| 1. The structure of the water molecule. | ||
| Water has a polar molecule. Oxygen, as a more electronegative atom, draws upon itself the electron density it shares with the hydrogen atom and therefore carries a partial negative charge; the hydrogen atoms from which the electron density is displaced carry a partial positive charge. Thus, a water molecule isdipole, i.e. has positively and negatively charged areas. (The model on the right is three-dimensional; it can be rotated by pressing the left mouse button.) |
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2. Hydrogen bonds.
3. Water as a solvent. |
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In relation to water, practically all substances can be divided into two groups:
1. Hydrophilic(from the Greek "phileo" - to love, having a positive affinity for water
). These substances have a polar molecule containing electronegative atoms (oxygen, nitrogen, phosphorus, etc.). As a result, individual atoms of such molecules also acquire partial charges and form hydrogen bonds with water molecules. Examples: sugars, amino acids, organic acids.
2. Hydrophobic(from the Greek "phobos" - fear, having a negative affinity for water
). The molecules of such substances are non-polar and do not mix with a polar solvent, such as water, but are highly soluble in organic solvents, for example, ether, and in fats. An example would be linear and cyclic hydrocarbons. including benzene.
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Question 2. Look closely at the two molecules on the right. Which of these molecules do you think is hydrophilic and which is hydrophobic? Why do you think so? Have you found out what these substances are? Among organic substances there are also compounds, one part of the molecule of which is non-polar and exhibits hydrophobic properties, and the other is polar and, therefore, hydrophilic. |
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| Such substances are called amphipathic
. Molecule phosphatidylserine(one of the phospholipids of the plasma membrane of cells, right) can serve as an example of amphipathic compounds. Question 3.
Look closely at this molecule. Which part do you think is hydrophilic and which is hydrophobic? Position the molecule so that it is as clear as possible, create a graphic file and in it indicate the hydrophilic and hydrophobic sections of the molecule. 4. Water as a solvent in living organisms.
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In addition, the transport function of internal fluids both in multicellular animals (blood, lymph, hemolymph, coelomic fluid) and in multicellular plants is directly related to the property of water as a solvent.
5. Water as a reagent.
The importance of water is also associated with its chemical properties - as an ordinary substance that enters into chemical reactions with other substances. The most important are the splitting of water under the influence of light ( photolysis) in the light phase photosynthesis, the participation of water as a necessary reagent in the reactions of the breakdown of complex biopolymers (it is no coincidence that such reactions are called hydrolysis reactions
). And, conversely, during reactions of the formation of biopolymers, polymerization, water is released.
Question 4.
What inaccuracy in the last sentence would a chemist correct?
Hydrophilic substances
Hydrophilic matters (substances)
Solids that have the property of being wetted by water. Not wetted by oily liquids.
A brief electronic reference book on basic oil and gas terms with a system of cross-references. - M.: Russian State University of Oil and Gas named after. I. M. Gubkina. M.A. Mokhov, L.V. Igrevsky, E.S. Novik. 2004 .
See what “Hydrophilic substances” are in other dictionaries:
Hydrophilic ointment bases- The style of this article is non-encyclopedic or violates the norms of the Russian language. The article should be corrected according to Wikipedia's stylistic rules. Main article: Ointment bases Hydrophilic ointment bases ointment bases used for ... ... Wikipedia
Hydrophilic- (from hydro and phil) “water-loving” substances whose molecules are electropolar and easily combine with water molecules. The opposite is hydrophobic (“water-hating”) substances... The beginnings of modern natural science
Sealing agents- high-polymer hydrophilic substances used to compact liquid nutrient media. In media for chemoorganotrophs as U.V. use agar (see) and gelatin (see), for autotrophic organisms silica gel (see). Less... ... Dictionary of microbiology
Substances that can accumulate (thicken) on the surface of contact of two bodies, called the phase interface, or interfacial surface. On the interfacial surface of P. a. V. form an adsorption layer of increased concentration... ... Great Soviet Encyclopedia
surfactants (surfactants)- substances that can be adsorbed at the interface and cause a decrease in surface (interfacial) tension. Typical surfactants are organic compounds whose molecules contain lyophilic and lyophobic (usually hydrophilic and... ... Encyclopedic Dictionary of Metallurgy
