Bioorganic chemistry (BOC), its importance in medicine. Bioorganic chemistry for medical students Purpose and objectives of the academic discipline
Chemistry- the science of the structure, properties of substances, their transformations and accompanying phenomena.
Tasks:
1. Study of the structure of matter, development of the theory of the structure and properties of molecules and materials. It is important to establish a connection between the structure and various properties of substances and, on this basis, to construct theories of the reactivity of a substance, the kinetics and mechanism of chemical reactions and catalytic phenomena.
2. Implementation of targeted synthesis of new substances with specified properties. Here it is also important to find new reactions and catalysts for more efficient synthesis of already known and industrially important compounds.
3. The traditional task of chemistry has acquired special significance. It is associated both with an increase in the number of chemical objects and properties being studied, and with the need to determine and reduce the consequences of human impact on nature.
Chemistry is a general theoretical discipline. It is designed to give students a modern scientific understanding of matter as one of the types of moving matter, about the ways, mechanisms and methods of converting some substances into others. Knowledge of basic chemical laws, mastery of chemical calculation techniques, understanding of the opportunities provided by chemistry with the help of other specialists working in its individual and narrow fields significantly speeds up obtaining the desired result in various fields of engineering and scientific activity.
The chemical industry is one of the most important industries in our country. The chemical compounds, various compositions and materials it produces are used everywhere: in mechanical engineering, metallurgy, agriculture, construction, electrical and electronic industries, communications, transport, space technology, medicine, everyday life, etc. The main directions of development of the modern chemical industry are: production new compounds and materials and increasing the efficiency of existing industries.
IN medical school students study general, bioorganic, biological chemistry, as well as clinical biochemistry. Students' knowledge of the complex of chemical sciences in their continuity and interconnection provides greater opportunity, greater scope for research and practical use of various phenomena, properties and patterns, and contributes to personal development.
Specific features studying chemical disciplines at a medical university are:
· interdependence between the goals of chemical and medical education;
· universality and fundamentality of these courses;
· the peculiarity of constructing their content depending on the nature and general goals of the doctor’s training and his specialization;
· the unity of the study of chemical objects at the micro and macro levels with the disclosure of different forms of their chemical organization as a single system and the different functions it exhibits (chemical, biological, biochemical, physiological, etc.) depending on their nature, environment and conditions;
· dependence on the connection of chemical knowledge and skills with reality and practice, including medical practice, in the system “society - nature - production - man”, due to the unlimited possibilities of chemistry in the creation of synthetic materials and their importance in medicine, the development of nanochemistry, as well as in solving environmental and many other global problems humanity.
1. The relationship between metabolic processes and energy in the body
Life processes on Earth are determined to a large extent by the accumulation of solar energy in nutrients - proteins, fats, carbohydrates and the subsequent transformations of these substances in living organisms with the release of energy. The understanding of the relationship between chemical transformations and energy processes in the body was realized especially clearly after works by A. Lavoisier (1743-1794) and P. Laplace (1749-1827). They showed by direct calorimetric measurements that the energy released in the process of life is determined by the oxidation of food by air oxygen inhaled by animals.
Metabolism and energy - a set of processes of transformation of substances and energy occurring in living organisms, and the exchange of substances and energy between the body and environment. Metabolism of substances and energy is the basis of the life of organisms and is one of the most important specific characteristics of living matter, distinguishing living from non-living. In metabolism, or metabolism, ensured by the most complex regulation on different levels, many enzyme systems are involved. During the metabolic process, substances entering the body are converted into tissues’ own substances and into final products excreted from the body. During these transformations, energy is released and absorbed.
With the development in the XIX-XX centuries. thermodynamics - the science of the interconversion of heat and energy - it became possible to quantitatively calculate the transformation of energy in biochemical reactions and predict their direction.
Energy exchange can be carried out by transferring heat or doing work. However, living organisms are not in equilibrium with their environment and therefore can be called non-equilibrium open systems. However, when observed over a certain period of time, there are no visible changes in the chemical composition of the body. But that doesn't mean that chemical substances, making up the body, do not undergo any transformations. On the contrary, they are constantly and quite intensively renewed, as can be judged by the rate of incorporation of stable isotopes and radionuclides into the complex substances of the body, introduced into the cell in the composition of more simple substances-predecessors.
There is one thing between metabolism and energy metabolism fundamental difference. The earth does not lose or gain any appreciable amount of matter. Matter in the biosphere is exchanged in a closed cycle, etc. used repeatedly. Energy exchange is carried out differently. It does not circulate in a closed cycle, but is partially dispersed into external space. Therefore, to maintain life on Earth, a constant flow of energy from the Sun is necessary. For 1 year in the process of photosynthesis on globe absorbed around 10 21 feces solar energy. Although it represents only 0.02% of the total energy of the Sun, it is immeasurably more than the energy used by all man-made machines. The amount of substance participating in the circulation is equally large.
2. Chemical thermodynamics as theoretical basis bioenergy. Subject and methods of chemical thermodynamics
Chemical thermodynamics studies the transitions of chemical energy into other forms - thermal, electrical, etc., establishes the quantitative laws of these transitions, as well as the direction and limits of the spontaneous occurrence of chemical reactions under given conditions.
The thermodynamic method is based on a number of strict concepts: “system”, “state of the system”, “internal energy of the system”, “state function of the system”.
Object studying in thermodynamics is a system
The same system can be in different states. Each state of the system is characterized by a certain set of values of thermodynamic parameters. Thermodynamic parameters include temperature, pressure, density, concentration, etc. A change in at least one thermodynamic parameter leads to a change in the state of the system as a whole. The thermodynamic state of a system is called equilibrium if it is characterized by constancy of thermodynamic parameters at all points of the system and does not change spontaneously (without the expenditure of work).
Chemical thermodynamics studies a system in two equilibrium states (final and initial) and on this basis determines the possibility (or impossibility) of a spontaneous process under given conditions in a specified direction.
Thermodynamics studies mutual transformations various types energies associated with the transfer of energy between bodies in the form of heat and work. Thermodynamics is based on two basic laws, called the first and second laws of thermodynamics. Subject of study in thermodynamics is energy and the laws of mutual transformations of energy forms during chemical reactions, processes of dissolution, evaporation, crystallization.
Chemical thermodynamics - section physical chemistry, studying the processes of interaction of substances using thermodynamic methods.
The main directions of chemical thermodynamics are:
Classical chemical thermodynamics, which studies thermodynamic equilibrium in general.
Thermochemistry, which studies the thermal effects accompanying chemical reactions.
The theory of solutions, which models the thermodynamic properties of a substance based on ideas about the molecular structure and data on intermolecular interactions.
Chemical thermodynamics is closely related to such branches of chemistry as analytical chemistry; electrochemistry; colloid chemistry; adsorption and chromatography.
The development of chemical thermodynamics proceeded simultaneously in two ways: thermochemical and thermodynamic.
The emergence of thermochemistry as an independent science should be considered the discovery by Herman Ivanovich Hess, a professor at St. Petersburg University, of the relationship between the thermal effects of chemical reactions -- Hess's laws.
3. Thermodynamic systems: isolated, closed, open, homogeneous, heterogeneous. The concept of phase.
System- this is a collection of interacting substances, mentally or actually isolated from the environment (test tube, autoclave).
Chemical thermodynamics considers transitions from one state to another, while some may change or remain constant. options:
· isobaric– at constant pressure;
· isochoric– at constant volume;
· isothermal– at constant temperature;
· isobaric - isothermal– at constant pressure and temperature, etc.
The thermodynamic properties of a system can be expressed using several system state functions, called characteristic functions: internal energyU , enthalpy H , entropy S , Gibbs energy G , Helmholtz energy F . Characteristic functions have one feature: they do not depend on the method (path) of achieving a given state of the system. Their value is determined by the parameters of the system (pressure, temperature, etc.) and depends on the amount or mass of the substance, so it is customary to refer them to one mole of the substance.
According to the method of transferring energy, matter and information between the system under consideration and the environment, thermodynamic systems are classified:
1. Closed (isolated) system- this is a system in which there is no exchange of energy, matter (including radiation), or information with external bodies.
2. Closed system- a system in which there is an exchange only with energy.
3. Adiabatically isolated system - This is a system in which there is an exchange of energy only in the form of heat.
4. Open system is a system that exchanges energy, matter, and information.
System classification:
1) if heat and mass transfer are possible: insulated, closed, open. An isolated system does not exchange either matter or energy with the environment. A closed system exchanges energy with the environment, but does not exchange matter. An open system exchanges both matter and energy with its environment. Concept isolated system used in physical chemistry as theoretical.
