Hydrophobic effect

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A droplet of water forms a spherical shape, minimizing contact with the hydrophobic leaf. Water drop on a leaf.jpg
A droplet of water forms a spherical shape, minimizing contact with the hydrophobic leaf.
Cocoa powder, an example of a "hydrophobic substance". Dutch process and natural cocoa.jpg
Cocoa powder, an example of a "hydrophobic substance".

The hydrophobic effect is the observed tendency of nonpolar substances to aggregate in an aqueous solution and to be excluded by water. [1] [2] The word hydrophobic literally means "water-fearing", and it describes the segregation of water and nonpolar substances, which maximizes the entropy of water and minimizes the area of contact between water and nonpolar molecules. In terms of thermodynamics, the hydrophobic effect is the free energy change of water surrounding a solute. [3] A positive free energy change of the surrounding solvent indicates hydrophobicity, whereas a negative free energy change implies hydrophilicity.

Contents

The hydrophobic effect is responsible for the separation of a mixture of oil and water into its two components. It is also responsible for effects related to biology, including: cell membrane and vesicle formation, protein folding, insertion of membrane proteins into the nonpolar lipid environment and protein-small molecule associations. Hence the hydrophobic effect is essential to life. [4] [5] [6] [7] Substances for which this effect is observed are known as hydrophobes.

Amphiphiles

Amphiphiles are molecules that have both hydrophobic and hydrophilic domains. Detergents are composed of amphiphiles that allow hydrophobic molecules to be solubilized in water by forming micelles and bilayers (as in soap bubbles). They are also important to cell membranes composed of amphiphilic phospholipids that prevent the internal aqueous environment of a cell from mixing with external water.

Folding of macromolecules

In the case of protein folding, the hydrophobic effect is important to understanding the structure of proteins that have hydrophobic amino acids (such as valine, leucine, isoleucine, phenylalanine, tryptophan and methionine) clustered together within the protein. Structures of globular proteins have a hydrophobic core in which hydrophobic side chains are buried from water, which stabilizes the folded state. Charged and polar side chains are situated on the solvent-exposed surface where they interact with surrounding water molecules. Minimizing the number of hydrophobic side chains exposed to water is the principal driving force behind the folding process, [8] [9] [10] although formation of hydrogen bonds within the protein also stabilizes protein structure. [11] [12]

The energetics of DNA tertiary-structure assembly were determined to be driven by the hydrophobic effect, in addition to Watson–Crick base pairing, which is responsible for sequence selectivity, and stacking interactions between the aromatic bases. [13] [14]

Protein purification

In biochemistry, the hydrophobic effect can be used to separate mixtures of proteins based on their hydrophobicity. Column chromatography with a hydrophobic stationary phase such as phenyl-sepharose will cause more hydrophobic proteins to travel more slowly, while less hydrophobic ones elute from the column sooner. To achieve better separation, a salt may be added (higher concentrations of salt increase the hydrophobic effect) and its concentration decreased as the separation progresses. [15]

Cause

Dynamic hydrogen bonds between molecules of liquid water, the shape of the molecules is sometimes compared to that of boomerangs. Liquid water hydrogen bond.png
Dynamic hydrogen bonds between molecules of liquid water, the shape of the molecules is sometimes compared to that of boomerangs.

The origin of the hydrophobic effect is not fully understood. Some argue that the hydrophobic interaction is mostly an entropic effect originating from the disruption of highly dynamic hydrogen bonds between molecules of liquid water by the nonpolar solute. [16] A hydrocarbon chain or a similar nonpolar region of a large molecule is incapable of forming hydrogen bonds with water. Introduction of such a non-hydrogen bonding surface into water causes disruption of the hydrogen bonding network between water molecules. The hydrogen bonds are reoriented tangentially to such surface to minimize disruption of the hydrogen bonded 3D network of water molecules, and this leads to a structured water "cage" around the nonpolar surface. The water molecules that form the "cage" (or clathrate) have restricted mobility. In the solvation shell of small nonpolar particles, the restriction amounts to some 10%. For example, in the case of dissolved xenon at room temperature a mobility restriction of 30% has been found. [17] In the case of larger nonpolar molecules, the reorientational and translational motion of the water molecules in the solvation shell may be restricted by a factor of two to four; thus, at 25 °C the reorientational correlation time of water increases from 2 to 4-8 picoseconds. Generally, this leads to significant losses in translational and rotational entropy of water molecules and makes the process unfavorable in terms of the free energy in the system. [18] By aggregating together, nonpolar molecules reduce the surface area exposed to water and minimize their disruptive effect.

