Editing Acid dissociation constant (section)

== Theoretical background ==

The acid dissociation constant for an acid is a direct consequence of the underlying [[chemical thermodynamics|thermodynamics]] of the dissociation reaction; the p''K''<sub>a</sub> value is directly proportional to the standard [[Gibbs free energy]] change for the reaction. The value of the p''K''<sub>a</sub> changes with temperature and can be understood qualitatively based on [[Le Chatelier's principle]]: when the reaction is [[endothermic]], ''K''<sub>a</sub> increases and p''K''<sub>a</sub> decreases with increasing temperature; the opposite is true for [[exothermic]] reactions.{{cn|date=May 2025}}

The value of p''K''<sub>a</sub> also depends on molecular structure of the acid in many ways. For example, [[Linus Pauling|Pauling]] proposed two rules: one for successive p''K''<sub>a</sub> of polyprotic acids (see [[Acid dissociation constant#Polyprotic acids|Polyprotic acids]] below), and one to estimate the p''K''<sub>a</sub> of oxyacids based on the number of =O and −OH groups (see [[Acid dissociation constant#Factors that affect pKa values|Factors that affect p''K''<sub>a</sub> values]] below). Other structural factors that influence the magnitude of the acid dissociation constant include [[inductive effect]]s, [[mesomeric effect]]s, and [[hydrogen bonding]]. [[Hammett equation|Hammett type equations]] have frequently been applied to the estimation of p''K''<sub>a</sub>.<ref name="Perrin">{{cite book
| last1 = Perrin
| first1 = DD
| last2 = Dempsey
| first2 = B
| last3 = Serjeant
| first3 = EP
| name-list-style = vanc
| title = p''K''<sub>a</sub> Prediction for Organic Acids and Bases
| publisher = Chapman & Hall
| year = 1981
| location = London
| isbn = 978-0-412-22190-3
| doi = 10.1007/978-94-009-5883-8
| chapter = Chapter 3: Methods of p''K''<sub>a</sub> Prediction
| pages = 21–26
| department = (secondary)
}}</ref><ref name="RMC_2013">{{cite encyclopedia
| last = Fraczkiewicz
| first = R
| title = Reference Module in Chemistry, Molecular Sciences and Chemical Engineering
| name-list-style = vanc
| chapter = In Silico Prediction of Ionization
| encyclopedia = Reference Module in Chemistry, Molecular Sciences and Chemical Engineering [Online]
| editor-last = Reedijk
| editor-first = J
| volume = 5
| publisher = Elsevier
| location = Amsterdam, the Netherlands
| year = 2013
| doi = 10.1016/B978-0-12-409547-2.02610-X
| isbn = 9780124095472
| department = (secondary)
}}</ref>

The quantitative behaviour of acids and bases in solution can be understood only if their p''K''<sub>a</sub> values are known. In particular, the [[pH]] of a solution can be predicted when the analytical concentration and p''K''<sub>a</sub> values of all acids and bases are known; conversely, it is possible to calculate the equilibrium concentration of the acids and bases in solution when the pH is known. These calculations find application in many different areas of chemistry, biology, medicine, and geology. For example, many compounds used for medication are weak acids or bases, and a knowledge of the p''K''<sub>a</sub> values, together with the [[octanol-water partition coefficient]], can be used for estimating the extent to which the compound enters the blood stream. Acid dissociation constants are also essential in [[aquatic chemistry]] and [[chemical oceanography]], where the acidity of water plays a fundamental role. In living organisms, [[acid–base homeostasis]] and [[enzyme kinetics]] are dependent on the p''K''<sub>a</sub> values of the many acids and bases present in the cell and in the body. In chemistry, a knowledge of p''K''<sub>a</sub> values is necessary for the preparation of [[buffer solution]]s and is also a prerequisite for a quantitative understanding of the interaction between acids or bases and metal ions to form [[Stability constants of complexes|complexes]]. Experimentally, p''K''<sub>a</sub> values can be determined by potentiometric (pH) [[titration]], but for values of p''K''<sub>a</sub> less than about 2 or more than about 11, [[spectrophotometry|spectrophotometric]] or [[nuclear magnetic resonance|NMR]] measurements may be required due to practical difficulties with pH measurements.