2) by internal structure and properties: homogeneous and heterogeneous. A system is called homogeneous, inside which there are no surfaces dividing the system into parts that differ in properties or chemical composition. Examples of homogeneous systems are aqueous solutions of acids, bases, and salts; gas mixtures; individual pure substances. Heterogeneous systems contain natural surfaces within them. Examples of heterogeneous systems are systems consisting of substances that differ in their state of aggregation: a metal and an acid, a gas and a solid, two liquids insoluble in each other.
Phase is a homogeneous part of a heterogeneous system, having the same composition, physical and Chemical properties, separated from other parts of the system by a surface, when passing through which the properties of the system change abruptly. The phases are solid, liquid and gaseous. A homogeneous system always consists of one phase, a heterogeneous one - of several. Based on the number of phases, systems are classified into single-phase, two-phase, three-phase, etc.
5.The first law of thermodynamics. Internal energy. Isobaric and isochoric thermal effects .
First law of thermodynamics- one of the three basic laws of thermodynamics, represents the law of conservation of energy for thermodynamic systems.
The first law of thermodynamics was formulated in the middle of the 19th century as a result of the work of the German scientist J. R. Mayer, the English physicist J. P. Joule and the German physicist G. Helmholtz.
According to the first law of thermodynamics, thermodynamic system can commit work only due to its internal energy or any external energy sources .
The first law of thermodynamics is often formulated as the impossibility of the existence of a perpetual motion machine of the first kind, which would do work without drawing energy from any source. A process occurring at a constant temperature is called isothermal, at constant pressure - isobaric, at constant volume – isochoric. If during a process the system is isolated from the external environment in such a way that heat exchange with the environment is excluded, the process is called adiabatic.
Internal energy of the system. When a system transitions from one state to another, some of its properties change, in particular internal energy U.
The internal energy of a system is its total energy, which consists of the kinetic and potential energies of molecules, atoms, atomic nuclei and electrons. Internal energy includes the energy of translational, rotational and oscillatory movements, as well as potential energy due to the forces of attraction and repulsion acting between molecules, atoms and intra-atomic particles. It does not include the potential energy of the system’s position in space and the kinetic energy of the system’s motion as a whole.
Internal energy is a thermodynamic function of the state of the system. This means that whenever the system finds itself in a given state, its internal energy takes on a certain value inherent in this state.
∆U = U 2 - U 1
where U 1 and U 2 are the internal energy of the system V final and initial states, respectively.
First law of thermodynamics. If a system exchanges thermal energy Q and mechanical energy (work) A with the external environment, and at the same time transitions from state 1 to state 2, the amount of energy that is released or absorbed by the system of forms of heat Q or work A is equal to total energy system during the transition from one state to another and is recorded.
BIOORGANIC CHEMISTRY studies the relationship between the structure of organic substances and their biological functions, using mainly methods of organic and physical chemistry, as well as physics and mathematics. Bioorganic chemistry completely covers the chemistry of natural compounds and partially overlaps with biochemistry and molecular biology. The objects of its study are biologically important natural compounds - mainly biopolymers (proteins, nucleic acids, polysaccharides and mixed biopolymers) and low-molecular biologically active substances - vitamins, hormones, antibiotics, toxins, etc., as well as synthetic analogues of natural compounds, drugs, pesticides, etc.
Bioorganic chemistry emerged as an independent field in the 2nd half of the 20th century at the intersection of biochemistry and organic chemistry based on the traditional chemistry of natural compounds. Its formation is associated with the names of L. Pauling (discovery of the α-helix and β-structure as the main elements of the spatial structure of the polypeptide chain in proteins), A. Todd (clarification chemical structure nucleotides and the first synthesis of a dinucleotide), F. Sanger (development of a method for determining the amino acid sequence in proteins and using it to decipher the primary structure of insulin), V. Du Vigneault (isolation, establishment of the structure and chemical synthesis of peptide hormones - oxytocin and vasopressin), D. Barton and V. Prelog (conformational analysis), R. Woodward (complete chemical synthesis of many complex natural compounds, including reserpine, chlorophyll, vitamin B 12), etc.; in the USSR, the works of N.D. Zelinsky, A.N. Belozersky, I.N. Nazarov, N.A. Preobrazhensky and others played a huge role. The initiator of research in bioorganic chemistry in the USSR in the early 1960s was M.M. Shemyakin. In particular, he began work (later widely developed) on the study of cyclic depsipeptides that perform the function of ionophores. The leader of domestic bioorganic chemistry in the 1970-80s was Yu.A. Ovchinnikov, under whose leadership the structure of dozens of proteins was established, including membrane proteins (for the first time) - bacteriorhodopsin and bovine visual rhodopsin.
The main areas of bioorganic chemistry include:
1. Development of methods for the isolation and purification of natural compounds. At the same time, to control the degree of purification, the specific biological function of the substance being studied is often used (for example, the purity of an antibiotic is controlled by its antimicrobial activity, of a hormone by its effect on a certain biological process, and so on). When separating complex natural mixtures, methods of high-performance liquid chromatography and electrophoresis are often used. Since the end of the 20th century, instead of searching for and isolating individual components, total screening of biological samples has been carried out for the maximum possible number of components of a particular class of compounds (see Proteomics).
2. Determination of the structure of the substances being studied. Structure is understood not only as the establishment of the nature and order of connections of atoms in a molecule, but also their spatial arrangement. For this, various methods are used, primarily chemical (hydrolysis, oxidative cleavage, treatment with specific reagents), which make it possible to obtain simpler substances with a known structure, from which the structure of the original substance is reconstructed. Automatic devices are widely used to quickly solve standard problems, especially in the chemistry of proteins and nucleic acids: analyzers for the quantitative determination of amino acid and nucleotide composition and sequencers for determining the sequence of amino acid residues in proteins and nucleotides in nucleic acids. An important role in studying the structure of biopolymers is played by enzymes, especially those that specifically cleave them at strictly defined bonds (for example, proteinases that catalyze the reactions of cleavage of peptide bonds at glutamic acid, proline, arginine and lysine residues, or restriction enzymes that specifically cleave phosphodiester bonds in polynucleotides ). Information about the structure of natural compounds is also obtained using physical research methods - mainly mass spectrometry, nuclear magnetic resonance and optical spectroscopy. Increasing the efficiency of chemical and physical methods is achieved through the simultaneous analysis of not only natural compounds, but also their derivatives containing characteristic, specially introduced groups and labeled atoms (for example, by growing bacteria - producers of a particular compound on a medium containing precursors of this compound, enriched stable or radioactive isotopes). The reliability of the data obtained from the study of complex proteins increases significantly with the simultaneous study of the structure of the corresponding genes. Spatial structure molecules and their analogues in the crystalline state are studied by X-ray diffraction analysis. The resolution in some cases reaches values of less than 0.1 nm. For solutions, the most informative method is NMR in combination with theoretical conformational analysis. Additional information is provided by optical spectral analysis methods (electronic and fluorescent spectra, circular dichroism spectra, etc.).
3. Synthesis of both natural compounds themselves and their analogues. In many cases, chemical or chemical-enzymatic synthesis is the only way to obtain the desired substance in large (preparative) quantities. For relatively simple low-molecular compounds, counter synthesis serves as an important criterion for the correctness of the previously determined structure. Automatic synthesizers of proteins and polynucleotides have been created that can significantly reduce synthesis time; with their help, a number of proteins and polynucleotides containing several hundred monomer units have been synthesized. Chemical synthesis- the main method of obtaining medicines of non-natural origin. In the case of natural substances, it often complements or competes with biosynthesis.
4. Establishment of the cellular and molecular target to which the action is directed biologically active substance, elucidation of the chemical mechanism of its interaction with a living cell and its components. Understanding the molecular mechanism of action is necessary for the productive use of biomolecules, with their often extremely high activity (for example, toxins), as tools for studying biological systems; it serves as the basis for the targeted synthesis of new, practically important substances with predetermined properties. In a number of cases (for example, when studying peptides that affect the activity nervous system) the substances obtained in this way have significantly enhanced activity, compared to the original natural prototype, changed in the desired direction.
