Chirality of the right and left hand. Chirality and optical activity. Chirality in inorganic chemistry

Deputy A

Deputy A

Fig.17

Rice. eighteen

A similar case of dissection of a cyclic substituent is illustrated by the example of the compound in Fig. 18 where structure IN illustrates the interpretation of the cyclohexyl ring (in the structure BUT). In this case, the correct sequence of precedence is di- n-gesylmethyl > cyclohexyl > di- n-pentylmethyl > H.

Now we are sufficiently prepared to consider such a substituent as phenyl (Fig. 19 structure BUT). We discussed the scheme for opening each multiple bond above. Since (in any Kekule structure) each of the six carbon atoms is double-bonded to another carbon atom, then (in the CIA system) each carbon atom of the ring carries an additional carbon as a "substituent". The ring supplemented in this way (Fig. 19, structure IN) is then expanded according to the rules for cyclic systems. As a result, the dissection is described by the diagram shown in Fig. 19, the structure FROM.

Rice. 19

6. Now we will consider chiral compounds in which the differences between the substituents are not of a material or constitutional nature, but are reduced to differences in configuration. Compounds containing more than one chiral center will be discussed below (see section 1.4) Here we will also touch on substituents that differ cis-trans– isomerism (olefin type). According to Prelog and Helmchen, the olefin ligand in which the senior substituent is located on the same side from the double bond of the olefin, which is the chiral center, has an advantage over the ligand in which the senior substituent is in trance-position to the chiral center. This position has nothing to do with classical cis-trans-, nor to E-Z - nomenclature for double bond configuration. Examples are shown in Figure 20.

Rice. twenty

Compounds with multiple chiral centers

If there are two chiral centers in a molecule, then since each center can have (R)- or ( S)-configuration, the existence of four isomers is possible - RR, SS, RS And SR:

Rice. 21

Since the molecule has only one mirror image, the enantiomer of the compound (RR) can only be an isomer (SS). Similarly, another pair of enantiomers form isomers (RS) And (SR). If the configuration of only one asymmetric center changes, then such isomers are called diastereomers. Diastereomers are stereoisomers that are not enantiomers. So, diastereomeric pairs (RR)/(RS), (RR)/(SR), (SS)/(RS) And (SS)/(SR). Although in the general case, the combination of two chiral centers produces four isomers, the combination of centers of the same chemical structure gives only three isomers: (RR) And (SS), which are enantiomers, and (RS), diastereomeric to both enantiomers (RR) And (SS). A typical example is tartaric acid (Fig. 22), which has only three isomers: a pair of enantiomers and meso form.

Rice. 22

Meso-Vinnaya acid is (R, S)-isomer, which is optically inactive, since the union of two mirror-symmetric fragments leads to the appearance of a symmetry plane (a). Meso-Vinnaya an acid is an example of an achiral meso-configuration compound, which is built from an equal number of chiral elements identical in structure but different in absolute configuration.

If the molecule has P chiral centers, the maximum number of stereoisomers can be calculated using formula 2 n; however, sometimes the number of isomers will be less due to the presence of meso forms.

For the names of stereoisomers of molecules containing two asymmetric carbon atoms, two substituents for each of which are the same, and the third are different, prefixes are often used erythro- And treo- from the names of sugars erythrose and threose. These prefixes characterize the system as a whole, and not each chiral center separately. When depicting such compounds using Fischer projections in a pair erythro- isomers, the same groups are located on the same side, and if the different groups (C1 and Br in the example below) were the same, a meso form would be obtained. Paired with treo- isomers, the same groups are located on different sides, and if the different groups were the same, the new pair would remain an enantiomeric pair.

Rice. 23

All examples of compounds considered above have a center of chirality. Such a center is an asymmetric carbon atom. However, other atoms (silicon, phosphorus, sulfur) can also be the center of chirality, as, for example, in methylnaphthylphenylsilane, o-anisylmethylphenylphosphine, methyl-p-tolyl sulfoxide (Fig. 24)

Rice. 24

Chirality of molecules devoid of chiral centers

A necessary and sufficient condition for the chirality of a molecule is its incompatibility with its mirror image. The presence of a single (configurationally stable) chiral center in a molecule is a sufficient, but by no means necessary, condition for the existence of chirality. Consider chiral molecules lacking chiral centers. Some examples are shown in figures 25 and 26.

Rice. 25

Rice. 26

These are compounds with axes of chirality ( axial chirality type): allenes; alkylidenecycloalkanes; spiranes; the so-called atropisomers (biphenyls and similar compounds whose chirality arises due to hindered rotation around a single bond). Another element of chirality is the chirality plane ( planar chirality type). Examples of such compounds are ansa compounds (in which the alicyclic ring is too small for the aromatic ring to pass through); paracyclophanes; metallocenes. Finally, the chirality of a molecule can be related to the helical organization of the molecular structure. The molecule can wrap either in the left or in the right helix. In this case, one speaks of helicity (helical type of chirality).

