What is bioorganic chemistry. Subject of bioorganic chemistry

LECTURE 1

Bioorganic chemistry (BOC), its importance in medicine

HOH is a science that studies the biological function of organic substances in the body.

HOB arose in the second half of the twentieth century. The objects of its study are biopolymers, bioregulators and individual metabolites.

Biopolymers are high-molecular natural compounds that are the basis of all organisms. These are peptides, proteins, polysaccharides, nucleic acids (NA), lipids, etc.

Bioregulators are compounds that chemically regulate metabolism. These are vitamins, hormones, antibiotics, alkaloids, drugs, etc.

Knowledge of the structure and properties of biopolymers and bioregulators makes it possible to understand the essence of biological processes. Thus, the establishment of the structure of proteins and NA made it possible to develop ideas about the matrix protein biosynthesis and the role of NA in the preservation and transmission of genetic information.

HOC plays an important role in establishing the mechanism of action of enzymes, drugs, processes of vision, respiration, memory, nerve conduction, muscle contraction, etc.

The main problem of HOC is to elucidate the relationship between the structure and mechanism of action of compounds.

HBO is based on organic chemistry material.

ORGANIC CHEMISTRY

This is the science that studies the compounds of carbon. Currently, there are ~ 16 million organic substances.

Reasons for the diversity of organic substances.

1. Connections of C atoms with each other and other elements of the periodic system of D. Mendeleev. In this case, chains and cycles are formed:

Straight chain Branched chain

Tetrahedral planar configuration

the configuration of the C atom of the C atom

2. Homology is the existence of substances with similar properties, where each member of the homological series differs from the previous one by a group
-CH 2 -. For example, the homologous series of saturated hydrocarbons:

3. Isomerism is the existence of substances that have the same qualitative and quantitative composition, but a different structure.

A.M. Butlerov (1861) created a theory of the structure of organic compounds, which to this day serves as the scientific basis of organic chemistry.

The main provisions of the theory of the structure of organic compounds:

1) atoms in molecules are connected to each other by chemical bonds in accordance with their valency;

2) atoms in the molecules of organic compounds are interconnected in a certain sequence, which determines the chemical 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 molecules there is a mutual influence of atoms, both connected and not directly connected with each other;

5) the chemical structure of a substance can be determined as a result of studying its chemical transformations and, conversely, its properties can be characterized by the structure of a substance.

Let us consider some provisions of the theory of the structure of organic compounds.

Structural isomerism

She shares:

1) Chain isomerism

2) Isomerism of the position of multiple bonds and functional groups

3) Isomerism of functional groups (interclass isomerism)

Newman formulas

Cyclohexane

The shape of the "chair" is more energetically favorable than the "bath".

Configuration isomers

These are stereoisomers, the molecules of which have a different arrangement of atoms in space, regardless of conformations.

According to the type of symmetry, all stereoisomers are divided into enantiomers and diastereomers.

Enantiomers (optical isomers, mirror isomers, antipodes) are stereoisomers whose molecules relate to each other as an object and an incompatible mirror image. This phenomenon is called enantiomerism. All chemical and physical properties of enantiomers are the same, except for two: the rotation of the plane of polarized light (in the polarimeter device) and biological activity. Enantiomeric conditions: 1) C atom is in a state of sp 3 hybridization; 2) the absence of any symmetry; 3) the presence of an asymmetric (chiral) C atom, i.e. an atom that has four different substitutes.

Many hydroxy and amino acids have the ability to rotate the plane of polarization of a light beam to the left or right. This phenomenon is called optical activity, and the molecules themselves are optically active. The deviation of the light beam to the right is marked with a "+" sign, to the left - "-" and indicate the angle of rotation in degrees.

The absolute configuration of molecules is determined by complex physicochemical methods.

The relative configuration of optically active compounds is determined by comparison with a glyceraldehyde standard. Optically active substances having the configuration of dextrorotatory or levorotatory glyceraldehyde (M. Rozanov, 1906) are called things of the D- and L-series. An equal mixture of right and left isomers of one compound is called a racemate and is optically inactive.

Studies have shown that the sign of the rotation of light cannot be associated with the belonging of a thing to the D- and L-series, it is determined only experimentally in devices - polarimeters. For example, L-milk acid has a rotation angle of +3.8 o, D-milk acid - -3.8 o.

Enantiomers are depicted using Fisher's formulas.

L-row D-row

Among the enantiomers, there may be symmetrical molecules that do not have optical activity, and are called mesoisomers.

For example: Wine list

D - (+) - row L - (-) - row

Mezovinnaya to - that

Racemate - grape acid

Optical isomers that are not mirror isomers, which differ in the configuration of several, but not all, asymmetric C atoms, which have different physical and chemical properties, are called s- di-A-stereoisomers.

p-Diastereomers (geometric isomers) are stereomers that have a p-bond in the molecule. They are found in alkenes, unsaturated higher carboxylic to-t, unsaturated dicarboxylic to-t

The biological activity of organic things is related to their structure.

For example:

Cis-butenedioic acid, Trans-butenedioic acid,

maleic acid - fumaric acid - non-toxic,

very toxic contained in the body

All natural unsaturated higher carboxylic acids are cis-isomers.

LECTURE 2

Related systems

In the simplest case, conjugated systems are systems with alternating double and single bonds. They can be open and closed. An open system exists in diene hydrocarbons (HC).

Examples:

CH 2 \u003d CH - CH \u003d CH 2

Butadiene-1, 3

Chlorothene

CH 2 \u003d CH - Cl

Here, p-electrons conjugate with p-electrons. This type of conjugation is called p, p-conjugation.

A closed system exists in aromatic hydrocarbons.

C 6 H 6

Benzene

Aromaticity

This is a concept that includes various properties of aromatic compounds. Aromaticity conditions: 1) a flat closed cycle, 2) all C atoms are in sp 2 - hybridization, 3) a single conjugated system of all cycle atoms is formed, 4) the Hückel rule is fulfilled: “4n + 2 p-electrons participate in conjugation, where n = 1, 2, 3...”

The simplest representative of aromatic hydrocarbons is benzene. It satisfies all four conditions of aromaticity.

Hückel's rule: 4n+2 = 6, n = 1.

Mutual influence of atoms in a molecule

In 1861, the Russian scientist A.M. Butlerov stated the position: "Atoms in molecules mutually influence each other." At present, this influence is transmitted in two ways: inductive and mesomeric effects.

Inductive effect

This is the transfer of electronic influence through the s-bond chain. It is known that the bond between atoms with different electronegativity (EO) is polarized, i.e. shifted to a more EO atom. This leads to the appearance of effective (real) charges (d) on the atoms. Such an electronic displacement is called inductive and is denoted by the letter I and the arrow ®.

, X \u003d Hal -, BUT -, NS -, NH 2 - and others.

The inductive effect can be positive or negative. If the X substituent attracts chemical bond electrons more strongly than the H atom, then it exhibits - I. I (H) \u003d O. In our example, X exhibits - I.

If the X substituent attracts bond electrons weaker than the H atom, then it exhibits +I. All alkyls (R = CH 3 -, C 2 H 5 -, etc.), Me n + show +I.

mesomeric effect

The mesomeric effect (conjugation effect) is the influence of a substituent transmitted through a conjugated system of p-bonds. Indicated by the letter M and a curved arrow. The mesomeric effect can be "+" or "-".

It was said above that there are two types of conjugation p, p and p, p.

A substituent that attracts electrons from a conjugated system exhibits -M and is called an electron acceptor (EA). These are substituents having double

new connection, etc.

A substituent donating electrons to a conjugated system exhibits + M and is called an electron donor (ED). These are substituents with single bonds having an unshared electron pair (etc.).