Bioorganic chemistry is closely related to the solution practical problems medicine and Agriculture(obtaining vitamins, hormones, antibiotics and other medicines, plant growth stimulants, animal behavior regulators, including insects), chemical, food and microbiological industries. As a result of the combination of methods of bioorganic chemistry and genetic engineering, it has become possible to practically solve the problem of industrial production of complex, biologically important substances of protein-peptide nature, including such high-molecular substances as human insulin, α-, β- and γ-interferons, and human growth hormone.
Lit.: Dugas G., Penny K. Bioorganic chemistry. M., 1983; Ovchinnikov Yu. A. Bioorganic chemistry. M., 1996.
“ … There were so many amazing incidents,
That nothing seemed at all possible to her now ”
L. Carroll "Alice in Wonderland"
Bioorganic chemistry developed on the border between two sciences: chemistry and biology. Currently, medicine and pharmacology have joined them. All these four sciences use modern methods physical research, mathematical analysis and computer modeling.
In 1807 J.Ya. Berzelius proposed that substances like olive oil or sugar, which are common in living nature, should be called organic.
By this time, many natural compounds were already known, which later began to be defined as carbohydrates, proteins, lipids, and alkaloids.
In 1812, a Russian chemist K.S. Kirchhoff converted starch by heating it with acid into sugar, later called glucose.
In 1820, a French chemist A. Braconno, by treating protein with gelatin, he obtained the substance glycine, which belongs to a class of compounds that later Berzelius named amino acids.
The birth date of organic chemistry can be considered the work published in 1828 F. Velera, who was the first to synthesize a substance of natural origin – urea- from the inorganic compound ammonium cyanate.
In 1825, the physicist Faraday isolated benzene from a gas that was used to illuminate the city of London. The presence of benzene may explain the smoky flames of London lamps.
In 1842 N.N. Zinin carried out synthe z aniline,
In 1845 A.V. Kolbe, a student of F. Wöhler, synthesized acetic acid - undoubtedly a natural organic compound - from starting elements (carbon, hydrogen, oxygen)
In 1854 P. M. Bertlot heated glycerin with stearic acid and obtained tristearin, which turned out to be identical to the natural compound isolated from fats. Further P.M. Berthelot took other acids that were not isolated from natural fats and obtained compounds very similar to natural fats. With this, the French chemist proved that it is possible to obtain not only analogues of natural compounds, but also create new ones, similar and at the same time different from natural ones.
Many major achievements in organic chemistry in the second half of the 19th century are associated with the synthesis and study of natural substances.
In 1861, the German chemist Friedrich August Kekule von Stradonitz (always called simply Kekule in scientific literature) published a textbook in which he defined organic chemistry as the chemistry of carbon.
During the period 1861-1864. Russian chemist A.M. Butlerov created a unified theory of the structure of organic compounds, which made it possible to transfer all existing achievements to a single scientific basis and opened the way to the development of the science of organic chemistry.
During the same period, D.I. Mendeleev. known throughout the world as the scientist who discovered and formulated periodic law changes in the properties of elements, published the textbook “Organic Chemistry”. We have at our disposal its 2nd edition (corrected and expanded, Publication of the Partnership “Public Benefit”, St. Petersburg, 1863. 535 pp.)
In his book, the great scientist clearly defined the connection between organic compounds and vital processes: “We can reproduce many of the processes and substances that are produced by organisms artificially, outside the body. Thus, protein substances, being destroyed in animals under the influence of oxygen absorbed by the blood, are converted into ammonium salts, urea, mucus sugar, benzoic acid and other substances usually excreted in urine... Taken separately, each vital phenomenon is not the result of some special force , but is done by general laws nature" At that time, bioorganic chemistry and biochemistry had not yet emerged as
independent directions, at first they were united physiological chemistry, but gradually they grew on the basis of all achievements into two independent sciences.
The science of bioorganic chemistry studies connection between the structure of organic substances and their biological functions, using mainly methods of organic, analytical, physical chemistry, as well as mathematics and physics
The main distinguishing feature of this subject is the study of the biological activity of substances in connection with the analysis of their chemical structure
Objects of study of bioorganic chemistry: biologically important natural biopolymers - proteins, nucleic acids, lipids, low molecular weight substances - vitamins, hormones, signal molecules, metabolites - substances involved in energy and plastic metabolism, synthetic drugs.
The main tasks of bioorganic chemistry include:
1. Development of methods for isolating and purifying natural compounds, using medical methods to assess the quality of a drug (for example, a hormone based on the degree of its activity);
2. Determination of the structure of a natural compound. All methods of chemistry are used: determination of molecular weight, hydrolysis, analysis of functional groups, optical research methods;
3. Development of methods for the synthesis of natural compounds;
4. Study of the dependence of biological action on structure;
5. Clarification of the nature of biological activity, molecular mechanisms of interaction with various cell structures or with its components.
The development of bioorganic chemistry over the decades is associated with the names of Russian scientists: D.I.Mendeleeva, A.M. Butlerov, N.N. Zinin, N.D. Zelinsky A.N. Belozersky N.A. Preobrazhensky M.M. Shemyakin, Yu.A. Ovchinnikova.
The founders of bioorganic chemistry abroad are scientists who have made many major discoveries: the structure of the secondary structure of proteins (L. Pauling), the complete synthesis of chlorophyll, vitamin B 12 (R. Woodward), the use of enzymes in the synthesis of complex organic substances. including gene (G. Koran) and others
In the Urals in Yekaterinburg in the field of bioorganic chemistry from 1928 to 1980. worked as the head of the department of organic chemistry of UPI, academician I.Ya. Postovsky, known as one of the founders in our country of the scientific direction of search and synthesis of drugs and the author of a number of drugs (sulfonamides, antitumor, anti-radiation, anti-tuberculosis). His research is continued by students who work under the leadership of academicians O.N. Chupakhin, V.N. Charushin at USTU-UPI and at the Institute of Organic Synthesis named after. AND I. Postovsky Russian Academy Sci.
Bioorganic chemistry is closely related to the tasks of medicine and is necessary for the study and understanding of biochemistry, pharmacology, pathophysiology, and hygiene. All scientific language bioorganic chemistry, the notation adopted and the methods used are no different from the organic chemistry you studied in school
Bioorganic chemistry is a science that studies the structure and properties of substances involved in life processes in direct connection with the knowledge of their biological functions.
Bioorganic chemistry is the science that studies the structure and reactivity of biologically significant compounds. The subject of bioorganic chemistry is biopolymers and bioregulators and their structural elements.
Biopolymers include proteins, polysaccharides (carbohydrates) and nucleic acids. This group also includes lipids, which are not BMCs, but are usually associated with other biopolymers in the body.
Bioregulators are compounds that chemically regulate metabolism. These include vitamins, hormones, and many synthetic compounds, including medicinal substances.
Bioorganic chemistry is based on the ideas and methods of organic chemistry.
Without knowledge general patterns organic chemistry, it is difficult to study bioorganic chemistry. Bioorganic chemistry is closely related to biology, biological chemistry, medical physics.
The set of reactions occurring under the conditions of an organism is called metabolism.
Substances formed during metabolism are called - metabolites.
Metabolism has two directions:
Catabolism is the reaction of the breakdown of complex molecules into simpler ones.
Anabolism is the process of synthesizing complex molecules from simpler substances using energy.
The term biosynthesis is applied to chemical reaction IN VIVO (in the body), IN VITRO (outside the body)
There are antimetabolites - competitors of metabolites in biochemical reactions.
Conjugation as a factor in increasing the stability of molecules. Mutual influence of atoms in molecules of organic compounds and methods of its transmission
Lecture outline:
Pairing and its types:
p, p - pairing,
r,p - conjugation.
Conjugation energy.
Open circuit coupled systems.
Vitamin A, carotenes.
Conjugation in radicals and ions.
Coupled closed-circuit systems. Aromaticity, aromaticity criteria, heterocyclic aromatic compounds.
Covalent bond: non-polar and polar.
Inductive and mesomeric effects. EA and ED are substitutes.
The main type of chemical bonds in organic chemistry are covalent bonds. In organic molecules, atoms are connected by s and p bonds.
Atoms in molecules of organic compounds are connected by covalent bonds, which are called s and p bonds.
Single s - bond in SP 3 - hybridized state is characterized by l - length (C-C 0.154 nm), E-energy (83 kcal/mol), polarity and polarizability. For example:
A double bond is characteristic of unsaturated compounds, in which, in addition to the central s-bond, there is also an overlap perpendicular to the s-bond, which is called a π-bond).
