Editing Acid dissociation constant (section)

== Applications and significance ==
A knowledge of p''K''<sub>a</sub> values is important for the quantitative treatment of systems involving acid–base equilibria in solution. Many applications exist in [[biochemistry]]; for example, the p''K''<sub>a</sub> values of proteins and [[amino acid]] side chains are of major importance for the activity of enzymes and the stability of proteins.<ref>{{cite journal
| last = Onufriev
| first = A.
| author2 = Case, D.A
| author3 = Ullmann G.M.
| year = 2001
| title = A Novel View of pH Titration in Biomolecules
| journal = Biochemistry
| volume = 40
| pages = 3413–3419
| doi = 10.1021/bi002740q
| pmid = 11297406
| issue = 12
}}</ref> [[Protein pKa calculations|Protein p''K''<sub>a</sub> values]] cannot always be measured directly, but may be calculated using theoretical methods. [[Buffer solutions]] are used extensively to provide solutions at or near the physiological pH for the study of biochemical reactions;<ref>{{cite journal
| last = Good
| first = N.E.
| author2 = Winget, G.D.
| author3 = Winter, W.
| author4 = Connolly, T.N.
| author5 = Izawa, S.
| author6 = Singh, R.M.M.
| title = Hydrogen Ion Buffers for Biological Research
| year = 1966
| journal = Biochemistry
| volume = 5
| issue = 2
| pages = 467–477
| doi = 10.1021/bi00866a011
| pmid = 5942950
}}</ref> the design of these solutions depends on a knowledge of the p''K''<sub>a</sub> values of their components. Important buffer solutions include [[MOPS]], which provides a solution with pH&nbsp;7.2, and [[tricine]], which is used in [[gel electrophoresis]].<ref>{{cite book
| title = Gel Electrophoresis: Proteins
| last = Dunn
| first = M.J.
| year = 1993
| publisher = Bios Scientific Publishers
| isbn = 1-872748-21-X
| url-access = registration
| url = https://archive.org/details/gelelectrophores0000dunn
}}</ref><ref>{{cite book
| title = Gel Electrophoresis: Nucleic Acids
| last = Martin
| first = R.
| year = 1996
| publisher = Bios Scientific Publishers
| isbn = 1-872748-28-7
}}</ref> Buffering is an essential part of [[acid base physiology]] including [[acid–base homeostasis]],<ref>{{cite book
 |title = Acid–Base and Potassium Homeostasis
 |editor-last = Brenner
 |editor-first = B.M.
 |editor2 = Stein, J.H.
 |year = 1979
 |publisher = Churchill Livingstone
 |isbn = 0-443-08017-8
 |url-access = registration
 |url = https://archive.org/details/acidbasepotassiu0002unse
}}</ref> and is key to understanding disorders such as [[acid–base disorder]].<ref>{{cite book
 | title = Fundamentals of Acids, Bases, Buffers & Their Application to Biochemical Systems
 | last = Scorpio
 | first = R.
 | year = 2000
 | publisher = Kendall/Hunt Pub. Co.
 | isbn = 0-7872-7374-0
}}</ref><ref>{{cite book
 |title = Buffer Solutions: The Basics
 |last = Beynon
 |first = R.J.
 |author2 = Easterby, J.S.
 |year = 1996
 |publisher = Oxford University Press
 |location = Oxford
 |isbn = 0-19-963442-4
 |url-access = registration
 |url = https://archive.org/details/buffersolutions0000beyn
}}</ref><ref>{{cite book
| title = Buffers for pH and Metal Ion Control
| last = Perrin
| first = D.D.
| author2 = Dempsey, B.
| year = 1974
| publisher = Chapman & Hall
| location = London
| isbn = 0-412-11700-2
}}</ref> The [[isoelectric point]] of a given molecule is a function of its p''K'' values, so different molecules have different isoelectric points. This permits a technique called [[isoelectric focusing]],<ref>{{cite book
| editor-last = [[QPNC-PAGE|Garfin]]
| editor-first = D.
| editor2 = Ahuja, S.
| title = Handbook of Isoelectric Focusing and Proteomics
| publisher = Elsevier
| year = 2005
| volume = 7
| isbn = 0-12-088752-5
}}</ref> which is used for separation of proteins by [[two-dimensional gel electrophoresis|2-D gel polyacrylamide gel electrophoresis]].

Buffer solutions also play a key role in [[analytical chemistry]]. They are used whenever there is a need to fix the pH of a solution at a particular value. Compared with an aqueous solution, the pH of a buffer solution is relatively insensitive to the addition of a small amount of strong acid or strong base. The buffer capacity<ref>{{cite book
 | last = Hulanicki
 | first = A.
 | title = Reactions of Acids and Bases in Analytical Chemistry
 | publisher = Horwood
 | year = 1987
 | isbn = 0-85312-330-6
 | others = Masson, M.R. (translation editor)
}}</ref> of a simple buffer solution is largest when pH&nbsp;=&nbsp;p''K''<sub>a</sub>. In [[acid–base extraction]], the efficiency of extraction of a compound into an organic phase, such as an [[ether]], can be optimised by adjusting the pH of the aqueous phase using an appropriate buffer. At the optimum pH, the concentration of the electrically neutral species is maximised; such a species is more soluble in organic solvents having a low [[dielectric constant]] than it is in water. This technique is used for the purification of weak acids and bases.<ref>{{cite journal
 | last = Eyal
 | first = A.M
 | year = 1997
 | title = Acid Extraction by Acid–Base-Coupled Extractants
 | journal = Ion Exchange and Solvent Extraction: A Series of Advances
 | volume = 13
 | pages = 31–94
}}</ref>

A [[pH indicator]] is a weak acid or weak base that changes colour in the transition pH range, which is approximately p''K''<sub>a</sub>&nbsp;±&nbsp;1. The design of a [[universal indicator]] requires a mixture of indicators whose adjacent p''K''<sub>a</sub> values differ by about two, so that their transition pH ranges just overlap.