Table 1 Electronic effects of substituents

Deputies	Orientants in C 6 H 5 -R	I	M
Alk (R-): CH 3 -, C 2 H 5 -...	Orientants of the first kind: direct ED substituents to ortho- and para-positions	+
– Н 2 , –NНR, –NR 2	–	+
– N, – N, – R	–	+
–H L	–	+
LECTURE 3 Acidity and basicity To characterize the acidity and basicity of organic compounds, the Bronsted theory is used. The main provisions of this theory: 1) An acid is a particle that donates a proton (donor H +); a base is a particle that accepts a proton (acceptor H +). 2) Acidity is always characterized in the presence of bases and vice versa. A - H +: B Û A - + B - H + basic kit CH 3 COOH + HOH Û CH 3 COO - + H 3 O + K-ta Basic Conjugate Conjugate basic kit HNO 3 + CH 3 COOH Û CH 3 COOH 2 + + NO 3 - K-ta Basic Conjugate Conjugate to-that basic Bronsted acids 3) Bronsted acids are divided into 4 types depending on the acid center: SN to-you (thiols), OH to-you (alcohols, phenols, carboxylic to-you), NH to-you (amines, amides), CH to-you (HC). In this row, from top to bottom, acidity decreases. 4) The strength of the to-you is determined by the stability of the resulting anion. The more stable the anion, the stronger the acid. The stability of the anion depends on the delocalization (distribution) of the "-" charge throughout the particle (anion). The more delocalized the "-" charge, the more stable the anion and the stronger the acid. The charge delocalization depends on: a) on the electronegativity (EO) of the heteroatom. The more EO of a heteroatom, the stronger the corresponding acid. For example: R - OH and R - NH 2 Alcohols are stronger to-you than amines, tk. EO(O) > EO(N). b) on the polarizability of the heteroatom. The greater the polarizability of a heteroatom, the stronger the corresponding to-ta. For example: R - SN and R - OH Thiols are stronger to-you than alcohols, tk. The S atom is more polarized than the O atom. c) on the nature of the R substituent (its length, the presence of a conjugated system, delocalization of the electron density). For example: CH 3 - OH, CH 3 - CH 2 - OH, CH 3 - CH 2 - CH 2 - OH Acidity<, т.к. увеличивается длина радикала With the same acid center, the strength of alcohols, phenols and carboxylic acids is not the same. For example, CH 3 - OH, C 6 H 5 - OH, Your strength is increasing Phenols are stronger acids than alcohols due to the p, p-conjugation (+ M) of the –OH group. The О–Н bond is more polarized in phenols. Phenols can even interact with salts (FeС1 3) - a qualitative reaction to phenols. Carbon to-you, compared with alcohols containing the same R, are stronger to-tami, tk. the O–H bond is significantly polarized due to the –M effect of the > C = O group: In addition, the carboxylate anion is more stable than the alcohol anion due to p,p conjugation in the carboxyl group. d) from the introduction of substituents in the radical. EA substituents increase acidity, ED substituents decrease acidity. For example: p-Nitrophenol is stronger to-that than p-aminophenol, because. the -NO 2 group is EA. CH 3 -COOH CCl 3 -COOH pK 4.7 pK 0.65 Trichloroacetic acid is many times stronger than CH 3 COOH due to - I Cl atoms as EA. Formic acid H-COOH is stronger than CH 3 COOH due to the + I group of CH 3 - acetic acid. e) the nature of the solvent. If the solvent is a good H + proton acceptor, then the force k-you increases and vice versa. Founding of Bronsted 5) They are divided into: a) p-bases (compounds with multiple bonds); b) n-bases (ammonium, containing an atom, oxonium containing an atom, sulfonium containing an atom) The strength of the base is determined by the stability of the resulting cation. The more stable the cation, the stronger the base. In other words, the strength of the base is the greater, the less strong the bond with the heteroatom (O, S, N) that has a free electron pair attacked by H + . The stability of the cation depends on the same factors as the stability of the anion, but with the opposite effect. All factors that increase acidity decrease basicity. The strongest bases are amines, because the nitrogen atom has a lower EO compared to O. At the same time, secondary amines are stronger bases than primary ones, tertiary amines are weaker than secondary ones due to the steric factor, which makes it difficult for a proton to access N. Aromatic amines are weaker bases than aliphatic ones, which is explained by the +M of the –NH 2 group. The electron pair of nitrogen, participating in conjugation, becomes inactive. The stability of the conjugated system hinders the addition of H + . In urea NH 2 -CO - NH 2 there is an EA group> C \u003d O, which significantly reduces the basic properties and urea forms salts with only one equivalent of to-you. Thus, the stronger the to-ta, the weaker the basis formed by it and vice versa. Alcohols These are hydrocarbon derivatives in which one or more H atoms are replaced by an –OH group. Classification: I. By the number of OH groups, monohydric, dihydric and polyhydric alcohols are distinguished: CH 3 -CH 2 -OH Ethanol Ethylene glycol Glycerin II. By the nature of R, there are: 1) limiting, 2) unlimiting, 3) cyclic, 4) aromatic. 2) CH 2 \u003d CH-CH 2 -OH allyl alcohol 3) Unsaturated cyclic alcohols include: retinol (vitamin A) and cholesterol Inositol vitamin-like

III. According to the position of –OH distinguish between primary, secondary and tertiary alcohols.

IV. According to the number of C atoms, low molecular weight and high molecular weight are distinguished.

CH 3 - (CH 2) 14 -CH 2 -OH (C 16 H 33 OH) CH 3 - (CH 2) 29 -CH 2 OH (C 31 H 63 OH)

Cetyl alcohol Myricyl alcohol

Cetyl palmitate is the basis of spermaceti, myricyl palmitate is found in beeswax.

Nomenclature:

Trivial, rational, MN (root + ending "ol" + Arabic numeral).

Isomerism:

chains, positions gr. -ON, optical.

The structure of the alcohol molecule

CH-acid Nu center

Electrophilic Center Acid

core center center

R-tion of oxidation

1) Alcohols are weak acids.

2) Alcohols are weak bases. Attach H + only from strong acids, but they are stronger Nu.

3) -I effect gr. –OH increases the mobility of H at the adjacent carbon atom. Carbon acquires d+ (electrophilic center, S E) and becomes the center of nucleophilic attack (Nu). The C–O bond breaks more easily than H–O, therefore, characteristic of alcohols is the p-tion S N. They tend to go in an acidic environment, because. protonation of the oxygen atom increases the d+ of the carbon atom and facilitates bond breaking. This type includes district formation of ethers, halogen derivatives.

4) The shift of the electron density from H in the radical leads to the appearance of a CH-acid center. In this case, there are districts of oxidation and elimination (E).

Physical properties

Lower alcohols (C 1 -C 12) are liquids, higher alcohols are solids. Many properties of alcohols are explained by the formation of an H-bond:

Chemical properties

I. Acid-base

Alcohols are weak amphoteric compounds.

2R–OH + 2Na ® 2R–ONa + H 2

Alcoholate

Alcoholates are easily hydrolyzed, which shows that alcohols are weaker acids than water:

R– OHa + HOH ® R–OH + NaOH

The main center in alcohols is the O heteroatom:

CH 3 -CH 2 -OH + H + ® CH 3 -CH 2 - -H ® CH 3 -CH 2 + + H 2 O

If p-tion goes with hydrogen halides, then the halide ion will join: CH 3 -CH 2 + + Cl - ® CH 3 -CH 2 Cl

HC1 RON R-COOH NH 3 C 6 H 5 ONa

C1 - R-O - R-COO - NH 2 - C 6 H 5 O -

Anions in such p-tions act as nucleophiles (Nu) due to the “-” charge or lone electron pair. Anions are stronger bases and nucleophilic reagents than alcohols themselves. Therefore, in practice, to obtain simple and complex esters, alcoholates are used, and not the alcohols themselves. If the nucleophile is another alcohol molecule, then it attaches to the carbocation:

Ether

CH 3 -CH 2 + + ® CH 3 -CH 2 + - - H CH 3 -CH 2 -O-R

This is the p-tion of alkylation (the introduction of alkyl R into the molecule).

Replace -OH gr. halogen is possible under the action of PCl 3 , PCl 5 and SOCl 2 .

According to this mechanism, tertiary alcohols react more easily.

The p-tion S E in relation to the alcohol molecule is the p-tion of the formation of esters with organic and mineral acids:

R - O H + H O - R - O - + H 2 O

Ester

This is the district of acylation - the introduction of acyl into the molecule.

CH 3 -CH 2 -OH + H + CH 3 -CH 2 - -H CH 3 -CH 2 +

With an excess of H 2 SO 4 and a higher temperature than in the case of the formation of ethers, the catalyst is regenerated and an alkene is formed:

CH 3 -CH 2 + + HSO 4 -® CH 2 \u003d CH 2 + H 2 SO 4

Easier is p-tion E for tertiary alcohols, more difficult for secondary and primary, tk. in the latter cases less stable cations are formed. In these p-tions, the rule of A. Zaitsev is fulfilled: “During the dehydration of alcohols, the H atom splits off from the neighboring C atom with a lower content of H atoms.”

CH 3 -CH \u003d CH -CH 3

Butanol-2

In the body of -OH turns into an easy-going one by the formation of esters with H 3 RO 4:

CH 3 -CH 2 -OH + HO-RO 3 H 2 CH 3 -CH 2 -ORO 3 H 2

IV. R-tion of oxidation

1) Primary and secondary alcohols are oxidized by CuO, solutions of KMnO 4, K 2 Cr 2 O 7 when heated to form the corresponding carbonyl-containing compounds:

3)

Nitroglycerin is a colorless oily liquid. In the form of dilute alcohol solutions (1%), it is used for angina pectoris, because. has a vasodilating effect. Nitroglycerin is a strong explosive that can explode on impact or when heated. In this case, in a small volume occupied by a liquid substance, a very large volume of gases is instantly formed, which causes a strong blast wave. Nitroglycerin is part of dynamite, gunpowder.

Representatives of pentites and hexites - xylitol and sorbitol - respectively, penta- and six-atomic alcohols with an open chain. The accumulation of –OH groups leads to the appearance of a sweet taste. Xylitol and sorbitol are sugar substitutes for diabetics.

Glycerophosphates - structural fragments of phospholipids, are used as a general tonic.

benzyl alcohol

Position isomers

, antibiotics, pheromones, signal substances, biologically active substances of plant origin, as well as synthetic regulators of biological processes (drugs, pesticides, etc.). As an independent science, it was formed in the second half of the 20th century at the intersection of biochemistry and organic chemistry and is associated with the practical problems of medicine, agriculture, chemical, food and microbiological industries.

Methods

The main arsenal is the methods of organic chemistry; a variety of physical, physicochemical, mathematical and biological methods are involved in solving structural and functional problems.