Surfactants- (a. surfactants; n. grenzflachenaktive Stoffe, oberflachenaktive Stoffe; f. substances tensio actives; i. surfac tantes), substances with an asymmetric mol. structure, the molecules of which have a diphilic structure, i.e. contain lyophilic and... Geological encyclopedia
surfactants- Surfactant Substances that can be adsorbed at the interface and cause a decrease in surface area. (interfacial) tension. Typical surfactants are organic. compounds whose molecules contain lyophilic and lyophobic (usually hydrophilic and hydrophobic) at... Technical Translator's Guide
Surfactant species Substances with an asymmetric molecular structure, the molecules of which have a diphilic structure, that is, they contain lyophilic and lyophobic (usually hydrophilic polar groups and hydrophobic radicals) atomic groups. Diphilic... ... Oil and Gas Microencyclopedia
Cell membranes- This term has other meanings, see Membrane A picture of a cell membrane. The small blue and white balls correspond to the hydrophilic “heads” of the lipids, and the lines attached to them correspond to the hydrophobic “tails”. In the picture... ... Wikipedia
Selective permeability- This term has other meanings, see Membrane A picture of a cell membrane. The small blue and white balls correspond to the hydrophilic “heads” of the lipids, and the lines attached to them correspond to the hydrophobic “tails”. The figure shows... ... Wikipedia
The term hydrophilicity (derived from the ancient Greek words “water” and “love”) is a characteristic of the intensity of interaction of a substance with water at the molecular level, that is, the ability of a material to intensively absorb moisture, as well as the high wettability of water by the surface of the substance. This concept can be applied to solids, as a property of the surface, and to individual ions, atoms, molecules and their groups.
Hydrophilicity is characterized by the magnitude of the bond between adsorption water molecules and the molecules of a substance; in this case, compounds are formed in which the amount of water is distributed according to the bond energy values.
Hydrophilicity is inherent in substances that have ionic crystal lattices (hydroxides, oxides, sulfates, silicates, clays, phosphates, glasses, etc.) that have polar groups -OH, -NO 2, -COOH, etc. Hydrophilicity and hydrophobicity- special cases of interaction of substances with solvents (lyophilicity, lyophobicity).
Hydrophobicity can be considered as a small degree of hydrophilicity, because the action of intermolecular forces of attraction will always be more or less present between the molecules of any body and water. Hydrophilicity and hydrophobicity can be distinguished by the way a drop of water spreads on a body with a smooth surface. The drop will spread completely on the hydrophilic surface, and partially on the hydrophobic one, while the value of the angle formed between the surface of the wetted material and the drop is influenced by the degree of hydrophobicity of the given body. Hydrophilic substances are substances in which the strength of molecular (ionic, atomic) interactions is quite strong. Hydrophobic are metals that are devoid of oxide films, organic compounds that have hydrocarbon groups in the molecule (waxes, fats, paraffins, some plastics), graphite, sulfur and other substances that have weak interactions at the intermolecular level.
The concepts of hydrophilicity and hydrophobicity are applied both in relation to bodies and their surfaces, and in relation to individual molecules or individual parts of molecules. For example, the molecules of surface active substances contain polar (hydrophilic) and hydrocarbon (hydrophobic) compounds. The hydrophilicity of the surface part of the body can change dramatically due to the adsorption of such substances.
Hydrophilization is the process of increasing hydrophilicity, and hydrophobization is the process of decreasing it. These phenomena are of great importance in the cosmetics industry, in textile technology for hydrophilization of fabrics (fibers) to improve the quality of washing, bleaching, dyeing, etc.
Hydrophilicity in cosmetics
The perfumery and cosmetics industry produces hydrophilic creams and gels that protect the skin from impurities that are not soluble in water. Such products contain hydrophilic components that form a film that prevents the penetration of water-insoluble pollutants into the surface layer of the skin.
Hydrophilic creams are made from an emulsion that is stabilized with suitable emulsifiers or with a water-oil-water or oil-water base. In addition, these include dispersed colloidal systems in which hydrophilic surfactant components are stabilized and consisting of water-dispersed or water-glycol mixed solvents of higher fatty acids or alcohols.
Hydrogels (hydrophilic gels) are prepared from bases consisting of water, a mixed non-aqueous or hydrophilic solvent (ethyl alcohol, propylene glycol, glycerin) and a hydrophilic gelling agent (cellulose derivatives, carbomers).
Hydrophilic properties of creams and gels:
· quickly and well absorbed;
· nourish the skin;
· after their use there is no feeling of greasyness;
· cleanse the skin;
· have a strengthening effect on the skin;
· reduce the effect of negative environmental factors;
Help the skin maintain its natural ability to regenerate.