The hydrophobic effect can be quantified by measuring the partition coefficients of non-polar molecules between water and non-polar solvents. The partition coefficients can be transformed to free energy of transfer which includes enthalpic and entropic components, ΔG = ΔH - TΔS. These components are experimentally determined by calorimetry. The hydrophobic effect was found to be entropy-driven at room temperature because of the reduced mobility of water molecules in the solvation shell of the non-polar solute; however, the enthalpic component of transfer energy was found to be favorable, meaning it strengthened water-water hydrogen bonds in the solvation shell due to the reduced mobility of water molecules. At the higher temperature, when water molecules become more mobile, this energy gain decreases along with the entropic component. The hydrophobic effect depends on the temperature, which leads to "cold denaturation" of proteins. [19]

The hydrophobic effect can be calculated by comparing the free energy of solvation with bulk water. In this way, the hydrophobic effect not only can be localized but also decomposed into enthalpic and entropic contributions. [3]

See also

Related Research Articles

<span class="mw-page-title-main">Denaturation (biochemistry)</span> Loss of structure in proteins and nucleic acids due to external stress

In biochemistry, denaturation is a process in which proteins or nucleic acids lose folded structure present in their native state due to various factors, including application of some external stress or compound, such as a strong acid or base, a concentrated inorganic salt, an organic solvent, agitation and radiation, or heat. If proteins in a living cell are denatured, this results in disruption of cell activity and possibly cell death. Protein denaturation is also a consequence of cell death. Denatured proteins can exhibit a wide range of characteristics, from conformational change and loss of solubility or dissociation of cofactors to aggregation due to the exposure of hydrophobic groups. The loss of solubility as a result of denaturation is called coagulation. Denatured proteins lose their 3D structure, and therefore, cannot function.

<span class="mw-page-title-main">Hydrogen bond</span> Intermolecular attraction between a hydrogen-donor pair and an acceptor

In chemistry, a hydrogen bond is primarily an electrostatic force of attraction between a hydrogen (H) atom which is covalently bonded to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a lone pair of electrons—the hydrogen bond acceptor (Ac). Such an interacting system is generally denoted Dn−H···Ac, where the solid line denotes a polar covalent bond, and the dotted or dashed line indicates the hydrogen bond. The most frequent donor and acceptor atoms are the period 2 elements nitrogen (N), oxygen (O), and fluorine (F).

<span class="mw-page-title-main">Hydrophobe</span> Molecule or surface that has no attraction to water

In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water.

<span class="mw-page-title-main">Solvent</span> Substance dissolving a solute resulting in a solution

A solvent is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for polar molecules, and the most common solvent used by living things; all the ions and proteins in a cell are dissolved in water within the cell.

<span class="mw-page-title-main">Solvation</span> Association of molecules of a solvent with molecules or ions of a solute

Solvation describes the interaction of a solvent with dissolved molecules. Both ionized and uncharged molecules interact strongly with a solvent, and the strength and nature of this interaction influence many properties of the solute, including solubility, reactivity, and color, as well as influencing the properties of the solvent such as its viscosity and density. If the attractive forces between the solvent and solute particles are greater than the attractive forces holding the solute particles together, the solvent particles pull the solute particles apart and surround them. The surrounded solute particles then move away from the solid solute and out into the solution. Ions are surrounded by a concentric shell of solvent. Solvation is the process of reorganizing solvent and solute molecules into solvation complexes and involves bond formation, hydrogen bonding, and van der Waals forces. Solvation of a solute by water is called hydration.

<span class="mw-page-title-main">Protein folding</span> Change of a linear protein chain to a 3D structure

Protein folding is the physical process by which a protein, after synthesis by a ribosome as a linear chain of amino acids, changes from an unstable random coil into a more ordered three-dimensional structure. This structure permits the protein to become biologically functional.

<span class="mw-page-title-main">Solubility</span> Capacity of a substance to dissolve in a homogeneous way

In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution.

<span class="mw-page-title-main">Globular protein</span> Spherical, water-soluble type of protein

In biochemistry, globular proteins or spheroproteins are spherical ("globe-like") proteins and are one of the common protein types. Globular proteins are somewhat water-soluble, unlike the fibrous or membrane proteins. There are multiple fold classes of globular proteins, since there are many different architectures that can fold into a roughly spherical shape.

<span class="mw-page-title-main">Transmembrane protein</span> Protein spanning across a biological membrane

A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently undergo significant conformational changes to move a substance through the membrane. They are usually highly hydrophobic and aggregate and precipitate in water. They require detergents or nonpolar solvents for extraction, although some of them (beta-barrels) can be also extracted using denaturing agents.

Salting out is a purification technique that utilizes the reduced solubility of certain molecules in a solution of very high ionic strength. Salting out is typically used to precipitate large biomolecules, such as proteins or DNA. Because the salt concentration needed for a given protein to precipitate out of the solution differs from protein to protein, a specific salt concentration can be used to precipitate a target protein. This process is also used to concentrate dilute solutions of proteins. Dialysis can be used to remove the salt if needed.