In order to determine the configuration of a molecule that has axis of chirality, it is necessary to introduce an additional clause in the sequence rule: the groups closest to the observer are considered older than the groups remote from the observer. This addition must be made, since for molecules with axial chirality, the presence of identical substituents at opposite ends of the axis is permissible. Applying this rule to the molecules shown in Fig. 25 shown in fig. 27.

Rice. 27

In all cases, the molecules are considered along the chiral axis on the left. In this case, it should be understood that if the molecules are considered from the right, then the configuration descriptor will remain the same. Thus, the spatial arrangement of the four support groups corresponds to the vertices of the virtual tetrahedron and can be represented using the corresponding projections (Fig. 27). To determine the appropriate descriptor, we use the standard rules R, S- nomenclature. In the case of biphenyls, it is important to note that ring substituents are considered from the center (through which the chirality axis passes) to the periphery, in violation of standard sequence rules. Thus, for biphenyl in Fig. 25 correct sequence of substituents in the right ring C-OCH 3 >C-H; the chlorine atom is too far away to be taken into account. The reference atoms (those by which the configuration symbol is determined) are the same when the molecule is viewed from the right. Sometimes descriptors are used to distinguish axial chirality from other types. aR And aS (or R a And S a), but the use of the prefix " a' is not mandatory.

Alternatively, molecules with axes of chirality can be thought of as helical, and their configuration can be denoted by the symbols R And M. In this case, to determine the configuration, only substituents with the highest priority are considered both in the front and back (remote from the observer) parts of the structure (substituents 1 and 3 in Fig. 27). If the transition from the highest priority front substituent 1 to the priority rear substituent 3 is clockwise, then this is the configuration R; if counterclockwise, is the configuration M.

On fig. 26 shows molecules with chirality planes. It is not so easy to give a definition of the plane of chirality, and it is not as unambiguous as the definition of the center and axis of chirality. This is a plane that contains as many atoms of a molecule as possible, but not all. In fact, chirality is because (and only because) that at least one substituent (often more) does not lie in the chirality plane. Thus, the chiral plane of the ansa compound BUT is the plane of the benzene ring. In paracyclophane IN the most substituted (lower) ring is considered as the chiral plane. In order to determine the descriptor for planar-chiral molecules, the plane is viewed from the side of the atom closest to the plane, but not lying in this plane (if there are two or more candidates, then the one closest to the atom with the highest priority is chosen according to the rules of sequence ). This atom, sometimes called a test or pilot atom, is marked with an arrow in Fig. 26. Then, if three consecutive atoms (a, b, c) with the highest priority form a broken line in the chiral plane, curving clockwise, then the compound configuration pR (or R p), and if the polyline curves counterclockwise, then the configuration descriptor PS(or S p). Planar chirality, like axial chirality, can alternatively be viewed as a kind of chirality. In order to determine the direction (configuration) of the helix, one must consider the pilot atom together with the atoms a,b, and c, as defined above. From here it is clear that pR- connections corresponds R-, but PS- connections - M– helicity.

Stereoisomers, their types

Definition 1

Stereoisomers are substances in which the atoms are related to each other in the same way, but their arrangement in space is different.

Stereoisomers are divided into:

• Enantiomers (optical isomers). They have the same physical and chemical properties (density, boiling and melting points, solubility, spectral properties) in an achiral environment, but different optical activity.
• Diasteromers are compounds that may contain two or more chiral centers.

Chirality is the ability of an object not to match its mirror image. That is, molecules that do not have mirror-rotational symmetry are chiral.

Definition 2

A prochiral molecule is a molecule that can be made chiral by a single change in any of its fragments.

In chiral and prochiral molecules, some groups of nuclei, which at first glance are chemically equivalent, are magnetically nonequivalent, which is confirmed by nuclear magnetic resonance spectra. This phenomenon is called nuclear diastereotopia and can be observed in nuclear magnetic resonance spectra if there are prochiral and chiral fragments in one molecule.

For example, in a prochiral molecule, two OPF2 groups are equivalent, but in each group of $PF_2$ atoms, the fluorine atoms are not equivalent.

This is manifested in the spin-spin interaction constant 2/$FF$.

If the molecule is optically active, then the non-equivalence of X nuclei in tetrahedral groups –$MX_2Y$ (for example, -$CH_2R$, -$SiH_2R$, etc.) or pyramidal groups –$MX_2$ (for example, -$PF_2$, -$NH_2 $, etc.) does not depend on the height of the barrier of internal rotation of these groups. During the rotation of flat groups –$MX_2$ and tetrahedral –$MX_3$ the potential barrier is very low, as a result of which the nuclei $X$ become equivalent.

Construction of the names of chiral molecules

The modern naming system for chiral molecules was proposed by Ingold, Kahn, and Prelog. According to this system, for all possible groups $A$, $B$, $C$, $D$ with an asymmetric carbon atom, the order of precedence is determined. The larger the atomic number, the older it is:

If the atoms are the same, then compare the second environment:

Assume that the groups are arranged in descending order of precedence: $A → B → C → D$. Let's turn the molecule in such a way that the junior substituent $D$ is directed beyond the plane of the figure, away from us. Then the decrease in seniority in the remaining groups can occur either clockwise or counterclockwise.