Hydrophilic creams and gels are designed to protect the skin when working with water-immiscible oils, fuel oil, petroleum, paints, resins, graphite, soot, organic solvents, cooling and lubricating solutions, construction foam and numerous other mildly aggressive substances. They are also indispensable when repairing a car, renovating an apartment, during construction, in the country when working with fertilizers and soil.
The KorolevPharm company produces various types of perfumery and cosmetic products, including hydrophilic and hydrophobic creams. The company is a contract manufacturer and carries out all stages of production: development of recipes, certification, launching production, serial production of products. The production site is equipped with modern equipment.
The enterprise is certified for compliance with the requirements
A lotus leaf on which water runs, collected in balls, water-repellent surfaces and protective compounds for shoes, mugs of oil floating in a broth - all these are examples of a property of molecules called hydrophobicity. Besides, hydrophobic effect plays an important biological role: the folding and proper functioning of protein molecules, the formation of biomembranes, and the recognition of molecules by each other are also “programmed” using hydrophobic properties. Interestingly, the hydrophobic effect is not reduced to “ordinary” physical interactions: behind it stands the Second Law of Thermodynamics and a quantity called entropy.
Rabies
Hydrophobia, or hydrophobia(from ancient Greek. νδωρ - “water” and φοβος - “fear”) is the fear of painful swallowing spasms when trying to take a sip of water, at the sight of water, or at any mention of it. It is observed in cases of tetanus, hysteria, rabies (and rabies itself was previously called by this very word).
So, hydrophobicity, which will be discussed, is about the properties of molecules, and not symptoms in people.
The expression “water off a duck’s back”, familiar to everyone from childhood, shows that hydrophobicity- not such an unprecedented phenomenon as its name might suggest. Indeed, the effect of “repulsion” of water is often found around us: just look at a goose feather or lotus leaf (Fig. 1 A), along which a drop of water runs down, like a ball of mercury on the surface of glass, leaving no trace behind it. Classical ideas about hydrophobic surfaces say that the indicator here is the contact angle θ, which for wetted surfaces is less than a right angle (90°), and for non-wettable surfaces it is greater than it (Fig. 1 b) . In particular, for a drop of water on the surface of paraffin θ = 109°, and on the surface of the most hydrophobic known material - fluoroplastic - it will be 112°. At the same time, an “absolutely” hydrophobic surface would be described by an angle of 180°, when water rolls off the surface without stopping for a second.
So is goose really more hydrophobic than fluoroplastic? In fact, this is true, but this is achieved through a small trick: the surface of a goose feather (as well as a lotus leaf) is not smooth, but covered with microscopic pyramids or hairs, which reduces the contact area with the drop and effective adhesion (Fig. 1 V) . Based on the same principle superhydrophobic surfaces that repel water almost perfectly (video 1).
Figure 1. Lotus leaf: an example of a hydrophobic surface. A - Hydrophobic actually means non-wettability when water rolls off the surface completely, leaving no wet marks. b - Determination of hydrophobic surface based on contact angle θ: at θ< 90° поверхность называют смачиваемой (гидрофильной), при θ >90° - non-wettable (hydrophobic). The effect of absolute hydrophobicity (or superhydrophobicity) is achieved due to microscopic roughnesses that reduce the area of contact of the drop with the surface. V - How the surface of a lotus is structured: microscopic spines prevent drops of water from moistening the surface, and they roll off the leaf. A drop of water cannot “flow” between the spines either, because at this scale, surface tension no longer allows the drop to split into smaller ones.
Video 1. Superhydrophobic surface. Microscale surface roughness ( cm. rice. 1 b) reduces the effective area of contact with a drop of water, which on this scale behaves like an elastic body due to surface tension.
To understand Why Some substances are happily wetted by water, but water rolls off the duck, as the proverb says. You need to go down to the level of individual molecules and consider how the molecules interact with each other.
Hydrophobic molecules
From the point of view of chemical structure hydrophobic(or, what is the same, non-polar) are molecules that do not contain chemical groups capable of forming hydrogen bonds with water. For example, these are benzene and other liquid hydrocarbons (gasoline components). However, the most interesting properties have amphiphilic molecules containing both polar and nonpolar parts: this leads to the fact that they form quite complex structures in mixtures with water: micelles, vesicles, layers and more complex forms. The formation of all these complex forms is controlled hydrophobic effect.