Double bonds are localized, that is, the electron density covers only 2 nuclei of the bonded atoms.
Most often you and I will deal with conjugated systems. If double bonds alternate with single bonds (and in the general case, an atom connected to a double bond has a p-orbital, then the p-orbitals of neighboring atoms can overlap each other, forming a common p-electron system). Such systems are called conjugated or delocalized . For example: butadiene-1,3
p, p - conjugate systems
All atoms in butadiene are in the SP 2 hybridized state and lie in the same plane (Pz is not a hybrid orbital). Рz – orbitals are parallel to each other. This creates conditions for their mutual overlap. The overlap of the Pz orbital occurs between C-1 and C-2 and C-3 and C-4, as well as between C-2 and C-3, that is, it occurs delocalized covalent bond. This is reflected in changes in bond lengths in the molecule. The length of the bond between C-1 and C-2 is increased, and between C-2 and C-3 is shortened, compared to a single bond.
l-C -С, 154 nm l С=С 0.134 nm
l С-N 1.147 nm l С =O 0.121 nm
r, p - pairing
An example of a p, π conjugated system is a peptide bond.
r, p - conjugate systems
The C=0 double bond is extended to 0.124 nm compared to the usual length of 0.121, and the C–N bond becomes shorter and becomes 0.132 nm compared to 0.147 nm in the normal case. That is, the process of electron delocalization leads to equalization of bond lengths and a decrease in the internal energy of the molecule. However, ρ,p – conjugation occurs in acyclic compounds, not only when alternating = bonds with single C-C bonds, but also when alternating with a heteroatom:
An X atom with a free p-orbital may be located near the double bond. Most often, these are O, N, S heteroatoms and their p-orbitals that interact with p-bonds, forming p, p-conjugation.
For example:
CH 2 = CH – O – CH = CH 2
Conjugation can occur not only in neutral molecules, but also in radicals and ions:
Based on the above, in open systems, pairing occurs under the following conditions:
All atoms participating in the conjugated system are in the SP 2 - hybridized state.
Pz – the orbitals of all atoms are perpendicular to the s-skeleton plane, that is, parallel to each other.
When a conjugated multicenter system is formed, the bond lengths are equalized. There are no “pure” single and double bonds here.
Delocalization of p-electrons in a conjugated system is accompanied by the release of energy. The system moves to a lower energy level, becomes more stable, more stable. Thus, the formation of a conjugated system in the case of butadiene - 1,3 leads to the release of energy in the amount of 15 kJ/mol. It is due to conjugation that the stability of allylic-type ion radicals and their prevalence in nature increases.
The longer the conjugation chain, the greater the release of energy of its formation.
This phenomenon is quite widespread in biologically important compounds. For example:
We will constantly encounter issues of thermodynamic stability of molecules, ions, and radicals in the course of bioorganic chemistry, which includes a number of ions and molecules widespread in nature. For example: 
Closed-loop coupled systems
Aromaticity. In cyclic molecules, under certain conditions, a conjugated system can arise. An example of a p, p - conjugated system is benzene, where the p - electron cloud covers carbon atoms, such a system is called - aromatic.
The energy gain due to conjugation in benzene is 150.6 kJ/mol. Therefore, benzene is thermally stable up to a temperature of 900 o C.
The presence of a closed electron ring was proven using NMR. If a benzene molecule is placed in an external magnetic field, an inductive ring current occurs.
Thus, the criterion for aromaticity formulated by Hückel is:
the molecule has a cyclic structure;
all atoms are in SP 2 – hybridized state;
there is a delocalized p - electronic system, containing 4n + 2 electrons, where n is the number of cycles.
For example: 
A special place in bioorganic chemistry is occupied by the question aromaticity of heterocyclic compounds.
In cyclic molecules containing heteroatoms (nitrogen, sulfur, oxygen), a single p-electron cloud is formed with the participation of p-orbitals of carbon atoms and a heteroatom.
Five-membered heterocyclic compounds
The aromatic system is formed by the interaction of 4 p-orbitals C and one orbital of a heteroatom, which has 2 electrons. Six p electrons form the aromatic skeleton. Such a conjugated system is electronically redundant. In pyrrole, the N atom is in the SP 2 hybridized state.
Pyrrole is part of many biologically important substances. Four pyrrole rings form porphine, an aromatic system with 26 p - electrons and high conjugation energy (840 kJ/mol)
The porphin structure is part of hemoglobin and chlorophyll 
Six-membered heterocyclic compounds
The aromatic system in the molecules of these compounds is formed by the interaction of five p-orbitals of carbon atoms and one p-orbital of a nitrogen atom. Two electrons in two SP 2 orbitals are involved in the formation of s - bonds with the carbon atoms of the ring. The P orbital with one electron is included in the aromatic skeleton. SP 2 – an orbital with a lone pair of electrons lies in the s-skeleton plane.
The electron density in pyrimidine is shifted towards N, that is, the system is depleted of p - electrons, it is electron deficient.
Many heterocyclic compounds may contain one or more heteroatoms 
Pyrrole, pyrimidine, and purine nuclei are part of many biologically active molecules.
Mutual influence of atoms in molecules of organic compounds and methods of its transmission
As already noted, bonds in molecules of organic compounds are carried out due to s and p bonds; electron density is evenly distributed between bonded atoms only when these atoms are the same or close in electronegativity. Such connections are called non-polar. 
CH 3 -CH 2 →CI polar bond
More often in organic chemistry we deal with polar bonds.
If the electron density is shifted towards a more electronegative atom, then such a bond is called polar. Based on the values of bond energy, the American chemist L. Pauling proposed a quantitative characteristic of the electronegativity of atoms. Below is the Pauling scale.
Na Li H S C J Br Cl N O F
0,9 1,0 2,1 2,52,5 2,5 2,8 3,0 3,0 3,5 4,0
Carbon atoms in different states of hybridization differ in electronegativity. Therefore, s - the bond between SP 3 and SP 2 hybridized atoms - is polar 
Inductive effect
The transfer of electron density through the mechanism of electrostatic induction along a chain of s-bonds is called by induction, the effect is called inductive and is denoted by J. The effect of J, as a rule, is attenuated through three bonds, but closely located atoms experience a rather strong influence of the nearby dipole.
Substituents that shift the electron density along the s-bond chain in their direction exhibit a -J – effect, and vice versa +J effect. 
An isolated p-bond, as well as a single p-electron cloud of an open or closed conjugated system, can easily be polarized under the influence of EA and ED substituents. In these cases, the inductive effect is transferred to the p-connection, therefore denoted by Jp. 
Mesomeric effect (conjugation effect)
The redistribution of electron density in a conjugated system under the influence of a substituent that is a member of this conjugated system is called mesomeric effect(M-effect). 
In order for a substituent to be part of a conjugated system, it must have either a double bond (p,p conjugation) or a heteroatom with a lone pair of electrons (r,p conjugation). M – the effect is transmitted through the coupled system without attenuation.
Substituents that lower the electron density in a conjugated system (displaced electron density in its direction) exhibit an -M effect, and substituents that increase the electron density in a conjugated system exhibit a +M effect.
Electronic effects of substituents 
The reactivity of organic substances largely depends on the nature of the J and M effects. Knowledge of the theoretical possibilities of electronic effects allows us to predict the course of certain chemical processes.
Acid-base properties of organic compounds Classification of organic reactions.
Lecture outline
The concept of substrate, nucleophile, electrophile.
Classification of organic reactions.
reversible and irreversible
radical, electrophilic, nucleophilic, synchronous.
mono- and bimolecular
substitution reactions
addition reactions
elimination reactions
oxidation and reduction
acid-base interactions
Reactions are regioselective, chemoselective, stereoselective.
Electrophilic addition reactions. Morkovnikov's rule, anti-Morkovnikov's accession.
Electrophilic substitution reactions: orientants of the 1st and 2nd kind.
Acid-base properties of organic compounds.
Bronsted acidity and basicity
Lewis acidity and basicity
Theory of hard and soft acids and bases.
Classification of organic reactions
Systematization of organic reactions makes it possible to reduce the diversity of these reactions to a relatively small a large number types. Organic reactions can be classified:
towards: reversible and irreversible
by the nature of changes in bonds in the substrate and reagent.
Substrate– a molecule that provides a carbon atom to form a new bond
Reagent- a compound acting on the substrate.