Objects of study

• Mixed type biopolymers
• natural signal substances
• Biologically active substances of plant origin
• Synthetic regulators (drugs, pesticides, etc.).

Sources

• Ovchinnikov Yu. A.. - M .: Education, 1987. - 815 p.
• Bender M., Bergeron R., Komiyama M.
• Dugas G., Penny K. Bioorganic chemistry. - M.: Mir, 1983.
• Tyukavkina N. A., Baukov Yu. I.

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An excerpt characterizing Bioorganic Chemistry

- Ma chere, il y a un temps pour tout, [Darling, there is time for everything,] - said the countess, pretending to be strict. “You spoil her all the time, Elie,” she added to her husband.
- Bonjour, ma chere, je vous felicite, [Hello, my dear, I congratulate you,] - said the guest. - Quelle delicuse enfant! [What a lovely child!] she added, turning to her mother.
A dark-eyed, big-mouthed, ugly but lively girl, with her childlike open shoulders, which, shrinking, moved in her corsage from a quick run, with her black curls knocked back, thin bare arms and small legs in lace pantaloons and open shoes, was at that sweet age when the girl is no longer a child, and the child is not yet a girl. Turning away from her father, she ran up to her mother and, paying no attention to her stern remark, hid her flushed face in the lace of her mother's mantilla and laughed. She was laughing at something, talking abruptly about the doll she had taken out from under her skirt.
“See?… Doll… Mimi… See.
And Natasha could no longer talk (everything seemed ridiculous to her). She fell on her mother and burst out laughing so loudly and resoundingly that everyone, even the prim guest, laughed against her will.
- Well, go, go with your freak! - said the mother, pushing her daughter away in mock angrily. “This is my smaller one,” she turned to the guest.
Natasha, tearing her face away from her mother's lace scarf for a moment, looked at her from below through tears of laughter, and again hid her face.
The guest, forced to admire the family scene, considered it necessary to take some part in it.
“Tell me, my dear,” she said, turning to Natasha, “how do you have this Mimi? Daughter, right?
Natasha did not like the tone of condescension to the childish conversation with which the guest turned to her. She did not answer and looked seriously at the guest.
Meanwhile, all this young generation: Boris - an officer, the son of Princess Anna Mikhailovna, Nikolai - a student, the eldest son of the count, Sonya - the fifteen-year-old niece of the count, and little Petrusha - the youngest son, all settled in the living room and, apparently, tried to keep within the boundaries of decency animation and gaiety that still breathed in every feature. It was evident that there, in the back rooms, whence they had all come running so swiftly, they had more cheerful conversations than here about city gossip, the weather, and comtesse Apraksine. [about Countess Apraksina.] From time to time they glanced at each other and could hardly restrain themselves from laughing.

Grodno" href="/text/category/grodno/" rel="bookmark">Grodno State Medical University", Candidate of Chemical Sciences, Associate Professor;

Associate Professor of the Department of General and Bioorganic Chemistry of the Educational Establishment "Grodno State Medical University", Candidate of Biological Sciences, Associate Professor

Reviewers:

Department of General and Bioorganic Chemistry of the Educational Establishment "Gomel State Medical University";

– head Department of Bioorganic Chemistry, Educational Establishment "Belarusian State Medical University", Candidate of Medical Sciences, Associate Professor.

Department of General and Bioorganic Chemistry Educational Institution "Grodno State Medical University"

(minutes dated 01.01.01)

Central Scientific and Methodological Council of the Educational Establishment "Grodno State Medical University"

(minutes dated 01.01.01)

Section on the specialty 1Medical and psychological business of the educational and methodological association of universities of the Republic of Belarus for medical education

(minutes dated 01.01.01)

Release Responsible:

First Vice-Rector of the Educational Establishment "Grodno State Medical University", Professor, Doctor of Medical Sciences

Explanatory note

The relevance of studying the academic discipline

"Bioorganic Chemistry"

Bioorganic chemistry is a fundamental natural science discipline. Bioorganic chemistry was formed as an independent science in the 2nd half of the 20th century at the intersection of organic chemistry and biochemistry. The relevance of the study of bioorganic chemistry is due to the practical problems facing medicine and agriculture (obtaining vitamins, hormones, antibiotics, plant growth stimulants, animal and insect behavior regulators, and other medicines), the solution of which is impossible without the use of the theoretical and practical potential of bioorganic chemistry.

Bioorganic chemistry is constantly enriched with new methods for the isolation and purification of natural compounds, methods for the synthesis of natural compounds and their analogues, knowledge about the relationship between the structure and biological activity of compounds, etc.

The latest approaches to medical education, related to overcoming the reproductive style in teaching, ensuring the cognitive and research activity of students, open up new prospects for realizing the potential of both the individual and the team.

The purpose and objectives of the discipline

Target: formation of the level of chemical competence in the system of medical education, which ensures the subsequent study of biomedical and clinical disciplines.

Tasks:

Mastering by students the theoretical foundations of chemical transformations of organic molecules in relation to their structure and biological activity;

Formation: knowledge of the molecular basis of life processes;

Development of skills to navigate the classification, structure and properties of organic compounds acting as medicines;

Formation of the logic of chemical thinking;

Development of skills to use the methods of qualitative analysis
organic compounds;

Chemical knowledge and skills, which form the basis of chemical competence, will contribute to the formation of the professional competence of the graduate.

Requirements for mastering the academic discipline

Requirements for the level of mastering the content of the discipline "Bioorganic chemistry" are determined by the educational standard of higher education of the first stage in the cycle of general professional and special disciplines, which is developed taking into account the requirements of the competency-based approach, which indicates the minimum content for the discipline in the form of generalized chemical knowledge and skills that make up bioorganic competence university graduate:

a) generalized knowledge:

- understand the essence of the subject as a science and its relationship with other disciplines;

Significance in understanding metabolic processes;

The concept of the unity of the structure and reactivity of organic molecules;

Fundamental laws of chemistry necessary to explain the processes occurring in living organisms;

Chemical properties and biological significance of the main classes of organic compounds.

b) generalized skills:

Predict the reaction mechanism based on knowledge of the structure of organic molecules and methods of breaking chemical bonds;

Explain the significance of reactions for the functioning of living systems;

Use the acquired knowledge in the study of biochemistry, pharmacology and other disciplines.

Structure and content of the academic discipline

In this program, the structure of the content of the discipline "bioorganic chemistry" consists of an introduction to the discipline and two sections that cover general issues of the reactivity of organic molecules, as well as the properties of hetero- and polyfunctional compounds involved in life processes. Each section is divided into topics arranged in a sequence that ensures optimal study and assimilation of the program material. For each topic, generalized knowledge and skills are presented that make up the essence of students' bioorganic competence. In accordance with the content of each topic, the requirements for competencies are defined (in the form of a system of generalized knowledge and skills), for the formation and diagnosis of which tests can be developed.

Teaching methods

The main teaching methods that adequately meet the objectives of studying this discipline are:

Explanation and consultation;

Laboratory lesson;

Elements of problem-based learning (educational and research work of students);

Introduction to bioorganic chemistry

Bioorganic chemistry as a science that studies the structure of organic substances and their transformations in relation to biological functions. Objects of study of bioorganic chemistry. The role of bioorganic chemistry in the formation of a scientific basis for the perception of biological and medical knowledge at the modern molecular level.

The theory of the structure of organic compounds and its development at the present stage. Isomerism of organic compounds as the basis for the diversity of organic compounds. Types of isomerism of organic compounds.

Physico-chemical methods for the isolation and study of organic compounds that are important for biomedical analysis.

Basic rules of IUPAC systematic nomenclature for organic compounds: substitutional and radical-functional nomenclature.

The spatial structure of organic molecules, its relationship with the type of hybridization of the carbon atom (sp3-, sp2- and sp-hybridization). stereochemical formulas. configuration and conformation. Conformations of open chains (shielded, hindered, beveled). Energy characteristics of conformations. Newman's projection formulas. Spatial convergence of certain sections of the chain as a result of conformational equilibrium and as one of the reasons for the predominant formation of five- and six-membered rings. Conformations of cyclic compounds (cyclohexane, tetrahydropyran). Energy characteristics of chair and bath conformations. Axial and equatorial connections. Relationship of spatial structure with biological activity.

Competency requirements:

Know the objects of study and the main tasks of bioorganic chemistry,

· Be able to classify organic compounds according to the structure of the carbon skeleton and the nature of functional groups, use the rules of systematic chemical nomenclature.

· Know the main types of isomerism of organic compounds, be able to determine the possible types of isomers by the structural formula of the compound.

· To know the different types of hybridization of carbon atomic orbitals, the spatial orientation of the bonds of the atom, their type and number depending on the type of hybridization.

· Know the energy characteristics of the conformations of cyclic (chair, bath conformations) and acyclic (inhibited, skewed, eclipsed conformations) molecules, be able to represent them using Newman projection formulas.

· Know the types of stresses (torsion, angular, van der Waals) arising in various molecules, their influence on the stability of the conformation and the molecule as a whole.

