BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 2. THE ROLE OF WATER, MACRO- AND MICROELEMENTS IN THE VITAL ACTIVITY OF ORGANISMS

2.3. Hydrophobic Interactions, Macromolecules, and Water

The dissolution of various substances in Water, including those that interact weakly, can lead to a significant increase in: a) the number of H-bonds; b) the degree of order. The first effect produces an enthalpic contribution ΔH to The change in Free energy ΔF, whereas the second determines the entropic contribution ΔS. The sign of ΔF = ΔH - TΔS (where T is the absolute Temperature) is determined by The ratio of both quantities.

When ions and small polar molecules dissolve in water, the enthalpic contribution exceeds the entropic one, and ΔF < 0. In the case of small polar molecules (such as noble and organic gases, e.g., methane), which interact weakly with water molecules yet cause significant changes in ΔH because they fit perfectly into the openwork water lattice (see Fig. 2.5) without disrupting The formation of all four possible H-bonds. Therefore, although ΔS is negative and large in this case, the ΔH contribution is greater, resulting in ΔF < 0. This accounts for the high stability of gas clathrates.

In the case of large non-polar molecules—such as CARBOHYDRATES, Amino Acids with non-polar radicals, and the like—the enthalpic contribution to the Free energy of dissolution is smaller than the entropic one, because not all water molecules surrounding these molecules can form the maximum number of H-bonds. However, they are highly immobilized and make a large negative contribution to Entropy. As a result, the free energy

of their dissolution in water is positive, and their solubility is low. The low solubility of non-polar molecules is caused not by their Structure/103.html">Van der Waals interaction energy being greater than their interaction with water molecules, as previously assumed, but by the fact that their presence in water leads to thermodynamically unfavorable changes in water structure—its ordering. Water, in turn, attempts to minimize The impact of these molecules by reducing unfavorable contacts. This "salting-out" or expelling EFFECT OF WATER on non-polar groups (Fig. 2.1, D) is termed hydrophobic interaction; that is, hydrophobic interaction is specific to water and is caused by the peculiarities of its structure—its capacity for ordering and its "reluctance" to become ordered.

Attention to such interactions is steadily growing, especially among biochemists, since Biomolecules contain A large number of hydrophobic groups that crucially determine molecular conformation in water. The endothermic nature of hydrophobic interactions causes them to be enhanced with rising temperature. The disruption of hydrophobic interactions is an exothermic process, and their exothermicity decreases as the temperature drops. The endothermicity of hydrophobic bond disruption is accompanied by the formation of a large number of H-bonds. Hence the Conclusion: macromolecular Conformations whose ordering effect on water is minimal will be the most stable. If one part of a macromolecule's groups generates hydrophobic interactions, promotes a more compact structure, and partially orders water, another part primarily orders water and ensures the macromolecule's solubility in water.

The Presence of water profoundly affects macromolecular properties. Judging by the sorption-desorption curves of water on Proteins, macromolecules behave not as a rigid, inert substrate, but as a reactive substance capable of deformation. The removal of water disrupts even such a robust structure as the DNA double helix. However, the effect on the water molecule is not unilateral. The state of water under METABOLISM/18.html">The Influence of macromolecules also changes. To describe such processes, the term "Hydration" is used, denoting The amount of water that is under the substantial influence of a macromolecule. Hydrated water is considered to be water with low mobility, or bound water. However, it is not water mechanically trapped within macromolecular cavities, as it belongs to free water enclosed within large pores.

Based on the fact that bound water differs little thermodynamically from ice, one can determine the number of water molecules that do not participate in melting and are consequently "frozen" by the presence of macromolecules. Thus, bound water can be defined as water that does not freeze upon cooling and does not melt upon warming of the solution. This is one of the initial Definitions of bound water. In concentrated macromolecular solutions, there is virtually no free water that would freeze upon cooling. Free water appears only when it is present in the solution in excess of a critical amount, which determines the magnitude of hydration.

There is a Denaturation effect of hydration. During thermal denaturation of macromolecules, their hydration increases. In the case of Globular proteins, the magnitude of this effect is directly related to the completeness of the unfolding of the compact structure upon thermal denaturation. When an H-bond in a macromolecule breaks, an exchange reaction takes place: the bond between groups is replaced by two bonds with water molecules. In other words, ΔH_b (the enthalpy change of the H-bond) is effectively the difference in enthalpy of H-bond formation between the polar groups of the macromolecule on the one hand, and between the polar groups of the macromolecule and water molecules on the other. This means that the Structure and properties of macromolecules are closely linked to water and directly determined by its state. Most electrolytes affect the stability of macromolecules not by acting on them directly, but through water, by increasing or decreasing its Structuring. For instance, adding NaClO₄ to water leads to the same changes in NMR absorption lines as raising the temperature. Furthermore, DNA denaturation occurs regardless of what causes it: The addition of NaClO₄, a temperature increase, or both.

The amount of bound water in Tissues is close to or less than the hydration value of molecules. The reason is that the contact surface area between macromolecules and water is significantly smaller in tissues (where they form supramolecular structures such as Organelles) than in a molecular solution. Thus, the amount of bound water can serve as an indicator of the total contact surface area between Cellular Structures and water, or the "dispersity" of these structures. According to experimental data, Brain tissue is the least dispersed. This is logical, given that a large mass of brain tissue consists of axons with thick myelin sheaths.

Crucial for biological systems is the long-range action mechanism inherent to water in general, and even more so to structured water. As already noted, water can transmit energy without dissipation and conduct charges at high speed along ordered chains. It is quite possible that the interrelations between macromolecular structure and water are of particular importance, forming a feedback system that can change its sign and be regulated by the presence of ions. In such a case, water may prove to be the link through which chain reactions develop, or the medium via which auto-oscillations occur. Indeed, if water plays a significant role in denaturation transitions, it cannot fail to play a role in the more subtle changes in molecular structures that take place during their functioning.

The question of the Role of water in biological systems has in recent years become one of the most pressing topics in biochemistry. The cooperative mechanism of H-bond formation between water molecules is extremely important, as it determines water's crucially distinctive property that sets it apart from other liquids—the associative nature of its structure. Equally important is the interaction of water molecules with Biomacromolecules, characterized by the hydration parameter: the amount of water under a stronger Influence of the macromolecule compared to the Influence of other water molecules. Hydrated water is considered to be water with reduced mobility—bound water, which thermodynamically differs very little from ice. The "macromolecule-water" structure can also be viewed as a feedback system involved in the self-regulation of biological systems featuring auto-oscillatory processes.

A decisive role in shaping a unified approach to the diverse problems of bound water belongs to the molecular aspect. At THE MOLECULAR LEVEL, the entire world of aqueous systems—hydrates, solutions, and their mutual transformations—is governed by a single force localized in H-bonds and ion-dipole interactions between water molecules and solute particles. These weak binding forces are responsible for water's unique ability to form compounds with a vast number of substances, determining the manifestations of important properties and behavioral features of hydrates. These include crystallization, phase transformations (including ferroelectricity), and partial or total dehydration. In aqueous solutions, the reorganization of short-range order in molecular arrangements can lead to phase transitions within the liquid, namely phase Separation. This phenomenon consists in the fact that, under certain conditions, a solution spontaneously separates into pure components. Phase separation is realized in biological systems as one of the mechanisms regulating their activity.