Reactions based on the nature of changes in bonds in the substrate and reagent can be divided into:
radical R
electrophilic E
nucleophilic N(Y)
synchronous or coordinated 
Mechanism of SR reactions
Initiation
Chain growth
Open circuit 
CLASSIFICATION BY FINAL RESULT
Correspondence to the final result of the reaction is:
A) substitution reactions
B) addition reactions
B) elimination reactions
D) regroupings
D) oxidation and reduction
E) acid-base interactions
Reactions also happen:
Regioselective– preferably flowing through one of several reaction centers.
Chemoselective– preferential reaction for one of the related functional groups.
Stereoselective– preferential formation of one of several stereoisomers.
Reactivity of alkenes, alkanes, alkadienes, arenes and heterocyclic compounds
The basis of organic compounds are hydrocarbons. We will consider only those reactions carried out under biological conditions and, accordingly, not with hydrocarbons themselves, but with the participation of hydrocarbon radicals.
Unsaturated hydrocarbons include alkenes, alkadienes, alkynes, cycloalkenes and aromatic hydrocarbons. The unifying principle for them is π – the electron cloud. Under dynamic conditions, organic compounds also tend to be attacked by E+
However, interaction reactions for alkynes and arenes with reagents lead to different results, since in these compounds the nature of the π - electron cloud is different: localized and delocalized.
We will begin our consideration of reaction mechanisms with reactions A E. As we know, alkenes interact with 
Mechanism of hydration reaction
According to Markovnikov's rule - the addition to unsaturated hydrocarbons of an asymmetrical structure of compounds with the general formula HX - a hydrogen atom is added to the most hydrogenated carbon atom, if the substituent is ED. In anti-Markovnikov addition, a hydrogen atom is added to the least hydrogenated one if the substituent is EA.
Electrophilic substitution reactions in aromatic systems have their own characteristics. The first feature is that interaction with a thermodynamically stable aromatic system requires strong electrophiles, which are usually generated using catalysts.
Reaction mechanism S E 
ORIENTING INFLUENCE
DEPUTY
If there is any substituent in the aromatic ring, then it necessarily affects the distribution of the electron density of the ring. ED - substituents (orientants of the 1st row) CH 3, OH, OR, NH 2, NR 2 - facilitate substitution compared to unsubstituted benzene and direct the incoming group to the ortho- and para-position. If the ED substituents are strong, then a catalyst is not required; these reactions proceed in 3 stages.
EA substituents (orientants of the second kind) hinder electrophilic substitution reactions compared to unsubstituted benzene. The SE reaction occurs under more stringent conditions; the incoming group enters a meta position. Type II substituents include:
COOH, SO 3 H, CHO, halogens, etc.
SE reactions are also typical for heterocyclic hydrocarbons. Pyrrole, furan, thiophene and their derivatives belong to π-excess systems and quite easily enter into SE reactions. They are easily halogenated, alkylated, acylated, sulfonated, and nitrated. When choosing reagents, it is necessary to take into account their instability in a strongly acidic environment, i.e. acidophobicity.
Pyridine and other heterocyclic systems with a pyridine nitrogen atom are π-insufficient systems, they are much more difficult to enter into SE reactions, and the incoming electrophile occupies the β-position relative to the nitrogen atom. 
Acidic and basic properties of organic compounds
The most important aspects reactivity organic compounds are the acid-base properties of organic compounds.
Acidity and basicity Also important concepts, which determine many functional physicochemical and biological properties of organic compounds. Acid and base catalysis is one of the most common enzymatic reactions. Weak acids and bases are common components of biological systems that play an important role in metabolism and its regulation.
There are several concepts of acids and bases in organic chemistry. The Brønsted theory of acids and bases, generally accepted in inorganic and organic chemistry. According to Brønsted, acids are substances that can donate a proton, and bases are substances that can accept a proton. 
Bronsted acidity
In principle, most organic compounds can be considered as acids, since in organic compounds H is bonded to C, N O S
Organic acids are accordingly divided into C – H, N – H, O – H, S-H – acids. 
Acidity is assessed in the form of Ka or - log Ka = pKa, the lower the pKa, the stronger the acid.
Quantitative assessment of the acidity of organic compounds has not been determined for all organic substances. Therefore, it is important to develop the ability to conduct a qualitative assessment of the acidic properties of various acid sites. For this purpose, a general methodological approach is used.
The strength of the acid is determined by the stability of the anion (conjugate base). The more stable the anion, the stronger the acid.
The stability of the anion is determined by a combination of a number of factors:
electronegativity and polarizability of the element in the acid center.
the degree of delocalization of the negative charge in the anion.
the nature of the radical associated with the acid center.
solvation effects (influence of solvent)
Let us consider the role of all these factors sequentially:
Effect of electronegativity of elements
The more electronegative the element, the more delocalized the charge and the more stable the anion, the stronger the acid.
C (2.5) N (3.0) O (3.5) S (2.5)
Therefore, acidity changes in the series CH< NН < ОН For SH acids, another factor predominates - polarizability. The sulfur atom is larger in size and has vacant d orbitals. therefore, the negative charge is able to delocalize over a large volume, resulting in greater stability of the anion. Thiols, as stronger acids, react with alkalis, as well as with oxides and salts of heavy metals, while alcohols (weak acids) can only react with active metals The relatively high acidity of tols is used in medicine and in the chemistry of drugs. For example: Used for poisoning with As, Hg, Cr, Bi, the effect of which is due to the binding of metals and their removal from the body. For example: When assessing the acidity of compounds with the same atom in the acid center, the determining factor is the delocalization of the negative charge in the anion. The stability of the anion increases significantly with the emergence of the possibility of delocalization of the negative charge along the system of conjugated bonds. A significant increase in acidity in phenols, compared to alcohols, is explained by the possibility of delocalization in ions compared to the molecule. The high acidity of carboxylic acids is due to the resonance stability of the carboxylate anion Charge delocalization is facilitated by the presence of electron-withdrawing substituents (EA), they stabilize anions, thereby increasing acidity. For example, introducing a substituent into an EA molecule Effect of substituent and solvent a - hydroxy acids are stronger acids than the corresponding carboxylic acids. ED - substituents, on the contrary, reduce acidity. Solvents have a greater influence on the stabilization of the anion; as a rule, small ions with a low degree of charge delocalization are better solvated. The effect of solvation can be traced, for example, in the series: If an atom in an acid center carries a positive charge, this leads to increased acidity. Question to the audience: which acid - acetic or palmitic C 15 H 31 COOH - should have a lower pKa value? If the atom at the acid center carries a positive charge, this leads to increased acidity. One can note the strong CH - acidity of the σ - complex formed in the electrophilic substitution reaction. Bronsted basicity In order to form a bond with a proton, an unshared electron pair is necessary on the heteroatom, or be anions. There are p-bases and π bases, where the center of basicity is electrons of a localized π bond or π electrons of a conjugated system (π components) The strength of the base depends on the same factors as acidity, but their influence is opposite. The greater the electronegativity of an atom, the more tightly it holds a lone pair of electrons, and the less available it is for bonding with a proton. Then, in general, the strength of n-bases with the same substituent changes in the series: The most basic organic compounds are amines and alcohols: Salts of organic compounds with mineral acids are highly soluble. Many medicines are used in the form of salts. Acid-base center in one molecule (amphoteric) Hydrogen bonds as acid-base interactions For all α - amino acids there is a predominance of cationic forms in strongly acidic and anionic in strongly alkaline environments. The presence of weak acidic and basic centers leads to weak interactions - hydrogen bonds. For example: imidazole, with a low molecular weight, has a high boiling point due to the presence of hydrogen bonds. J. Lewis proposed a more general theory of acids and