Section 1. Reactivity of organic molecules as a result of mutual influence of atoms, mechanisms of organic reactions

Topic 1. Conjugated systems, aromaticity, electronic effects of substituents

Conjugated systems and aromaticity. Conjugation (p, p - and p, p-conjugation). Conjugated open chain systems: 1,3-dienes (butadiene, isoprene), polyenes (carotenoids, vitamin A). Conjugate systems with a closed circuit. Aromaticity: aromaticity criteria, Hückel's aromaticity rule. Aromaticity of benzoid (benzene, naphthalene, phenanthrene) compounds. Conjugation energy. Structure and causes of thermodynamic stability of carbo- and heterocyclic aromatic compounds. Aromaticity of heterocyclic (pyrrole, imidazole, pyridine, pyrimidine, purine) compounds. Pyrrole and pyridine nitrogen atoms, p-excessive and p-deficient aromatic systems.

Mutual influence of atoms and methods of its transmission in organic molecules. Electron delocalization as one of the factors for increasing the stability of molecules and ions, its widespread occurrence in biologically important molecules (porphin, heme, hemoglobin, etc.). Polarization of bonds. Electronic effects of substituents (inductive and mesomeric) as the reason for the uneven distribution of electron density and the appearance of reaction centers in the molecule. Inductive and mesomeric effects (positive and negative), their graphic designation in the structural formulas of organic compounds. Electron donor and electron acceptor substituents.

Competency requirements:

· Know the types of conjugation and be able to determine the type of conjugation by the structural formula of the connection.

· To know the criteria of aromaticity, to be able to determine the belonging to aromatic compounds of carbo- and heterocyclic molecules by the structural formula.

· To be able to evaluate the electronic contribution of atoms to the creation of a single conjugated system, to know the electronic structure of pyridine and pyrrole nitrogen atoms.

· Know the electronic effects of substituents, their causes and be able to graphically depict their action.

· Be able to classify substituents as electron-donating or electron-withdrawing substituents on the basis of their inductive and mesomeric effects.

· Be able to predict the effect of substituents on the reactivity of molecules.

Topic 2. Reactivity of hydrocarbons. Reactions of radical substitution, electrophilic addition and substitution

General patterns of reactivity of organic compounds as a chemical basis for their biological functioning. Chemical reaction as a process. Concepts: substrate, reagent, reaction center, transition state, reaction product, activation energy, reaction rate, mechanism.

Classification of organic reactions according to the result (addition, substitution, elimination, redox) and according to the mechanism - radical, ionic (electrophilic, nucleophilic), consistent. Reagent types: radical, acidic, basic, electrophilic, nucleophilic. Homolytic and heterolytic cleavage of covalent bonds in organic compounds and resulting particles: free radicals, carbocations and carbanions. The electronic and spatial structure of these particles and the factors that determine their relative stability.

Reactivity of hydrocarbons. Radical substitution reactions: homolytic reactions involving CH-bonds of the sp3-hybridized carbon atom. The mechanism of radical substitution on the example of the reaction of halogenation of alkanes and cycloalkanes. The concept of chain processes. The concept of regioselectivity.

Ways of formation of free radicals: photolysis, thermolysis, redox reactions.

Electrophilic addition reactions ( AE) in the series of unsaturated hydrocarbons: heterolytic reactions involving p-bonds between sp2-hybridized carbon atoms. Mechanism of hydration and hydrohalogenation reactions. acid catalysis. Markovnikov's rule. Influence of static and dynamic factors on the regioselectivity of electrophilic addition reactions. Features of electrophilic addition reactions to diene hydrocarbons and small cycles (cyclopropane, cyclobutane).

Electrophilic substitution reactions ( SE): heterolytic reactions involving the p-electron cloud of the aromatic system. The mechanism of reactions of halogenation, nitration, alkylation of aromatic compounds: p - and s- complexes. The role of the catalyst (Lewis acid) in the formation of an electrophilic particle.

Influence of substituents in the aromatic nucleus on the reactivity of compounds in electrophilic substitution reactions. Orienting influence of substituents (orientants of I and II kind).

Competency requirements:

· Know the concepts of substrate, reagent, reaction center, reaction product, activation energy, reaction rate, reaction mechanism.

· Know the classification of reactions according to various criteria (by the end result, by the method of breaking bonds, by mechanism) and the types of reagents (radical, electrophilic, nucleophilic).

· Know the electronic and spatial structure of reagents and the factors that determine their relative stability, be able to compare the relative stability of similar reagents.

· To know the ways of formation of free radicals and the mechanism of reactions of radical substitution (SR) on the examples of reactions of halogenation of alkanes and cycloalakanes.

· Be able to determine the statistical probability of the formation of possible products in radical substitution reactions and the possibility of a regioselective process.

· Know the mechanism of electrophilic addition (AE) reactions in the reactions of halogenation, hydrohalogenation and hydration of alkenes, be able to qualitatively assess the reactivity of substrates based on the electronic effects of substituents.

· Know Markovnikov's rule and be able to determine the regioselectivity of the reactions of hydration and hydrohalogenation based on the influence of static and dynamic factors.

· Know the features of electrophilic addition reactions to conjugated diene hydrocarbons and small cycles (cyclopropane, cyclobutane).

· Know the mechanism of electrophilic substitution reactions (SE) in the reactions of halogenation, nitration, alkylation, acylation of aromatic compounds.

· To be able, based on the electronic effects of substituents, to determine their influence on the reactivity of the aromatic nucleus and their orienting action.

Topic 3. Acid-base properties of organic compounds

Acidity and basicity of organic compounds: theories of Bronsted and Lewis. The stability of an acid anion is a qualitative indicator of acidic properties. General patterns in the change of acidic or basic properties in relation to the nature of the atoms in the acidic or basic center, the electronic effects of substituents at these centers. Acid properties of organic compounds with hydrogen-containing functional groups (alcohols, phenols, thiols, carboxylic acids, amines, CH-acidity of molecules and cabrications). p-bases and n- bases. The main properties of neutral molecules containing heteroatoms with lone pairs of electrons (alcohols, thiols, sulfides, amines) and anions (hydroxide, alkoxide ions, anions of organic acids). Acid-base properties of nitrogen-containing heterocycles (pyrrole, imidazole, pyridine). Hydrogen bond as a specific manifestation of acid-base properties.

Comparative characteristics of the acid properties of compounds containing a hydroxyl group (monohydric and polyhydric alcohols, phenols, carboxylic acids). Comparative characteristics of the main properties of aliphatic and aromatic amines. Influence of the electronic nature of a substituent on the acid-base properties of organic molecules.

Competency requirements:

· Know the definitions of acids and bases according to the Bronsted protolytic theory and the Lewis electron theory.

· Know the Bronsted classification of acids and bases, depending on the nature of the atoms of the acidic or basic centers.

· Know the factors that affect the strength of acids and the stability of their conjugate bases, be able to conduct a comparative assessment of the strength of acids based on the stability of their corresponding anions.

· To know the factors influencing the strength of the Bronsted bases, to be able to conduct a comparative assessment of the strength of the bases, taking into account these factors.

· Know the causes of hydrogen bonding, be able to interpret the formation of a hydrogen bond as a specific manifestation of the acid-base properties of a substance.

· Know the causes of keto-enol tautomerism in organic molecules, be able to explain them from the standpoint of the acid-base properties of compounds in relation to their biological activity.

· Know and be able to carry out qualitative reactions that allow to distinguish polyhydric alcohols, phenols, thiols.

Topic 4. Reactions of nucleophilic substitution at the tetragonal carbon atom and competitive elimination reactions

Reactions of nucleophilic substitution at the sp3-hybridized carbon atom: heterolytic reactions due to the polarization of the carbon-heteroatom bond (halogen derivatives, alcohols). Easily and difficultly leaving groups: the connection between the ease of leaving a group and its structure. Influence of the solvent, electronic and spatial factors on the reactivity of compounds in the reactions of mono- and bimolecular nucleophilic substitution (SN1 and SN2). Stereochemistry of nucleophilic substitution reactions.

Hydrolysis reactions of halogen derivatives. Alkylation reactions of alcohols, phenols, thiols, sulfides, ammonia, amines. The role of acid catalysis in the nucleophilic substitution of the hydroxyl group. Halogen derivatives, alcohols, esters of sulfuric and phosphoric acids as alkylating agents. The biological role of alkylation reactions.

Mono - and bimolecular elimination reactions (E1 and E2): (dehydration, dehydrohalogenation). Increased CH-acidity as a cause of elimination reactions accompanying nucleophilic substitution at the sp3-hybridized carbon atom.

Competency requirements:

· Know the factors that determine the nucleophilicity of reagents, the structure of the most important nucleophilic particles.

· Know the general patterns of nucleophilic substitution reactions at a saturated carbon atom, the influence of static and dynamic factors on the reactivity of a substance in a nucleophilic substitution reaction.

· Know the mechanisms of mono- and bimolecular nucleophilic substitution, be able to evaluate the influence of steric factors, the influence of solvents, the influence of static and dynamic factors on the reaction by one of the mechanisms.

· Know the mechanisms of mono- and bimolecular elimination, the reasons for the competition between the reactions of nucleophilic substitution and elimination.

· Know Zaitsev's rule and be able to determine the main product in the reactions of dehydration and dehydrohalogenation of unsymmetrical alcohols and haloalkanes.

