Acid dissociation constant

The larger the value of pK, the smaller the extent of dissociation at any given pH (see HendersonHasselbalch
equation)that is, the weaker the acid. A weak acid has
a pK value in the approximate range 2 to 12 in water.
Acids with a pK value of less than about 2 are said to
be strong acids; the dissociation of a strong acid is effectively complete such that concentration of the undissociated acid is too small to be measured. pK values
for strong acids can, however, be estimated by theoretical means.

Acetic acid, a weak acid, donates a proton (hydrogen ion, highlighted in green) to water in an equilibrium reaction to give the
acetate ion and the hydronium ion. Red: oxygen, black: carbon,
white: hydrogen.

An acid dissociation constant, K, (also known as

acidity constant, or acid-ionization constant) is a
quantitative measure of the strength of an acid in solution.
It is the equilibrium constant for a chemical reaction
known as dissociation in the context of acid-base reactions. In aqueous solution, the equilibrium of acid dissociation can be written symbolically as:

pK, is sometimes also (but incorrectly) referred to as an

acid dissociation constant.
The denition can be extended to non-aqueous solvents,
such as acetonitrile and dimethylsulfoxide. Denoting a
solvent molecule by S

HA + S A + SH+ ; Ka =

HA + H2 O A + H3 O+

[A ][SH+ ]
[HA][S]

where HA is a generic acid that dissociates into A , When the concentration of solvent molecules can be taken
known as the conjugate base of the acid and a hydrogen to be constant, K = [A ][H+ ] , as before.
a
[HA]
ion which combines with a water molecule to make an
hydronium ion. In the example shown in the gure, HA
represents acetic acid, and A represents the acetate ion,
1 Theoretical background
the conjugate base.
The chemical species HA, A and H3 O+ are said to be in
equilibrium when their concentrations do not change with
the passing of time. The dissociation constant is usually
written as a quotient of the equilibrium concentrations (in
mol/L), denoted by [HA], [A ] and [H3 O+ ]

Ka =

The acid dissociation constant for an acid is a direct consequence of the underlying thermodynamics of the dissociation reaction; the pK value is directly proportional
to the standard Gibbs energy change for the reaction.
The value of the pK changes with temperature and can
be understood qualitatively based on Le Chateliers principle: when the reaction is endothermic, the pK decreases with increasing temperature; the opposite is true
for exothermic reactions.

[A ][H3 O+ ]
[HA][H2 O]

In all but the most concentrated aqueous solutions of an

acid the concentration of water can be taken as constant The value of pK also depends on molecular structure in
and can be ignored. The denition can then be written many ways. For example, Pauling proposed two rules:
one for successive pK of polyprotic acids (see Polyprotic
more simply
acids below), and one to estimate the pK of oxyacids
based on the number of =O and OH groups (see Factors
[A ][H+ ]
that aect pK values below). Other structural factors

+
HA A + H : Ka =
[HA]
that inuence the magnitude of the acid dissociation constant include inductive eects, mesomeric eects, and
This is the denition in common usage. For many prachydrogen bonding.
tical purposes it is more convenient to discuss the logaThe quantitative behaviour of acids and bases in solution
rithmic constant, pK
can be understood only if their pK values are known. In
particular, the pH of a solution can be predicted when
the analytical concentration and pK values of all acids
pKa = log10 Ka
1

3 EQUILIBRIUM CONSTANT

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 nd
application in many dierent areas of chemistry, biology,
medicine, and geology. For example, many compounds
used for medication are weak acids or bases, and a knowledge of the pK values, together with the wateroctanol
partition coecient, 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, acidbase homeostasis and enzyme kinetics are dependent on
the pK values of the many acids and bases present in
the cell and in the body. In chemistry, a knowledge of
pK values is necessary for the preparation of buer solutions and is also a prerequisite for a quantitative understanding of the interaction between acids or bases and
metal ions to form complexes. Experimentally, pK values can be determined by potentiometric (pH) titration,
but for values of pK less than about 2 or more than about
11, spectrophotometric or NMR measurements may be
required due to practical diculties with pH measurements.

The acid loses a proton, leaving a conjugate base; the proton is transferred to the base, creating a conjugate acid.
For aqueous solutions of an acid HA, the base is water;
the conjugate base is A and the conjugate acid is the hydronium ion. The BrnstedLowry denition applies to
other solvents, such as dimethyl sulfoxide: the solvent S
acts as a base, accepting a proton and forming the conjugate acid SH+ .
HA + S A + SH+ .
In solution chemistry, it is common to use H+ as an abbreviation for the solvated hydrogen ion, regardless of the
solvent. In aqueous solution H+ denotes a solvated hydronium ion rather than a proton.[5][6]
The designation of an acid or base as conjugate depends
on the context. The conjugate acid BH+ of a base B dissociates according to
BH+ + OH B + H2 O
which is the reverse of the equilibrium
H2 O (acid) + B (base) OH (conjugate base) +
BH+ (conjugate acid).

Denitions

The hydroxide ion OH , a well known base, is here actAccording to Arrhenius's original denition, an acid is a ing as the conjugate base of the acid water. Acids and
substance that dissociates in aqueous solution, releasing bases are thus regarded simply as donors and acceptors
of protons respectively.
the hydrogen ion H+ (a proton):[1]
A broader denition of acid dissociation includes
hydrolysis, in which protons are produced by the splitting
HA A + H .
of water molecules. For example, boric acid (B(OH)3 )
+
[7]
The equilibrium constant for this dissociation reaction is produces H3 O as if it were a proton donor, but it has
known as a dissociation constant. The liberated proton been conrmed by Raman spectroscopy that this is due
[8]
combines with a water molecule to give a hydronium (or to the hydrolysis equilibrium:
oxonium) ion H3 O+ (naked protons do not exist in soluB(OH)3 + 2 H2 O B(OH)4 + H3 O+ .
tion), and so Arrhenius later proposed that the dissociation should be written as an acidbase reaction:
Similarly, metal ion hydrolysis causes ions such as
[Al(H2 O)6 ]3+ to behave as weak acids:[9]
HA + H2 O A + H3 O+ .

[Al(H2 O)6 ]3+ +H2 O [Al(H2 O)5 (OH)]2+ +

H3 O+ .

Acetic acid, a weak acid, donates a proton (hydrogen ion, highlighted in green) to water in an equilibrium reaction to give the
acetate ion and the hydronium ion. Red: oxygen, black: carbon,
white: hydrogen.

According to Lewis's original denition, an acid is a substance that accepts an electron pair to form a coordinate
covalent bond :[10]

3 Equilibrium constant

Brnsted and Lowry generalised this further to a proton An acid dissociation constant is a particular example of
exchange reaction:[2][3][4]
an equilibrium constant. For the specic equilibrium between a monoprotic acid, HA and its conjugate base A ,
acid + base conjugate base + conjugate acid.
in water,

3.1

Monoprotic acids

HA + H2 O A + H3 O+
the thermodynamic equilibrium constant, K
dened by[11]

K =

can be

{A }{H3 O+ }
{HA}{H2 O}

where {A} is the activity of the chemical species A etc.

Ka =

[A ][H+ ]
[HA]

is obtained. This is the denition in common use.[12] pK

is dened as log10 K. Note, however, that all published dissociation constant values refer to the specic
ionic medium used in their determination and that different values are obtained with dierent conditions, as
shown for acetic acid in the illustration above. When published constants refer to an ionic strength other than the
one required for a particular application, they may be adjusted by means of specic ion theory (SIT) and other
theories.[13]

is dimensionless since activity is dimensionless. AcK

tivities of the products of dissociation are placed in the
numerator, activities of the reactants are placed in the denominator. See activity coecient for a derivation of this Although K appears to have the dimension of concentraexpression.
tion, the exact denition uses chemical activities, which
are dimensionless. Therefore, K, as dened properly, is
also dimensionless. Nevertheless it is not unusual, particularly in texts relating to biochemical equilibria, to see
a value quoted with a dimension as, for example, "K =
300 M.