Remark 1

If the decrease in precedence occurs clockwise, the symbol $R$ (right) is used in the designation of the isomer, if counterclockwise - $S$ (left). The concepts of "left" and "right" do not reflect the real direction of rotation of linearly polarized light.

Emil Fischer proposed the $DL$ nomenclature, according to which the dextrorotatory enantiomer is denoted by the letter $D$, and the left-handed enantiomer by $L$. This nomenclature is widely used for amino acids and carbohydrates.

Stereospecificity of physiological activity of optical isomers

Optical isomers exhibit different physiological activities. The active sites of enzymes and receptors consist of amino acid residues, which are optically active elements.

The receptor recognizes a physiologically active molecule according to the "key in the lock" principle. When a substrate molecule is attached, the active center changes its geometry.

For example, the nicotinic alkaloid contains one center of optical isomerism and can exist as two enantiomers. $S$ - the isomer is located on the right and is poisonous to humans (lethal dose is 20 mg), $R$ - the isomer is less poisonous:

$L$ - glutamic acid

widely used as a meat flavor enhancer in the preparation of canned food. $D$ - glutamic acid does not have such properties.

In conjunction

there are two asymmetric carbon atoms, therefore, the existence of 4 isomers ($2^n$) is possible. But only one ($R,R$)-isomer - chloromycetin - exhibits antibiotic properties

Obtaining pure optical isomers is an important chemical-technological problem.

Ways to obtain pure enantiomers.

) — the geometric property of a rigid object (spatial structure) to be incompatible with its mirror image in an ideal flat mirror.

Description

A chiral object does not have elements of symmetry of the 2nd kind, such as planes of symmetry, centers of symmetry, and mirror-rotation axes. If at least one of these symmetry elements is present, the object is achiral. Chiral are molecules, crystals, (for example,).

Chiral molecules can exist as two optical isomers (enantiomers) that are mirror images of each other and differ in their ability to rotate the plane of polarization of light clockwise (D-isomers) or counterclockwise (L-isomers) (Fig.). Enantiomers are characterized by the same physical properties, as well as the same chemical properties when interacting with achiral substances. At the same time, the separation of enantiomers, for example, the chiral method, can be based on differences in the interaction of the enantiomers of a given substance with a specific optical isomer of another substance. In chemistry, chirality is most often associated with the presence of an asymmetric carbon center bearing four different substituents.

In the presence of several asymmetric centers in a molecule, one speaks of diastereoisomerism. In this case, several pairs of enantiomers may exist (a pair of enantiomers must be characterized by a mutually opposite configuration of all asymmetric centers), and the properties of diastereomers from different enantiomeric pairs may differ greatly.

Almost all biomolecules are chiral, including naturally occurring amino acids and sugars. In nature, most of these substances have a certain spatial configuration: for example, most amino acids belong to the L spatial configuration, and sugars to D. In this regard, enantiomeric purity is a necessary requirement for biologically active drugs.

Illustrations

author

• Eremin Vadim Vladimirovich

Sources

1. Chemical encyclopedia. T. 5. - M.: Great Russian Encyclopedia, 1998. S. 538.
2. Compendium of Chemical Technology. IUPAC Recommendations. — Blackwell, 1997.

Chirality is the incompatibility of an object with its mirror image by any combination of rotations and displacements in three-dimensional space. We are talking only about an ideal flat mirror. It turns right-handed into left-handed and vice versa.

Chirality is typical of plants and animals, and the term itself comes from the Greek. χείρ - hand.

Crossbills have right and left shells and even right and left beaks (Fig. 1).

"Mirror" is common in inanimate nature (Fig. 2).

Rice. 2. Photo from the site scienceblogs.com ("Troitsky variant" No. 24(218), 06.12.2016)"border="0">

Recently, “chiral”, i.e., mirror watches have become fashionable (pay attention to the inscription on the dial) (Fig. 3).

And even in linguistics there is a place for chirality! These are palindromes: words and sentences-shifters, for example: I WILL HIT UNCLE, AUNT RADUE, I WILL HIT AUNT, UNCLE RADUE or LEENSON - BOA, BUT HE DID NOT EAT NOSE IN HELL!

Chirality is very important for chemists and pharmacists. Chemistry deals with objects at the nanoscale (the buzzword "nano" comes from the Greek. νάννος - dwarf). A monograph is devoted to chirality in chemistry, on the cover of which (pictured) on right) are chiral columns and two chiral hexahelicene molecules (from helix- spiral).

