Editing Hydrophobic effect

{{Short description|Aggregation of non-polar molecules in aqueous solutions}}
[[Image: Water drop on a leaf.jpg|thumbnail|250px|A droplet of water forms a spherical shape, minimizing contact with the hydrophobic leaf.]]
[[File:Dutch process and natural cocoa.jpg|thumb|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#Properties|water]].<ref>{{GoldBookRef|title=hydrophobic interaction|file=H02907}}</ref><ref name="pmid16193038">{{cite journal | vauthors = Chandler D | title = Interfaces and the driving force of hydrophobic assembly | journal = Nature | volume = 437 | issue = 7059 | pages = 640–7 | year = 2005 | pmid = 16193038 | doi = 10.1038/nature04162 | bibcode = 2005Natur.437..640C | s2cid = 205210634 }}</ref>  The word hydrophobic literally means "water-fearing", and it describes the [[Segregation in materials|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.<ref name='pmimd27442443'>{{cite journal |last1=Schauperl |first1=M |last2=Podewitz |first2=M |last3=Waldner |first3=BJ |last4=Liedl |first4=KR |title=Enthalpic and Entropic Contributions to Hydrophobicity. |journal=Journal of Chemical Theory and Computation |volume=12 |issue=9 |pages=4600–10 |year = 2016 |doi=10.1021/acs.jctc.6b00422 |pmid=27442443 |pmc=5024328}}</ref> A positive free energy change of the surrounding solvent indicates hydrophobicity, whereas a negative free energy change implies hydrophilicity.

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 protein]]s into the nonpolar lipid environment and protein-[[small molecule]] associations.  Hence the hydrophobic effect is essential to life.<ref>{{cite book | vauthors = Kauzmann W | title = Advances in Protein Chemistry Volume 14 | chapter = Some factors in the interpretation of protein denaturation | journal = Advances in Protein Chemistry | volume = 14 | pages = 1–63 | year = 1959 | publisher = Academic Press | pmid = 14404936 | doi = 10.1016/S0065-3233(08)60608-7 | isbn = 9780120342143 }}</ref><ref>{{cite journal | vauthors = Charton M, Charton BI | title = The structural dependence of amino acid hydrophobicity parameters | journal = Journal of Theoretical Biology | volume = 99 | issue = 4 | pages = 629–644 | year = 1982 | pmid = 7183857 | doi = 10.1016/0022-5193(82)90191-6 | bibcode = 1982JThBi..99..629C }}</ref><ref name="pmid23788494">{{cite journal | vauthors = Lockett MR, Lange H, Breiten B, Heroux A, Sherman W, Rappoport D, Yau PO, Snyder PW, Whitesides GM | title = The binding of benzoarylsulfonamide ligands to human carbonic anhydrase is insensitive to formal fluorination of the ligand | journal = Angew. Chem. Int. Ed. Engl. | volume = 52 | issue = 30 | pages = 7714–7 | year = 2013 | pmid = 23788494 | doi = 10.1002/anie.201301813 | s2cid = 1543705 | url = http://nrs.harvard.edu/urn-3:HUL.InstRepos:12362620| url-access = subscription }}</ref><ref name="pmid24044696">{{cite journal | vauthors = Breiten B, Lockett MR, Sherman W, Fujita S, Al-Sayah M, Lange H, Bowers CM, Heroux A, Krilov G, Whitesides GM | title = Water networks contribute to enthalpy/entropy compensation in protein-ligand binding | journal = J. Am. Chem. Soc. | volume = 135 | issue = 41 | pages = 15579–84 | year = 2013 | pmid = 24044696 | doi = 10.1021/ja4075776 | bibcode = 2013JAChS.13515579B | citeseerx = 10.1.1.646.8648 | s2cid = 17554787 }}</ref> Substances for which this effect is observed are known as [[hydrophobe]]s.