Topic 5. Reactions of nucleophilic addition and substitution at the trigonal carbon atom

Nucleophilic addition reactions: heterolytic reactions involving carbon-oxygen p-bond (aldehydes, ketones). The mechanism of reactions of interaction of carbonyl compounds with nucleophilic reagents (water, alcohols, thiols, amines). The influence of electronic and spatial factors, the role of acid catalysis, the reversibility of nucleophilic addition reactions. Hemiacetals and acetals, their preparation and hydrolysis. The biological role of acetalization reactions. Aldol addition reactions. main catalysis. The structure of the enolate ion.

Reactions of nucleophilic substitution in the series of carboxylic acids. Electronic and spatial structure of the carboxyl group. Reactions of nucleophilic substitution at the sp2-hybridized carbon atom (carboxylic acids and their functional derivatives). Acylating agents (acid halides, anhydrides, carboxylic acids, esters, amides), comparative characteristics of their reactivity. Acylation reactions - the formation of anhydrides, esters, thioethers, amides - and their reverse hydrolysis reactions. Acetyl coenzyme A is a natural macroergic acylating agent. The biological role of acylation reactions. The concept of nucleophilic substitution at phosphorus atoms, phosphorylation reactions.

Oxidation and reduction reactions of organic compounds. Specificity of redox reactions of organic compounds. The concept of one-electron transfer, hydride ion transfer and the action of the NAD + ↔ NADH system. Oxidation reactions of alcohols, phenols, sulfides, carbonyl compounds, amines, thiols. Recovery reactions of carbonyl compounds, disulfides. The role of redox reactions in life processes.

Competency requirements:

· Know the electronic and spatial structure of the carbonyl group, the influence of electronic and steric factors on the reactivity of the oxo group in aldehydes and ketones.

· Know the mechanism of reactions of nucleophilic addition of water, alcohols, amines, thiols to aldehydes and ketones, the role of a catalyst.

· Know the mechanism of aldol condensation reactions, the factors that determine the participation of the compound in this reaction.

· Know the mechanism of reduction reactions of oxo compounds with metal hydrides.

· Know the reaction centers available in the molecules of carboxylic acids. To be able to carry out a comparative assessment of the strength of carboxylic acids depending on the structure of the radical.

· Know the electronic and spatial structure of the carboxyl group, be able to conduct a comparative assessment of the ability of the carbon atom of the oxo group in carboxylic acids and their functional derivatives (acid halides, anhydrides, esters, amides, salts) to undergo nucleophilic attack.

· Know the mechanism of nucleophilic substitution reactions using examples of acylation, esterification, hydrolysis of esters, anhydrides, acid halides, amides.

Topic 6. Lipids, classification, structure, properties

Lipids are saponifiable and unsaponifiable. neutral lipids. Natural fats as a mixture of triacylglycerols. The main natural higher fatty acids that make up lipids are: palmitic, stearic, oleic, linoleic, linolenic. Arachidonic acid. Features of unsaturated fatty acids, w-nomenclature.

Peroxide oxidation of unsaturated fatty acid fragments in cell membranes. The role of lipid peroxidation of membranes in the action of low doses of radiation on the body. Antioxidant defense systems.

Phospholipids. Phosphatic acids. Phosphatidylcolamines and phosphatidylserines (cephalins), phosphatidylcholines (lecithins) are structural components of cell membranes. lipid bilayer. Sphingolipids, ceramides, sphingomyelins. Brain glycolipids (cerebrosides, gangliosides).

Competency requirements:

Know the classification of lipids, their structure.

· Know the structure of the structural components of saponifiable lipids - alcohols and higher fatty acids.

· To know the mechanism of reactions of formation and hydrolysis of simple and complex lipids.

· Know and be able to carry out qualitative reactions to unsaturated fatty acids and oils.

· Know the classification of unsaponifiable lipids, have an idea about the principles of classification of terpenes and steroids, their biological role.

· Know the biological role of lipids, their main functions, have an idea about the main stages of lipid peroxidation and the consequences of this process for the cell.

Section 2. Stereoisomerism of organic molecules. Poly - and heterofunctional compounds involved in vital processes

Topic 7. Stereoisomerism of organic molecules

Stereoisomerism in a series of compounds with a double bond (p-diastereomerism). Cis - and trans-isomerism of unsaturated compounds. E, Z are the notation for p-diastereomers. Comparative stability of p-diastereomers.

chiral molecules. Asymmetric carbon atom as a center of chirality. Stereoisomerism of molecules with one center of chirality (enantiomerism). optical activity. Fisher projection formulas. Glyceraldehyde as a configuration standard, absolute and relative configuration. D, L-system of stereochemical nomenclature. R, S-system of stereochemical nomenclature. Racemic mixtures and methods for their separation.

Stereoisomerism of molecules with two or more centers of chirality. Enantiomers, diastereomers, mesoforms.

Competency requirements:

· Know the causes of stereoisomerism in the series of alkenes and diene hydrocarbons.

· To be able to determine the possibility of the existence of p-diastereomers by the abbreviated structural formula of an unsaturated compound, to distinguish between cis-trans-isomers, to evaluate their comparative stability.

· Know the symmetry elements of molecules, the necessary conditions for the occurrence of chirality in an organic molecule.

· Know and be able to depict enantiomers using Fisher projection formulas, calculate the number of expected stereoisomers based on the number of chiral centers in a molecule, the principles for determining the absolute and relative configuration, D - , L-system of stereochemical nomenclature.

· Know the ways of separating racemates, the basic principles of the R, S-system of stereochemical nomenclature.

Topic 8. Physiologically active poly- and heterofunctional compounds of aliphatic, aromatic and heterocyclic series

Poly- and heterofunctionality as one of the characteristic features of organic compounds involved in vital processes and being the founders of the most important groups of drugs. Features in the mutual influence of functional groups depending on their relative location.

Polyhydric alcohols: ethylene glycol, glycerin. Esters of polyhydric alcohols with inorganic acids (nitroglycerin, glycerol phosphates). Dihydric phenols: hydroquinone. Oxidation of diatomic phenols. Hydroquinone-quinone system. Phenols as antioxidants (free radical scavengers). Tocopherols.

Dibasic carboxylic acids: oxalic, malonic, succinic, glutaric, fumaric. The conversion of succinic acid to fumaric acid as an example of a biologically important dehydrogenation reaction. Decarboxylation reactions, their biological role.

Amino alcohols: aminoethanol (colamine), choline, acetylcholine. The role of acetylcholine in the chemical transmission of nerve impulses in synapses. Aminophenols: dopamine, norepinephrine, epinephrine. The concept of the biological role of these compounds and their derivatives. Neurotoxic effects of 6-hydroxydopamine and amphetamines.

Hydroxy and amino acids. Cyclization reactions: the influence of various factors on the process of cycle formation (implementation of the corresponding conformations, the size of the resulting cycle, the entropy factor). Lactones. lactams. Hydrolysis of lactones and lactams. Elimination reaction of b-hydroxy and amino acids.

Aldegido - and keto acids: pyruvic, acetoacetic, oxaloacetic, a-ketoglutaric. Acid properties and reactivity. Reactions of decarboxylation of b-keto acids and oxidative decarboxylation of a-keto acids. Acetoacetic ester, keto-enol tautomerism. Representatives of "ketone bodies" - b-hydroxybutyric, b-ketobutyric acids, acetone, their biological and diagnostic significance.

Heterofunctional derivatives of the benzene series as drugs. Salicylic acid and its derivatives (acetylsalicylic acid).

Para-aminobenzoic acid and its derivatives (anesthesin, novocaine). The biological role of p-aminobenzoic acid. Sulfanilic acid and its amide (streptocide).

Heterocycles with several heteroatoms. Pyrazole, imidazole, pyrimidine, purine. Pyrazolone-5 is the basis of non-narcotic analgesics. Barbituric acid and its derivatives. Hydroxypurines (hypoxanthine, xanthine, uric acid), their biological role. Heterocycles with one heteroatom. Pyrrole, indole, pyridine. Biologically important pyridine derivatives are nicotinamide, pyridoxal, isonicotinic acid derivatives. Nicotinamide is a structural component of the NAD+ coenzyme, which determines its participation in OVR.

Competency requirements:

· To be able to classify heterofunctional compounds by composition and by their mutual arrangement.

· Know the specific reactions of amino and hydroxy acids with a, b, g - arrangement of functional groups.

· Know the reactions leading to the formation of biologically active compounds: choline, acetylcholine, adrenaline.

· Know the role of keto-enol tautomerism in the manifestation of the biological activity of keto acids (pyruvic, oxaloacetic, acetoacetic) and heterocyclic compounds (pyrazole, barbituric acid, purine).

· Know the methods of redox transformations of organic compounds, the biological role of redox reactions in the manifestation of the biological activity of diatomic phenols, nicotinamide, the formation of ketone bodies.

Subject9 . Carbohydrates, classification, structure, properties, biological role

Carbohydrates, their classification in relation to hydrolysis. Classification of monosaccharides. Aldoses, ketoses: trioses, tetroses, pentoses, hexoses. Stereoisomerism of monosaccharides. D - and L-series of stereochemical nomenclature. Open and cyclic forms. Fisher formulas and Haworth formulas. Furanoses and pyranoses, a - and b-anomers. Cyclo-oxo-tautomerism. Conformations of pyranose forms of monosaccharides. The structure of the most important representatives of pentoses (ribose, xylose); hexose (glucose, mannose, galactose, fructose); deoxysugars (2-deoxyribose); amino sugars (glucosamine, mannosamine, galactosamine).