And the importance of chirality for medicine is symbolized by the cover of the June issue of the American magazine Journal of Chemical Education for 1996 (Fig. 4). On the side of a good-naturedly wagging dog's tail is the structural formula of penicillamine. The dog looks in the mirror, and from there a terrible beast looks at him with a bared fanged mouth, eyes burning with fire and hair standing on end. The same structural formula is depicted on the side of the beast in the form of a mirror image of the first. The title of the article on chiral drugs published in this issue was no less eloquent: "When Drug Molecules Look in a Mirror." Why does the "mirror reflection" so dramatically change the appearance of the molecule? And how did you know that the two molecules are "mirror antipodes"?

Polarization of light and optical activity

Since the time of Newton, there has been a debate in science about whether light is waves or particles. Newton believed that light consists of particles with two poles - "north" and "south". The French physicist Etienne Louis Malus introduced the concept of polarized light, with one "pole" direction. The theory of Malus was not confirmed, but the name remained.

In 1816, the French physicist Augustin Jean Fresnel expressed an idea, unusual for that time, that light waves are transverse, like waves on the surface of water.

Fresnel also explained the phenomenon of light polarization: in ordinary light, oscillations occur randomly, in all directions perpendicular to the direction of the beam. But, passing through some crystals, such as Icelandic spar or tourmaline, the light acquires special properties: the waves in it oscillate in only one plane. Figuratively speaking, a beam of such light is like a woolen thread that is pulled through a narrow gap between two sharp razor blades. If a second similar crystal is placed perpendicular to the first one, polarized light will not pass through it.

It is possible to distinguish ordinary light from polarized light with the help of optical devices - polarimeters; they are used, for example, by photographers: polarizing filters help to get rid of glare in a photograph, which occurs when light is reflected from the surface of the water.

It turned out that when polarized light passes through some substances, the plane of polarization rotates. This phenomenon was first discovered in 1811 by the French physicist Francois Dominique Arago in quartz crystals. This is due to the structure of the crystal. Natural quartz crystals are asymmetric, and they are of two types, which differ in their shape, like an object from its mirror image (Fig. 5). These crystals rotate the plane of polarization of light in opposite directions; they were called right- and left-handed.

In 1815, the French physicist Jean Baptiste Biot and the German physicist Thomas Johann Seebeck found out that some organic substances, such as sugar and turpentine, also have the ability to rotate the plane of polarization, not only in crystalline, but also in liquid, dissolved and even gaseous states. It turned out that each “color beam” of white light rotates through a different angle. The plane of polarization rotates the most for violet rays, the least for red ones. Therefore, a colorless substance in polarized light can become colored.

As in the case of crystals, some chemical compounds could exist in both dextrorotatory and levorotatory varieties. However, it remained unclear what property of the molecules this phenomenon is associated with: the most careful chemical analysis could not detect any differences between them! Such varieties of substances were called optical isomers, and the compounds themselves were called optically active. It turned out that optically active substances also have a third type of isomer - optically inactive. This was discovered in 1830 by the famous Swedish chemist Jöns Jacob Berzelius: tartaric acid C 4 H 6 O 6 is optically inactive, and tartaric acid of exactly the same composition has right-hand rotation in solution. But no one knew whether there was a non-naturally occurring "left" tartaric acid - the antipode of dextrorotatory.

Pasteur's discovery

The optical activity of crystals of physics was associated with their asymmetry; completely symmetrical crystals, such as cubic salt crystals, are optically inactive. The reason for the optical activity of molecules remained completely mysterious for a long time. The first discovery that shed light on this phenomenon was made in 1848 by the then unknown French scientist Louis Pasteur. While still a student, he became interested in chemistry and crystallography, working under the aforementioned Jean Baptiste Biot and the prominent French organic chemist Jean Baptiste Dumas. After graduating from the Higher Normal School in Paris, the young (he was only 26 years old) Pasteur worked as a laboratory assistant for Antoine Balard. Balar was already a famous chemist who, 22 years earlier, had become famous for the discovery of a new element - bromine. He gave his assistant a topic in crystallography, not expecting that this would lead to an outstanding discovery.

In the course of his research, Pasteur prepared a solution of the sodium ammonium salt of the optically inactive tartaric acid and obtained beautiful prismatic crystals of this salt by slowly evaporating the water. These crystals, in contrast to the crystals of tartaric acid, turned out to be asymmetric. Some of the crystals had one characteristic face on the right, while others had one on the left, and the shape of the two types of crystals was, as it were, a mirror image of each other.

Those and other crystals turned out equally. Knowing that in such cases quartz crystals rotate in different directions, Pasteur decided to check whether this phenomenon would be observed on the salt he received. Armed with a magnifying glass and tweezers, Pasteur carefully divided the crystals into two piles. Their solutions, as expected, had the opposite optical rotation, and the mixture of solutions was optically inactive (the right and left polarizations were mutually compensated). Pasteur did not stop there. From each of the two solutions, with the help of strong sulfuric acid, he displaced the weaker organic acid. It could be assumed that in both cases the original tartaric acid would be obtained, which is optically inactive. However, it turned out that not grape acid, but the well-known dextrorotatory tartaric acid, was formed from one solution, and tartaric acid was also obtained from another solution, but rotating to the left! These acids are called d- wine (from lat. dexter- right) and l- wine (from lat. laevus- left). Subsequently, the direction of optical rotation began to be denoted by the signs (+) and (–), and the absolute configuration of the molecule in space - by letters R And S. So, inactive tartaric acid turned out to be a mixture of equal amounts of the known “right” tartaric acid and the previously unknown “left” one. That is why an equal mixture of their molecules in a crystal or in solution does not have optical activity. For such a mixture, the name "racemate" began to be used, from lat. racemus- grape. Two antipodes that, when mixed in equal amounts, give an optically inactive mixture, are called enantiomers (from the Greek. έναντίος - opposite).