bases, based on the structure of electronic shells. A Lewis acid can be an atom, molecule, or cation that has a vacant orbital capable of accepting a pair of electrons to form a bond. Representatives of Lewis acids are the halides of elements of groups II and III of the periodic system D.I. Mendeleev. Lewis bases are an atom, molecule, or anion capable of donating a pair of electrons. Lewis bases include amines, alcohols, ethers, thiols, thioethers, and compounds containing π bonds. For example, the interaction below can be represented as a Lewis acid-base interaction An important consequence of Lewis's theory is that any organic substance can be represented as an acid-base complex. In organic compounds, intramolecular hydrogen bonds occur much less frequently than intermolecular ones, but they also occur in bioorganic compounds and can be considered as acid-base interactions. The concepts of “hard” and “soft” are not identical to strong and weak acids and bases. These are two independent characteristics. The essence of LCMO is that hard acids react with hard bases and soft acids react with soft bases. According to Pearson's principle of hard and soft acids and bases (HABP), Lewis acids are divided into hard and soft. Hard acids are acceptor atoms with small size, large positive charge, high electronegativity and low polarizability. Soft acids are large acceptor atoms with a small positive charge, low electronegativity and high polarizability. The essence of LCMO is that hard acids react with hard bases and soft acids react with soft bases. For example: Oxidation and reduction of organic compounds Redox reactions are of utmost importance for life processes. With their help, the body satisfies its energy needs, since the oxidation of organic substances releases energy. On the other hand, these reactions serve to convert food into cell components. Oxidation reactions promote detoxification and removal of drugs from the body. Oxidation is the process of removing hydrogen to form a multiple bond or new more polar bonds. Reduction is the reverse process of oxidation. The oxidation of organic substrates proceeds more easily, the stronger its tendency to give up electrons. Oxidation and reduction must be considered in relation to specific classes of compounds. Oxidation of C–H bonds (alkanes and alkyls) When alkanes burn completely, CO 2 and H 2 O are formed and heat is released. Other ways of their oxidation and reduction can be represented by the following schemes: The oxidation of saturated hydrocarbons occurs under harsh conditions (the chromium mixture is hot); softer oxidizers do not affect them. Intermediate oxidation products are alcohols, aldehydes, ketones, and acids. Hydroperoxides R – O – OH are the most important intermediate products of the oxidation of C – H bonds under mild conditions, in particular in vivo An important oxidation reaction of C–H bonds under body conditions is enzymatic hydroxylation. An example would be the production of alcohols through the oxidation of food. Due to molecular oxygen and its active forms. carried out in vivo. Hydrogen peroxide can serve as a hydroxylating agent in the body. Excess peroxide must be decomposed by catalase into water and oxygen. The oxidation and reduction of alkenes can be represented by the following transformations: Alkene reduction Oxidation and reduction of aromatic hydrocarbons Benzene is extremely difficult to oxidize even under harsh conditions according to the following scheme: The ability to oxidize increases markedly from benzene to naphthalene and further to anthracene. ED substituents facilitate the oxidation of aromatic compounds. EA – hinder oxidation. Benzene recovery. C 6 H 6 + 3 H 2 Enzymatic hydroxylation of aromatic compounds Oxidation of alcohols Compared to hydrocarbons, the oxidation of alcohols occurs under milder conditions The most important reaction of diols under body conditions is the transformation in the quinone-hydroquinone system The transfer of electrons from the substrate to oxygen occurs in metachondria. Oxidation and reduction of aldehydes and ketones One of the most easily oxidized classes of organic compounds 2H 2 C = O + H 2 O CH 3 OH + HCOOH flows especially easily in the light Oxidation of nitrogen-containing compounds Amines oxidize quite easily; the end products of oxidation are nitro compounds Exhaustive reduction of nitrogen-containing substances leads to the formation of amines. Oxidation of amines in vivo Oxidation and reduction of thiols Comparative characteristics of O-B properties of organic compounds. Thiols and 2-atomic phenols are most easily oxidized. Aldehydes oxidize quite easily. Alcohols are more difficult to oxidize, and primary ones are easier than secondary and tertiary ones. Ketones are resistant to oxidation or oxidize with the cleavage of the molecule. Alkynes oxidize easily even at room temperature. The most difficult to oxidize are compounds containing carbon atoms in the Sp3-hybridized state, that is, saturated fragments of molecules. ED – substituents facilitate oxidation EA – hinder oxidation. Specific properties of poly- and heterofunctional compounds. Lecture outline Poly- and heterofunctionality as a factor increasing the reactivity of organic compounds. Specific properties of poly- and heterofunctional compounds: amphotericity formation of intramolecular salts. intramolecular cyclization of γ, δ, ε – heterofunctional compounds. intermolecular cyclization (lactides and deketopypyrosines) chelation. elimination reactions of beta-heterofunctional connections. keto-enol tautomerism. Phosphoenolpyruvate, as macroergic compound. decarboxylation. stereoisomerism Poly- and heterofunctionality as the reason for the appearance of specific properties in hydroxy, amino and oxo acids. The presence of several identical or different functional groups in a molecule is a characteristic feature of biologically important organic compounds. A molecule may contain two or more hydroxyl groups, amino groups, or carboxyl groups. For example: An important group of substances involved in vital activity are heterofunctional compounds that have a pairwise combination of different functional groups. For example: In aliphatic compounds, all of the above functional groups exhibit an EA character. Due to their influence on each other, their reactivity is mutually enhanced. For example, in oxoacids, the electrophilicity of each of the two carbonyl carbon atoms is enhanced by the -J of the other functional group, leading to easier attack by nucleophilic reagents. Since the I effect fades after 3–4 bonds, an important circumstance is the proximity of the location of functional groups in the hydrocarbon chain. Heterofunctional groups can be located on the same carbon atom (α - arrangement), or on different carbon atoms, both neighboring (β arrangement) and more distant from each other (γ, delta, epsilon) locations. Each heterofunctional group retains its own reactivity; more precisely, heterofunctional compounds enter into a “double” number of chemical reactions. When the mutual arrangement of heterofunctional groups is sufficiently close, the reactivity of each of them is mutually enhanced. With the simultaneous presence of acidic and basic groups in the molecule, the compound becomes amphoteric. For example: amino acids. Interaction of heterofunctional groups The molecule of gerofunctional compounds may contain groups capable of interacting with each other. For example, in amphoteric compounds, such as α-amino acids, the formation of internal salts is possible. Therefore, all α - amino acids occur in the form of biopolar ions and are highly soluble in water. In addition to acid-base interactions, other types of chemical reactions become possible. For example, the reaction S N at SP 2 is a hybrid of a carbon atom in the carbonyl group due to interaction with the alcohol group, the formation of esters, a carboxyl group with an amino group (formation of amides). Depending on the relative arrangement of functional groups, these reactions can occur both within one molecule (intramolecular) and between molecules (intermolecular). Since the reaction results in the formation of cyclic amides and esters. then the determining factor becomes the thermodynamic stability of the cycles. In this regard, the final product usually contains six-membered or five-membered rings. In order for intramolecular interaction to form a five or six-membered ester (amide) ring, the heterofunctional compound must have a gamma or sigma arrangement in the molecule. Then in class Plan 1. Subject and significance of bioorganic chemistry 2. Classification and nomenclature of organic compounds 3. Methods of depicting organic molecules 4. Chemical bonding in bioorganic molecules 5. Electronic effects. Mutual influence of atoms in a molecule 6. Classification of chemical reactions and reagents 7. Concept of the mechanisms of chemical reactions 2
Subject of bioorganic chemistry 3 Bioorganic chemistry is an independent branch of chemical science that studies the structure, properties and biological functions of chemical compounds of organic origin that take part in the metabolism of living organisms.
