Chirality (chemistry)

Chirality(molecular chirality) - in chemistry, the property of a molecule to be incompatible with its mirror image by any combination of rotations and displacements in three-dimensional space.

Enzymes (and they are chiral) often differ between the two enantiomers of a chiral substrate. Imagine that the enzyme has a glove-shaped depression that binds the substrate. If the glove is right handed, then one enantiomer will go in and bind, while the other enantiomer will not fit well and there is little chance of binding. The D-form of amino acids is usually sweet in taste, while the L-form is usually tasteless. Peppermint leaves and cumin seeds contain L-carvone and D-carvone, respectively, enantiomers of carvone. They smell differently because most people's olfactory receptors also contain chiral molecules that behave differently in the presence of different enantiomers.

Chirality in pharmacology

Many chiral drugs are made in high enantiometric purity due to the side effects of the other enantiomer (which may even be therapeutically inactive).

• Thalidomide: Thalidomide is racemic. One enantiomer is effective against nausea and the other is teratogenic. In this case, the administration of one of the enantiomers to a pregnant patient will not help, since both enantiomers are easily converted into each other in the body. And if you give a person a different enantiomer, then both D- and L-isomers will be present in the patient's plasma.
• Ethambutol: one enantiomer is used in the treatment of tuberculosis, the other causes blindness.
• Naproxen: One enantiomer treats arthritis, but the other causes liver poisoning without analgesic effect.
• The location of steroid receptors also shows the specificity of the stereoisomers.
• The activity of penicillin is stereodependent. The antibiotic must mimic the D-alanine chains that are present in cell walls bacteria to react with the enzyme transpeptidase and gradually absorb it.
• Only L-Inderal is a powerful adrenergic receptor, while D-Inderal is not. However, both isomers of anaprilin have a local anesthetic effect.
• L-methorphan (levomethorphan) is a powerful opioid analgesic, while the D-isomer, dextromethorphan, is a dissociative cough reliever.
• S-carvedilol, an adrenoceptor-reactive agent, is 100 times more β-blocking than the R(+) isomer. But both isomers approximately equally block α-receptors.
• The D-isomers of pervitin and amphetamine are strong CNS stimulants, and the L-isomers of both lack the major CNS stimulant properties but instead stimulate the PNS (peripheral nervous system). Therefore, the L-isomer of Pervitin is available as a nasal agent, and the dextroisomer is banned for medical use in almost all (with rare exceptions) countries of the world and is strictly controlled where it is allowed.
• S-amlodipine, the pure optically active isomer of amlodipine, is responsible for calcium channel blockade and vasodilation.
• levocetirizine, RR-cytirizine, an antihistamine drug, an active blocker of histamine receptors in the composition of cytirizine.
• S-pantaprozole, a pure optically active isomer of pantaprozole, selectively blocks the proton pump of the parietal cells of the gastric mucosa.
• R-rabeprozole, a pure optically active isomer of rabeprozole, selectively blocks the proton pump of the parietal cells of the gastric mucosa.
• dexibuprofen, a pure optically active isomer of ibuprofen, selectively blocking cyclooxygenase.
• dexketoprofen, a pure optically active isomer of ketoprofen, selectively blocking cyclooxygenase.
• esetodolac, a pure optically active isomer of ietodolac, selectively and selectively blocking cyclooxygenase.
• Esomeprazole, a pure optically active isomer of omeprozole, selectively blocks the proton pump of the parietal cells of the gastric mucosa.
• S-metoprolol, a selective blocker of beta-adrenergic receptors of the heart and blood vessels, isolated from racemic metoprolol
• Levomycetin.
• quinine.
• quinidine.
• L-lysine.
• L-thyroxine.
• L-dopa.
• levotiracetam.
• R-sibutramine. Not widely used (probably only in India), due to the FDA ban on the use of racemic sibutramine for the treatment of obesity due to side effects. According to Indian researchers, R-sibutramine is maximally devoid of these side effects, however, the effectiveness of R-sibutramine for safe weight loss has not been proven.
• L-carnitine. Used in food supplements.