Realizing the significance of his experiment, Pasteur ran out of the laboratory and, meeting a laboratory assistant in the physics office, rushed to him and exclaimed: “I have just made a great discovery!” By the way, Pasteur was very lucky with the substance: in the future, chemists discovered only a few similar cases of crystallization at a certain temperature of a mixture of optically different crystals, large enough to be separated under a magnifying glass with tweezers.

Pasteur discovered two more methods for dividing a racemate into two antipodes. The biochemical method is based on the selective ability of some microorganisms to absorb only one of the isomers. During a visit to Germany, one of the pharmacists gave him a long-standing bottle of grape acid, in which green mold started up. In his laboratory, Pasteur discovered that once inactive acid had become left-handed. It turned out that the green mold fungus Penicillum glaucum“eats” only the right isomer, leaving the left one unchanged. This mold has the same effect on the racemate of mandelic acid, only in this case it “eats” the levorotatory isomer without touching the dextrorotatory one.

The third way to separate racemates was purely chemical. For him, it was necessary to have an optically active substance, which, when interacting with a racemic mixture, would bind differently to each of the enantiomers. As a result, the two substances in the mixture will not be antipodes (enantiomers) and can be separated as two different substances. This can be explained by such a model on a plane. Let's take a mixture of two antipodes - I and R. Their chemical properties are the same. Let us introduce an asymmetric (chiral) component into the mixture, for example, Z, which can react with any site in these enantiomers. We get two substances: RZ and ZR (or RZ and RZ). These structures are not mirror symmetrical, so such substances will differ purely physically (melting point, solubility, something else) and they can be separated.

Pasteur made many more discoveries, including vaccinations against anthrax and rabies, introduced aseptic and antiseptic methods.

Pasteur's study, proving the possibility of "splitting" an optically inactive compound into antipodes - enantiomers, initially aroused distrust among many chemists, however, like his subsequent work, it attracted the closest attention of scientists. Soon, the French chemist Joseph Achille Le Bel, using the third Pasteur method, split several alcohols into optically active antipodes. The German chemist Johann Wislicenus established that there are two lactic acids: optically inactive, formed in sour milk (fermented lactic acid), and dextrorotatory, which appears in the working muscle (meat-lactic acid). There were more and more such examples, and a theory was needed to explain how the molecules of antipodes differ from each other.

Van't Hoff theory

Such a theory was created by the young Dutch scientist Jacob Hendrik van't Hoff, who in 1901 received the first ever Nobel Prize in Chemistry. According to his theory, molecules, like crystals, can be chiral - "right" and "left", being a mirror image of each other. The simplest example is molecules that have a so-called asymmetric carbon atom surrounded by four different groups. This can be demonstrated using the simplest amino acid alanine as an example. The two depicted molecules cannot be combined in space by any rotations (Fig. 6, top).

Many scientists reacted to Van't Hoff's theory with distrust. And the famous German organic chemist, an outstanding experimenter, professor at the University of Leipzig, Adolf Kolbe, burst into an obscenely harsh article in Journal fur praktische Chemie with the malicious title "Zeiche der Zeit" ("Signs of the Times"). He compared van't Hoff's theory to "the dregs of the human mind", with "a cocotte dressed in fashionable clothes and covering her face with white and rouge in order to get into a decent society in which there is no place for her." Kolbe wrote that " a certain doctor van't Hoff, who holds a position at the Utrecht veterinary school, obviously does not like exact chemical research. He found it more pleasant to sit on a Pegasus (probably borrowed from a veterinary school) and tell the world what he had seen from the chemical Parnassus ... Real researchers are amazed how almost unknown chemists are taken so confidently to judge the highest problem of chemistry - the question of spatial position atoms, which, perhaps, will never be solved ... Such an approach to scientific questions is not far from belief in witches and spirits. And such chemists should be excluded from the ranks of real scientists and reckoned with the camp of natural philosophers, who differ very little from spiritualists.».

Over time, van't Hoff's theory gained full recognition. Every chemist knows that if there are equal numbers of "right" and "left" molecules in a mixture, the substance as a whole will be optically inactive. It is these substances that are obtained in the flask as a result of conventional chemical synthesis. And only in living organisms, with the participation of asymmetric agents, such as enzymes, asymmetric compounds are formed. So, in nature amino acids and sugars of only one configuration predominate, and the formation of their antipodes is suppressed. In some cases, different enantiomers can be distinguished without any instruments - when they interact differently with asymmetric receptors in our body. A striking example is the amino acid leucine: its dextrorotatory isomer is sweet, and its levorotatory is bitter.