3.1 Monoprotic acids

See also: Acid Monoprotic acids
After rearranging the expression dening K, and putting

100

Variation of pKa of acetic acid with ionic strength

Since activity is the product of concentration and activity

coecient () the denition could also be written as

K =

[A ][H3 O+ ] A H3 O+
[A ][H3 O+ ]

[HA][H2 O]
HA H2 O
[HA][H2 O]

where [HA] represents the concentration of HA and is

a quotient of activity coecients.
To avoid the complications involved in using activities,
dissociation constants are determined, where possible, in
a medium of high ionic strength, that is, under conditions in which can be assumed to be always constant.[11]
For example, the medium might be a solution of 0.1 M
sodium nitrate or 3 M potassium perchlorate (1 M = 1
moldm3 , a unit of molar concentration). Furthermore,
in all but the most concentrated solutions it can be assumed that the concentration of water, [H2 O], is constant,

% formation

AH
50

0
2

0
1
pHpKa

Variation of the % formation of a monoprotic acid, AH, and its

conjugate base, A , with the dierence between the pH and the
pKa of the acid

pH = log10 [H+ ], one obtains[14]

pH = pKa + log

[A ]
[HA]

approximately 55 moldm3 . On dividing K

by the
constant terms and writing [H+ ] for the concentration of This is a form of the HendersonHasselbalch equation,
from which the following conclusions can be drawn.
the hydronium ion the expression

3 EQUILIBRIUM CONSTANT
At half-neutralization [A ]/[HA] = 1; since log(1)
=0, the pH at half-neutralization is numerically
equal to pK. Conversely, when pH = pK, the concentration of HA is equal to the concentration of A .
The buer region extends over the approximate
range pK 2, though buering is weak outside the
range pK 1. At pK 1, [A ]/[HA] = 10 or 1/10.
If the pH is known, the ratio may be calculated. This
ratio is independent of the analytical concentration
of the acid.

In water, measurable pK values range from about 2 for

a strong acid to about 12 for a very weak acid (or strong
base). All acids with a pK value of less than 2 are more
than 99% dissociated at pH 0 (1 M acid). This is known
as solvent leveling since all such acids are brought to the
same level of being strong acids, regardless of their pK
values. Likewise, all bases with a pK value larger than Phosphoric acid speciation
the upper limit are more than 99% protonated at all attainable pH values and are classied as strong bases.[3]
10. The species distribution diagram shows that the conAn example of a strong acid is hydrochloric acid, HCl, centrations of the two ions are maximum at pH 5.5 and
which has a pK value, estimated from thermodynamic 10.
quantities, of 9.3 in water.[15] The concentration of
undissociated acid in a 1 moldm3 solution will be less
than 0.01% of the concentrations of the products of dissociation. Hydrochloric acid is said to be fully dissociated in aqueous solution because the amount of undissociated acid is imperceptible. When the pK and analytical
concentration of the acid are known, the extent of dissociation and pH of a solution of a monoprotic acid can be
easily calculated using an ICE table.
A buer solution of a desired pH can be prepared as a
mixture of a weak acid and its conjugate base. In practice
the mixture can be created by dissolving the acid in water,
and adding the requisite amount of strong acid or base.
The pK of the acid must be less than two units dierent
from the target pH.

3.2

Polyprotic acids

Polyprotic acids are acids that can lose more than one proton. The constant for dissociation of the rst proton may
be denoted as K and the constants for dissociation of
successive protons as K, etc. Phosphoric acid, H3 PO4 ,
is an example of a polyprotic acid as it can lose three protons.

% species formation calculated with the program HySS for a 10

millimolar solution of citric acid. pKa1=3.13, pKa2 = 4.76,
pKa3=6.40.

When the dierence between successive pK values is less

than about four there is overlap between the pH range of
existence of the species in equilibrium. The smaller the
dierence, the more the overlap. The case of citric acid
When the dierence between successive pK values is is shown at the right; solutions of citric acid are buered
about four or more, as in this example, each species may over the whole range of pH 2.5 to 7.5.
be considered as an acid in its own right;[17] In fact salts According to Paulings rst rule, successive pK values of
of H2 PO4 may be crystallised from solution by adjust- a given acid increase (pK > pK).[18] For oxyacids with
ment of pH to about 5.5 and salts of HPO4 2 may be more than one ionizable hydrogen on the same atom, the
crystallised from solution by adjustment of pH to about pK values often increase by about 5 units for each pro-

3.3

Water self-ionization

ton removed,[19][20] as in the example of phosphoric acid 3.3 Water self-ionization

above.
Main article: Self-ionization of water
In the case of a diprotic acid, H2 A, the two equilibria are
H2 A HA + H+

HA A

+H

it can be seen that the second proton is removed from

a negatively charged species. Since the proton carries
a positive charge extra work is needed to remove it;
that is the cause of the trend noted above. Phosphoric
acid values (above) illustrate this rule, as do the values
for vanadic acid, H3 VO4 . When an exception to the
rule is found it indicates that a major change in structure is occurring. In the case of VO2 + (aq), the vanadium is octahedral, 6-coordinate, whereas vanadic acid is
tetrahedral, 4-coordinate. This is the basis for an explanation of why pK > pK for vanadium(V) oxoacids.

3.2.1

Isoelectric point

Main article: isoelectric point

Water possesses both acidic and basic properties. It is

amphiprotic. The equilibrium constant for the equilibrium
2 H2 O OH + H3 O+
is given by

Ka =

[H3 O+ ][OH ]
[H2 O]

When, as is usually the case, the concentration of water

can be assumed to be constant, this expression may be
replaced by

Kw = [H3 O+ ][OH ]
The self-ionization constant of water, K , is thus just a
special case of an acid dissociation constant.

These data can be tted to a parabola with

For substances in solution the isoelectric point (pI) is dened as the pH at which the sum, weighted by charge
pK = 14.94 - 0.04209 T + 0.0001718 T2
value, of concentrations of positively charged species is
equal to the weighted sum of concentrations of negatively
charged species. In the case that there is one species of From this equation, pK = 14 at 24.87 C. At that temand hydroxide ions have a coneach type, the isoelectric point can be obtained directly perature both hydrogen
7
3
centration
of
10
mol
dm
.
from the pK values. Take the example of glycine, dened
as AH. There are two dissociation equilibria to consider.
AH2 + AH + H+ ; [AH][H+ ] = K1 [AH2 + ]
AH A + H+ ; [A ][H+ ] = K2 [AH]
Substitute the expression for [AH] into the rst equation
[A ][H+ ]2 = K1 K2 [AH2 + ]

3.4 Amphoteric substances

An amphoteric substance is one that can act as an acid
or as a base, depending on pH. Water (above) is amphoteric. Another example of an amphoteric molecule is the
bicarbonate ion HCO3 that is the conjugate base of the
carbonic acid molecule H2 CO3 in the equilibrium

At the isoelectric point the concentration of the positively

H2 CO3 + H2 O HCO3 + H3 O+
charged species, AH2 + , is equal to the concentration of
the negatively charged species, A , so
but also the conjugate acid of the carbonate ion CO3 2 in
(the reverse of) the equilibrium
[H+ ]2 = K1 K2
Therefore, taking cologarithms, the pH is given by
pK1 + pK2
pI =
2
pI values for amino acids are listed at Proteinogenic
amino acid#Chemical properties. When more than two
charged species are in equilibrium with each other a full
speciation calculation may be needed.

HCO3 + OH CO3 2 + H2 O.
Carbonic acid equilibria are important for acid-base
homeostasis in the human body.
An amino acid is also amphoteric with the added complication that the neutral molecule is subject to an internal acid-base equilibrium in which the basic amino group
attracts and binds the proton from the acidic carboxyl
group, forming a zwitterion.