Interestingly, the question of the molecular nature of hydrophobicity goes back to Benjamin Franklin, who, in his free time from government affairs, studied the spreading of olive oil over the surface of a pond. The area of the stain from one spoon of oil was the same all the time - half an acre - and the thickness was actually equal to one molecule. This was in 1774, and although at that time ideas about the molecular nature of substances were still extremely vague, the general curiosity of statesmen was, as we see, not like today. One way or another, the experiment with oil marked the beginning of studies of monomolecular lipid films, from which it undoubtedly became clear: some molecules “dislike” water so much that they not only do not mix with it, but are also ready to get rid of water in all possible ways - for example, by accumulating in the form of a layer one molecule thick (monolayer) at the interface between water and air. (More details on studies of lipid films can be found in the article “ Mermaid molecules » .)
Another important type of amphiphile molecules are soaps, which are widely used in everyday life and in the national economy. The principle of their operation can be gleaned even from commercials: the non-polar part of the detergent molecules “sticks” with pollutant molecules (usually hydrophobic), and the polar part actively interacts with water molecules. As a result, it happens solubilization: dirt comes off the surface and is enclosed within aggregating soap molecules, exposing the polar fragments “outside” and hiding the hydrophobic parts “inside”.
However, what allows us to enjoy the commercial qualities of the best detergents is an even more important quality of amphiphilic molecules (namely, lipids): they serve as the shell for all known forms of life, forming a cell membrane under which all life processes take place ( cm. « The lipid foundation of life » ). This important fact tells us that the molecular nature of the hydrophobic effect is not an idle thing, but is of fundamental importance for all biology, not to mention applied industries.
But upon closer examination, it turns out that no fundamental physical interaction, such as gravity or electrostatic forces, is responsible for the “attraction” of hydrophobic particles to each other and their “repulsion” from water. Its nature lies in a physical principle that imposes restrictions on the direction of most spontaneous processes, namely, in Second law of thermodynamics.
A little thermodynamics
Thermodynamics is one of the first sciences to build a bridge between the microscopic world of atoms and molecules and “our” macroscopic world. Its birth is associated with the study of the operation of steam engines and the name of Nicolas Carnot (1796–1832), after whom the thermodynamic cycles that determine the amount of work that a machine can produce are named. His work was continued by Joule, Kelvin and Clausius, who brought a powerful theoretical basis to this initially purely practical area.
Through the efforts of these scientists, the basic laws, or started, thermodynamics, summarizing centuries of empirical experience in observing thermal processes. The first principle speaks about the conservation of energy of an isolated system (“the law of conservation of energy”), and the second principle speaks about the direction of spontaneous processes. (There are also zero and third principles, but we will not talk about them here.) The concept of entropy(S), which has gained fame as the most mysterious thermodynamic quantity. Initially formally defined by Clausius as the ratio of heat imparted to a system to temperature (ΔS = ΔQ/T), entropy later acquired the meaning of a global “measure of chaos.” Since then, entropy has become the basis of the modern formulation of the Second Law:
Spontaneous processes in an isolated system are accompanied by an increase in entropy.
Ludwig Boltzmann (1844–1906) connected this entire thermal “kitchen” with the level of the atoms that make up matter, even before the atomic structure of matter became generally accepted. He considered the main achievement of his life to be the discovery (in 1877) of a statistical formula for calculating entropy: S = k × logW, where S is entropy, k is a constant, later named by Planck after Boltzmann himself, and W is the statistical weight of the state (the number microstates, which implements this macrostate). Despite poor eyesight, he saw significantly deeper than others “into the depths” of matter: he was the first to feel the power of the statistical approach to describing thermodynamic ensembles and applied it to molecular physics. There is a version that Boltzmann committed suicide due to a misunderstanding of his contemporaries, whom he was radically ahead of. The above-mentioned formula is carved on his tombstone in the cemetery in Vienna.
Despite all the mystery of the concept of entropy, the meaning of the Second Law is quite simple: if a system is isolated (that is, it does not exchange either matter or energy with the outside world), then it will tend to the state thermodynamic equilibrium, - such a macrostate that is realized by the maximum possible number of microstates (in other words, which has maximum entropy). For example, a broken cup will never stick itself back together again: the initial state (the whole cup) is realized in only one way (S=0), but the final state (the broken cup) is realized in an astronomically large number of ways (S>>0). Therefore, alas, from a global perspective, all cups are doomed. The wonderful popular science book by Peter Atkins, Order and Disorder in Nature, is devoted to an explanation of the Second Law “for housewives.”