A chaotropic agent is a molecule in water solution that can disrupt the hydrogen bonding network between water molecules. This has an effect on the stability of the native state of other molecules in the solution, mainly macromolecules by weakening the hydrophobic effect. For example, a chaotropic agent reduces the amount of order in the structure of a protein formed by water molecules, both in the bulk and the hydration shells around hydrophobic amino acids, and may cause its denaturation.

In physics, an entropic force acting in a system is an emergent phenomenon resulting from the entire system's statistical tendency to increase its entropy, rather than from a particular underlying force on the atomic scale.

In chemistry, a non-covalent interaction differs from a covalent bond in that it does not involve the sharing of electrons, but rather involves more dispersed variations of electromagnetic interactions between molecules or within a molecule. The chemical energy released in the formation of non-covalent interactions is typically on the order of 1–5 kcal/mol. Non-covalent interactions can be classified into different categories, such as electrostatic, π-effects, van der Waals forces, and hydrophobic effects.

<span class="mw-page-title-main">Salt bridge (protein and supramolecular)</span> Combination of hydrogen and ionic bonding in chemistry

In chemistry, a salt bridge is a combination of two non-covalent interactions: hydrogen bonding and ionic bonding. Ion pairing is one of the most important noncovalent forces in chemistry, in biological systems, in different materials and in many applications such as ion pair chromatography. It is a most commonly observed contribution to the stability to the entropically unfavorable folded conformation of proteins. Although non-covalent interactions are known to be relatively weak interactions, small stabilizing interactions can add up to make an important contribution to the overall stability of a conformer. Not only are salt bridges found in proteins, but they can also be found in supramolecular chemistry. The thermodynamics of each are explored through experimental procedures to access the free energy contribution of the salt bridge to the overall free energy of the state.

<span class="mw-page-title-main">Cyclol</span> Structural model of a folded, globular protein

The cyclol hypothesis is the now discredited first structural model of a folded, globular protein, formulated in the 1930s. It was based on the cyclol reaction of peptide bonds proposed by physicist Frederick Frank in 1936, in which two peptide groups are chemically crosslinked. These crosslinks are covalent analogs of the non-covalent hydrogen bonds between peptide groups and have been observed in rare cases, such as the ergopeptides.

<span class="mw-page-title-main">Hydrophobic collapse</span> Process in protein folding

Hydrophobic collapse is a proposed process for the production of the 3-D conformation adopted by polypeptides and other molecules in polar solvents. The theory states that the nascent polypeptide forms initial secondary structure creating localized regions of predominantly hydrophobic residues. The polypeptide interacts with water, thus placing thermodynamic pressures on these regions which then aggregate or "collapse" into a tertiary conformation with a hydrophobic core. Incidentally, polar residues interact favourably with water, thus the solvent-facing surface of the peptide is usually composed of predominantly hydrophilic regions.

Implicit solvation is a method to represent solvent as a continuous medium instead of individual “explicit” solvent molecules, most often used in molecular dynamics simulations and in other applications of molecular mechanics. The method is often applied to estimate free energy of solute-solvent interactions in structural and chemical processes, such as folding or conformational transitions of proteins, DNA, RNA, and polysaccharides, association of biological macromolecules with ligands, or transport of drugs across biological membranes.

Protein metabolism denotes the various biochemical processes responsible for the synthesis of proteins and amino acids (anabolism), and the breakdown of proteins by catabolism.

<span class="mw-page-title-main">Lower critical solution temperature</span> Critical temperature below which components of a mixture are miscible for all compositions

The lower critical solution temperature (LCST) or lower consolute temperature is the critical temperature below which the components of a mixture are miscible in all proportions. The word lower indicates that the LCST is a lower bound to a temperature interval of partial miscibility, or miscibility for certain compositions only.

Hydrophobicity scales are values that define the relative hydrophobicity or hydrophilicity of amino acid residues. The more positive the value, the more hydrophobic are the amino acids located in that region of the protein. These scales are commonly used to predict the transmembrane alpha-helices of membrane proteins. When consecutively measuring amino acids of a protein, changes in value indicate attraction of specific protein regions towards the hydrophobic region inside lipid bilayer.