4 ACIDITY IN NONAQUEOUS SOLUTIONS

NH2 CHRCO2 H NH3 + CHRCO2

3.6 Temperature dependence

At pH less than about 5 both the carboxylate group and All equilibrium constants vary with temperature accord[23]
the amino group are protonated. As pH increases the acid ing to the van 't Ho equation
dissociates according to
NH3 + CHRCO2 H NH3 + CHRCO2 + H+
At high pH a second dissociation may take place.
NH3 + CHRCO2 NH2 CHRCO2 + H+

d ln K
H
=
dT
RT 2
R is the gas constant and T is the absolute temperature
. Thus, for exothermic reactions, (the standard enthalpy
change, H

, is negative) K decreases with tempera-

Thus the zwitter ion, NH3 + CHRCO2 , is amphoteric because it may either be protonated or deprotonated.

ture, but for endothermic reactions (H

increases with temperature.

3.5

4 Acidity in nonaqueous solutions

Bases and basicity

is positive) K

Historically, the equilibrium constant K for a base has

been dened as the association constant for protonation A solvent will be more likely to promote ionization of a dissolved acidic molecule in the following
of the base, B, to form the conjugate acid, HB+ .
circumstances:[24]
B + H2 O HB+ + OH
Using similar reasoning to that used before

Kb =

[HB+ ][OH ]
[B]

1. It is a protic solvent, capable of forming hydrogen

bonds.
2. It has a high donor number, making it a strong Lewis
base.
3. It has a high dielectric constant (relative permittivity), making it a good solvent for ionic species.

K is related to K for the conjugate acid. In water,

the concentration of the hydroxide ion, [OH ], is related
usto the concentration of the hydrogen ion by K = [H+ ] pK values of organic compounds are often obtained [24]
dimethyl
sulfoxide
(DMSO)
ing
the
aprotic
solvents

[OH ], therefore
and acetonitrile (ACN).[25]

DMSO is widely used as an alternative to water because

it has a lower dielectric constant than water, and is less
polar and so dissolves non-polar, hydrophobic substances
more easily. It has a measurable pK range of about 1
Substitution of the expression for [OH ] into the expres- to 30. Acetonitrile is less basic than DMSO, and, so,
sion for K gives
in general, acids are weaker and bases are stronger in
this solvent. Some pK values at 25 C for acetonitrile
(ACN)[26][27][28] and dimethyl sulfoxide (DMSO)[29] are
[HB+ ]Kw
Kw
shown in the following tables. Values for water are inKb =
=
[B][H+ ]
Ka
cluded for comparison.

Kw
[OH ] = +
[H ]

When K, K and K are determined under the same conditions of temperature and ionic strength, it follows, taking cologarithms, that pK or basicity"= pK pK. In
aqueous solutions at 25 C, pK is 13.9965,[22] so

pKb 14 pKa

Ionization of acids is less in an acidic solvent than in water. For example, hydrogen chloride is a weak acid when
dissolved in acetic acid. This is because acetic acid is a
much weaker base than water.
HCl + CH3 CO2 H Cl + CH3 C(OH)2 +
acid + base conjugate base + conjugate acid

with sucient accuracy for most practical purposes. In

eect there is no need to dene pK separately from pK, Compare this reaction with what happens when acetic
but it is done here as often only pK values can be found acid is dissolved in the more acidic solvent pure sulfuric
in the older literature.
acid[30]

7
H2 SO4 + CH3 CO2 H HSO4 + CH3 C(OH)2 +

right, the pK value rises steeply with increasing percentage of dioxane as the dielectric constant of the mixture is
The unlikely geminal diol species CH3 C(OH)2 + is sta- decreasing.
ble in these environments. For aqueous solutions the pH
A pK value obtained in a mixed solvent cannot be used
scale is the most convenient acidity function.[31] Other
directly for aqueous solutions. The reason for this is
acidity functions have been proposed for non-aqueous
that when the solvent is in its standard state its activity
media, the most notable being the Hammett acidity funcis dened as one. For example, the standard state of
tion, H 0 , for superacid media and its modied version H
water:dioxane 9:1 is precisely that solvent mixture, with
for superbasic media.[32]
no added solutes. To obtain the pK value for use with
aqueous solutions it has to be extrapolated to zero cosolvent concentration from values obtained from various
co-solvent mixtures.
These facts are obscured by the omission of the solvent
from the expression that is normally used to dene pK,
but pK values obtained in a given mixed solvent can be
compared to each other, giving relative acid strengths.
The same is true of pK values obtained in a particular
non-aqueous solvent such a DMSO.
Dimerization of a carboxylic acid

As of 2008, a universal, solvent-independent, scale for

In aprotic solvents, oligomers, such as the well-known acid dissociation constants has not been developed, since
acetic acid dimer, may be formed by hydrogen bonding. there is no known way to compare the standard states of
An acid may also form hydrogen bonds to its conjugate two dierent solvents.
base. This process, known as homoconjugation, has the
eect of enhancing the acidity of acids, lowering their
eective pK values, by stabilizing the conjugate base.
5 Factors that aect pK values
Homoconjugation enhances the proton-donating power
of toluenesulfonic acid in acetonitrile solution by a factor
of nearly 800.[33] In aqueous solutions, homoconjugation Paulings second rule is that the value of the rst pK for
does not occur, because water forms stronger hydrogen acids of the formula XO (OH) depends primarily on the
number of oxo groups m, and is approximately indepenbonds to the conjugate base than does the acid.
dent of the number of hydroxy groups n, and also of the
central atom X. Approximate values of pK are 8 for m =
4.1 Mixed solvents
0, 2 for m = 1, 3 for m = 2 and < 10 for m = 3.[18] Alternatively, various numerical formulas have been proposed
including pK = 8 5n (known as Bells rule),[19][36] pK
= 7 5n,[20][37] or pK = 9 7n.[19] The dependence on
m correlates with the oxidation state of the central atom,
X: the higher the oxidation state the stronger the oxyacid.
For example, pK for HClO is 7.2, for HClO2 is 2.0, for
HClO3 is 1 and HClO4 is a strong acid (pK << 0).[3]
This rule can help assign molecular structure: for example phosphorous acid (H3 PO3 ) has a pK near 2 suggested
that the structure is HPO(OH)2 , as later conrmed by
NMR spectroscopy, and not P(OH)3 which would be expected to have a pK near 8.[37]
With organic acids inductive eects and mesomeric effects aect the pK values. A simple example is provided by the eect of replacing the hydrogen atoms in
acetic acid by the more electronegative chlorine atom.
pKa of acetic acid in dioxane/water mixtures. Data at 25 C The electron-withdrawing eect of the substituent makes
from Pine et al.[34]
ionisation easier, so successive pK values decrease in the
series 4.7, 2.8, 1.4 and 0.7 when 0,1, 2 or 3 chlorine atoms
When a compound has limited solubility in water it is are present.[38] The Hammett equation, provides a general
common practice (in the pharmaceutical industry, for ex- expression for the eect of substituents.[39]
ample) to determine pK values in a solvent mixture such
as water/dioxane or water/methanol, in which the compound is more soluble.[35] In the example shown at the
log K = log K0 + .

5 FACTORS THAT AFFECT PKA VALUES

someric eects.[41][42]
Alcohols do not normally behave as acids in water, but the
presence of a double bond adjacent to the OH group can
substantially decrease the pK by the mechanism of ketoenol tautomerism. Ascorbic acid is an example of this
eect. The diketone 2,4-pentanedione (acetylacetone) is
also a weak acid because of the keto-enol equilibrium. In
aromatic compounds, such as phenol, which have an OH
substituent, conjugation with the aromatic ring as a whole
greatly increases the stability of the deprotonated form.