Hydrophobic effect from the point of view of statistical physics
So, knowing the Second Law, we understand why a cup of tea on the table will definitely cool down to room temperature, but will never warm up again on its own, taking heat away from the air in the kitchen. (If not, then you should definitely read Atkins' book.) But do the same reasoning apply to explain, for example, the immiscibility of water and oil? After all, the Second Law strives to “level everything,” and water and oil, on the contrary, refuse to dissolve in each other (Fig. 2 A).
Figure 2. Illustration of the hydrophobic effect. A - The hydrophobic effect (essentially the Second Law of Thermodynamics) causes water to “repel” non-polar molecules (such as oil) and reduce the area of contact with them. Because of this, many small droplets of oil in the water will eventually merge together and form a layer. b - The formation of an ordered (“icy”) layer of water molecules near a hydrophobic surface is necessary so that water molecules can form hydrogen bonds with each other. But this leads to a drop in entropy, which is disadvantageous in connection with the Second Law. V - A natural opportunity to increase entropy is to reduce the area of contact of hydrophobic molecules with water, which occurs when several non-polar molecules aggregate together. In the case of amphiphilic molecules, self-organization appears and the formation of rather complex supramolecular structures such as micelles, bilayers and vesicles ( cm. rice. 3).
Indeed, if we consider only oil, it will seem that thermodynamics does not work: dissolving an oil film in the thickness of a liquid would clearly increase entropy compared to a monolayer. But everyone knows that in fact the opposite happens: even if you shake water and oil, the emulsion will disintegrate after some time, and the oil will again form a film, leaving the aqueous phase.
The fact is that water in this example is an equal participant in the system under consideration, and in no case should it be overlooked. As is known, the properties of water (even its liquid state under normal conditions) are determined by the ability to form hydrogen bonds. Each water molecule can form up to four bonds with its “neighbors,” but for this to happen, the water must be “in the water.” If there is a non-polar surface in water, the molecules adjacent to it no longer feel “free”: in order to form the desired hydrogen bonds, these molecules have to be oriented in a strictly defined way, forming an “icy” shell (Fig. 2 b) around a hydrophobic object. This forced ordering is characterized by a significant drop in the entropy of the oil-water system, which forces hydrophobic molecules to aggregate among themselves, reducing the area of contact with the polar environment, and therefore an unfavorable decrease in the entropy factor. In fact, it is the water that causes the oil to coalesce into one large drop or spot, implementing the dialectical principle of “like to like.”
This interaction of polar and non-polar phases is called hydrophobic effect. This phenomenon causes detergent molecules to form micelles in solution, and lipids to form mono- and bilayers. The latter can close on themselves with the formation of vesicles (liposomes) or biological membranes surrounding the cell (Fig. 3). More complex forms of lipid polymorphism have also been found, for example cubic lipid phase, widely used in structural studies of membrane proteins.
Figure 3. Lipid polymorphism. Depending on the shape and other properties of the molecule, characterizing the asymmetrical structure of the head and tail, lipids form various supramolecular structures. Top down: 1 - with the reverse conical shape of the molecule, structures with positive curvature are formed (micelles and the hexagonal phase H I); 2 - the cylindrical shape gives flat (lamellar) structures such as bilayers; 3 - with a conical shape, both inverted hexagonal (H II) and micellar phases are formed.
“Deep into” the hydrophobic effect
In the case of biological molecules, the hydrophobic effect plays a special role, since it forms biomembranes, without which life is impossible, and also makes a decisive (up to 90% of all work) contribution to the folding of protein molecules, the side chains of amino acid residues of which can have a different nature: hydrophobic or hydrophilic . The presence of such different entities within one linear molecule gives all the diversity of forms and functions that is observed in proteins.
However, on a submolecular scale, the hydrophobic effect manifests itself differently than in the case of an extended non-polar surface or a whole spoon of oil: apparently, a cluster of hydrophobic particles will be stable only if its size exceeds a threshold value (≈1 nm); otherwise it will be destroyed by the thermal movement of molecules. Molecular dynamics (MD) simulations show differences in the structure of “pure” water and water near small (<1 нм) и большой (>>1 nm) hydrophobic particles. If in the first two cases each a water molecule can form up to four hydrogen bonds, but in the case of a large hydrophobic particle there is no such possibility, and water molecules have to line up in an “icy” shell around this particle (Figure 2 b and 4).