Of course, the question immediately arises of how the first optically active chemical compounds appeared on Earth, for example, the same natural dextrorotatory tartaric acid, or how "asymmetric" microorganisms that feed on only one of the enantiomers arose. Indeed, in the absence of a person, there was no one to carry out a directed synthesis of optically active substances, there was no one to divide crystals into right and left! However, such questions turned out to be so complex that there is no unambiguous answer to them to this day. Scientists agree only that there are asymmetric inorganic or physical agents (asymmetric catalysts, polarized sunlight, polarized magnetic field) that could give an initial impetus to the asymmetric synthesis of organic substances. We observe a similar phenomenon in the case of the asymmetry "matter - antimatter", since all cosmic bodies consist only of matter, and selection occurred at the earliest stages of the formation of the Universe.

Chiral drugs

Chemists often refer to enantiomers as a single compound because their chemical properties are identical. However, their biological activity can be completely different. Man is a chiral being. And this applies not only to his appearance. "Right" and "left" drugs, interacting with chiral molecules in the body, such as enzymes, can act differently. The "correct" drug fits into its receptor like a key to a lock and starts the desired biochemical reaction. The action of the “wrong” antipode can be likened to an attempt to shake the left hand of your guest with your right hand. The need for optically pure enantiomers is also explained by the fact that often only one of them has the required therapeutic effect, while the second antipode can be useless at best, and at worst cause unwanted side effects or even be toxic. This became apparent after the sensational tragic story of thalidomide, a drug that was prescribed to pregnant women in the 1960s as an effective sleeping pill and sedative. However, over time, its teratogenic side effect (from the Greek. τέρας - monster) action, and a lot of babies with congenital deformities were born. Only in the late 1980s did it become clear that only one of the enantiomers of thalidomide, dextrorotatory, was the cause of the misfortune, and only the levorotatory isomer is a powerful tranquilizer (Fig. 6, below). Unfortunately, such a difference in the action of dosage forms was not previously known, so the marketed thalidomide was a racemic mixture of both antipodes. They differ in the mutual arrangement in space of two fragments of the molecule.

One more example. Penicillamine, whose structure was drawn on a dog and a wolf on the cover of a magazine, is a fairly simple derivative of the amino acid cysteine. This substance is used for acute and chronic poisoning with copper, mercury, lead, and other heavy metals, since it has the ability to form strong complexes with ions of these metals; the resulting complexes are removed by the kidneys. Penicillamine is also used in various forms of rheumatoid arthritis, in a number of other cases. In this case, only the "left" form of the drug is used, since the "right" form is toxic and can lead to blindness.

It also happens that each enantiomer has its own specific action. Yes, left hand S Thyroxine (Levotroid) is a naturally occurring thyroid hormone. A dextrorotatory R-thyroxine (dextroid) lowers blood cholesterol. Some manufacturers come up with palindromic trade names for such cases, such as darvon and novrad for a synthetic narcotic analgesic and cough medicine, respectively.

Currently, many drugs are produced in the form of optically pure compounds. They are obtained by three methods: separation of racemic mixtures, modification of natural optically active compounds and direct synthesis. The latter also requires chiral sources, since any other conventional synthetic methods yield a racemate. This, by the way, is one of the reasons for the very high cost of some drugs, since the directed synthesis of only one of them is a difficult task. Therefore, it is not surprising that of the many synthetic chiral drugs produced throughout the world, only a small part is optically pure, the rest are racemates.

For the chirality of molecules, see also:
Chapter The Origin of Chiral Purity from Mikhail Nikitin's book

concept chirality- one of the most important in modern stereochemistry. A model is chiral if it does not have any symmetry elements (plane, center, mirror-rotation axes), except for simple rotation axes. We call a molecule that is described by such a model chiral (meaning "like a hand", from the Greek . hero- hand) for the reason that, like hands, molecules are not compatible with their mirror images. In fig. 1 shows a number of simple chiral molecules. Two facts are absolutely obvious: firstly, the pairs of the given molecules represent mirror reflections of each other, and secondly, these mirror reflections cannot be combined with each other. It can be seen that in each case the molecule contains a carbon atom with four different substituents. Such atoms are called asymmetric. The asymmetric carbon atom is a chiral or stereogenic center. This is the most common type of chirality. If a molecule is chiral, then it can exist in two isomeric forms, related as an object and its mirror image and incompatible in space. Such isomers (pair) are called enantiomers.