Chirality in inorganic chemistry

Many complex compounds are chiral, for example, the well-known 2+ complex, in which three bipyridine ligands assume a chiral propeller arrangement. In this case, the ruthenium atom can be considered a stereogenic center in a complex with point chirality. The two enantiomers of complexes, such as 2+ , can be referred to as Λ (left turn of the propeller described by ligands) and Δ (right turn). Hexol is a chiral cobalt-containing complex, first discovered by Alfred Werner. Solid hexol is important as the first carbon-free substance to reflect optical activity.

Chirality of amines

Tertiary amines are chiral in a manner similar to carbon-containing compounds: the nitrogen atom carries four different substituent groups, including a lone pair. However, the energy barrier to stereocenter inversion is generally around 30 kJ/mol, which means that the two stereoisomers quickly convert into each other at room temperature. As a result, amines such as NHRR' cannot be recognized by sight, but NRR'R'' can be recognized when R, R' and R'' are enclosed in cyclic structures.

Chirality in literature

Although little was known about chirality at the time of Lewis Carroll, his work Alice Through the Looking-Glass contains a prescient reference to various types biological activity of enantiometric drugs: "Perhaps the looking-glass milk is undrinkable," Alice said to her cat. In James Blish's novel Spock Must Die! a series " Star Trek The tachyon mirrored by Mr. Spock is revealed to be stealing chemicals from the medical bay and using them to convert certain amino acids and oppositely chiral isomers.

Achirality and prochirality

The absence of chirality is denoted by the term "achirality". Achiral molecules can exhibit induced optical activity. A molecule is said to be prochiral if it can be made chiral by replacing a single atom, such as the hydrogen atom in CH 2 BrCl, with fluorine. When the chiral and prochiral fragments are combined in one molecule, the phenomenon of nuclear diastereotopy occurs, which is observed in the spectra of nuclear magnetic resonance. One of the methods for detecting the chirality of molecules is based on this.

see also

Notes

Links

• A. Borisova Chemists have flattened carbon. Gazeta.ru (30.07.2010). - Contains a description of some features of chirality. Archived from the original on August 22, 2011. Retrieved August 22, 2010.

Structural chemistry
Chemical bond:	Aromaticity | Covalent bond | Ionic bond | Metal connection | Hydrogen bond | Donor-acceptor bond | Tautomerism | Van der Waals connection
Structure display:	Functional group | Structural formula | Skeletal formula of organic compounds | Chemical formula | Ligand | Coordination geometry | Coordination sphere
Electronic properties:	Electronegativity | Electron affinity | Ionization energy | Polarity of chemical bonds | Octet rule

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. 8. 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 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.

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).

1. ru.wikipedia.org/wiki/Klest-elovik#

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

2. http://scienceblogs.com

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

3. www.bookofjoe.com

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 ( buzzword"nano" comes from the Greek. νάννος - dwarf). A monograph is devoted to chirality in chemistry, on the cover of which () - 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).

4. http://pubs.acs.org

On the side of a good-naturedly wagging tail dog is depicted structural formula 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 asymmetrical, and they are of two types, which differ in their shape, like an object from its mirror image. 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 ray" white light turns on 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 with crystals, some chemical compounds could exist in the form of both right- and left-handed varieties. However, it remained unclear what property of molecules this phenomenon is associated with: the most thorough chemical analysis couldn't find any difference between them! Such varieties of substances were called optical isomers, and the compounds themselves were called optically active. It turned out that the optical active substances there is a third type of isomers - 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

Louis Pasteur (https://ru.wikipedia.org)

The optical activity of crystals of physics was associated with their asymmetry; completely symmetrical crystals, such as cubic crystals table salt, 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, which, 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: I Z and ZR (or I Z and R.Z.). These structures are not mirror symmetric, 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

Jacob Hendrik van't Hoff (https://ru.wikipedia.org)

Such a theory was created by a 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- molecules in which there is 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.