Figure 4. Different configurations of water molecules near a small ( A) and big ( b) hydrophobic particles(in both cases shown red spheres). According to MD data, particles smaller than 1 nm can be easily surrounded by water without limiting its “freedom” and the ability to form hydrogen bonds. In the case of larger particles, in order to form a hydrogen bond, the boundary water molecule has to be oriented in a special way relative to the hydrophobic surface, which leads to the ordering of an entire water layer (or several) and a decrease in the entropy of the solvent. In this case, the average number of hydrogen bonds per water molecule decreases to three. It is interesting that the nature of the dependence of the solvation energy of a particle on its size also changes here: up to 1 nm, the energy depends on the volume of the particle, and above this threshold, on its surface area.
This same “threshold size” was also confirmed in an experiment to determine the contribution of the hydrophobic effect to the folding of the polymer chain depending on the size of the monomer side group and temperature. The registration of the free energy of solvation was carried out using an atomic force microscope, which “unbraided” the polymer molecule one link at a time. Interestingly, the cutoff value of 1 nm approximately coincides with the size of large side chains of amino acid residues that determine the folding of the protein molecule.
Since the hydrophobic effect is entropic in nature, its role in various processes (that is, contribution to free energy) depends on temperature. It is curious that this contribution is maximum precisely under normal conditions - at the same temperature and pressure at which life mainly exists. (Under the same conditions, the main biological solvent - water - is close to the equilibrium between liquid and vapor.) This leads to the idea that life deliberately “chooses” conditions of existence close to phase transitions and equilibrium points: apparently, this provides the possibility of especially reliable control and fine control of such seemingly “inert” things as the structure of membranes and protein molecules.
Research in recent years has further emphasized the role of water both in the hydrophobic effect and in intermolecular recognition (for example, when an enzyme binds its substrate or a receptor binds the ligand it recognizes). In the active center of a protein, as a rule, there are “bound” (and therefore ordered) water molecules. When the ligand penetrates the binding site on the protein surface, water is “released”, which makes a positive contribution to entropy (Fig. 5); however, the enthalpy component of the free energy change can be either negative or positive. Using calorimetric titration and molecular modeling, the thermodynamic pattern of binding by the enzyme carbonic anhydrase of many ligands, similar in structure, but differing in the size of hydrophobic groups, was established. The analysis showed that the contribution of enthalpy and entropy to the Gibbs free energy in each case can be individual, and it is impossible to say in advance which process will play a decisive role. It is only absolutely clear that the structure and dynamics of the layers of water molecules closest to the active site play in intermolecular recognition the same important role as the correspondence of the ligand to the receptor, which introduces a new level of complexity into the “classical” models of interaction of two molecules of the “key-lock” type. or "glove hand".
The folding of homo- and heteropolymers can be divided into several stages (Fig. 6):
- If you start with an elongated chain, the first stage will be entropy folding, which is a direct consequence of the Second Law of Thermodynamics: a fully straightened polypeptide chain has zero entropy, which is instantly “corrected” by statistical forces that turn the thread into "statistical ball".
- In the random coil conformation, hydrophobic side residues are brought closer together in space and aggregate under the influence of the hydrophobic effect. This is confirmed by observation of the principles of three-dimensional packaging of protein globules: inside there is a “core” of hydrophobic residues, and on the surface of the molecule there are polar and charged amino acid residues. The resulting form at this stage is called molten globule.
- In the case of biopolymers, the matter does not end there: specific interactions between residues close in space make the packing even more dense (true globule). The free energy then experiences a significant drop, and this is often considered a criterion for a “well-packed” structure.
Figure 6. The role of hydrophobic collapse in the folding of three polymer chains with different hydrophobicities of the constituent monomers: a hydrophobic polymer, a hydrophobic-hydrophilic copolymer, and a globular protein (from top to bottom) - free energy plotted as a function of the radius of gyration, indicating the compactness of the chain packing. 1) Any linear chain from a fully stretched state quickly twists into statistical tangle. 2) The spatial proximity of nonpolar side chains leads to hydrophobic collapse of the coil and the formation molten globule. 3) In the case of proteins, evolutionarily selected specific contacts between the side chains of adjacent amino acid residues (such as hydrogen bonds or electrostatic interactions) further reduce the free energy and pack the protein into a dense globules. Hydrophobic polymers do not have such interactions and therefore their folding stops at the random coil stage.