The term "chiral" does not allow free interpretation. When a molecule is chiral, it, by analogy with a hand, must be either left or right. When we call a substance or some sample of it chiral, it simply means that it (it) consists of chiral molecules; in this case, it is not at all necessary that all molecules are the same in terms of chirality (left or right, R or S, see section 1.3). Two limiting cases can be distinguished. In the first, the sample consists of molecules that are identical in terms of chirality (homochiral, only R or only S); such a pattern is called enantiomerically pure. In the second (opposite) case, the sample consists of the same number of molecules that are different in terms of chirality (heterochiral, the molar ratio R: S=1:1); such a sample is also chiral, but racemic. There is also an intermediate case - a non-equimolar mixture of enantiomers. Such a mixture is called scalemic or non-racemic. Thus, the assertion that a macroscopic sample (unlike an individual molecule) is chiral should be considered not quite clear and therefore insufficient in some cases. Additional indication may be required as to whether the sample is racemic or non-racemic. The lack of accuracy in understanding this leads to a certain kind of misconception, for example, in the headings of articles, when the synthesis of some chiral compound is proclaimed, but it remains unclear whether the author simply wants to draw attention to the very fact of the chirality of the structure discussed in the article, or whether the product was actually obtained in the form a single enantiomer (i.e., an ensemble of homochiral molecules; this ensemble, however, should not be called a homochiral sample). Thus, in the case of a chiral non-racemic sample, it is more correct to say "enantiomerically enriched" or " enantiomerically pure".

Methods for displaying optical isomers

The image method is chosen by the author solely for reasons of ease of information transfer. In Figure 1, images of enantiomers are given using perspective pictures. In this case, it is customary to draw connections lying in the image plane with a solid line; connections that go beyond the plane - dotted line; and the connections directed to the observer are marked with a thick line. This method of representation is quite informative for structures with one chiral center. The same molecules can be depicted as a Fischer projection. This method was proposed by E. Fisher for more complex structures (in particular, carbohydrates) having two or more chiral centers.

Mirror plane

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To construct Fisher's projection formulas, the tetrahedron is rotated so that two bonds lying in the horizontal plane are directed towards the observer, and two bonds lying in the vertical plane are directed away from the observer. Only an asymmetric atom falls on the image plane. In this case, the asymmetric atom itself, as a rule, is omitted, retaining only the intersecting lines and substituent symbols. To keep in mind the spatial arrangement of the substituents, a broken vertical line is often kept in the projection formulas (the upper and lower substituents are removed beyond the plane of the drawing), but this is often not done. Below are examples of different ways to image the same structure with a certain configuration (Fig. 2)

Fisher projection

Deputy A

Deputy A

Fig.17

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A similar case of dissection of a cyclic substituent is illustrated by the example of the compound in Fig. 18 where structure IN illustrates the interpretation of the cyclohexyl ring (in the structure BUT). In this case, the correct sequence of precedence is di- n-gesylmethyl > cyclohexyl > di- n-pentylmethyl > H.

Now we are sufficiently prepared to consider such a substituent as phenyl (Fig. 19 structure BUT). We discussed the scheme for opening each multiple bond above. Since (in any Kekule structure) each of the six carbon atoms is double-bonded to another carbon atom, then (in the CIA system) each carbon atom of the ring carries an additional carbon as a "substituent". The ring supplemented in this way (Fig. 19, structure IN) is then expanded according to the rules for cyclic systems. As a result, the dissection is described by the diagram shown in Fig. 19, the structure FROM.

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6. Now we will consider chiral compounds in which the differences between the substituents are not of a material or constitutional nature, but are reduced to differences in configuration. Compounds containing more than one chiral center will be discussed below (see section 1.4) Here we will also touch on substituents that differ cis-trans– isomerism (olefin type). According to Prelog and Helmchen, the olefin ligand in which the senior substituent is located on the same side from the double bond of the olefin, which is the chiral center, has an advantage over the ligand in which the senior substituent is in trance-position to the chiral center. This position has nothing to do with classical cis-trans-, nor to E-Z - nomenclature for double bond configuration. Examples are shown in Figure 20.

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Compounds with multiple chiral centers

If there are two chiral centers in a molecule, then since each center can have (R)- or ( S)-configuration, the existence of four isomers is possible - RR, SS, RS And SR:

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Since the molecule has only one mirror image, the enantiomer of the compound (RR) can only be an isomer (SS). Similarly, another pair of enantiomers form isomers (RS) And (SR). If the configuration of only one asymmetric center changes, then such isomers are called diastereomers. Diastereomers are stereoisomers that are not enantiomers. So, diastereomeric pairs (RR)/(RS), (RR)/(SR), (SS)/(RS) And (SS)/(SR). Although in the general case, the combination of two chiral centers produces four isomers, the combination of centers of the same chemical structure gives only three isomers: (RR) And (SS), which are enantiomers, and (RS), diastereomeric to both enantiomers (RR) And (SS). A typical example is tartaric acid (Fig. 22), which has only three isomers: a pair of enantiomers and meso form.

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Meso-Vinnaya acid is (R, S)-isomer, which is optically inactive, since the union of two mirror-symmetric fragments leads to the appearance of a symmetry plane (a). Meso-Vinnaya an acid is an example of an achiral meso-configuration compound, which is built from an equal number of chiral elements identical in structure but different in absolute configuration.