Fumaric acid

OH O
O

OH

Maleic acid

Structural eects can also be important. The dierence

between fumaric acid and maleic acid is a classic example. Fumaric acid is (E)1,4-but-2-enedioic acid, a
trans isomer, whereas maleic acid is the corresponding
cis isomer, i.e. (Z)1,4-but-2-enedioic acid (see cistrans isomerism). Fumaric acid has pK values of approximately 3.0 and 4.5. By contrast, maleic acid has
pK values of approximately 1.5 and 6.5. The reason for
this large dierence is that when one proton is removed
from the cis- isomer (maleic acid) a strong intramolecular
hydrogen bond is formed with the nearby remaining carboxyl group. This favors the formation of the maleate H+ ,
and it opposes the removal of the second proton from that
species. In the trans isomer, the two carboxyl groups are
always far apart, so hydrogen bonding is not observed.[43]
Proton sponge, 1,8-bis(dimethylamino)naphthalene, has
a pK value of 12.1. It is one of the strongest amine
bases known. The high basicity is attributed to the relief
of strain upon protonation and strong internal hydrogen
bonding.[44][45]

proton sponge

K is the dissociation constant of a substituted compound,

K0 is the dissociation constant when the substituent is
hydrogen, is a property of the unsubstituted compound
and has a particular value for each substituent. A plot
of log K against is a straight line with intercept log
K0 and slope . This is an example of a linear free energy relationship as log K is proportional to the standard
fee energy change. Hammett originally[40] formulated
the relationship with data from benzoic acid with dierent substiuents in the ortho- and para- positions: some
numerical values are in Hammett equation. This and
other studies allowed substituents to be ordered according to their electron-withdrawing or electron-releasing
power, and to distinguish between inductive and me-

Eects of the solvent and solvation should be mentioned

also in this section. It turns out, these inuences are
more subtle than that of a dielectric medium mentioned
above. For example, the expected (by electronic eects
of methyl substituents) and observed in gas phase order of
basicity of methylamines, Me3 N > Me2 NH > MeNH2 >
NH3 , is changed by water to Me2 NH > MeNH2 > Me3 N
> NH3 . Neutral methylamine molecules are hydrogenbonded to water molecules mailnly through one acceptor,
N-HOH, interaction and only occasionally just one more
donor bond, NH-OH2 . Hence, methylamines are stabilized to about the same extent by hydration, regardless
of the number of methyl groups. In stark contrast, corresponding methylammonium cations always utilize all
the available protons for donor NH-OH2 bonding. Relative stabilization of methylammonium ions thus decreases
with the number of methyl groups explaining the order of
water basicity of methylamines.[46]

5.1 Thermodynamics
An equilibrium constant is related to the standard Gibbs
energy change for the reaction, so for an acid dissociation
constant

= RT ln K 2.303 RT pK.

R is the gas constant and T is the absolute temperature.

Note that pK= log K and 2.303 ln 10. At 25 C
G in kJmol1 = 5.708 pK (1 kJmol1 = 1000 Joules
per mole). Free energy is made up of an enthalpy term
and an entropy term.[7]

= H

TS

The standard enthalpy change can be determined by

A calculated titration curve of oxalic acid titrated with a solution
calorimetry or by using the van 't Ho equation, though
of sodium hydroxide
the calorimetric method is preferable. When both the
standard enthalpy change and acid dissociation constant
have been determined, the standard entropy change is
easily calculated from the equation above. In the follow- 6 Experimental determination
ing table, the entropy terms are calculated from the experimental values of pK and H . The data were crit- See also: Determination of equilibrium constants
ically selected and refer to 25 C and zero ionic strength,
in water.[7]
The experimental determination of pK values is commonly performed by means of titrations, in a medium
of high ionic strength and at constant temperature.[48] A

G
= 2.303RT pKa
typical procedure would be as follows. A solution of the
compound in the medium is acidied with a strong acid

Computed here, from H and G values supto the point where the compound is fully protonated. The
solution is then titrated with a strong base until all the pro= G
plied in the citation, using TS
tons have been removed. At each point in the titration pH
H
is measured using a glass electrode and a pH meter. The
equilibrium constants are found by tting calculated pH
The rst point to note is that, when pK is positive, the values to the observed values, using the method of least
[49]
standard free energy change for the dissociation reaction squares.
is also positive. Second, some reactions are exothermic The total volume of added strong base should be small
and some are endothermic, but, when H
is negative compared to the initial volume of titrand solution in order to keep the ionic strength nearly constant. This will
TS
is the dominant factor, which determines that ensure that pK remains invariant during the titration.
is positive. Last, the entropy contribution is al- A calculated titration curve for oxalic acid is shown at
the right. Oxalic acid has pK values of 1.27 and 4.27.
< 0) in these reactions. Ions Therefore the buer regions will be centered at about pH
ways unfavourable (S
in aqueous solution tend to orient the surrounding water 1.3 and pH 4.3. The buer regions carry the information
molecules, which orders the solution and decreases the necessary to get the pK values as the concentrations of
entropy. The contribution of an ion to the entropy is the acid and conjugate base change along a buer region.
partial molar entropy which is often negative, especially
for small or highly charged ions.[47] The ionization of a Between the two buer regions there is an end-point, or
neutral acid involves formation of two ions so that the en- equivalence point, at about pH 3. This end-point is not
sharp and is typical of a diprotic acid whose buer retropy decreases (S
< 0). On the second ionization of gions overlap by a small amount: pK pK is about
the same acid, there are now three ions and the anion has three in this example. (If the dierence in pK values
a charge, so the entropy again decreases.
were about two or less, the end-point would not be noNote that the standard free energy change for the reac- ticeable.) The second end-point begins at about pH 6.3
tion is for the changes from the reactants in their standard and is sharp. This indicates that all the protons have been
states to the products in their standard states. The free removed. When this is so, the solution is not buered
energy change at equilibrium is zero since the chemical and the pH rises steeply on addition of a small amount of
potentials of reactants and products are equal at equilib- strong base. However, the pH does not continue to rise
rium.
indenitely. A new buer region begins at about pH 11
G

10

7 APPLICATIONS AND SIGNIFICANCE

(pK 3), which is where self-ionization of water becomes important.

It is very dicult to measure pH values of less than two
in aqueous solution with a glass electrode, because the
Nernst equation breaks down at such low pH values. To
determine pK values of less than about 2 or more than
about 11 spectrophotometric[50] [51] or NMR[12][52] measurements may be used instead of, or combined with, pH
measurements.

cannot always be measured directly, but may be calculated using theoretical methods. Buer solutions are used
extensively to provide solutions at or near the physiological pH for the study of biochemical reactions;[55] the design of these solutions depends on a knowledge of the pK
values of their components. Important buer solutions
include MOPS, which provides a solution with pH 7.2,
and tricine, which is used in gel electrophoresis.[56][57]
Buering is an essential part of acid base physiology including acid-base homeostasis,[58] and is key to understanding disorders such as acid-base imbalance.[59][60][61]
The isoelectric point of a given molecule is a function of
its pK values, so dierent molecules have dierent isoelectric points. This permits a technique called isoelectric
focusing,[62] which is used for separation of proteins by
2-D gel polyacrylamide gel electrophoresis.

