Chirality in biology. Butin K.P.
8.2.2.b. Symmetric definition of chirality
Now consider the question: to which point symmetry groups must a molecule belong in order for it to be chiral? In other words, what should be the nature of the dissymmetry of the molecule, and what elements of symmetry must be absent? First of all, it is obvious that any truly asymmetric molecule belonging to the C 1 group is chiral, having no symmetry elements other than identity (and the C 1 axis, since C 1 E). It is also obvious that molecules having a plane of symmetry (s) or a center of symmetry (i) are achiral, since they consist of two identical "halves" and in mirror image the left and right halves are transformed into each other or without rotations (in the presence of a plane) , or with a rotation of 180 0 (if there is an inversion center). Molecules that have mirror-rotation axes (S n) are also aligned with their mirror image, and therefore are achiral. Consequently, only molecules belonging to the axial point groups С n and D n are chiral.
Thus, we can formulate the following symmetry criterion for chirality:
any molecule that does not have an improper axis of rotation S n is chiral.
The old definition of optical isomerism, namely, "a molecule must have neither a plane nor a center of symmetry", is not accurate enough. Since S 1 s and S 2 i, if the molecule does not have an improper axis of rotation, then it should not have either s or i. There are molecules that have neither i nor s but have an S n axis and are therefore achiral. An example is the 1,3,5,7-tetramethylcyclooctatetraene (XI) molecule, which has neither a plane nor a center of symmetry, but has a mirror-rotation axis S 4 . It is optically inactive.
The first proof of the validity of the above definition of chiral molecules was obtained in the study of isomeric quaternary ammonium salts with a spirane nitrogen atom IV, V, VII, and IX. Isomers IV and V are asymmetric (group C 1), isomer VII is dissymmetric (group D 2). Therefore, these three isomers must be chiral. Indeed, they were obtained in an optically active form. However, isomer VIII belongs to the S 4 group; achiral, and it cannot be obtained in an optically active form.
8.2.2.c. Rules for classifying molecules by symmetry
The structure of the molecules of organic compounds is so complex that the search for possible symmetry elements is often a very difficult task. Therefore, some practically reasonable method of successive actions in the classification of molecules according to point symmetry groups is needed. The scheme of the method proposed by F. Cotton in 1971 is described below.
1) First you need to determine whether the molecule belongs to one of the following groups: (СҐ v (cone symmetry), DҐ h (cylinder symmetry), I h, O h, T d (type 4, Table 8.1). These groups are conditionally Let us call them “special.” Note that only linear molecules belong to the СҐ v or DҐ h group, for example, H-C C-Cl (СҐ v), H-C C-H, Cl-C C-Cl (DҐ h), etc.
2) If the molecule does not belong to one of the special groups, it is necessary to look for its own axis of rotation С n . Having found such an axis, we proceed to operation (3). If there is no own rotation axis, it is necessary to look for the center of symmetry i or the mirror plane s. If the molecule has an inversion center, it belongs to the point group C i , and if it turns out to be a mirror plane, it belongs to the point group C s . If a molecule has no symmetry elements (other than E), it belongs to the C 1 group.
3) Next, we find main axis With n , i.e. the axis with the highest n value. We determine whether there is a mirror-rotary axis S 2n that coincides with the main axis. If it exists, but there are no other elements except possibly i, the molecule belongs to one of the groups S n , where n is an even number. If there is an axis S 2n, but there are other elements, or if there is no element S 2n, it is necessary to proceed to operation (4).
4) We are looking for a set of n axes of the second order, lying in a plane perpendicular to C n . If such a set is found, the molecule belongs to one of the groups D n , D nh or D nd . Then we pass to operation (5). If there are no such axes, the molecule belongs to the group С n , or C nh , or C nv . Then we pass to operation (6).
5) If a molecule has a plane of symmetry s h perpendicular to the main axis, it belongs to the group D nh . If there is no such element, it is necessary to look for a set of n diagonal planes s d (i.e., planes of symmetry in which the main axis lies, but none of the perpendicular axes of the second order lies). If both s d and s h are absent, the molecule belongs to the group D n .