If the molecule has P chiral centers, the maximum number of stereoisomers can be calculated using formula 2 n; however, sometimes the number of isomers will be less due to the presence of meso forms.

For the names of stereoisomers of molecules containing two asymmetric carbon atoms, two substituents for each of which are the same, and the third are different, prefixes are often used erythro- And treo- from the names of sugars erythrose and threose. These prefixes characterize the system as a whole, and not each chiral center separately. When depicting such compounds using Fischer projections in a pair erythro- isomers, the same groups are located on the same side, and if the different groups (C1 and Br in the example below) were the same, a meso form would be obtained. Paired with treo- isomers, the same groups are located on different sides, and if the different groups were the same, the new pair would remain an enantiomeric pair.

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All examples of compounds considered above have a center of chirality. Such a center is an asymmetric carbon atom. However, other atoms (silicon, phosphorus, sulfur) can also be the center of chirality, as, for example, in methylnaphthylphenylsilane, o-anisylmethylphenylphosphine, methyl-p-tolyl sulfoxide (Fig. 24)

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Chirality of molecules devoid of chiral centers

A necessary and sufficient condition for the chirality of a molecule is its incompatibility with its mirror image. The presence of a single (configurationally stable) chiral center in a molecule is a sufficient, but by no means necessary, condition for the existence of chirality. Consider chiral molecules lacking chiral centers. Some examples are shown in figures 25 and 26.

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These are compounds with axes of chirality ( axial chirality type): allenes; alkylidenecycloalkanes; spiranes; the so-called atropisomers (biphenyls and similar compounds whose chirality arises due to hindered rotation around a single bond). Another element of chirality is the chirality plane ( planar chirality type). Examples of such compounds are ansa compounds (in which the alicyclic ring is too small for the aromatic ring to pass through); paracyclophanes; metallocenes. Finally, the chirality of a molecule can be related to the helical organization of the molecular structure. The molecule can wrap either in the left or in the right helix. In this case, one speaks of helicity (helical type of chirality).

In order to determine the configuration of a molecule that has axis of chirality, it is necessary to introduce an additional clause in the sequence rule: the groups closest to the observer are considered older than the groups remote from the observer. This addition must be made, since for molecules with axial chirality, the presence of identical substituents at opposite ends of the axis is permissible. Applying this rule to the molecules shown in Fig. 25 shown in fig. 27.

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In all cases, the molecules are considered along the chiral axis on the left. In this case, it should be understood that if the molecules are considered from the right, then the configuration descriptor will remain the same. Thus, the spatial arrangement of the four support groups corresponds to the vertices of the virtual tetrahedron and can be represented using the corresponding projections (Fig. 27). To determine the appropriate descriptor, we use the standard rules R, S- nomenclature. In the case of biphenyls, it is important to note that ring substituents are considered from the center (through which the chirality axis passes) to the periphery, in violation of standard sequence rules. Thus, for biphenyl in Fig. 25 correct sequence of substituents in the right ring C-OCH 3 >C-H; the chlorine atom is too far away to be taken into account. The reference atoms (those by which the configuration symbol is determined) are the same when the molecule is viewed from the right. Sometimes descriptors are used to distinguish axial chirality from other types. aR And aS (or R a And S a), but the use of the prefix " a' is not mandatory.

Alternatively, molecules with axes of chirality can be thought of as helical, and their configuration can be denoted by the symbols R And M. In this case, to determine the configuration, only substituents with the highest priority are considered both in the front and back (remote from the observer) parts of the structure (substituents 1 and 3 in Fig. 27). If the transition from the highest priority front substituent 1 to the priority rear substituent 3 is clockwise, then this is the configuration R; if counterclockwise, is the configuration M.

On fig. 26 shows molecules with chirality planes. It is not so easy to give a definition of the plane of chirality, and it is not as unambiguous as the definition of the center and axis of chirality. This is a plane that contains as many atoms of a molecule as possible, but not all. In fact, chirality is because (and only because) that at least one substituent (often more) does not lie in the chirality plane. Thus, the chiral plane of the ansa compound BUT is the plane of the benzene ring. In paracyclophane IN the most substituted (lower) ring is considered as the chiral plane. In order to determine the descriptor for planar-chiral molecules, the plane is viewed from the side of the atom closest to the plane, but not lying in this plane (if there are two or more candidates, then the one closest to the atom with the highest priority is chosen according to the rules of sequence ). This atom, sometimes called a test or pilot atom, is marked with an arrow in Fig. 26. Then, if three consecutive atoms (a, b, c) with the highest priority form a broken line in the chiral plane, curving clockwise, then the compound configuration pR (or R p), and if the polyline curves counterclockwise, then the configuration descriptor PS(or S p). Planar chirality, like axial chirality, can alternatively be viewed as a kind of chirality. In order to determine the direction (configuration) of the helix, one must consider the pilot atom together with the atoms a,b, and c, as defined above. From here it is clear that pR- connections corresponds R-, but PS- connections - M– helicity.