When the glass electrode cannot be employed, as with

non-aqueous solutions, spectrophotometric methods are
frequently used.[27] These may involve absorbance or
uorescence measurements. In both cases the measured quantity is assumed to be proportional to the sum
of contributions from each photo-active species; with
absorbance measurements the Beer-Lambert law is asBuer solutions also play a key role in analytical chemsumed to apply.
istry. They are used whenever there is a need to x the
Aqueous solutions with normal water cannot be used for pH of a solution at a particular value. Compared with an
1
H NMR measurements but heavy water, D2 O, must be aqueous solution, the pH of a buer solution is relatively
used instead. 13 C NMR data, however, can be used with insensitive to the addition of a small amount of strong
normal water and 1 H NMR spectra can be used with non- acid or strong base. The buer capacity[63] of a simple
aqueous media. The quantities measured with NMR are buer solution is largest when pH = pK. In acid-base extime-averaged chemical shifts, as proton exchange is fast traction, the eciency of extraction of a compound into
on the NMR time-scale. Other chemical shifts, such as an organic phase, such as an ether, can be optimised by
those of 31 P can be measured.
adjusting the pH of the aqueous phase using an appropriate buer. At the optimum pH, the concentration of the
electrically neutral species is maximised; such a species
6.1 Micro-constants
is more soluble in organic solvents having a low dielectric
constant than it is in water. This technique is used for the
purication of weak acids and bases.[64]
H

H2N

N
H

NH2

spermine

A base such as spermine has a few dierent sites where

protonation can occur. In this example the rst proton can
go on the terminal -NH2 group, or either of the internal
-NH- groups. The pK values for dissociation of spermine protonated at one or other of the sites are examples
of micro-constants. They cannot be determined directly
by means of pH, absorbance, uorescence or NMR measurements. Nevertheless, the site of protonation is very
important for biological function, so mathematical methods have been developed for the determination of microconstants.[53]

Applications and signicance

A pH indicator is a weak acid or weak base that changes

colour in the transition pH range, which is approximately
pK 1. The design of a universal indicator requires a
mixture of indicators whose adjacent pK values dier 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
lipophilicity (log 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 pK of an ionizable group.[65]
Knowledge of pK values is important for the understanding of coordination complexes, which are formed by the
interaction of a metal ion, Mm+ , 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

A knowledge of pK values is important for the quanti[M(H2 O)n]m+

+LH
tative treatment of systems involving acidbase equilib[M(H2 O)nL](m1)+ + H3 O+
ria in solution. Many applications exist in biochemistry;
for example, the pK values of proteins and amino acid To determine the equilibrium constant for this reaction,
side chains are of major importance for the activity of en- in which the ligand loses a proton, the pK of the prozymes and the stability of proteins.[54] Protein pKa values tonated ligand must be known. In practice, the ligand

11
may be polyprotic; for example EDTA4 can accept four
protons; in that case, all pK values must be known. In
addition, the metal ion is subject to hydrolysis, that is, it
behaves as a weak acid, so the pK values for the hydrolysis reactions must also be known.[66] Assessing the hazard
associated with an acid or base may require a knowledge of pK values.[67] For example, hydrogen cyanide
is a very toxic gas, because the cyanide ion inhibits the
iron-containing enzyme cytochrome c oxidase. Hydrogen cyanide is a weak acid in aqueous solution with a pK
of about 9. In strongly alkaline solutions, above pH 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 acidbase equilibria are important for lakes[68] and rivers;[69][70] for example, humic
acids are important components of natural waters. Another example occurs in chemical oceanography:[71] in
order to quantify the solubility of iron(III) in seawater at
various salinities, the pK values for the formation of the
iron(III) hydrolysis products Fe(OH)2+ , Fe(OH)2 + and
Fe(OH)3 were determined, along with the solubility product of iron hydroxide.[72]

Values for common substances

There are multiple techniques to determine the pK of a

chemical, leading to some discrepancies between dierent sources. Well measured values are typically within
0.1 units of each other. Data presented here were taken
at 25 C in water.[3][73] More values can be found in
thermodynamics, above.

See also
Acids in wine: tartaric, malic and citric are the principal acids in wine.
Ocean acidication: dissolution of atmospheric carbon dioxide aects seawater pH. The reaction depends on total inorganic carbon and on solubility
equilibria with solid carbonates such as limestone
and dolomite.
Grotthuss mechanism: how protons are transferred
between hydronium ions and water molecules, accounting for the exceptionally high ionic mobility of
the proton (animation).
Predominance diagram: relates to equilibria involving polyoxyanions. pK values are needed to construct these diagrams.

Proton anity: a measure of basicity in the gas

phase.
Stability constants of complexes: formation of a
complex can often be seen as a competition between
proton and metal ion for a ligand, which is the product of dissociation of an acid.
Hammett acidity function: a measure of acidity that
is used for very concentrated solutions of strong
acids, including superacids.
Acidosis
Alkalosis
Arterial blood gas
Chemical equilibrium
pCO2
pH

10 References
[1] Miessler, G. (1991). Inorganic Chemistry (2nd ed.). Prentice Hall. ISBN 0-13-465659-8. Chapter 6: Acid-Base
and Donor-Acceptor Chemistry
[2] Bell, R.P. (1973). The Proton in Chemistry (2nd ed.).
London: Chapman & Hall. ISBN 0-8014-0803-2. Includes discussion of many organic Brnsted acids.
[3] Shriver, D.F; Atkins, P.W. (1999). Inorganic Chemistry
(3rd ed.). Oxford: Oxford University Press. ISBN 0-19850331-8. Chapter 5: Acids and Bases
[4] Housecroft, C. E.; Sharpe, A. G. (2008). Inorganic Chemistry (3rd ed.). Prentice Hall. ISBN 978-0131755536.
Chapter 6: Acids, Bases and Ions in Aqueous Solution
[5] Headrick, J.M.; Diken, E.G.; Walters, R. S.; Hammer, N. I.; Christie, R.A.; Cui, J.; Myshakin,
E.M.; Duncan, M.A.; Johnson, M.A.; Jordan, K.D.
(2005).
Spectral Signatures of Hydrated Proton Vibrations in Water Clusters.
Science 308
(5729): 176569.
Bibcode:2005Sci...308.1765H.
doi:10.1126/science.1113094. PMID 15961665.
[6] Smiechowski, M.; Stangret, J. (2006). Proton hydration in aqueous solution: Fourier transform infrared
studies of HDO spectra. J. Chem. Phys. 125
(20): 204508204522. Bibcode:2006JChPh.125t4508S.
doi:10.1063/1.2374891. PMID 17144716.
[7] Goldberg, R.; Kishore, N.; Lennen, R. (2002).
Thermodynamic Quantities for the Ionization Reactions of Buers (PDF). J. Phys. Chem. Ref. Data
31 (2): 231370. Bibcode:1999JPCRD..31..231G.
doi:10.1063/1.1416902.
[8] Jolly, William L. (1984). Modern Inorganic Chemistry.
McGraw-Hill. p. 198. ISBN 978-0-07-032760-3.

12

10

REFERENCES

[9] Burgess, J. (1978). Metal Ions in Solution. Ellis Horwood.

ISBN 0-85312-027-7. Section 9.1 Acidity of Solvated
Cations lists many pK values.

[24] Loudon, G. Marc (2005), Organic Chemistry (4th ed.),

New York: Oxford University Press, pp. 317318, ISBN
0-19-511999-1

[10] Petrucci, R.H.; Harwood, R.S.; Herring, F.G. (2002).

General Chemistry (8th ed.). Prentice Hall. ISBN 0-13014329-4. p.698

[25] March, J.; Smith, M. (2007). Advanced Organic Chemistry (6th ed.). New York: John Wiley & Sons. ISBN
978-0-471-72091-1. Chapter 8: Acids and Bases

[11] Rossotti, F.J.C.; Rossotti, H. (1961). The Determination

of Stability Constants. McGrawHill. Chapter 2: Activity
and Concentration Quotients

[26] Ktt, A.; Movchun, V.; Rodima, T,; Dansauer, T.;

Rusanov, E.B. ; Leito, I.; Kaljurand, I.; Koppel, J.;
Pihl, V.; Koppel, I.; Ovsjannikov, G.; Toom, L.;
Mishima, M.; Medebielle, M.; Lork, E.; Rschenthaler, G-V.; Koppel, I.A.; Kolomeitsev, A.A. (2008).
Pentakis(triuoromethyl)phenyl, a Sterically Crowded
and Electron-withdrawing Group: Synthesis and Acidity
of Pentakis(triuoromethyl)benzene, -toluene, -phenol,
and -aniline. J. Org. Chem. 73 (7): 26072620.
doi:10.1021/jo702513w. PMID 18324831.

[12] Popov, K.; Ronkkomaki, H.; Lajunen, L.H.J. (2006).