Previously, it was believed that the third stage is an indispensable feature of a functional protein, but recently more and more attention has been paid to the so-called underordered proteins (intrinsically disordered proteins), which do not have a clearly defined spatial form, and in fact there is no stage of formation of specific contacts. (By the way, the proportion of hydrophobic residues in them is significantly smaller compared to globular proteins.) Perhaps this allows them to interact in a living cell not with one protein or ligand, but with tens or even hundreds of structurally different partner molecules, taking part in a very subtle regulation of cellular processes.
The hydrophobic effect also plays a decisive role in the folding of membrane proteins (MPs), which perform many vital functions from the transport of molecules and ions through the membrane to the reception and recognition of each other by cells. Due to the fact that most of them are immersed in the hydrophobic bilayer of the membrane, the structure of the transmembrane (TM) domain differs significantly from the packaging of soluble globular proteins: their TM segments are significantly more hydrophobic, and hydrophobic side chains are located not only inside the protein (as in the case globular proteins), but also on the surface where the protein comes into contact with the hydrocarbon chains of lipid molecules.
It is important that hydrophobicity also comes into play before that how the protein ends up in its place of work (that is, in the membrane). During ribosomal synthesis, MBs do not enter the cytoplasm, like globular proteins, but into translocon- a rather complex molecular machine, built in the form of a channel and responsible for both the secretion of proteins and the delivery of MB into membranes. It turned out that the translocon can “feel” the hydrophobicity of a protein fragment passed through it and, upon reaching a certain threshold of hydrophobicity, “spits out” this fragment not “forward” (through the channel into the extracellular space), but “sideways” (through the wall of the channel) - directly into the membrane. So, fragment by fragment, membrane proteins are inserted into the membrane, and therefore N-the end of the MB is always in the extracellular region, and where will it be C-end - depends on the number of TM segments.
In an elegant experiment on the Sec61 translocon of the endoplasmic reticulum, a “biological scale of hydrophobicity” was established, which assigns a specific hydrophobicity value to each amino acid residue. Interestingly, in general terms this scale coincides with previously established physicochemical scales, which allows the translocon to be assigned the role of a sensor of hydrophobic interaction.
So, a cell can “measure” hydrophobicity using a translocon, and in the laboratory this property can be roughly estimated by the nature of its interaction with water. But is it possible to calculate hydrophobicity theoretically and include this calculation in practically important problems?
How to calculate hydrophobicity theoretically?
It was already said above that the hydrophobic effect is actually one of the faces of the Second Law of Thermodynamics, so calculating it accurately is, perhaps, no easier than modeling the entire system, and at a physically correct level. In other words, “hydrophobic interactions” are in no way reducible to pairwise contacts, such as the attraction or repulsion of two charges or the interaction between a hydrogen bond donor and acceptor. The only theoretically correct way is to analyze a huge number of microstates in thermodynamic ensembles, which is quite difficult to do in practice.
However, at least an approximate assessment of the hydrophobic and hydrophilic properties of molecules is still in demand in molecular modeling and its applications (for example, biotechnological or industrial). Usually, they focus on the characteristic that describes the hydrophobicity of the entire molecule - the distribution coefficient ( P, from partitioning) of this substance between water (polar phase) and a non-polar phase (for example, benzene or n-octanol). The fact is that this parameter, unlike all other thermodynamic characteristics, is quite simple to measure experimentally by determining the concentration of the substance under study in water and a non-polar medium (which, as we remember, almost do not mix) and dividing one by the other. The hydrophobicity coefficient is taken to be the logarithm of this coefficient - log P.
Several empirical methods are aimed at predicting this coefficient, which boil down to using a “training set” of substances with an accurately measured log P determine the contributions of individual fragments of a molecule or even its individual atoms (taking into account the chemical environment), in order to then calculate hydrophobicity for unknown molecules based on the calculated fragmentary or atomic hydrophobicity constants. In fact, this is an attempt to assign a “hydrophobic charge” to each atom in a molecule, although it must be borne in mind that this does not make physical sense. Summing these constants for all atoms in the molecule will give the desired value of log P, and the use of an approach similar to the calculation of the electrostatic potential at points in space (φ ~ q/r) gave rise to the Molecular Hydrophobic Potential (MHP) method, which has proven itself in molecular modeling (Fig. 7). The PLATINUM program is dedicated to IHL calculations.
