclic anhydrides. This reaction course is due to the formation of a stable five- or six-membered ring.

3.3

3.4 By direct esterification of an acid, its full esters can be obtained, and by reacting the anhydride with an equimolar amount of alcohol, the corresponding acid esters can be obtained:

3.4.1

3.4.2

3.5 Preparation of imides . By heating the ammonium salt of succinic acid, its imide (succinimide) is obtained. The mechanism of this reaction is the same as when preparing amides of monocarboxylic acids from their salts:

In succinimide, the hydrogen atom in the imino group has significant proton mobility, which is caused by the electron-withdrawing influence of two neighboring carbonyl groups. This is the basis for obtaining N-bromo-succinimide is a compound widely used as a brominating agent for introducing bromine into the allylic position:

Individual representatives. Oxalic (ethane) acid NOOS– UNS. It is found in the form of salts in the leaves of sorrel, sorrel, and rhubarb. Salts and esters of oxalic acid have the common name oxalates. Oxalic acid exhibits restorative properties:

This reaction is used in analytical chemistry to determine the exact concentration of potassium permanganate solutions. When heated in the presence of sulfuric acid, decarboxylation of oxalic acid occurs, followed by decomposition of the resulting formic acid:

A qualitative reaction for the detection of oxalic acid and its salts is the formation of insoluble calcium oxalate.

Oxalic acid is easily oxidized, quantitatively transforming into carbon dioxide and water:

The reaction is so sensitive that it is used in volumetric analysis to establish the titers of potassium permanganate solutions.

Malonic (propanedioic) acid NOOS– CH 2 – UNS. Contained in sugar beet juice. Malonic acid is distinguished by significant proton mobility of hydrogen atoms in the methylene group, due to the electron-withdrawing effect of two carboxyl groups.

The hydrogen atoms of the methylene group are so mobile that they can be replaced by a metal. However, with a free acid this transformation is impossible, since the hydrogen atoms of the carboxyl groups are much more mobile and are replaced first.

Replace α -hydrogen atoms of the methylene group to sodium is possible only by protecting the carboxyl groups from interaction, which allows complete esterification of malonic acid:

Malonic ester reacts with sodium, eliminating hydrogen, to form sodium malonic ester:

Anion Na-malonic ester is stabilized by conjugation NEP carbon atom c π -bond electrons C=ABOUT. Na-malonic ester, as a nucleophile, easily interacts with molecules containing an electrophilic center, for example, with haloalkanes:

The above reactions make it possible to use malonic acid for the synthesis of a number of compounds:

succinic acid is a colorless crystalline substance with m.p. 183 °C, soluble in water and alcohols. Succinic acid and its derivatives are quite accessible and are widely used in organic synthesis.

Adipic (hexanedioic) acid NOOS–(SN 2 ) 4 –COOH. It is a colorless crystalline substance with mp. 149 °C, slightly soluble in water, better in alcohols. A large amount of adipic acid is used to make polyamide nylon fiber. Due to its acidic properties, adipic acid is used in everyday life to remove scale from enamel dishes. It reacts with calcium and magnesium carbonates, converting them into soluble salts, and at the same time does not damage the enamel, like strong mineral acids.

Complexons (polyaminopolycarboxylic acids) are among the most widely used polydentate ligands. Interest in complexones, derivatives of dicarboxylic acids, and especially succinic acid derivatives (SCDA), has increased in recent years, which is associated with the development of simple and accessible methods for their synthesis and the presence of a number of specific practically useful properties.

The most important method for the synthesis of CPAA is based on the interaction of maleic acid with various compounds containing a primary or secondary amino group. If aliphatic monoaminomonocarboxylic acids are taken as such compounds, mixed-type complexons (MCTs) are obtained, and when maleic acid reacts with ammonia, iminodisuccinic acid (IDAS), the simplest representative of MCAC, is obtained. Syntheses take place under mild conditions, without requiring high temperatures or pressure, and are characterized by fairly high yields.

Speaking about the practical application of CPAC, we can highlight the following areas.

1. Production of building materials. The use of CPACs in this area is based on their pronounced ability to slow down the hydration process of binders (cement, concrete, gypsum, etc.). This property is important in itself, since it allows you to regulate the setting speed of binders, and in the production of cellular concrete it also allows you to save significant amounts of cement. The most effective in this regard are IDYAK and KST.

2. Water-soluble fluxes for soft soldering. Such fluxes are especially relevant for the electrical and radio engineering industries, in which the technology for producing printed circuit boards requires the mandatory removal of flux residues from the finished product. Typically, rosin fluxes used for soldering are removed only with alcohol-acetone mixtures, which is extremely inconvenient due to the fire hazard of this procedure, while fluxes based on some KPYAK are washed off with water.

3. Antianemic and antichlorotic drugs for agriculture. It was found that complexes of ions of a number of 3d transition metals (Cu 2+, Zn 2+, Co 2+, etc.) with CPAC have high biological activity. This made it possible to create on their basis effective antianemic drugs for the prevention and treatment of nutritional anemia of fur-bearing animals (primarily minks) in fur farming and antichlorosis drugs for the prevention and treatment of chlorosis of fruit and berry crops (especially grapes) grown on carbonate soils (southern regions of the country ) and for this reason prone to chlorosis. It is also important to note that due to the ability to undergo exhaustive destruction in environmental conditions, CPACs are environmentally friendly products.