Many scientists reacted to Van't Hoff's theory with distrust. And the well-known 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 so confidently to judge the highest problem of chemistry - the question of the spatial position of 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 everything space 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 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.
effects or even be toxic. This became apparent after the sensational tragic history with thalidomide, a drug that was prescribed to pregnant women in the 1960s as an effective sleeping pill and sedative. However, over time, its side teratogenic (from the Greek. τέρας - monster) action manifested itself, and
a lot of babies were born with congenital deformities. It was not until the late 1980s that it became clear that only one of the enantiomers of thalidomide, the dextrorotatory enantiomer, was the cause of the misfortune, and only the levorotatory isomer is a powerful tranquilizer. 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 for various forms rheumatoid arthritis, in some 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. So, levorotatory S-thyroxine ( medicinal product Levotroid is a naturally occurring thyroid hormone. And right-rotating 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 - 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.

Ilya Leenson,
cand. chem. Sciences, art. scientific collaborator Faculty of Chemistry, Moscow State University

Along with structural isomers, there are spatial isomers in the alkanes series. This can be represented by the example of 3-methylhexane.

The carbon atom, designated C*, is connected to four different groups. In this hydrocarbon, with the same order of binding of atoms, alkyl groups can be differently located in the space around the C* carbon atom. There are several ways to depict spatial isomers on a plane (Fig. 6.1, 6.2).

Rice. 6.1. Volumetric image using "wedges"

Rice. 6.2. Projection formulas Fisher

In Figure 6.2, the C* carbon atom is in the center, the horizontal line indicates the bond between the C* carbon and the groups protruding in front of the drawing plane, and the vertical line shows the bond between the C* atom and the groups located behind the drawing plane. Fisher projections can only be rotated in the drawing plane and only 180 degrees, not 90 degrees or 270 degrees. These formulas represent two different compounds. They differ from each other in the same way as an object and its mirror image, or like a left and right hand. The left and right hands are two objects very similar to each other, but it is impossible to combine them (not to put the left glove on the right hand), which means they are two different objects.

Two compounds: an object and its mirror image (I and II), incompatible with each other, are called enantiomers (from the Greek “enantio” - opposite).

The property of a compound to exist in the form of enantiomers is called chirality (from the Greek "chiros" - hand), and the compound itself is called chiral.

The 3-methylhexane molecule does not have a symmetry plane and therefore can exist in the form of enantiomers (see Fig. 6.1).

A molecule has chirality if it does not have a plane of symmetry. There are a number of structural elements that can make a molecule not identical to its mirror image. The most important of these is the chiral carbon atom.

A chiral atom or chiral center is a carbon atom bonded to four different groups and is designated C*.

A molecule in which two or more identical groups are attached to a carbon atom has a plane of symmetry and, therefore, does not have chirality, since the molecule and its mirror image are identical. Such molecules are called achiral .

For example, isopentane cannot exist as enantiomers and does not have chirality.

Enantiomers exhibit the same physical properties, except one. For example, the 2-bromobutane molecule exists as two enantiomers. They have the same boiling point, melting point, density, solubility, refractive index. One enantiomer can be distinguished from another by the sign of rotation of plane polarized light. Enantiomers rotate the plane of polarized light by the same angle, but in different directions: one - clockwise, the other - by the same angle, but counterclockwise.

Enantiomers have the same chemical properties, the rate of their interaction with reagents that do not have chirality is the same. In the case of a reaction with an optically active reagent, the reaction rates of the enantiomers are different. Sometimes they differ so much that the reaction of a given reagent with one of the enantiomers does not proceed at all.

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 their symmetry. Molecule achiral (non-chiral), if and only if it has axis of improper rotation, that is, an n-fold rotation (rotation by 360°/n) with subsequent reflection in a plane perpendicular to this axis reflects the molecule onto itself. So the molecule 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 (i.e. without symmetry), as they may have other forms. symmetry. However, all amino acids (except glycine) and many sugars are indeed both asymmetric and dissymmetric.