Figure 7. Molecular Hydrophobic Potential (MHP). The point of the IHL approach, which allows one to calculate the spatial distribution of hydrophobic/hydrophilic properties, is to establish an empirical system atomic hydrophobicity constants (f i), technically similar to partial charges. The sum of these constants over all atoms will give an estimate of the hydrophobicity coefficient log P(Where P- coefficient of distribution of a substance between water and octanol), and the calculation of the “potential” from a system of point “hydrophobic charges” taking into account attenuation in space (according to the law d(r), equal to, for example, 1/r) allows us to imagine the distribution of hydrophobicity on the molecular surfaces. The figure shows the hydrophobic properties of the main phospholipid of the plasma membrane of eukaryotes -e.
Calculation of the MHP allows one to estimate the effective value of the hydrophobicity of a particular fragment of a molecule and clearly visualize the hydrophobic properties of its surface, and this, in turn, can tell about the mechanisms of intermolecular interaction and point the way to a targeted change in the properties of molecules or the way they interact with each other. Thus, using spatial mapping of the hydrophobic properties of short α-helical antimicrobial peptides(AMP) were able to reveal that these molecules are characterized by an amphiphilic nature - when one side of the helix is hydrophobic, and the other is polar and positively charged. This motif is clearly visible on the MGP “sweep” maps, emphasizing the mechanism of interaction of the peptide with the membrane and antimicrobial action (Fig. 8). With the help of such cards it was possible to modify natural AMP latarcin, creating analogs that have high antibacterial activity, but do not destroy red blood cells, and, therefore, are a potential prototype of the drug (Fig. 8).
Figure 8. Design of beneficial properties in the antimicrobial peptide latarcin 2a (Ltc2a). Top row left The spatial structure of Ltc2a and the distribution of hydrophobic properties (see Fig. 7) on its surface are shown. In the center a “sweep” map of the IHL is shown in cylindrical coordinates (α; Z). It shows a clear amphiphilic pattern that determines the interaction of the peptide with the cell membrane. Top row right the cytolytic activity of the peptide is shown: it quite effectively kills both bacteria (“gram+”, “gram−”) and animal cells (“erythrocytes”) [column “wt”].
The task was as follows: while maintaining antimicrobial activity, eliminate hemolytic activity(i.e., create a prototype of a bactericidal drug). It was assumed that changing the nature of the hydrophobic “spot” on the MGP map would change the interaction with the membranes of bacteria and erythrocytes differently, and the task could be completed. We tested three peptides into which point mutations were introduced: Ile7→Gln, Phe10→Lys and Gly11→Leu. The corresponding changes in the hydrophobic pattern are shown in three map fragments at the bottom. One mutant, Ile7→Gln, had the desired activities: high bactericidal and low hemolytic.
Taking into account the hydrophobic properties of biomolecules is also used in other areas of molecular modeling - in particular, when predicting the position of transmembrane regions in the amino acid sequence or clarifying the spatial structure of receptor-ligand complexes based on the principle of hydrophobic correspondence.
Despite the complex physical nature of the hydrophobicity phenomenon, even a very superficial consideration of it in molecular modeling can be beneficial. From the above example it is clear that spatial mapping of the properties of molecules, calculated using the MHP technique, makes it possible to draw a connection between the structure of the peptide molecule and its activity, and this is a long-standing dream of chemists, biologists and pharmacologists. The ability to find such a connection means the ability to rationally design the required properties in molecules, which, of course, is in demand in fundamental research, biotechnology, and medicine.
And again a word about water
A closer look at the hydrophobic effect allows us to understand that we are actually talking about the statistical behavior of a large number of molecules, which is described by the laws of thermodynamics and statistical physics. But something else is more interesting here - we are once again convinced of the uniqueness of such a seemingly simple substance as water. Water itself has many amazing qualities, but as a biological solvent it has no equal. By interacting with other molecules, water changes its dynamics and structure, causing the entire system to change. This is exactly what we observe when we study the self-organization of amphiphilic molecules into bilayers and vesicles - after all, it is water that “forces” them to assemble into such complex forms.
The role of water is difficult to overestimate in the life of the main biological “machines” - proteins. Their folding from a linear chain into a dense globule, in which each atom knows its place, is also the merit of water. This means that water also deserves the title of one of the most biological molecules, although according to the chemical classification it is an inorganic substance.
Mermaid molecules Signature of hydrophobic hydration in a single polymer;