In addition to the above areas, the presence of anti-corrosion activity in CPACs has been shown, and the possibility of their use in chemical analysis, medicine and some other areas has been shown. Methods for obtaining CPACs and their practical application in various fields are protected by the authors of this report with numerous copyright certificates and patents.

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Complexons and metal complexonates - Dyatlova N.M.

It has been established that complexons stabilize non-transition elements in the +3 oxidation state in relation to the processes of hydrolysis and polymerization that are very characteristic of them. As a result, for example, indium in the presence of complexons is able to interact with ligands such as ammonia, pyridine, thio-sulfate, sulfite ion; thallium(III)-with o-phenantroline, for which coordination with these elements is uncharacteristic.

Mixed-ligand complexes exhibit significant stability. The probability of their formation increases with increasing radius during the transition from aluminum to thallium and as the denticity of the complexone decreases. In the case of indium, as a rule, the number of monodentate ligands included in the coordination sphere does not exceed three; for example, very stable complexonates are known: 2-, 3~, 3-. Indium complexonates have been successfully used to produce indium-gold alloys from alkaline media.

In normal complexes with complexones - derivatives of dicarboxylic acids, in particular 1,3-diaminopropylene-Ni-disuccinic and 2-hydroxy-1,3-diaminopropylene-Ni-disuccinic, the same patterns are observed as for traditional ligands type EDTA, however, differences in the stability of complexonates of neighboring elements of the group are significantly lower than those of EDTA complexes. The absolute values ​​of the stability constants were also lower. Thus, for aluminum and gallium the ratio Kod/Km for both dicarboxylic acids is approximately equal to 10.

Increased stability of gallium and indium complexonates was recorded in normal complexons N,N"-6hc(2-hydroxybenzyl)ethylenediamine-Ni-diacetic acid. For both elements, the value of /Cml turned out to be equal to ^lO40 (at 25°C and [x = 0 ,1). However, the difference in the values ​​of the logarithms of the stability constants was only 0.09. For phosphorus-containing complexons, the differences in the stability of aluminum and indium complexonates also turned out to be insignificant.

Thallium (III) is a strong oxidizing agent, so it is not typical for it to form complexes with complexones that have strong reducing properties. At the same time, the introduction of complexones into a solution containing Tl111 stabilizes it with respect to the action of reducing agents. For example, it is well known that the rate of redox

The interaction of thallium (III) with hydrazine sulfate is great. The introduction of complexons such as HTA, EDTA into a solution of Th (SO*) significantly slows down the reduction process with hydrazine sulfate, and in the case of DTPA at pH = 0.7-2.0, no redox interaction was detected even at 98 °C . It is noted that, in general, the rate of the redox reaction depends on pH in a rather complex way.

Complexons of the aminocarbon series can also be oxidized by thallium (III). It has been established that, as a result of complexation, a ligand such as ethylenediaminedimalonic acid is oxidized, albeit very slowly, in the acidic pH region already at room temperature; ethylenediaminedisuccinic acid is oxidized at 30-40 °C. In the case of CGDTA, oxidation occurs at a noticeable rate at 98 0C.

Thallium(I) is a weak complexing agent; the Kml value for aminocarboxylic acids lies in the range IO4-IO6. It is noteworthy that mono-protonated complexonates with CGDTA and DTPA were discovered for it; protonation of the complex does not lead, as in the case of alkali metal cations, to the complete destruction of the complexonate. However, there is a decrease in the stability of the complex by several orders of magnitude.

It is noteworthy that thallium(I) complexonate with CGDTA, despite its relatively low stability, turned out to be unstable on the NMR time scale, which made it an accessible object for spectroscopic studies.

Of the complexonates of non-transition elements of the germanium subgroup, compounds of germanium(IV), tin(IV), tin(II) and lead(II) have been described.

Due to their strong tendency to hydrolysis, germanium(IV) and tin(IV) form stable mononuclear complexonates only with highly dentate ligands, for example EDTA, HEDTA, EDTP, DTPP. Aqua-hydroxy ions of these elements, like similar complexes THTaHa(IV), zirconium(IV) and hafnium(IV), are relatively easily polymerized to form polygermanium and polytin acids. Often this process of enlargement ends with the formation of colloidal particles. The introduction of complexones into aqueous solutions allows one to significantly expand the boundaries of the existence of true solutions of germanium (IV) and tin (IV). For example, germanium(IV) forms a mononuclear complex with EDTA, which is stable in neutral and alkaline environments up to pH = 10. The formation of complexes stable in aqueous solutions with ligands of the aminophosphone series NTP, EDTP, DTPP is observed in a wide range - from pH = 2 to alkaline solutions. Increasing the metal:ligand ratio

361 (above 1) leads to the formation of practically water-insoluble polynuclear compounds in germanium - phosphorus-containing ligand systems.