The objects of study of bioorganic chemistry are low-molecular biomolecules and biopolymers (proteins, nucleic acids and polysaccharides), bioregulators (enzymes, hormones, vitamins and others), natural and synthetic physiologically active compounds, including drugs and substances with toxic effects. Biomolecules are bioorganic compounds that are part of living organisms and specialized for the formation of cellular structures and participation in biochemical reactions, form the basis of metabolism (metabolism) and the physiological functions of living cells and multicellular organisms in general. 4 Classification of bioorganic compounds
Metabolism is a set of chemical reactions that occur in the body (in vivo). Metabolism is also called metabolism. Metabolism can occur in two directions - anabolism and catabolism. Anabolism is the synthesis in the body of complex substances from relatively simple ones. It occurs with the expenditure of energy (endothermic process). Catabolism, on the contrary, is the breakdown of complex organic compounds into simpler ones. It occurs with the release of energy (exothermic process). Metabolic processes take place with the participation of enzymes. Enzymes play the role of biocatalysts in the body. Without enzymes, biochemical processes would either not occur at all, or would proceed very slowly, and the body would not be able to maintain life. 5
Bioelements. The composition of bioorganic compounds, in addition to carbon atoms (C), which form the basis of any organic molecule, also includes hydrogen (H), oxygen (O), nitrogen (N), phosphorus (P) and sulfur (S). These bioelements (organogens) are concentrated in living organisms in quantities that are over 200 times higher than their content in inanimate objects. The noted elements make up over 99% of the elemental composition of biomolecules. 6
Bioorganic chemistry arose from the depths of organic chemistry and is based on its ideas and methods. In the history of development, organic chemistry has the following stages: empirical, analytical, structural and modern. The period from man's first acquaintance with organic substances to the end of the 18th century is considered empirical. The main result of this period was that people realized the importance of elemental analysis and the establishment of atomic and molecular masses. The theory of vitalism - life force (Berzelius). The analytical period continued until the 60s of the 19th century. It was marked by the fact that from the end of the first quarter of the 19th century a number of promising discoveries were made that dealt a crushing blow to the vitalistic theory. The first in this series was Berzelius's student, the German chemist Wöhler. He made a number of discoveries in 1824 - the synthesis of oxalic acid from cyanogen: (CN) 2 HOOC - COOH r. – synthesis of urea from ammonium cyanate: NH 4 CNO NH 2 – C – NH 2 O 8
In 1853, C. Gerard developed the “theory of types” and used it to classify organic compounds. According to Gerard, more complex organic compounds can be produced from the following four main types of substances: HHHH type HHHH O type WATER H Cl type HYDROGEN CHLORIDE HHHHN N type AMMONIA Since 1857, at the suggestion of F. A. Kekule, hydrocarbons began to be classified as methane type HHHNNHH C 9
Basic provisions of the theory of the structure of organic compounds (1861) 1) atoms in molecules are connected to each other by chemical bonds in accordance with their valency; 2) atoms in molecules of organic substances are connected to each other in a certain sequence, which determines the chemical structure (structure) of the molecule; 3) the properties of organic compounds depend not only on the number and nature of their constituent atoms, but also on the chemical structure of the molecules; 4) in organic molecules there is interaction between atoms, both bound to each other and unbound; 5) the chemical structure of a substance can be determined by studying its chemical transformations and, conversely, its properties can be characterized by the structure of a substance. 10
Basic provisions of the theory of the structure of organic compounds (1861) A structural formula is an image of the sequence of bonds of atoms in a molecule. Gross formula - CH 4 O or CH 3 OH Structural formula Simplified structural formulas are sometimes called rational Molecular formula - the formula of an organic compound, which indicates the number of atoms of each element in the molecule. For example: C 5 H 12 - pentane, C 6 H 6 - gasoline, etc. eleven
Stages of development of bioorganic chemistry As a separate field of knowledge that combines the conceptual principles and methodology of organic chemistry on the one hand and molecular biochemistry and molecular pharmacology on the other hand, bioorganic chemistry was formed in the twentieth century based on developments in the chemistry of natural substances and biopolymers. Modern bioorganic chemistry has acquired fundamental significance thanks to the work of W. Stein, S. Moore, F. Sanger (analysis of amino acid composition and determination of the primary structure of peptides and proteins), L. Pauling and H. Astbury (clarification of the structure of the -helix and -structure and their significance in the implementation of the biological functions of protein molecules), E. Chargaff (deciphering the features of the nucleotide composition of nucleic acids), J. Watson, Fr. Crick, M. Wilkins, R. Franklin (establishing the patterns of the spatial structure of the DNA molecule), G. Corani (chemical gene synthesis), etc. 14
Classification of organic compounds according to the structure of the carbon skeleton and the nature of the functional group The huge number of organic compounds prompted chemists to classify them. The classification of organic compounds is based on two classification criteria: 1. The structure of the carbon skeleton 2. The nature of the functional groups Classification according to the method of structure of the carbon skeleton: 1. Acyclic (alkanes, alkenes, alkynes, alkadienes); 2. Cyclic 2.1. Carbocyclic (alicyclic and aromatic) 2.2. Heterocyclic 15 Acyclic compounds are also called aliphatic. These include substances with an open carbon chain. Acyclic compounds are divided into saturated (or saturated) C n H 2n+2 (alkanes, paraffins) and unsaturated (unsaturated). The latter include alkenes C n H 2n, alkynes C n H 2n -2, alkadienes C n H 2n -2.
16 Cyclic compounds contain rings (cycles) within their molecules. If the cycles contain only carbon atoms, then such compounds are called carbocyclic. In turn, carbocyclic compounds are divided into alicyclic and aromatic. Alicyclic hydrocarbons (cycloalkanes) include cyclopropane and its homologues - cyclobutane, cyclopentane, cyclohexane, and so on. If the cyclic system, in addition to the hydrocarbon, also includes other elements, then such compounds are classified as heterocyclic.
Classification by the nature of a functional group A functional group is an atom or a group of atoms connected in a certain way, the presence of which in a molecule of an organic substance determines the characteristic properties and its belonging to one or another class of compounds. Based on the number and homogeneity of functional groups, organic compounds are divided into mono-, poly- and heterofunctional. Substances with one functional group are called monofunctional; substances with several identical functional groups are called polyfunctional. Compounds containing several different functional groups are heterofunctional. It is important that compounds of the same class are combined into homologous series. A homologous series is a series of organic compounds with the same functional groups and the same structure; each representative of the homologous series differs from the previous one by a constant unit (CH 2), which is called the homologous difference. Members of a homologous series are called homologues. 17
Nomenclature systems in organic chemistry - trivial, rational and international (IUPAC) Chemical nomenclature is a set of names of individual chemical substances, their groups and classes, as well as rules for compiling their names. Chemical nomenclature is a set of names of individual chemical substances, their groups and classes, as well as rules compiling their names. The trivial (historical) nomenclature is associated with the process of obtaining substances (pyrogallol - a product of pyrolysis of gallic acid), the source of origin from which it was obtained (formic acid), etc. Trivial names of compounds are widely used in the chemistry of natural and heterocyclic compounds (citral, geraniol, thiophene, pyrrole, quinoline, etc.). Trivial (historical) nomenclature is associated with the process of obtaining substances (pyrogallol is a product of pyrolysis of gallic acid), the source of origin, from which was obtained (formic acid), etc. Trivial names of compounds are widely used in the chemistry of natural and heterocyclic compounds (citral, geraniol, thiophene, pyrrole, quinoline, etc.). Rational nomenclature is based on the principle of dividing organic compounds into homologous series. All substances in a certain homologous series are considered as derivatives of the simplest representative of this series - the first or sometimes the second. In particular, for alkanes - methane, for alkenes - ethylene, etc. The rational nomenclature is based on the principle of dividing organic compounds into homologous series. All substances in a certain homologous series are considered as derivatives of the simplest representative of this series - the first or sometimes the second. In particular, for alkanes - methane, for alkenes - ethylene, etc. 18
International nomenclature (IUPAC). The rules of modern nomenclature were developed in 1957 at the 19th Congress of the International Union of Pure and Applied Chemistry (IUPAC). Radical functional nomenclature. These names are based on the name of the functional class (alcohol, ether, ketone, etc.), which is preceded by the names of hydrocarbon radicals, for example: alyl chloride, diethyl ether, dimethyl ketone, propyl alcohol, etc. Substitute nomenclature. Nomenclature rules. The parent structure is the structural fragment of the molecule (molecular skeleton) underlying the name of the compound, the main carbon chain of atoms for alicyclic compounds, and the cycle for carbocyclic compounds. 19
Chemical bond in organic molecules Chemical bond is the phenomenon of interaction between the outer electron shells (valence electrons of atoms) and atomic nuclei, which determines the existence of a molecule or crystal as a whole. As a rule, an atom, accepting or donating an electron or forming a common electron pair, tends to acquire a configuration of the outer electron shell similar to that of noble gases. The following types of chemical bonds are characteristic of organic compounds: - ionic bond - covalent bond - donor - acceptor bond - hydrogen bond There are also some other types chemical bond(metallic, one-electron, two-electron three-center), however, they are practically never found in organic compounds. 20