Chirality and life

Virtually all biological polymers must be homochiral in order to function (all of their constituent monomers have the same directionality. Another term used is optically pure or 100% optically active). All amino acids in proteins are "left handed" while all sugars in DNA, RNA and metabolic pathways are "right handed".

A mixture of 50% right and 50% left forms is called racemate or racemic mixture. Racemic polypeptides cannot form the special shapes required by enzymes, because in this case their side chains stick out randomly. Also, an amino acid with the wrong chirality destroys the stabilizing α-helix in proteins. DNA could not be stable in the form of a helix if there were at least one monomer with the wrong chirality - it would be impossible for it to form long chains. This means that DNA would not be able to store much information and sustain life.

Conventional chemistry produces racemates

A respected textbook on organic chemistry boldly quotes a universal chemical rule:

"The synthesis of chiral compounds from achiral reagents always results in a racemic modification"."Optically inactive reagents produce optically inactive products"

This is a consequence of the Laws of Thermodynamics. The right and left forms have the same free energy (G), so the free energy difference (ΔG) is zero. Constant chemical equilibrium(K) - a value expressing the mutual dependence between the concentrations of substances in the system when chemical equilibrium is reached. The equilibrium constant for any reaction (K) is the equilibrium ratio of the concentration of products to the active substance. The reaction between these two elements at any Kelvin temperature (T) is represented using the standard formula:

K = exp(–ΔG/RT)

Where R is the absolute gas constant (= Avogadro's number * Boltzmann's constant k) = 8.314 j./K.mol

For the reaction of changing "left" amino acids to "right" (L → R), or vice versa (R → L), ΔG \u003d 0, so K \u003d 1. Thus, the reaction reaches equilibrium when the concentration of "left" forms and " right" forms of molecules is the same, i.e. a racemate is produced. This explains the tutorial rule above.

Separating the left forms from the right

In order to resolve the racemate (that is, to separate the two enantiomers), another homochiral substance must be introduced. The procedure is explained in an organic chemistry textbook. The idea is that "left" and "right" forms of matter have the same properties, except when dealing with a chiral phenomenon. Analogy: Our left and right hands grab an achiral object like a baseball bat in the same way, but they fit differently on chiral objects like the left hand glove. Thus, to solve a racemate, a chemist usually uses a ready-made homochiral substance from living organisms. The reaction products of the R and L enantiomers with the exclusively right-handed substance R´, i.e. R-R´ and L-R´ (called diastereoisomers), are not mirror images of each other. Thus, they have different physical properties, such as water solubility, which means that they can be separated.

However, this does not solve the mystery of the original origin of optical activity in living organisms. Recent international conference "The Origin of Homochirality and Life" clearly showed that the origin of this chirality is a complete mystery to evolutionists. The probability of random formation of one homochiral polymer from N monomers is 2 –N. For a small protein of 100 amino acids, this probability is = 2 -100 = 10 -30. Note that this is the probability of generating any homochiral polypeptide. The probability of the formation of a functional homochiral polymer is extremely low, since the exact sequence of amino acids in many places is required. Of course, many homochiral polymers are necessary for life, so the probabilities must be multiplied. The case is thus not an alternative.

Another problem is that homochiral biological substances racemize over time. This is the basis of the amino acid racemization dating method. As a dating method, it is not very reliable, since the degree of racemization is highly dependent on temperature and pH, and depends on the type of amino acid. Racemization is also a huge problem in the synthesis and hydrolysis of peptides. This shows that the tendency of inanimate chemistry is towards death, not towards life.

A tragic reminder of the importance of chirality is thalidomide. In the early 1960s, this medicine was prescribed to pregnant women suffering from morning sickness and vomiting. However, while the left forms are a strong tranquilizer, the right forms can disrupt the development of the fetus, leading to serious birth defects. Unfortunately, the synthesis of the drug produced the racemate, as might be expected, and the wrong enantiomer was not removed before the drug was marketed.