6) If a molecule has s h , it belongs to the point group C nh . If s h is absent, one must look for a set of n planes s v (passing through the main axis). The presence of such planes makes it possible to attribute the molecule to the C nv group. If a molecule has neither s v nor s h , it belongs to the point group C n .
The stated method is illustrated by the diagram shown in Scheme 8.1.
8.2.2.y. Chirality types
Adamantanes, whose tertiary carbon atoms have four different substituents, are chiral and optically active; for example, compound XIII has been separated into enantiomers. When comparing formulas XII and XIII, it is easy to see that the symmetry of both compounds is very similar. The adamantane backbone can be thought of as a "broken edge" tetrahedron, it has a T d symmetry that goes to C 1 when all four substituents on the tertiary carbons are different. The adamantane derivative XIII does not have an asymmetric carbon atom, as in a-bromopropionic acid, but there is a center located inside the molecule (the center of gravity of unsubstituted adamantane). asymmetric center is a special case of a more general concept chiral center. The chiral center can have not only asymmetric molecules, but also molecules of symmetry C n or D n . In the examples below, the chiral center is marked with an asterisk.
The chiral center is just one of the possible elements of chirality. Molecules whose chirality is due to the presence of a center of chirality are by far the most important in organic chemistry. However, in addition to the central one, there are also axial, planar and spiral types of chirality.
Axial chirality is possessed by molecules having a chiral axis. chiral axis easy to get by mentally "stretching" the center of chirality:
The chiral axis has such classes of molecules as allenes and diphenyls. In allenes, the central sp-carbon atom has two mutually perpendicular p-orbitals, each of which overlaps with the p-orbital of the adjacent carbon atom, as a result of which the remaining bonds of the terminal carbon atoms are located in perpendicular planes. The allene itself is chiral, since it has a mirror-rotary axis S 4 , but asymmetrically substituted allenes of the abC=C=Cab type are chiral.
Allenes are chiral only if both terminal carbons are substituted asymmetrically:
For any odd number of cumulated double bonds, the four end groups are no longer in different, but in the same plane, for example, for 1,2,3-butatriene:
Such molecules are achiral, but cis-trans isomerism is observed for them.
Thus, compound XIV was separated into optical isomers.
If one or both double bonds of a symmetrically substituted allene are replaced by a cyclic system, then the resulting molecules will also have axial chirality, for example:
In biphenyls containing four bulky groups in the ortho positions, free rotation around the central bond is hindered by steric hindrance, and therefore the two benzene rings do not lie in the same plane. By analogy with allenes, if one or both benzene rings are substituted symmetrically, the molecule is achiral; chiral molecules have only two asymmetrically substituted rings, for example:
Isomers that can be separated only because rotation around a single bond is difficult are called atropisomers.
Sometimes three or even two bulky substituents in the ortho positions are sufficient to prevent free rotation in biphenyls. So, it was possible to separate biphenyl-2,2-disulfonic acid (XV) into enantiomers. In compound XVI, free rotation is not completely inhibited, and although it can be obtained in an optically active form, when dissolved in ethanol, it quickly racemizes (half in 9 minutes at 25 0).
For some chiral molecules, the defining structural element is not the center, not the axis, but the plane. The simplest model planar chirality it is easy to construct from any flat figure that does not have axes of symmetry lying in this plane, and a single point outside the plane. Planar-chiral derivatives of ferrocene (XVII) are the most studied. Other examples are chromium tricarbonyl arene complexes (XVIII) and compounds XIX and XX.
Helical chirality is due to the helical shape of the molecule. The helix can be twisted to the left or to the right, giving enantiomeric helices. For example, in hexahelycene, one part of the molecule is forced to be located above the other due to spatial obstacles.
8.2.2.e. Chirality of macrocyclic molecules
Macrocycles containing several tens of atoms connected in a ring are capable of forming amazing types of molecular structures with left or right helicity.
For example, in compound XXI, the main chain has the form of a Möbius strip, which must exist in the form of two enantiomeric forms. Compound XXI was synthesized and indeed proved to be chiral.