References

  1. ↑ IUPAC , Compendium of Chemical Terminology , 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) " hydrophobic interaction ". doi : 10.1351/goldbook.H02907
  2. ↑ Chandler D (2005). "Interfaces and the driving force of hydrophobic assembly". Nature. 437 (7059): 640–7. Bibcode:2005Natur.437..640C. doi:10.1038/nature04162. PMID   16193038. S2CID   205210634.
  3. 1 2 Schauperl, M; Podewitz, M; Waldner, BJ; Liedl, KR (2016). "Enthalpic and Entropic Contributions to Hydrophobicity". Journal of Chemical Theory and Computation. 12 (9): 4600–10. doi:10.1021/acs.jctc.6b00422. PMC   5024328 . PMID   27442443.
  4. ↑ Kauzmann W (1959). "Some factors in the interpretation of protein denaturation". Advances in Protein Chemistry Volume 14. Vol. 14. pp. 1–63. doi:10.1016/S0065-3233(08)60608-7. ISBN   9780120342143. PMID   14404936.{{cite book}}: |journal= ignored (help)
  5. ↑ Charton M, Charton BI (1982). "The structural dependence of amino acid hydrophobicity parameters". Journal of Theoretical Biology. 99 (4): 629–644. Bibcode:1982JThBi..99..629C. doi:10.1016/0022-5193(82)90191-6. PMID   7183857.
  6. ↑ Lockett MR, Lange H, Breiten B, Heroux A, Sherman W, Rappoport D, Yau PO, Snyder PW, Whitesides GM (2013). "The binding of benzoarylsulfonamide ligands to human carbonic anhydrase is insensitive to formal fluorination of the ligand". Angew. Chem. Int. Ed. Engl. 52 (30): 7714–7. doi:10.1002/anie.201301813. PMID   23788494. S2CID   1543705.
  7. ↑ Breiten B, Lockett MR, Sherman W, Fujita S, Al-Sayah M, Lange H, Bowers CM, Heroux A, Krilov G, Whitesides GM (2013). "Water networks contribute to enthalpy/entropy compensation in protein-ligand binding". J. Am. Chem. Soc. 135 (41): 15579–84. CiteSeerX   10.1.1.646.8648 . doi:10.1021/ja4075776. PMID   24044696. S2CID   17554787.
  8. ↑ Pace CN, Shirley BA, McNutt M, Gajiwala K (1 January 1996). "Forces contributing to the conformational stability of proteins". FASEB J. 10 (1): 75–83. doi: 10.1096/fasebj.10.1.8566551 . PMID   8566551. S2CID   20021399.
  9. ↑ Compiani M, Capriotti E (Dec 2013). "Computational and theoretical methods for protein folding" (PDF). Biochemistry. 52 (48): 8601–24. doi:10.1021/bi4001529. PMID   24187909. Archived from the original (PDF) on 2015-09-04.
  10. ↑ Callaway, David J. E. (1994). "Solvent-induced organization: a physical model of folding myoglobin". Proteins: Structure, Function, and Bioinformatics. 20 (1): 124–138. arXiv: cond-mat/9406071 . Bibcode:1994cond.mat..6071C. doi:10.1002/prot.340200203. PMID   7846023. S2CID   317080.
  11. ↑ Rose GD, Fleming PJ, Banavar JR, Maritan A (2006). "A backbone-based theory of protein folding". Proc. Natl. Acad. Sci. U.S.A. 103 (45): 16623–33. Bibcode:2006PNAS..10316623R. doi: 10.1073/pnas.0606843103 . PMC   1636505 . PMID   17075053.
  12. ↑ Gerald Karp (2009). Cell and Molecular Biology: Concepts and Experiments. John Wiley and Sons. pp. 128–. ISBN   978-0-470-48337-4.
  13. ↑ Gilbert HF (2001). Basic concepts in biochemistry: a student's survival guide (2nd, International ed.). Singapore: McGraw-Hill. p.  9. ISBN   978-0071356572.
  14. ↑ Ho PS, van Holde KE, Johnson WC, Shing P (1998). Principles of physical biochemistry. Upper Saddle River, N.J.: Prentice-Hall. p. 18. ISBN   978-0137204595. See also thermodynamic discussion pages 137-144
  15. ↑ Ahmad, Rizwan (2012). Protein Purification. InTech. ISBN   978-953-307-831-1.
  16. ↑ Silverstein TP (January 1998). "The Real Reason Why Oil and Water Don't Mix". Journal of Chemical Education. 75 (1): 116. Bibcode:1998JChEd..75..116S. doi:10.1021/ed075p116.
  17. ↑ Haselmeier R, Holz M, Marbach W, Weingaertner H (1995). "Water Dynamics near a Dissolved Noble Gas. First Direct Experimental Evidence for a Retardation Effect". The Journal of Physical Chemistry. 99 (8): 2243–2246. doi:10.1021/j100008a001.
  18. ↑ Tanford C (1973). The hydrophobic effect: formation of micelles and biological membranes . New York: Wiley. ISBN   978-0-471-84460-0.
  19. ↑ Jaremko M, Jaremko Ł, Kim HY, Cho MK, Schwieters CD, Giller K, Becker S, Zweckstetter M (2013). "Cold denaturation of a protein dimer monitored at atomic resolution". Nat. Chem. Biol. 9 (4): 264–70. doi:10.1038/nchembio.1181. PMC   5521822 . PMID   23396077.
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