Guidelines for NMR Measurements for Determination
of High and Low pK Values (PDF). Pure Appl. Chem.
78 (3): 663675. doi:10.1351/pac200678030663.
[13] Project: Ionic Strength Corrections for Stability Constants. International Union of Pure and Applied Chemistry. Archived from the original on 29 October 2008.
Retrieved 2008-11-23.
[14] Mehta, Akul.
HendersonHasselbalch Equation:
Derivation of pKa and pKb.
PharmaXChange.
Retrieved 16 November 2014.
[15] Dasent, W.E. (1982). Inorganic Energetics: An Introduction. Cambridge University Press. ISBN 0-521-28406-6.
Chapter 5
[16] The values are for 25C and zero ionic strength Powell, Kipton J.; Brown, Paul L.; Byrne, Robert H.; Gajda,
Tams; Hefter, Glenn; Sjberg, Staan; Wanner, Hans
(2005). Chemical speciation of environmentally signicant heavy metals with inorganic ligands. Part 1:
The Hg2+ , Cl , OH , CO3 2 , SO4 2 , and PO4 3 aqueous systems. Pure Appl. Chem. 77 (4): 739800.
doi:10.1351/pac200577040739.
[17] Brown, T.E.; Lemay, H.E.; Bursten,B.E.; Murphy, C.;
Woodward, P. (2008). Chemistry: The Central Science
(11th ed.). New York: Prentice-Hall. p. 689. ISBN 013-600617-5.
[18] Greenwood, N.N.; Earnshaw, A. (1997). Chemistry of the
Elements (2nd ed.). Oxford: Butterworth-Heinemann. p.
50. ISBN 0-7506-3365-4.
[19] Miessler, Gary L.; Tarr Donald A. (1999). Inorganic
Chemistry (2nd ed.). Prentice Hall. p. 164. ISBN 013-465659-8.
[20] Huheey, James E. (1983). Inorganic Chemistry (3rd ed.).
Harper & Row. p. 297. ISBN 0-06-042987-9.
[21] Harned, H.S.; Owen, B.B (1958). The Physical Chemistry
of Electrolytic Solutions. New York: Reinhold Publishing
Corp. pp. 634649, 752754.

[27] Ktt, A.; Leito, I.; Kaljurand, I.; Soovli, L.; Vlasov,
V.M.; Yagupolskii, L.M.; Koppel, I.A. (2006). A Comprehensive Self-Consistent Spectrophotometric Acidity
Scale of Neutral Brnsted Acids in Acetonitrile. J. Org.
Chem. 71 (7): 28292838. doi:10.1021/jo060031y.
PMID 16555839.
[28] Kaljurand, I.; Ktt, A.; Soovli, L.; Rodima, T.; Memets,
V. Leito, I; Koppel, I.A. (2005). Extension of the SelfConsistent Spectrophotometric Basicity Scale in Acetonitrile to a Full Span of 28 pKa Units: Unication of Dierent Basicity Scales. J. Org. Chem. 70 (3): 10191028.
doi:10.1021/jo048252w. PMID 15675863.
[29] Bordwell pKa Table (Acidity in DMSO)". Archived
from the original on 9 October 2008. Retrieved 200811-02.
[30] Housecroft, C. E.; Sharpe, A. G. (2008). Inorganic Chemistry (3rd ed.). Prentice Hall. ISBN 978-0131755536.
Chapter 8: Non-Aqueous Media
[31] Rochester, C.H. (1970). Acidity Functions. Academic
Press. ISBN 0-12-590850-4.
[32] Olah, G.A; Prakash, S; Sommer, J (1985). Superacids.
New York: Wiley Interscience. ISBN 0-471-88469-3.
[33] Coetzee, J.F.; Padmanabhan, G.R. (1965). Proton Acceptor Power and Homoconjugation of Mono- and Diamines. J. Amer. Chem. Soc. 87 (22): 50055010.
doi:10.1021/ja00950a006.
[34] Pine, S.H.; Hendrickson, J.B.; Cram, D.J.; Hammond,
G.S. (1980). Organic chemistry. McGrawHill. p.
203. ISBN 0-07-050115-7.

[22] Lide, D.R. (2004). CRC Handbook of Chemistry and

Physics, Student Edition (84th ed.). CRC Press. ISBN
0-8493-0597-7. Section D152

[35] Box, K.J.; Vlgyi, G. Ruiz, R. Comer, J.E. Takcs-Novk,

K., Bosch, E. Rfols, C. Ross, M. (2007). Physicochemical Properties of a New Multicomponent Cosolvent System for the pKa Determination of Poorly Soluble
Pharmaceutical Compounds. Helv. Chim. Acta 90 (8):
15381553. doi:10.1002/hlca.200790161.

[23] Atkins, P.W.; de Paula, J. (2006). Physical Chemistry.

Oxford University Press. ISBN 0-19-870072-5. Section
7.4: The Response of Equilibria to Temperature

[36] Housecroft, Catherine E.; Sharpe, Alan G. (2006). Inorganic chemistry (2. ed., [Nachdr.] ed.). Harlow [u.a.]:
Prentice Hall. pp. 170171. ISBN 0130-39913-2.

13

[37] Douglas B., McDaniel D.H. and Alexander J.J. Concepts

and Models of Inorganic Chemistry (2nd ed. Wiley 1983)
p.526 ISBN 0-471-21984-3
[38] Pauling, L. (1960). The nature of the chemical bond and
the structure of molecules and crystals; an introduction to
modern structural chemistry (3rd ed.). Ithaca (NY): Cornell University Press. p. 277. ISBN 0-8014-0333-2.

[51] Box, K.J.; Donkor, R.E. Jupp, P.A. Leader, I.P. Trew,
D.F. Turner, C.H. (2008). The Chemistry of MultiProtic Drugs Part 1: A Potentiometric, Multi-Wavelength
UV and NMR pH Titrimetric Study of the MicroSpeciation of SKI-606. J. Pharm. Biomed. Anal. 47
(2): 303311. doi:10.1016/j.jpba.2008.01.015. PMID
18314291.

[39] Pine, S.H.; Hendrickson, J.B.; Cram, D.J.; Hammond,

G.S. (1980). Organic Chemistry. McGrawHill. ISBN
0-07-050115-7. Section 13-3: Quantitative Correlations
of Substituent Eects (Part B) The Hammett Equation

[52] Szakcs, Z.; Hgele, G. (2004). Accurate Determination

of Low pK Values by 1H NMR Titration. Talanta 62
(4): 819825. doi:10.1016/j.talanta.2003.10.007. PMID
18969368.

[40] Hammett, L.P. (1937). The Eect of Structure upon

the Reactions of Organic Compounds. Benzene Derivatives. J. Amer. Chem. Soc. 59 (1): 96103.
doi:10.1021/ja01280a022.

[53] Frassineti, C.; Alderighi, L; Gans, P; Sabatini, A;

Vacca, A; Ghelli, S. (2003). Determination of Protonation Constants of Some Fluorinated Polyamines by
Means of 13 C NMR Data Processed by the New Computer Program HypNMR2000. Protonation Sequence
in Polyamines.. Anal. Bioanal. Chem. 376 (7):
10411052. doi:10.1007/s00216-003-2020-0. PMID
12845401.