Cycles of 60 or more members can exist as knots (XXII) tied from left to right or right to left and must therefore be chiral.
Appropriately substituted catenanes and rotaxanes may also be chiral. These compounds consist of two or more independent parts that are not linked by valence bonds, but are nevertheless held together. Catenans are built from two or more cycles connected like links in a chain; in rotaxanes, a linear molecule is threaded through a cyclic molecule and cannot slip out of it due to the presence of bulky end groups.
Cathenans and rotaxanes can be prepared either by random synthesis or directed synthesis. The principle of statistical synthesis is explained by the following scheme.
Compound A binds at both ends with compound B in the presence of a huge excess of macrocyclic compound C. Before the reaction with molecules B, some part of molecules A must accidentally pass through cycle C, and therefore, along with products E and E, a certain amount of rotaxane D is also formed. .Examples are shown below.
Chiral catenanes and rotaxanes have not yet been obtained.
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 the photo, 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 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, which is 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 saw from the chemical Parnassus ... Real researchers are amazed how almost unknown chemists are taken to judge so confidently 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
Molecules with the same chemical structure may differ in spatial structure, i.e. exist in the form of spatial isomers - stereoisomers.
The spatial structure of molecules is the mutual arrangement of atoms and atomic groups in three-dimensional space.
stereoisomers- compounds in the molecules of which there is the same sequence of chemical bonds of atoms, but a different arrangement of these atoms relative to each other in space.
In turn, stereoisomers can be configuration and conformational isomers, i.e., differ in configuration and conformation, respectively .
Configuration- this is the arrangement of atoms in space without taking into account the differences that arise due to rotation around single bonds.
Configurational isomers can transform into each other by breaking one and forming other chemical bonds and can exist separately as individual compounds. They are divided into two main types - enantiomers and diastereomers. .
Enantiomers- stereoisomers related to each other as an object and an incompatible mirror image.
Only enantiomers exist as enantiomers. chiral molecules.
Chirality is the property of an object to be incompatible with its mirror image. Chiral (from the Greek. cheir- hand), or asymmetric, the objects are the left and right hand, as well as gloves, boots, etc. These paired objects represent an object and its mirror image (Fig. 8, a). Such items cannot be completely combined with each other.
At the same time, there are many objects around us that are compatible with their mirror image, i.e. they are achiral (symmetrical), such as plates, spoons, glasses, etc. Achiral objects have at least one plane of symmetry , which divides the object into two mirror-identical parts (see Fig. 8, b).
Similar relationships are also observed in the world of molecules, i.e. molecules are divided into chiral and achiral. Achiral molecules have planes of symmetry, chiral ones do not.
Chiral molecules have one or more centers of chirality. In organic compounds, the asymmetric carbon atom most often acts as the center of chirality. .
Rice. eight. Reflection in the mirror of a chiral object (a) and a plane of symmetry cutting the achiral object (b)
Asymmetric is a carbon atom bonded to four different atoms or groups.
When depicting the stereochemical formula of a molecule, the symbol "C" of the asymmetric carbon atom is usually omitted.
To determine whether a molecule is chiral or achiral, it is not necessary to represent it with a stereochemical formula, it is enough to carefully consider all the carbon atoms in it. If there is at least one carbon atom with four different substituents, then this carbon atom is asymmetric and the molecule, with rare exceptions, is chiral. So, of the two alcohols - propanol-2 and butanol-2 - the first is achiral (two CH 3 groups at the C-2 atom), and the second is chiral, since in its molecule at the C-2 atom all four substituents are different (H, OH, CH 3 and C 2 H 5). An asymmetric carbon atom is sometimes marked with an asterisk (C*).
Therefore, the butanol-2 molecule is able to exist as a pair of enantiomers that do not combine in space (Fig. 9).
Rice. 9. Enantiomers of chiral molecules of butanol-2 do not combine
Properties of enantiomers. Enantiomers have the same chemical and physical properties (melting and boiling points, density, solubility, etc.), but exhibit different optical activity, i.e. e. the ability to deflect the plane of polarized light.