Chemical properties of monosaccharides. Reactions of nucleophilic substitution involving an anomeric center. O - and N-glycosides. hydrolysis of glycosides. Phosphates of monosaccharides. Oxidation and reduction of monosaccharides. Reducing properties of aldoses. Glyconic, glycaric, glycuronic acids.

Oligosaccharides. Disaccharides: maltose, cellobiose, lactose, sucrose. Structure, cyclo-oxo-tautomerism. Hydrolysis.

Polysaccharides. General characteristics and classification of polysaccharides. Homo- and heteropolysaccharides. Homopolysaccharides: starch, glycogen, dextrans, cellulose. Primary structure, hydrolysis. The concept of the secondary structure (starch, cellulose).

Competency requirements:

Know the classification of monosaccharides (according to the number of carbon atoms, the composition of functional groups), the structure of open and cyclic forms (furanose, pyranose) of the most important monosaccharides, their ratio of D - and L - series of stereochemical nomenclature, be able to determine the number of possible diastereomers, refer stereoisomers to diastereomers , epimers, anomers.

· To know the mechanism of monosaccharide cyclization reactions, the causes of mutarotation of monosaccharide solutions.

· Know the chemical properties of monosaccharides: redox reactions, reactions of formation and hydrolysis of O - and N-glycosides, esterification reactions, phosphorylation.

· To be able to carry out qualitative reactions on the diol fragment and the presence of the reducing properties of monosaccharides.

· Know the classification of disaccharides and their structure, the configuration of an anomeric carbon atom forming a glycosidic bond, tautomeric transformations of disaccharides, their chemical properties, biological role.

· Know the classification of polysaccharides (in relation to hydrolysis, according to monosaccharide composition), the structure of the most important representatives of homopolysaccharides, the configuration of the anomeric carbon atom that forms a glycosidic bond, their physical and chemical properties, and biological role. Have an understanding of the biological role of heteropolysaccharides.

Topic 10.a- Amino acids, peptides, proteins. Structure, properties, biological role

Structure, nomenclature, classification of a-amino acids that make up proteins and peptides. Stereoisomerism of a-amino acids.

Biosynthetic pathways for the formation of a-amino acids from oxo acids: reductive amination and transamination reactions. Essential amino acids.

Chemical properties of a-amino acids as heterofunctional compounds. Acid-base properties of a-amino acids. Isoelectric point, methods for separation of a-amino acids. Formation of intracomplex salts. Esterification, acylation, alkylation reactions. Interaction with nitrous acid and formaldehyde, the significance of these reactions for the analysis of amino acids.

g-Aminobutyric acid is an inhibitory neurotransmitter of the CNS. Antidepressant action of L-tryptophan, serotonin as a sleep neurotransmitter. Mediator properties of glycine, histamine, aspartic and glutamic acids.

Biologically important reactions of a-amino acids. Deamination and hydroxylation reactions. Decarboxylation of a-amino acids - the way to the formation of biogenic amines and bioregulators (colamine, histamine, tryptamine, serotonin.) Peptides. Electronic structure of the peptide bond. Acid and alkaline hydrolysis of peptides. Establishment of the amino acid composition using modern physical and chemical methods (Sanger and Edman methods). The concept of neuropeptides.

The primary structure of proteins. Partial and complete hydrolysis. The concept of secondary, tertiary and quaternary structures.

Competency requirements:

· Know the structure, stereochemical classification of a-amino acids, belonging to the D- and L-stereochemical series of natural amino acids, essential amino acids.

· Know the ways of synthesis of a-amino acids in vivo and in vitro, know the acid-base properties and methods of transferring a-amino acids to an isoelectric state.

· Know the chemical properties of a-amino acids (reactions on amino - and carboxyl groups), be able to carry out qualitative reactions (xantoprotein, with Сu (OH) 2, ninhydrin).

Know the electronic structure of the peptide bond, the primary, secondary, tertiary and quaternary structure of proteins and peptides, know how to determine the amino acid composition and amino acid sequence (Sanger method, Edman method), be able to carry out the biuret reaction for peptides and proteins.

· Know the principle of the method of synthesis of peptides using the protection and activation of functional groups.

Topic 11. Nucleotides and nucleic acids

Nucleic bases that make up nucleic acids. Pyrimidine (uracil, thymine, cytosine) and purine (adenine, guanine) bases, their aromaticity, tautomeric transformations.

Nucleosides, reactions of their formation. The nature of the connection of the nucleic base with the carbohydrate residue; configuration of the glycosidic center. Hydrolysis of nucleosides.

Nucleotides. The structure of mononucleotides that form nucleic acids. Nomenclature. Hydrolysis of nucleotides.

The primary structure of nucleic acids. Phosphodiester bond. Ribonucleic and deoxyribonucleic acids. Nucleotide composition of RNA and DNA. Hydrolysis of nucleic acids.

The concept of the secondary structure of DNA. The role of hydrogen bonds in the formation of the secondary structure. Complementarity of nucleic bases.

Drugs based on modified nucleic bases (5-fluorouracil, 6-mercaptopurine). The principle of chemical similarity. Changes in the structure of nucleic acids under the influence of chemicals and radiation. Mutagenic action of nitrous acid.

Nucleoside polyphosphates (ADP, ATP), features of their structure, allowing them to perform the functions of macroergic compounds and intracellular bioregulators. The structure of cAMP - an intracellular "intermediary" of hormones.

Competency requirements:

· Know the structure of pyrimidine and purine nitrogenous bases, their tautomeric transformations.

· To know the mechanism of reactions of formation of N-glycosides (nucleosides) and their hydrolysis, the nomenclature of nucleosides.

· Know the fundamental similarities and differences between natural and synthetic nucleosides-antibiotics in comparison with nucleosides that are part of DNA and RNA.

· Know the reactions of formation of nucleotides, the structure of mononucleotides that make up nucleic acids, their nomenclature.

· Know the structure of nucleoside cyclo- and polyphosphates, their biological role.

· Know the nucleotide composition of DNA and RNA, the role of the phosphodiester bond in creating the primary structure of nucleic acids.

· Know the role of hydrogen bonds in the formation of the secondary structure of DNA, the complementarity of nitrogenous bases, the role of complementary interactions in the implementation of the biological function of DNA.

Know the factors that cause mutations, and the principle of their action.

Information part

Bibliography

Main:

1. Romanovsky, bioorganic chemistry: a textbook in 2 parts /. - Minsk: BSMU, 20s.

2. Romanovsky, to the workshop on bioorganic chemistry: textbook / edited. - Minsk: BSMU, 1999. - 132 p.

3. Tyukavkina, N. A., Bioorganic chemistry: textbook /,. - Moscow: Medicine, 1991. - 528 p.

Additional:

4. Ovchinnikov, chemistry: monograph / .

- Moscow: Education, 1987. - 815 p.

5. Potapov,: textbook /. - Moscow:

Chemistry, 1988. - 464 p.

6. Riles, A. Fundamentals of organic chemistry: textbook / A. Rice, K. Smith,

R. Ward. - Moscow: Mir, 1989. - 352 p.

7. Taylor, G. Fundamentals of organic chemistry: textbook / G. Taylor. -

Moscow: Mirs.

8. Terney, A. Modern organic chemistry: textbook in 2 volumes /

A. Terney. - Moscow: Mir, 1981. - 1310 p.

9. Tyukavkina, for laboratory studies on bioorganic

chemistry: textbook / [and others]; edited by N. A.

Tyukavkina. - Moscow: Medicine, 1985. - 256 p.

10. Tyukavkina, N. A., Bioorganic chemistry: A textbook for students

medical institutes / , . - Moscow.

Hello! Many students of medical universities are now studying bioorganic chemistry, also known as BOC.

In some universities, this subject ends with a test, in others - with an exam. Sometimes it happens that the test in one university is comparable in complexity to the exam in another.

At my university, bioorganic chemistry was just an exam during the summer session at the very end of the first year. I must say that BOH is one of those subjects that at first terrify and can inspire the thought - "it's impossible to pass." This is especially true, of course, for people with a weak base of organic chemistry (and, oddly enough, there are quite a lot of such people at medical universities).

Programs for studying bioorganic chemistry at different universities can vary greatly, and teaching methods even more so.

However, the requirements for students are approximately the same everywhere. To put it very simply, in order to pass bioorganic chemistry at 5, you must know the names, properties, structural features and typical reactions of a number of organic substances.

Our teacher, a respected professor, presented the material as if every student was the best in school in organic chemistry (and bioorganic chemistry is essentially a complicated course in school organic chemistry). He was probably right in his approach, everyone should reach up and try to be the best. However, this led to the fact that some students, who did not partially understand the material in the first 2-3 classes, stopped understanding everything at all towards the middle of the semester.

I decided to write this material in large part because I was just such a student. At school, I was very fond of inorganic chemistry, but I always did not work out with organic chemistry. Even when I was preparing for the Unified State Examination, I chose the strategy of strengthening all my knowledge of inorganics, while at the same time fixing only the base of organics. By the way, it almost turned out sideways for me in terms of introductory points, but that's another story.

It was not in vain that I said about the teaching methodology, because ours was also very unusual. We were immediately, almost in the first class, shown the manuals according to which we had to take tests and then the exam.