[41] Hansch, C.; Leo, A.; Taft, R. W. (1991). A Survey of Hammett Substituent Constants and Resonance
and Field Parameters. Chem. Rev. 91 (2): 165195.
doi:10.1021/cr00002a004.
[42] Shorter, J (1997). Compilation and critical evaluation
of structure-reactivity parameters and equations: Part 2.
Extension of the Hammett scale through data for the
ionization of substituted benzoic acids in aqueous solvents
at 25 C (Technical Report)". Pure and Applied Chemistry
69 (12): 24972510. doi:10.1351/pac199769122497.
[43] Pine, S.H.; Hendrickson, J.B.; Cram, D.J.; Hammond,
G.S. (1980). Organic chemistry. McGrawHill. ISBN 007-050115-7. Section 6-2: Structural Eects on Acidity
and Basicity
[44] Alder, R.W.; Bowman, P.S.; Steele, W.R.S.; Winterman, D.R. (1968). The Remarkable Basicity of 1,8bis(dimethylamino)naphthalene. Chem. Commun. (13):
723724. doi:10.1039/C19680000723.
[45] Alder, R.W. (1989). Strain Eects on Amine Basicities.
Chem.
Rev.
89 (5): 12151223.
doi:10.1021/cr00095a015.
[46] Fraczkiewicz, R (2013). In Silico Prediction of Ionization. In Reedijk, J. Reference Module in Chemistry, Molecular Sciences and Chemical Engineering [Online]. vol. 5. Amsterdam, The Netherlands: Elsevier.
doi:10.1016/B978-0-12-409547-2.02610-X.
[47] Atkins, Peter William; De Paula, Julio (2006). Atkins
physical chemistry. New York: W H Freeman. p. 94.
ISBN 9780716774334.
[48] Martell, A.E.; Motekaitis, R.J. (1992). Determination and
Use of Stability Constants. Wiley. ISBN 0-471-188174. Chapter 4: Experimental Procedure for Potentiometric
pH Measurement of Metal Complex Equilibria
[49] Leggett, D.J. (1985). Computational Methods for the Determination of Formation Constants. Plenum. ISBN 0306-41957-2.
[50] Allen, R.I.; Box,K.J.; Comer, J.E.A.; Peake, C.; Tam,
K.Y. (1998). Multiwavelength Spectrophotometric Determination of Acid Dissociation Constants of Ionizable
Drugs. J. Pharm. Biomed. Anal. 17 (45): 699641.
doi:10.1016/S0731-7085(98)00010-7.

[54] Onufriev, A.; Case, D.A; Ullmann G.M. (2001). A

Novel View of pH Titration in Biomolecules. Biochemistry 40 (12): 34133419. doi:10.1021/bi002740q.
PMID 11297406.
[55] Good, N.E.; Winget, G.D.; Winter, W.; Connolly, T.N.;
Izawa, S.; Singh, R.M.M. (1966). Hydrogen Ion Buers
for Biological Research. Biochemistry 5 (2): 467477.
doi:10.1021/bi00866a011. PMID 5942950.
[56] Dunn, M.J. (1993). Gel Electrophoresis: Proteins. Bios
Scientic Publishers. ISBN 1-872748-21-X.
[57] Martin, R. (1996). Gel Electrophoresis: Nucleic Acids.
Bios Scientic Publishers. ISBN 1-872748-28-7.
[58] Brenner, B.M. (Editor); Stein, J.H. (Editor) (1979). Acid
Base and Potassium Homeostasis. Churchill Livingstone.
ISBN 0-443-08017-8.
[59] Scorpio, R. (2000). Fundamentals of Acids, Bases,
Buers & Their Application to Biochemical Systems.
Kendall/Hunt Pub. Co. ISBN 0-7872-7374-0.
[60] Beynon, R.J.; Easterby, J.S. (1996). Buer Solutions: The
Basics. Oxford: Oxford University Press. ISBN 0-19963442-4.
[61] Perrin, D.D.; Dempsey, B. (1974). Buers for pH and
Metal Ion Control. London: Chapman & Hall. ISBN 0412-11700-2.
[62] Garn, D.(Editor); Ahuja, S. (Editor) (2005). Handbook
of Isoelectric Focusing and Proteomics 7. Elsevier. ISBN
0-12-088752-5.
[63] Hulanicki, A. (1987). Reactions of Acids and Bases in
Analytical Chemistry. Masson, M.R. (translation editor).
Horwood. ISBN 0-85312-330-6.
[64] Eyal, A.M (1997). Acid Extraction by AcidBaseCoupled Extractants. Ion Exchange and Solvent Extraction: A Series of Advances 13: 3194.

14

12

[65] Avdeef, A. (2003). Absorption and Drug Development:

Solubility, Permeability, and Charge State. New York: Wiley. ISBN 0-471-42365-3.
[66] Beck, M.T.; Nagypl, I. (1990). Chemistry of Complex
Equilibria. Horwood. ISBN 0-85312-143-5.
[67] van Leeuwen, C.J.; Hermens, L. M. (1995). Risk Assessment of Chemicals: An Introduction. Springer. pp. 254
255. ISBN 0-7923-3740-9.
[68] Skoog, D.A; West, D.M.; Holler, J.F.; Crouch, S.R.
(2004). Fundamentals of Analytical Chemistry (8th ed.).
Thomson Brooks/Cole. ISBN 0-03-035523-0. Chapter
9-6: Acid Rain and the Buer Capacity of Lakes
[69] Stumm, W.; Morgan, J.J. (1996). Water Chemistry. New
York: Wiley. ISBN 0-471-05196-9.
[70] Snoeyink, V.L.; Jenkins, D. (1980). Aquatic Chemistry:
Chemical Equilibria and Rates in Natural Waters. New
York: Wiley. ISBN 0-471-51185-4.
[71] Millero, F.J. (2006). Chemical Oceanography (3rd ed.).
London: Taylor and Francis. ISBN 0-8493-2280-4.
[72] Millero, F.J.; Liu, X. (2002). The Solubility of
Iron in Seawater. Marine chemistry 77 (1): 4354.
doi:10.1016/S0304-4203(01)00074-3.
[73] Speight, J.G. (2005). Langes Handbook of Chemistry
(18th ed.). McGrawHill. ISBN 0-07-143220-5. Chapter 8

11

Further reading

Albert, A.; Serjeant, E.P. (1971). The Determination of Ionization Constants: A Laboratory Manual.
Chapman & Hall. ISBN 0-412-10300-1. (Previous
edition published as Ionization constants of acids and
bases. London (UK): Methuen. 1962.)
Atkins, P.W.; Jones, L. (2008). Chemical Principles: The Quest for Insight (4th ed.). W.H. Freeman.
ISBN 1-4292-0965-8.
Housecroft, C. E.; Sharpe, A. G. (2008). Inorganic Chemistry (3rd ed.). Prentice Hall. ISBN 9780131755536. (Non-aqueous solvents)
Hulanicki, A. (1987). Reactions of Acids and Bases
in Analytical Chemistry. Horwood. ISBN 0-85312330-6. (translation editor: Mary R. Masson)
Perrin, D.D.; Dempsey, B.; Serjeant, E.P. (1981).
pKa Prediction for Organic Acids and Bases. Chapman & Hall. ISBN 0-412-22190-X.
Reichardt, C. (2003). Solvents and Solvent Eects
in Organic Chemistry (3rd ed.). Wiley-VCH. ISBN
3-527-30618-8. Chapter 4: Solvent Eects on the
Position of Homogeneous Chemical Equilibria.
Skoog, D.A.; West, D.M.; Holler, J.F.; Crouch, S.R.
(2004). Fundamentals of Analytical Chemistry (8th
ed.). Thomson Brooks/Cole. ISBN 0-03-035523-0.