Types of bonds in organic compounds The most characteristic of organic compounds is a covalent bond. A covalent bond is the interaction of atoms, which is realized through the formation of a common electron pair. This type of bond is formed between atoms that have comparable electronegativity values. Electronegativity is a property of an atom that shows the ability to attract electrons to itself from other atoms. A covalent bond can be polar or non-polar. A non-polar covalent bond occurs between atoms with the same electronegativity value
Types of bonds in organic compounds A polar covalent bond is formed between atoms that have different electronegativity values. In this case, the bonded atoms acquire partial charges δ+δ+ δ-δ- A special subtype of covalent bond is the donor-acceptor bond. As in previous examples, this type of interaction is due to the presence of a common electron pair, but the latter is provided by one of the atoms forming the bond (donor) and accepted by another atom (acceptor) 24
Types of bonds in organic compounds An ionic bond is formed between atoms that differ greatly in electronegativity values. In this case, the electron from the less electronegative element (often a metal) is completely transferred to the more electronegative element. This electron transition causes the appearance of a positive charge on the less electronegative atom and a negative charge on the more electronegative one. Thus, two ions with opposite charges are formed, between which there is an electrovalent interaction. 25
Types of Bonds in Organic Compounds A hydrogen bond is an electrostatic interaction between a hydrogen atom, which is bonded in a highly polar manner, and electron pairs of oxygen, fluorine, nitrogen, sulfur and chlorine. This type of interaction is a rather weak interaction. Hydrogen bonding can be intermolecular or intramolecular. Intermolecular hydrogen bond (interaction between two molecules of ethyl alcohol) Intramolecular hydrogen bond in salicylic aldehyde 26
Chemical bonding in organic molecules The modern theory of chemical bonding is based on the quantum mechanical model of a molecule as a system consisting of electrons and atomic nuclei. The cornerstone concept of quantum mechanical theory is the atomic orbital. An atomic orbital is a part of space in which the probability of finding electrons is maximum. Bonding can thus be viewed as the interaction (“overlap”) of orbitals that each carry one electron with opposite spins. 27
Hybridization of atomic orbitals According to quantum mechanical theory, the number of covalent bonds formed by an atom is determined by the number of one-electron atomic orbitals (the number of unpaired electrons). The carbon atom in its ground state has only two unpaired electrons, but the possible transition of an electron from 2s to 2 pz makes it possible to form four covalent bonds. The state of a carbon atom in which it has four unpaired electrons is called “excited.” Despite the fact that carbon orbitals are unequal, it is known that the formation of four equivalent bonds is possible due to the hybridization of atomic orbitals. Hybridization is a phenomenon in which the same number of orbitals of the same shape and number are formed from several orbitals of different shapes and similar in energy. 28
Hybrid states of the carbon atom in organic molecules FIRST HYBRID STATE The C atom is in a state of sp 3 hybridization, forms four σ bonds, forms four hybrid orbitals, which are arranged in the shape of a tetrahedron (bond angle) σ bond 31
Hybrid states of the carbon atom in organic molecules SECOND HYBRID STATE The C atom is in a state of sp 2 hybridization, forms three σ-bonds, forms three hybrid orbitals, which are arranged in the shape of a flat triangle (bond angle 120) σ-bonds π-bond 32
Hybrid states of the carbon atom in organic molecules THIRD HYBRID STATE The C atom is in a state of sp-hybridization, forms two σ-bonds, forms two hybrid orbitals, which are arranged in a line (bond angle 180) σ-bonds π-bonds 33
Characteristics of chemical bonds POLING scale: F-4.0; O – 3.5; Cl – 3.0; N – 3.0; Br – 2.8; S – 2.5; C-2.5; H-2.1. difference 1.7 Characteristics of chemical bonds Bond polarizability is a shift in electron density under the influence of external factors. Bond polarizability is the degree of electron mobility. As the atomic radius increases, the polarizability of electrons increases. Therefore, the polarizability of the Carbon - halogen bond increases as follows: C-F Electronic effects. Mutual influence of atoms in a molecule 39 According to modern theoretical concepts, the reactivity of organic molecules is predetermined by the displacement and mobility of electron clouds that form a covalent bond. In organic chemistry, two types of electron displacements are distinguished: a) electronic displacements occurring in the -bond system, b) electronic displacements transmitted by the -bond system. In the first case, the so-called inductive effect takes place, in the second - a mesomeric effect. The inductive effect is a redistribution of electron density (polarization) resulting from the difference in electronegativity between the atoms of a molecule in a system of bonds. Due to the insignificant polarizability of the -bonds, the inductive effect quickly fades away and after 3-4 bonds it almost does not appear.
Electronic effects. Mutual influence of atoms in a molecule 40 The concept of the inductive effect was introduced by K. Ingold, and he also introduced the following designations: –I-effect in the case of a decrease in electron density by a substituent +I-effect in the case of an increase in electron density by a substituent A positive inductive effect is exhibited by alkyl radicals (CH 3, C 2 H 5 - etc.). All other substituents bonded to the carbon atom exhibit a negative inductive effect.
Electronic effects. Mutual influence of atoms in a molecule 41 The mesomeric effect is the redistribution of electron density along a conjugated system. Conjugated systems include molecules of organic compounds in which double and single bonds alternate or when an atom with a lone pair of electrons in the p-orbital is located next to the double bond. In the first case, - conjugation takes place, and in the second case, p, -conjugation takes place. Coupled systems come in open and closed circuit configurations. Examples of such compounds are 1,3-butadiene and gasoline. In the molecules of these compounds, carbon atoms are in a state of sp 2 hybridization and, due to non-hybrid p-orbitals, form -bonds that mutually overlap and form a single electron cloud, that is, conjugation takes place.
Electronic effects. Mutual influence of atoms in a molecule 42 There are two types of mesomeric effect - positive mesomeric effect (+M) and negative mesomeric effect (-M). A positive mesomeric effect is exhibited by substituents that provide p-electrons to the conjugated system. These include: -O, -S -NH 2, -OH, -OR, Hal (halogens) and other substituents that have a negative charge or a lone pair of electrons. The negative mesomeric effect is characteristic of substituents that absorb electron density from the conjugated system. These include substituents that have multiple bonds between atoms with different electronegativity: - N0 2 ; -SO 3 H; >C=O; -COON and others. The mesomeric effect is graphically reflected by a bent arrow, which shows the direction of electron displacement. Unlike the induction effect, the mesomeric effect does not go out. It is transmitted completely throughout the system, regardless of the length of the interfacing chain. C=O; -COON and others. The mesomeric effect is graphically reflected by a bent arrow, which shows the direction of electron displacement. Unlike the induction effect, the mesomeric effect does not go out. It is transmitted completely throughout the system, regardless of the length of the interfacing chain."> Types of chemical reactions 43 A chemical reaction can be considered as the interaction of a reagent and substrate. Depending on the method of breaking and forming a chemical bond in molecules, organic reactions divided into: a) homolytic b) heterolytic c) molecular Homolytic or free radical reactions are caused by homolytic cleavage of the bond, when each atom has one electron left, that is, radicals are formed. Homolytic cleavage occurs at high temperatures, the action of a light quantum, or catalysis.
Heterolytic or ionic reactions proceed in such a way that a pair of bonding electrons remains near one of the atoms and ions are formed. A particle with an electron pair is called nucleophilic and has a negative charge (-). A particle without an electron pair is called electrophilic and has a positive charge (+). 44 Types of chemical reactions
Mechanism of a chemical reaction 45 The mechanism of a reaction is the set of elementary (simple) stages that make up a given reaction. The reaction mechanism most often includes the following stages: activation of the reagent with the formation of an electrophile, nucleophile or free radical. To activate a reagent, a catalyst is usually needed. In the second stage, the activated reagent interacts with the substrate. In this case, intermediate particles (intermediates) are formed. The latter include -complexes, -complexes (carbocations), carbanions, and new free radicals. At the final stage, the addition or elimination of a particle to (from) the intermediate formed in the second stage takes place with the formation of the final reaction product. If a reagent generates a nucleophile upon activation, then these are nucleophilic reactions. They are marked with the letter N - (in the index). In the case where the reagent generates an electrophile, the reactions are classified as electrophilic (E). The same can be said about free radical reactions (R).
Nucleophiles are reagents that have a negative charge or an atom enriched in electron density: 1) anions: OH -, CN -, RO -, RS -, Hal - and other anions; 2) neutral molecules with lone pairs of electrons: NH 3, NH 2 R, H 2 O, ROH and others; 3) molecules with excess electron density (having - bonds). Electrophiles are reagents that have a positive charge or an atom depleted in electron density: 1) cations: H + (proton), HSO 3 + (hydrogen sulfonium ion), NO 2 + (nitronium ion), NO (nitrosonium ion) and other cations; 2) neutral molecules with a vacant orbital: AlCl 3, FeBr 3, SnCl 4, BF 4 (Lewis acids), SO 3; 3) molecules with depleted electron density on the atom. 46
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