Bioorganic chemistry - tests and exam

The entire course was divided into 4 major topics, each of which ended with a test lesson. We already had questions for each of the four tests from the first couples. They, of course, frightened, but at the same time they served as a kind of map on which to move.

The first test was quite elementary. It was devoted mainly to the nomenclature, trivial (household) and international names, and, of course, the classification of substances. Also, in one form or another, the signs of aromaticity were affected.

The second test after the first seemed much more difficult. There it was necessary to describe the properties and reactions of substances such as ketones, aldehydes, alcohols, carboxylic acids. For example, one of the most typical reactions of aldehydes is the silver mirror reaction. Quite a beautiful sight. If you add Tollens’ reagent, that is, OH, to any aldehyde, then on the wall of the test tube you will see a precipitate resembling a mirror, this is what it looks like:

The third standings against the background of the second did not seem so formidable. Everyone is already used to writing reactions and memorizing properties by classifications. In the third standings, it was about compounds with two functional groups - aminophenols, aminoalcohols, oxoacids and others. Each ticket also contained at least one carb ticket.

The fourth test in bioorganic chemistry was almost entirely devoted to proteins, amino acids and peptide bonds. A special highlight were questions that required the collection of RNA and DNA.

By the way, this is what an amino acid looks like - you can see the amino group (it's tinted yellow in this picture) and the carboxylic acid group (it's lilac). It was with substances of this class that I had to deal with in the fourth standings.

Each test was handed over at the blackboard - the student must, without prompting, write down and explain all the necessary properties in the form of reactions. For example, if you pass the second test, you have the properties of alcohols on your ticket. The teacher tells you - take propanol. You write the formula for propanol and 4-5 typical reactions to illustrate its properties. Could be exotic, like sulfur-containing compounds. An error even in the index of one reaction product often sent me to study this material further until the next attempt (which was in a week). Scary? Harsh? Certainly!

However, this approach has a very pleasant side effect. It was hard during regular seminars. Many passed tests 5-6 times. But on the other hand, the exam was very easy, because each ticket contained 4 questions. Namely, one of each already learned and solved test.

Therefore, I will not even describe the intricacies of preparing for the exam in bioorganic chemistry. In our case, all the preparation came down to how we prepared for the tests themselves. I confidently passed each of the four tests - before the exam, just look at your own drafts, write down the most basic reactions and everything will be restored right away. The fact is that organic chemistry is a very logical science. You need to memorize not huge strings of reactions, but the mechanisms themselves.

Yes, I note that this does not work with all items. Terrible anatomy cannot be passed simply by reading your notes the day before. A number of other items also have their own characteristics. Even if bioorganic chemistry is taught differently at your medical university, you may need to adjust your training and implement it a little differently than I did. In any case, good luck to you, understand and love science!

Bioorganic chemistry is a fundamental science that studies the structure and biological functions of the most important components of living matter, primarily biopolymers and low molecular weight bioregulators, focusing on elucidating the patterns of the relationship between the structure of compounds and their biological action.

Bioorganic chemistry is a science at the intersection of chemistry and biology, it contributes to the disclosure of the principles of the functioning of living systems. Bioorganic chemistry has a pronounced practical orientation, being the theoretical basis for obtaining new valuable compounds for medicine, agriculture, chemical, food and microbiological industries. The range of interests of bioorganic chemistry is unusually wide - this is the world of substances isolated from wildlife and playing an important role in life, and the world of artificially obtained organic compounds with biological activity. Bioorganic chemistry covers the chemistry of all substances of a living cell, tens and hundreds of thousands of compounds.

Objects of study, research methods and main tasks of bioorganic chemistry

Objects of study bioorganic chemistry are proteins and peptides, carbohydrates, lipids, mixed-type biopolymers - glycoproteins, nucleoproteins, lipoproteins, glycolipids, etc., alkaloids, terpenoids, vitamins, antibiotics, hormones, prostaglandins, pheromones, toxins, as well as synthetic regulators of biological processes : drugs, pesticides, etc.

The main arsenal of research methods bioorganic chemistry make up methods; physical, physicochemical, mathematical and biological methods are used to solve structural problems.

Main tasks bioorganic chemistry are:

• Isolation in an individual state and purification of the studied compounds using crystallization, distillation, various types of chromatography, electrophoresis, ultrafiltration, ultracentrifugation, etc. its influence on a certain physiological process, etc.);
• Establishment of the structure, including the spatial structure, based on the approaches of organic chemistry (hydrolysis, oxidative cleavage, cleavage at specific fragments, for example, at methionine residues when establishing the structure of peptides and proteins, cleavage at 1,2-diol groups of carbohydrates, etc.) and physico - chemical chemistry using mass spectrometry, various types of optical spectroscopy (IR, UV, laser, etc.), X-ray diffraction analysis, nuclear magnetic resonance, electron paramagnetic resonance, optical rotation dispersion and circular dichroism, fast kinetic methods, etc. in combination with computer calculations. To quickly solve standard problems associated with establishing the structure of a number of biopolymers, automatic devices have been created and are widely used, the principle of operation of which is based on standard reactions and the properties of natural and biologically active compounds. These are analyzers for determining the quantitative amino acid composition of peptides, sequencers for confirming or establishing the sequence of amino acid residues in peptides and the nucleotide sequence in nucleic acids, etc. The use of enzymes that specifically cleave the studied compounds according to strictly defined bonds is important in studying the structure of complex biopolymers. Such enzymes are used in the study of the structure of proteins (trypsin, proteinases that cleave peptide bonds at glutamic acid, proline and other amino acid residues), nucleic acids and polynucleotides (nucleases, restriction enzymes), carbohydrate-containing polymers (glycosidases, including specific ones - galactosidases , glucuronidase, etc.). To increase the effectiveness of research, not only natural compounds are subjected to analysis, but also their derivatives containing characteristic, specially introduced groups and labeled atoms. Such derivatives are obtained, for example, by growing the producer on a medium containing labeled amino acids or other radioactive precursors, which include tritium, radioactive carbon or phosphorus. The reliability of the data obtained in the study of complex proteins increases significantly if this study is carried out in combination with the study of the structure of the corresponding genes.
• Chemical synthesis and chemical modification of the studied compounds, including total synthesis, synthesis of analogues and derivatives. For low molecular weight compounds, an important criterion for the correctness of the established structure is still the counter synthesis. The development of methods for the synthesis of natural and biologically active compounds is necessary to solve the next important problem of bioorganic chemistry - to elucidate the relationship between their structure and biological function.
• Elucidation of the relationship between the structure and biological functions of biopolymers and low molecular weight bioregulators; study of the chemical mechanisms of their biological action. This aspect of bioorganic chemistry is gaining more and more practical importance. Improvement in the arsenal of methods for the chemical and chemical-enzymatic synthesis of complex biopolymers (biologically active peptides, proteins, polynucleotides, nucleic acids, including actively functioning genes), in conjunction with the ever-improving technique for the synthesis of relatively simpler bioregulators, as well as methods for the selective cleavage of biopolymers, allow ever deeper understand the dependence of biological action on the structure of compounds. The use of highly efficient computer technology makes it possible to objectively compare numerous data from different researchers and find common patterns. The found particular and general patterns, in turn, stimulate and facilitate the synthesis of new compounds, which in some cases (for example, in the study of peptides that affect brain activity) makes it possible to find practically important synthetic compounds that are superior in biological activity to their natural counterparts. The study of the chemical mechanisms of biological action opens up the possibility of creating biologically active compounds with predetermined properties.
• Obtaining practically valuable drugs.
• Biological testing of the obtained compounds.

Formation of bioorganic chemistry. Historical reference

The formation of bioorganic chemistry in the world took place in the late 50s - early 60s, when the main objects of research in this area were four classes of organic compounds that play a key role in the life of the cell and organism - proteins, polysaccharides and lipids. Outstanding achievements of traditional chemistry of natural compounds, such as the discovery by L. Pauling of the α-helix as one of the main elements of the spatial structure of the polypeptide chain in proteins, the establishment by A. Todd of the chemical structure of nucleotides and the first synthesis of dinucleotide, the development by F. Senger of a method for determining the amino acid sequence in proteins and deciphering the structure of insulin with its help, the synthesis by R. Woodward of such complex natural compounds as reserpine, chlorophyll and vitamin B 12, the synthesis of the first peptide hormone oxytocin, marked, in essence, the transformation of the chemistry of natural compounds into modern bioorganic chemistry.

However, in our country, interest in proteins and nucleic acids arose much earlier. The first studies on the chemistry of protein and nucleic acids were started in the mid-1920s. within the walls of Moscow University, and it was here that the first scientific schools were formed, successfully working in these important areas of natural science to this day. So, in the 20s. on the initiative of N.D. Zelinsky began systematic research on protein chemistry, the main task of which was to elucidate the general principles of the structure of protein molecules. N.D. Zelinsky created the first protein chemistry laboratory in our country, in which important work was carried out on the synthesis and structural analysis of amino acids and peptides. An outstanding role in the development of these works belongs to M.M. Botvinnik and her students, who achieved impressive results in studying the structure and mechanism of action of inorganic pyrophosphatases, the key enzymes of phosphorus metabolism in the cell. By the end of the 1940s, when the leading role of nucleic acids in genetic processes began to emerge, M.A. Prokofiev and Z.A. Shabarova began work on the synthesis of nucleic acid components and their derivatives, thus laying the foundation for the chemistry of nucleic acids in our country. The first syntheses of nucleosides, nucleotides and oligonucleotides were carried out, a great contribution was made to the creation of domestic automatic nucleic acid synthesizers.