EXTERNAL LINKS

12 External links
Acidity-Basicity Data in Nonaqueous Solvents Extensive bibliography of pK values in DMSO,
acetonitrile, THF, heptane, 1,2-dichloroethane, and
in the gas phase
Curtipot All-in-one freeware for pH and acidbase equilibrium calculations and for simulation
and analysis of potentiometric titration curves with
spreadsheets
SPARC Physical/Chemical property calculator Includes a database with aqueous, non-aqueous, and
gaseous phase pK values than can be searched using SMILES or CAS registry numbers
Aqueous-Equilibrium Constants pK values for various acid and bases. Includes a table of some solubility products
Free guide to pK and log p interpretation and measurement Explanations of the relevance of these
properties to pharmacology
Free online prediction tool (Marvin) pK, logP, logD
etc. From ChemAxon
Chemicalize.org:List of predicted structure based
properties
Evans pKa Chart http://evans.harvard.edu/pdf/
evans_pka_table.pdf

15

13
13.1

Text and image sources, contributors, and licenses

Text

Acid dissociation constant Source: https://en.wikipedia.org/wiki/Acid_dissociation_constant?oldid=666032945 Contributors: Derek

Ross, Bryan Derksen, Rmrf1024, Michael Hardy, ESnyder2, Kku, Charles Matthews, Altenmann, Nurg, Pifactorial, Diberri, David Gerard,
Giftlite, Graeme Bartlett, Dratman, Michael Devore, Bensaccount, Eequor, Xwu, Brockert, Yath, H Padleckas, Filthybutter, Vsmith, Bender235, Konstantin~enwiki, Marx Gomes, ~K, Femto, Arcadian, KBi, Benjah-bmm27, EagleFalconn, Cburnett, TenOfAllTrades, Gene
Nygaard, Umbricht, LOL, The Wordsmith, Joerg Kurt Wegner, Graham87, V8rik, BD2412, Rjwilmsi, THE KING, Nihiltres, Shao, TheSun, Physchim62, Sbrools, Krishnavedala, Bubbachuck, YurikBot, Borgx, Mushin, Postglock, AVM, Hellbus, Gaius Cornelius, A!eX,
Derek.cashman, Tetracube, Eno-ja, Tsiaojian lee, Itub, Anthony Du, SmackBot, Ashley thomas80, Cpdilkus, Edgar181, Robsomebody,
DarkIye, Armeria, Chris the speller, Bluebot, Hichris, Analogue Kid, Lawrenceuniversity1, Shalom Yechiel, OrphanBot, JonHarder, Garbacie, Ctifumdope, Flyguy649, Fuhghettaboutit, Xcomradex, Smokefoot, Drphilharmonic, Mwtoews, DMacks, Clicketyclack, Euchiasmus,
Olin, Smith609, Tac2z, Meco, SandyGeorgia, AdultSwim, Simon12, Cheesy Yeast, Twas Now, Eyehawk78, Conrad.Irwin, Fvasconcellos,
A876, WillowW, Mike Christie, Skoddet, Rieman 82, Dasfrpsl, Christian75, Chrislk02, Paddles, Headbomb, Trevyn, Raj76, AntiVandalBot, Jayron32, TimVickers, Litch, Turgidson, Magioladitis, Albmont, Think outside the box, Sns, KConWiki, Giggy, Causesobad,
Dirac66, Talon Artaine, Ac44ck, Meduban, Bfesser, Nono64, Leyo, Slash, C.R.Selvakumar, Boghog, Derlay, Pisanidavid, L'Aquatique,
Vicodin addict, Sd31415, Jorfer, Sanji Bhal, Almazi, Alex Allardyce, Gabby8228, Geometry guy, Proteins, Shanata, Temporaluser, Tneils,
Hoopssheaer, Petergans, Dguire, Graham Beards, WereSpielChequers, RJaguar3, Dsstman, Janopus, Mike2vil, Pinkadelica, Steveroon,
Bob1960evens, Plastikspork, Spoladore, Unbuttered Parsnip, Ectomaniac, Niceguyedc, Thegeneralguy, 4zimuth, Peachypoh, Sdrtirs, KRMorison, Addbot, DOI bot, Element16, Wickey-nl, Giants2008, Yobmod, Aboctok, Download, Favonian, Loupeter, Yobot, TaBOT-zerem,
Aboalbiss, Raimundo Pastor, KDS4444, CyberScientist, Daniele Pugliesi, Citation bot, LilHelpa, BotPuppet, Arturkjakub, Dave3457, Retracc, FrescoBot, Citation bot 1, SUL, DrilBot, Spidey71, Double sharp, Trappist the monk, Oktanyum, Hmmwhatsthisdo, Quantumkinetics, Levoslashx, DASHBot, EmausBot, Erbrumar, Dcirovic, JSquish, Prayerfortheworld, Dmayank, Kittenono, Rmashhadi, Slowkow, ClueBot NG, Xinleiucd, Abk-sp3, MerlIwBot, Helpful Pixie Bot, Curb Chain, Bibcode Bot, Neeya The Great, LGreiner, Mark Arsten, Shadow
intelligence, Stubcoman, Blegat, Hieu nguyentrung12, Project Osprey, Ekips39, Kostaskal, Jewels Vern, Stamptrader, Avismith456 and
Anonymous: 207

13.2

Images

File:Acetic-acid-dissociation-3D-balls.png
Source:
https://upload.wikimedia.org/wikipedia/commons/9/96/
Acetic-acid-dissociation-3D-balls.png License: Public domain Contributors: Own work Original artist: Ben Mills
File:Acetic_acid_pK_dioxane_water.png Source: https://upload.wikimedia.org/wikipedia/commons/a/a9/Acetic_acid_pK_dioxane_
water.png License: Public domain Contributors: Transferred from en.wikipedia; transferred to Commons by User:QuiteUnusual using
CommonsHelper.
Original artist: Original uploader was Petergans at en.wikipedia
File:Carboxylic_acid_dimers.png Source: https://upload.wikimedia.org/wikipedia/commons/c/c9/Carboxylic_acid_dimers.png License: Public domain Contributors: ? Original artist: ?
File:Citric_acid_speciation.png Source: https://upload.wikimedia.org/wikipedia/commons/3/39/Citric_acid_speciation.png License:
Public domain Contributors: A species distribution diagram as described in Martell, A.E.; Motekaitis, R.J. (1992). Determination and
use of stability constants. Wiley. ISBN 0471188174. Section 2.4 Original artist: Petergans (talk)
File:Fumaric-acid-2D-skeletal.png Source: https://upload.wikimedia.org/wikipedia/commons/1/13/Fumaric-acid-2D-skeletal.png License: Public domain Contributors: Own work Original artist: Ben Mills
File:H3PO4_speciation.png Source: https://upload.wikimedia.org/wikipedia/commons/1/16/H3PO4_speciation.png License: CC BYSA 4.0 Contributors: Own work Original artist: Petergans
File:Maleic-acid-2D-skeletal-A.svg Source: https://upload.wikimedia.org/wikipedia/commons/1/13/Maleic-acid-2D-skeletal-A.svg
License: Public domain Contributors: Own work Original artist: Krishnavedala
File:Oxalic_acid_titration_grid.png Source: https://upload.wikimedia.org/wikipedia/commons/e/e6/Oxalic_acid_titration_grid.png
License: CC-BY-SA-3.0 Contributors: Transferred from en.wikipedia to Commons. Original artist: JWSchmidt at English Wikipedia
File:PK_acetic_acid.png Source: https://upload.wikimedia.org/wikipedia/commons/5/53/PK_acetic_acid.png License: Public domain
Contributors: Transferred from en.wikipedia; transferred to Commons by User:Sfan00_IMG using CommonsHelper.
Original artist: PeterGans. Original uploader was Petergans at en.wikipedia
File:Proton_sponge.svg Source: https://upload.wikimedia.org/wikipedia/commons/0/06/Proton_sponge.svg License: Public domain
Contributors: Own work Original artist: User:Bryan Derksen
File:Spermine.svg Source: https://upload.wikimedia.org/wikipedia/commons/d/db/Spermine.svg License: Public domain Contributors:
Selfmade with ChemDraw. Original artist: Calvero.
File:StrikeO.png Source: https://upload.wikimedia.org/wikipedia/commons/2/2d/StrikeO.png License: Public domain Contributors:
Transferred from en.wikipedia; transferred to Commons by User:Sfan00_IMG using CommonsHelper.
Original artist: . Original uploader was Petergans at en.wikipedia
File:Weak_acid_speciation.svg Source: https://upload.wikimedia.org/wikipedia/commons/a/ab/Weak_acid_speciation.svg License:
Public domain Contributors: Own work Original artist: Krishnavedala

13.3

Content license

Creative Commons Attribution-Share Alike 3.0