When such light passes through a solution of one of the enantiomers, the plane of polarization deviates to the left, the other - to the right by the same angle α. The value of the angle α reduced to standard conditions is the constant of the optically active substance and is called specific rotation[α]. Left rotation is denoted by a minus sign (-), right rotation is indicated by a plus sign (+), and enantiomers are called left and right rotation, respectively.
Other names of enantiomers are associated with the manifestation of optical activity - optical isomers or optical antipodes.
Each chiral compound can also have a third, optically inactive form - racemate. For crystalline substances, this is usually not just a mechanical mixture of crystals of two enantiomers, but a new molecular structure formed by the enantiomers. Racemates are optically inactive because the left rotation of one enantiomer is compensated by the right rotation of an equal amount of the other. In this case, a plus-minus sign (?) is sometimes placed before the name of the connection.
Modern natural science has come to another important discovery related to symmetry and concerning the difference between living and non-living. The point is that "living" molecules, i.e. molecules of organic substances that make up living organisms and obtained in the course of life, differ from "non-living", i.e. obtained artificially differ in mirror symmetry. Non-living molecules can be both mirror-symmetric and mirror-asymmetric, like, for example, a left and right glove. This property of mirror asymmetry of molecules is called chirality, or chirality. Inanimate chiral seacules are found in nature both in the "left" and in the "right" version, i.e. they are chirally impure. "Living" molecules can have only one orientation - "left" or "right", i.e. here one speaks of the chiral purity of the living. For example, the DNA molecule, as you know, has the form of a helix, and this helix is always right. Glucose produced in the body has a dextrorotatory form, while fructose has a levorotatory form.
The discovery of the chiral purity of molecules of biogenic origin sheds new light on the emergence of life on Earth, which could be caused by a spontaneous breaking of the mirror symmetry that existed before. Radiation, temperature, pressure, exposure to electromagnetic fields, etc. could be factors in the appearance of asymmetry. It is possible that life on Earth originated in the form of structures similar to the genes of modern organisms. It could be an act of self-organization of matter in the form of a jump, and not a gradual evolution. In this regard, they talk about the Big Biological Bang.
Research shows that in the course of the development of life, asymmetry more and more displaces symmetry from biological and chemical processes. Externally symmetrical hemispheres of the brain differ in their functions. A clearly asymmetric feature is the division of the sexes - a fairly "late acquisition" of evolution, with each sex introducing its genetic information into the process of reproduction. The symmetry and asymmetry of living things are also manifested in the most important factors of evolution. Thus, symmetry is manifested in the stability of species (heredity), and asymmetry is manifested in their variability.
Therefore, the most important ability of living organisms is to create chirally pure molecules. According to modern concepts, it is the chirality of molecules that determines the biochemical boundary between living and nonliving.
Many important and necessary molecules for life exist in two forms. These two forms are chiral, since their reflections in an ideal flat mirror cannot be superimposed. They relate to each other like a left and right hand. Therefore, this property is called chirality (from the Greek cheir - hand).
The two forms of molecules are called enantiomers or optical isomers. Enantiomers have the opposite meaning of chirality, i.e. opposite configuration. One of the enantiomers rotates the plane of polarization of plane polarized light to the right, and the other enantiomer rotates exactly the same angle to the left.
The chirality of a crystal or molecule is determined by its symmetry. A molecule is achiral (non-chiral) if and only if it has an axis of improper rotation, that is, an n-fold rotation (rotation by 360°/n) followed by reflection in a plane perpendicular to this axis reflects the molecule onto itself. Thus, a molecule is chiral if it does not have such an axis, i.e. if there are no symmetry operations other than the identity transformation that would reflect the molecule onto itself. Since chiral molecules do not have this kind of symmetry, they are called dissymmetric. They are not necessarily asymmetrical (that is, without symmetry), as they may have other kinds of symmetry. However, all amino acids (except glycine) and many sugars are indeed both asymmetric and dissymmetric.
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 the spectra of nuclear magnetic resonance in the presence of 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.