During my own chemistry education, one of the required experiments demonstrated these concepts. We synthesized the dissymmetric complex ion 3+ 9 from achiral reagents, so that a racemate was produced. We resolved it by reaction with a homochiral acid from a plant source, forming diastereoisomers that could be resolved by fractional crystallization. When the resulting homochiral crystals were dissolved and dissolved activated charcoal (catalyst) was added, the material rapidly racemized as the catalyst accelerated the equilibrium.

Researchers in the field of the origin of life tried to come up with other means of obtaining the necessary homochirality. There have been unsuccessful attempts to solve racemates in other ways.

UV light with circular polarization

In light with circular polarization, the direction electric field rotates along the beam, so this is a chiral phenomenon. Homochiral substances have different absorption intensities of the left and right CP light - this is called circular dichroism (CD). Similarly, CP light is absorbed differently by left-handed and right-handed enantiomers. Since photolysis (destruction by light) only occurs when photons of light are absorbed, CP light destroys one enantiomer more quickly and more readily than the other. However, because light also destroys the "correct" shape to a certain extent, this would not produce the 100% homochirality required for life. One of the best results was 20% optically pure camphor, but this happened after 99% of the starting material had been destroyed. 35.5% optical purity would come out after 99.99% degradation. "An almost optically pure mixture (99.99%) ... is reached at the asymptotic point where absolutely no material remains."

Another problem is that the magnitude and sign (ie, encouraging left or right forms) of the CD depends on the frequency of the CP light. This means that resolution can only occur with CP light in a narrow frequency band. In a wide band, however, enantioselective effects destroy it.

Recently, the idea of ​​circularly polarized light as a solution to the problem of chirality has been brought back to life in an article by Australian astronomer Jeremy Bailey, published in Science and received publicity in the media. His team has detected circularly polarized infrared radiation in the nebula. They agree in the paper that they found neither the necessary circularly polarized ultraviolet light nor evidence that amino acids are formed in the nebula. They are also aware of the extremely limited enantioselectivity of CP light and the fact that the effect is zero over the entire spectrum. However, their belief in chemical evolution influences how they interpret the data.

Not all evolutionists are convinced by Bailey's team's proposal. For example, Jeffrey Bada said: “It's just a sequence of steps called 'maybe'. For me, it makes the whole big picture a big "maybe""

Another proposed circularly polarized light source is the neutron star synchrotron, but this is speculation and does not solve chemical problems.

Beta decay and the strength of the weak nuclear force

Beta decay is a form of radioactive decay and is driven by one of the four fundamental forces in nature, the weak nuclear force. This force has a slight chirality called parity nonconservation, so some theorists have thought that β decay could be responsible for chirality in living organisms. However, the strength of the weak nuclear force is aptly named - the effect is very small - very far from producing the required 100% homochirality. One chirality expert, organic chemist William Bonnet, emeritus professor at Stanfoy University, said: "none of these works provided conclusive findings". Another researcher concluded:

"the necessary exceptional prebiological conditions do not support the idea of ​​β-radiolysis as a selection factor for the property of optical activity in wildlife"

Another aspect of parity nonconservation is that L-amino acids and D-sugars theoretically have slightly lower energies than their enantiomers. But the energy difference is immeasurable - only about 10–17 kT. This means that there will be only one excess L-enantiomer for every 6x10 17 molecules of the racemic mixture of amino acids!

Optically active quartz powders

Quartz is a widespread mineral, the most common form of silica (SiO 2 ) on Earth. Its crystals are hexagonal and dissymmetric. Some researchers have tried to use optically active quartz powders to absorb one enantiomer more than the other. But their attempts were unsuccessful. In addition, there are an equal number of right-handed and left-handed quartz crystals on Earth.

self-selection

Some chiral substances crystallize into homochiral crystals. Louis Pasteur was not only the founder of the germ theory of disease, but also a destroyer of ideas about the "spontaneous origin" of life and a creationist. He was also the first person in history to solve a racemate. He used tweezers to separate the left and right crystals of such a substance, sodium aluminate tartrate.