In [[pharmacology]], ionization of a compound alters its physical behaviour and macro properties such as solubility and [[partition coefficient|lipophilicity]], log&nbsp;''p''). For example, ionization of any compound will increase the solubility in water, but decrease the lipophilicity. This is exploited in [[drug development]] to increase the concentration of a compound in the blood by adjusting the p''K''<sub>a</sub> of an ionizable group.<ref name=avdeef>{{cite book
| title = Absorption and Drug Development: Solubility, Permeability, and Charge State
| last = Avdeef
| first = A.
| year = 2003
| publisher = Wiley
| location = New York
| isbn = 0-471-42365-3
}}</ref>

Knowledge of p''K''<sub>a</sub> values is important for the understanding of [[complex (chemistry)|coordination complexes]], which are formed by the interaction of a metal ion, M<sup>m+</sup>, acting as a [[Lewis acid]], with a [[ligand]], L, acting as a [[Lewis base]]. However, the ligand may also undergo protonation reactions, so the formation of a complex in aqueous solution could be represented symbolically by the reaction
:<math chem>[\ce{M(H2O)_\mathit{n}}]^{m+} + \ce{LH <=> } \ [\ce{M(H2O)}_{n - 1} \ce{L}]^{(m - 1)+} + \ce{H3O+}</math>

To determine the equilibrium constant for this reaction, in which the ligand loses a proton, the p''K''<sub>a</sub> of the protonated ligand must be known. In practice, the ligand may be polyprotic; for example [[EDTA]]<sup>4−</sup> can accept four protons; in that case, all p''K''<sub>a</sub> values must be known. In addition, the metal ion is subject to [[hydrolysis#Hydrolysis of metal aqua ions|hydrolysis]], that is, it behaves as a weak acid, so the p''K'' values for the hydrolysis reactions must also be known.<ref>{{cite book
| title = Chemistry of Complex Equilibria
| last = Beck
| first = M.T.
| author2 = Nagypál, I.
| year = 1990
| publisher = Horwood
| isbn = 0-85312-143-5
}}</ref>

Assessing the [[risk assessment|hazard]] associated with an acid or base may require a knowledge of p''K''<sub>a</sub> values.<ref>{{cite book
| title = Risk Assessment of Chemicals: An Introduction
| last = van Leeuwen
| first = C.J.
| author2 = Hermens, L. M.
| year = 1995
| publisher = Springer
| isbn = 0-7923-3740-9
| pages = 254–255
}}</ref> For example, [[hydrogen cyanide]] is a very toxic gas, because the [[cyanide#Toxicity|cyanide ion]] inhibits the iron-containing enzyme [[cytochrome c oxidase]]. Hydrogen cyanide is a weak acid in aqueous solution with a p''K''<sub>a</sub> of about 9. In strongly alkaline solutions, above pH&nbsp;11, say, it follows that sodium cyanide is "fully dissociated" so the hazard due to the hydrogen cyanide gas is much reduced. An acidic solution, on the other hand, is very hazardous because all the cyanide is in its acid form. Ingestion of cyanide by mouth is potentially fatal, independently of pH, because of the reaction with cytochrome c oxidase.

In [[environmental science]] acid–base equilibria are important for lakes<ref>{{cite book
| last = Skoog
| first = D.A
| author2 = West, D.M.
| author3 = Holler, J.F.
| author4 = Crouch, S.R.
| title = Fundamentals of Analytical Chemistry
| publisher = Thomson Brooks/Cole
| year = 2004
| edition = 8th
| isbn = 0-03-035523-0
}} Chapter 9-6: Acid Rain and the Buffer Capacity of Lakes</ref> and rivers;<ref name=stumm_morgan>{{cite book
 |title = Water Chemistry
 |last = Stumm
 |first = W.
 |author2 = Morgan, J.J.
 |year = 1996
 |publisher = Wiley
 |location = New York
 |isbn = 0-471-05196-9
 |url = https://archive.org/details/waterchemistry00snoerich
}}</ref><ref name=aquatic>{{cite book
| title = Aquatic Chemistry: Chemical Equilibria and Rates in Natural Waters
| last = Snoeyink
| first = V.L.
| author2 = Jenkins, D.
| year = 1980
| publisher = Wiley
| location = New York
| isbn = 0-471-51185-4
}}</ref> for example, [[humic acid]]s are important components of natural waters. Another example occurs in [[chemical oceanography]]:<ref>{{cite book
| title = Chemical Oceanography
| last = Millero
| first = F.J.
| edition = 3rd
| year = 2006
| publisher = Taylor and Francis
| location = London
| isbn = 0-8493-2280-4
}}</ref> in order to quantify the solubility of iron(III) in seawater at various [[salinity|salinities]], the p''K''<sub>a</sub> values for the formation of the iron(III) hydrolysis products {{chem2|Fe(OH)(2+)}}, {{chem2|Fe(OH)2+}} and {{chem2|Fe(OH)3}} were determined, along with the [[solubility product]] of [[iron hydroxide]].<ref>{{cite journal
| last = Millero
| first = F.J.
| author2 = Liu, X.
| year = 2002
| title = The Solubility of Iron in Seawater
| journal = Marine Chemistry
| volume = 77
| issue = 1
| pages = 43–54
| doi = 10.1016/S0304-4203(01)00074-3
| bibcode = 2002MarCh..77...43L
}}</ref>