== Amphiphiles ==

[[Amphiphiles]] are molecules that have both hydrophobic and hydrophilic domains. [[Detergent]]s are composed of amphiphiles that allow hydrophobic molecules to be [[solubilization|solubilized]] in water by forming [[micelle]]s and bilayers (as in [[soap bubbles]]). They are also important to [[cell membranes]] composed of amphiphilic [[phospholipid]]s 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 acid]]s (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 [[chemical polarity|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,<ref name="Pace">{{cite journal | vauthors = Pace CN, Shirley BA, McNutt M, Gajiwala K | title = Forces contributing to the conformational stability of proteins | journal = FASEB J. | volume = 10 | issue = 1 | pages = 75–83 | date = 1 January 1996 | pmid = 8566551 | url = http://www.fasebj.org/cgi/reprint/10/1/75 | doi=10.1096/fasebj.10.1.8566551| doi-access = free | s2cid = 20021399 | url-access = subscription }}</ref><ref name="pmid24187909">{{cite journal
 |vauthors=Compiani M, Capriotti E
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 |journal=Biochemistry
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}}</ref><ref name="pmid7846023">{{Cite journal
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}}</ref> although formation of hydrogen bonds within the protein also stabilizes protein structure.<ref name="Rose">{{cite journal | vauthors = Rose GD, Fleming PJ, Banavar JR, Maritan A | title = A backbone-based theory of protein folding | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 103 | issue = 45 | pages = 16623–33 | year = 2006 | pmid = 17075053 | pmc = 1636505 | doi = 10.1073/pnas.0606843103 | bibcode = 2006PNAS..10316623R | doi-access = free }}</ref><ref name="Karp2009">{{cite book|author=Gerald Karp
|title=Cell and Molecular Biology: Concepts and Experiments
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The [[energy|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 (chemistry)|stacking interactions]] between the aromatic bases.<ref>{{cite book | author = Gilbert HF | title = Basic concepts in biochemistry: a student's survival guide | year = 2001 | publisher = McGraw-Hill | location = Singapore | isbn = 978-0071356572 | edition = 2nd, International | page = [https://archive.org/details/basicconceptsinb00hira/page/9 9] | url-access = registration | url = https://archive.org/details/basicconceptsinb00hira/page/9 }}</ref><ref>{{cite book |vauthors=Ho PS, van Holde KE, Johnson WC, Shing P | title = Principles of physical biochemistry | year = 1998 | publisher = Prentice-Hall | location = Upper Saddle River, N.J. | isbn = 978-0137204595 | page = 18 | quote = See also thermodynamic discussion pages 137-144 }}</ref>

== 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.<ref>{{Cite book|title=Protein Purification|last=Ahmad|first=Rizwan|publisher=InTech|year=2012|isbn=978-953-307-831-1}}</ref>

== Cause ==

{{See also|Entropic force#Hydrophobic force}}
[[File:Liquid water hydrogen bond.png|right|thumb|200px|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 [[entropy|entropic]] effect originating from the disruption of highly dynamic [[hydrogen bond]]s between molecules of liquid water by the nonpolar solute.<ref name=Silverstein_1998>{{cite journal|author=Silverstein TP|title=The Real Reason Why Oil and Water Don't Mix|journal=Journal of Chemical Education|date=January 1998|volume=75|issue=1|pages=116|doi=10.1021/ed075p116|bibcode=1998JChEd..75..116S}}</ref> 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 hydrate|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.<ref name =Xenon>{{cite journal |vauthors=Haselmeier R, Holz M, Marbach W, Weingaertner H | title = Water Dynamics near a Dissolved Noble Gas. First Direct Experimental Evidence for a Retardation Effect | journal = The Journal of Physical Chemistry | volume = 99 | issue = 8 | pages = 2243–2246 | year = 1995 | doi = 10.1021/j100008a001 }}</ref> 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&nbsp;°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 [[Gibbs free energy|free energy]] in the system.<ref>{{cite book | author = Tanford C | title = The hydrophobic effect: formation of micelles and biological membranes | date = 1973 | publisher = Wiley | location = New York | isbn = 978-0-471-84460-0 | url-access = registration | url = https://archive.org/details/isbn_0471844608 }}</ref> By aggregating together, nonpolar molecules reduce the [[Accessible surface area|surface area exposed to water]] and minimize their disruptive effect.

The hydrophobic effect can be quantified by measuring the [[partition coefficient]]s of non-polar molecules between water and non-polar solvents. The partition coefficients can be transformed to [[Gibbs free energy|free energy]] of transfer which includes [[enthalpy|enthalpic]] and entropic components, ''ΔG = ΔH - TΔS''. These components are experimentally determined by [[Differential scanning calorimetry|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 (biochemistry)|denaturation]]" of proteins.<ref name="pmid23396077">{{cite journal | vauthors = Jaremko M, Jaremko Ł, Kim HY, Cho MK, Schwieters CD, Giller K, Becker S, Zweckstetter M | title = Cold denaturation of a protein dimer monitored at atomic resolution | journal = Nat. Chem. Biol. | volume = 9 | issue = 4 | pages = 264–70 | year = 2013 | pmid = 23396077 | doi = 10.1038/nchembio.1181 | pmc=5521822}}</ref>

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.<ref name='pmimd27442443' />

== See also ==
* [[Entropic force]]
* [[Hydrophobe]]
* [[Hydrophile]]
* [[Hydrophobicity scales]]
* [[Interfacial tension]]
* [[Superhydrophobe]]
* [[Superhydrophobic coating]]

== References ==
{{Reflist|35em}}

{{DEFAULTSORT:Hydrophobic Effect}}
[[Category:Chemical bonding]]
[[Category:Supramolecular chemistry]]
[[Category:Intermolecular forces]]