This separation happened due to the external intervention of an intelligent researcher who could recognize different patterns. There was no such explorer on the supposed primitive Earth. Therefore, the two forms, even if they could be separated by chance, would again dissolve together and again form a racemate.

Also, Pasteur was lucky to choose one of the few substances that self-decomposes into a crystalline form. And even this substance only has this property at temperatures below 23°C, so it was lucky that laboratories in the 19th century were not very well heated!

Successful seeding

Some theorists have suggested that the successful seeding of a solution supersaturated with a homochiral crystal would crystallize the same enantiomer. However, the "primordial soup", if it existed, would have been extremely thin and highly contaminated, as has been noted by many researchers. Also, nothing could be done with the growing homochiral crystal, as it would be immersed in a solution of the remaining wrong enantiomer. Concentrating the solution would crystallize the wrong enantiomer. Diluting the solution would dissolve the crystal, so the intended process would have to start over.

Homochiral template

Some researchers have proposed that the homochiral polymer arose by chance and served as a template. However, this assumption runs into serious problems. A template of 100% right polycytidylic acid (RNA containing only cytosine monomers) has been synthesized (by smart chemists!). This could direct oligomerization (formation of small chains) from (activated) G (guanine) nucleotides. Indeed, pure right-handed Gs oligomerized much more efficiently than pure left-handed Gs. But racemic Gs did not oligomerize because:

“monomers of opposite chirality are incorporated into the template as chain terminators… This suppression is a major problem for many theories of the origin of life”

tRNAs chose the correct enantiomers

One attempt to solve the chirality problem was made by Russell Doolittle, professor of biochemistry at the University of California, San Diego. He claimed: "From the very beginning of their [t-RNA synthase] existence, they probably bound only L-amino acids" He never explains how such complex enzymes could function if they were not themselves homochiral, or how they operated before RNA was composed of homochiral ribose. Doolittle's "solution" is nothing more than a go-ahead for the problem. It is hardly refutable if not for the fact that it appeared in a famous anti-creation book, which says something about the quality of their editing or the quality of the anti-creation arguments.

It seems that Doolittle was trying to explain his previous televised creation/evolution debate with biochemist Dwayne Gish, which took place in front of 5,000 people at Liberty University on October 13, 1981. Proevolutionary Journal Science described the debate as a "debacle" in favor of Gish. Next day pro-evolutionary Washington Post reported on the debate under the heading "Science Lost One Zero to Creationism". The article quoted Dullittle saying "How will I meet my wife?" which suggests that Dullittle himself knew he had lost.

Magnetic fields

Several German chemists led by Edhard Bremeier of the Institute Organic Chemistry and Biochemistry in Bonn stated that a very strong magnetic field (1.2–2.1 T) produced 98% homochiral products from achiral reagents. This has enabled chemists such as Philip Kosiensky of the University of Southampton to speculate that the Earth's magnetic field may have caused the homochirality of life. Although the Earth's magnetic field is nearly 10,000 times weaker than the one used in the experiment, Kosienski speculated that huge time spans would have resulted in the homochirality we see today. He probably forgot about the reversions of the paleomagnetic field!

Other chemists, like Tony Barret of Imperial College London, thought the German experiment "seems too good to be true." This caution paid off about six weeks ago. No one else was able to reproduce the results of the German team. It turns out that one researcher on the team, Guido Zadel, on whose dissertation the work was based, mixed the reagents with a homochiral additive.

[Magnetochiral dichroism - post script]

Conclusion

The tutorial quoted earlier says:

“We eat optically active bread and meat, live in houses, wear clothes and read books made from optically active cellulose. The proteins that make up our muscles, the glycogen in our liver and blood, the enzymes and hormones… all are optically active. Natural substances are optically active, since the enzymes that form them are ... optically active. As to the origin of optically active enzymes, we can only speculate."

If we can only "speculate" about the origin of life, why do so many people say that evolution is a "fact"? Repeat gossip often enough and people will swallow it.

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