In the 60s. this direction in our country has been developing consistently and rapidly, often ahead of similar steps and trends abroad. The fundamental discoveries of A.N. Belozersky, who proved the existence of DNA in higher plants and systematically studied the chemical composition of nucleic acids, the classical studies of V.A. Engelhardt and V.A. Belitser on the oxidative mechanism of phosphorylation, the world-famous studies of A.E. Arbuzov on the chemistry of physiologically active organophosphorus compounds, as well as the fundamental work of I.N. Nazarova and N.A. Preobrazhensky on the synthesis of various natural substances and their analogues, and other works. The greatest achievements in the creation and development of bioorganic chemistry in the USSR belong to Academician M.M. Shemyakin. He, in particular, began work on the study of atypical peptides - depsipeptides, which subsequently received wide development in connection with their function as ionophores. The talent, perspicacity and vigorous activity of this and other scientists contributed to the rapid growth of the international prestige of Soviet bioorganic chemistry, its consolidation in the most relevant areas and organizational strengthening in our country.

In the late 60s - early 70s. in the synthesis of biologically active compounds of complex structure, enzymes began to be used as catalysts (the so-called combined chemical-enzymatic synthesis). This approach was used by G. Korana for the first gene synthesis. The use of enzymes made it possible to carry out a strictly selective transformation of a number of natural compounds and obtain new biologically active derivatives of peptides, oligosaccharides, and nucleic acids in high yield. In the 70s. such branches of bioorganic chemistry as the synthesis of oligonucleotides and genes, the study of cell membranes and polysaccharides, and the analysis of the primary and spatial structures of proteins developed most intensively. The structures of important enzymes (transaminase, β-galactosidase, DNA-dependent RNA polymerase), protective proteins (γ-globulins, interferons), and membrane proteins (adenosine triphosphatases, bacteriorhodopsin) were studied. Works on the study of the structure and mechanism of action of peptides - regulators of nervous activity (the so-called neuropeptides) have acquired great importance.

Modern domestic bioorganic chemistry

Currently, domestic bioorganic chemistry occupies a leading position in the world in a number of key areas. Major advances have been made in the study of the structure and function of biologically active peptides and complex proteins, including hormones, antibiotics, and neurotoxins. Important results have been obtained in the chemistry of membrane-active peptides. The reasons for the unique selectivity and effectiveness of the action of dyspepside ionophores were investigated and the mechanism of functioning in living systems was elucidated. Synthetic analogs of ionophores with desired properties have been obtained, which are many times more effective than natural samples (V.T. Ivanov, Yu.A. Ovchinnikov). The unique properties of ionophores are used to create ion-selective sensors based on them, which are widely used in technology. The successes achieved in the study of another group of regulators - neurotoxins, which are inhibitors of the transmission of nerve impulses, have led to their widespread use as tools for studying membrane receptors and other specific structures of cell membranes (EV Grishin). The development of work on the synthesis and study of peptide hormones has led to the creation of highly effective analogues of the hormones oxytocin, angiotensin II and bradykinin, which are responsible for smooth muscle contraction and blood pressure regulation. A major success was the complete chemical synthesis of insulin preparations, including human insulin (N.A. Yudaev, Yu.P. Shvachkin and others). A number of protein antibiotics were discovered and studied, including gramicidin S, polymyxin M, actinoxanthin (G.F. Gause, A.S. Khokhlov, and others). Work is being actively developed to study the structure and function of membrane proteins that perform receptor and transport functions. The photoreceptor proteins rhodopsin and bacteriorhodopsin were obtained and the physicochemical foundations of their functioning as light-dependent ion pumps were studied (V.P. Skulachev, Yu.A. Ovchinnikov, M.A. Ostrovsky). The structure and mechanism of functioning of ribosomes, the main systems of protein biosynthesis in the cell, are widely studied (A.S. Spirin, A.A. Bogdanov). Large cycles of research are associated with the study of enzymes, the determination of their primary structure and spatial structure, the study of catalytic functions (aspartate aminotransferases, pepsin, chymotrypsin, ribonucleases, phosphorus metabolism enzymes, glycosidases, cholinesterases, etc.). Methods for the synthesis and chemical modification of nucleic acids and their components have been developed (D.G. Knorre, M.N. Kolosov, Z.A. Shabarova), approaches are being developed to create new generation drugs based on them for the treatment of viral, oncological and autoimmune diseases. Using the unique properties of nucleic acids and based on them, diagnostic preparations and biosensors, analyzers of a number of biologically active compounds are created (V.A. Vlasov, Yu.M. Evdokimov, etc.)

Significant progress has been made in the synthetic chemistry of carbohydrates (the synthesis of bacterial antigens and the creation of artificial vaccines, the synthesis of specific inhibitors of virus sorption on the cell surface, the synthesis of specific inhibitors of bacterial toxins (N.K. Kochetkov, A.Ya. Khorlin)). Significant progress has been made in the study of lipids, lipoamino acids, lipopeptides and lipoproteins (LD Bergelson, NM Sisakyan). Methods for the synthesis of many biologically active fatty acids, lipids and phospholipids have been developed. The transmembrane distribution of lipids in various types of liposomes, in bacterial membranes and in liver microsomes was studied.

An important area of ​​bioorganic chemistry is the study of various natural and synthetic substances capable of regulating various processes occurring in living cells. These are repellents, antibiotics, pheromones, signal substances, enzymes, hormones, vitamins and others (the so-called low molecular weight regulators). Methods have been developed for the synthesis and production of almost all known vitamins, a significant part of steroid hormones and antibiotics. Industrial methods have been developed for obtaining a number of coenzymes used as therapeutic drugs (coenzyme Q, pyridoxal phosphate, thiamine pyrophosphate, etc.). New strong anabolics have been proposed that are superior in action to known foreign drugs (I.V. Torgov, S.N. Ananchenko). The biogenesis and mechanisms of action of natural and transformed steroids have been studied. Significant progress has been made in the study of alkaloids, steroid and triterpene glycosides, and coumarins. Original studies were carried out in the field of pesticide chemistry, which led to the release of a number of valuable drugs (IN Kabachnik, N.N. Melnikov, etc.). There is an active search for new drugs needed for the treatment of various diseases. Preparations have been obtained that have proven their effectiveness in the treatment of a number of oncological diseases (dopan, sarcolysin, ftorafur, etc.).

Priority directions and prospects for the development of bioorganic chemistry

The priority areas of scientific research in the field of bioorganic chemistry are:

• study of the structural and functional dependence of biologically active compounds;
• design and synthesis of new biologically active drugs, including the creation of medicines and plant protection products;
• research of highly efficient biotechnological processes;
• study of the molecular mechanisms of processes occurring in a living organism.

Oriented basic research in the field of bioorganic chemistry is aimed at studying the structure and function of the most important biopolymers and low molecular weight bioregulators, including proteins, nucleic acids, carbohydrates, lipids, alkaloids, prostaglandins and other compounds. Bioorganic chemistry is closely related to the practical problems of medicine and agriculture (obtaining vitamins, hormones, antibiotics and other medicines, plant growth stimulants and animal and insect behavior regulators), chemical, food and microbiological industries. The results of scientific research are the basis for creating a scientific and technical base for technologies for the production of modern medical immunodiagnostics, reagents for medical genetic research and reagents for biochemical analysis, technologies for the synthesis of drug substances for use in oncology, virology, endocrinology, gastroenterology, as well as chemicals plant protection and technologies for their application to agriculture.

The solution of the main problems of bioorganic chemistry is important for the further progress of biology, chemistry and a number of technical sciences. Without elucidating the structure and properties of the most important biopolymers and bioregulators, it is impossible to know the essence of life processes, and even more so to find ways to control such complex phenomena as reproduction and transmission of hereditary traits, normal and malignant cell growth, immunity, memory, transmission of nerve impulses, and much more. At the same time, the study of highly specialized biologically active substances and the processes occurring with their participation can open up fundamentally new opportunities for the development of chemistry, chemical technology and technology. The problems, the solution of which is associated with research in the field of bioorganic chemistry, include the creation of strictly specific highly active catalysts (based on the study of the structure and mechanism of action of enzymes), the direct conversion of chemical energy into mechanical energy (based on the study of muscle contraction), the use of chemical storage principles in technology and transmission of information carried out in biological systems, the principles of self-regulation of multicomponent cell systems, primarily the selective permeability of biological membranes, and much more. points for the development of biochemical research, already related to the field of molecular biology. The breadth and importance of the problems to be solved, the variety of methods and close connection with other scientific disciplines ensure the rapid development of bioorganic chemistry. Bulletin of the Moscow University, series 2, Chemistry. 1999. V. 40. No. 5. S. 327-329.

Bender M, Bergeron R, Komiyama M. Bioorganic Chemistry of Enzymatic Catalysis. Per. from English. M.: Mir, 1987. 352 S.

Yakovishin L.A. Selected Chapters in Bioorganic Chemistry. Sevastopol: Strizhak-press, 2006. 196 p.

Nikolaev A.Ya. Biological Chemistry. M.: Medical Information Agency, 2001. 496 p.