Acid dissociation constant

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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, Ka, (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. The equilibrium can be written symbolically as: HA A− + H+,

where HA is a generic acid that dissociates by splitting into A−, known as the conjugate base of the acid, and the hydrogen ion or proton, H+, which, in the case of aqueous solutions, exists as a solvated hydronium ion. In the example shown in the figure, HA represents acetic acid, and A− the acetate ion. The chemical species HA, A− and H+ 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 [H+]:

Due to the many orders of magnitude spanned by Ka values, a logarithmic measure of the acid dissociation constant is more commonly used in practice. The logarithmic constant, pKa, which is equal to −log10 Ka, is sometimes also (but incorrectly) referred to as an acid dissociation constant:

The larger the value of pKa, the smaller the extent of dissociation. A weak acid has a pKa value in the approximate range −2 to 12 in water. Acids with a pKa value of less than about −2 are said to be strong acids; a strong acid is almost completely dissociated in aqueous solution, to the extent that the concentration of the undissociated acid becomes undetectable. pKa values for strong acids can, however, be estimated by theoretical means or by extrapolating from measurements in non-aqueous solvents in which the dissociation constant is smaller, such as acetonitrile and dimethylsulfoxide.


2. and a .2 Polyprotic acids  3.6 Temperature dependence 4. biology. and geology. the pKa decreases with increasing temperature. medicine. conversely. In particular.1 Mixed solvents 5.1 Micro-constants • • • • • • • • • 4 Acidity in nonaqueous solutions ○ ○ ○ 5 Factors that affect pKa values 6 Experimental determination 7 Applications and significance 8 Values for common substances 9 See also 10 References 11 Further reading 12 External links [edit] Theoretical background The acid dissociation constant for an acid is a direct consequence of the underlying thermodynamics of the dissociation reaction. many compounds used for medication are weak acids or bases. The quantitative behaviour of acids and bases in solution can be understood only if their pKa values are known. the pH of a solution can be predicted when the analytical concentration and pKa values of all acids and bases are known.3 Water self-ionization 3.1 Thermodynamics 6. mesomeric effects.1 Isoelectric point 3.• • • 1 Theoretical background 2 Definitions 3 Equilibrium constant ○ ○ ○ ○ ○ ○ 3. it is possible to calculate the equilibrium concentration of the acids and bases in solution when the pH is known. inductive effects. The value of the pKa changes with temperature and can be understood qualitatively based on Le Chatelier's principle: when the reaction is endothermic. For example. These calculations find application in many different areas of chemistry. The underlying structural factors that influence the magnitude of the acid dissociation constant include Pauling's rules for acidity constants.4 Amphoteric substances 3. the pKa value is directly proportional to the standard Gibbs energy change for the reaction. and hydrogen bonding. the opposite is true for exothermic reactions.1 Monoprotic acids 3.5 Bases 3.

Acid dissociation constants are also essential in aquatic chemistry and chemical oceanography. A broader definition of acid dissociation includes hydrolysis. Acids and bases are thus regarded simply as donors and acceptors of protons respectively. the base is water. such as dimethyl sulfoxide: the solvent S acts as a base. it is common to use H+ as an abbreviation for the solvated hydrogen ion. can be used for estimating the extent to which the compound enters the blood stream. where the acidity of water plays a fundamental role. The liberated proton combines with a water molecule to give a hydronium (or oxonium) ion H3O+. The hydroxide ion OH−. In chemistry. acid-base homeostasis and enzyme kinetics are dependent on the pKa values of the many acids and bases present in the cell and in the body. and so Arrhenius later proposed that the dissociation should be written as an acid–base reaction: HA + H2O A− + H3O+. together with the water–octanol partition coefficient. leaving a conjugate base. For aqueous solutions of an acid HA. is here acting as the conjugate base of the acid water. In aqueous solution H+ denotes a solvated hydronium ion rather than a proton. in which protons are produced by the splitting of water molecules.[5][6] The designation of an acid or base as "conjugate" depends on the context. Brønsted and Lowry generalised this further to a proton exchange reaction:[2][3][4] acid + base conjugate base + conjugate acid. spectrophotometric or NMR measurements may be required due to practical difficulties with pH measurements. Experimentally. In living organisms. but for values of pKa less than about 2 or more than about 11. [edit] Definitions According to Arrhenius's original definition. a well known base. releasing the hydrogen ion H+ (a proton):[1] HA A− + H+. The conjugate acid BH+ of a base B dissociates according to BH+ + OH− B + H2O which is the reverse of the equilibrium H2O (acid) + B (base) OH− (conjugate base) + BH+ (conjugate acid). a knowledge of pKa values is necessary for the preparation of buffer solutions and is also a prerequisite for a quantitative understanding of the interaction between acids or bases and metal ions to form complexes. The acid loses a proton. pKa values can be determined by potentiometric (pH) titration. The Brønsted–Lowry definition applies to other solvents. creating a conjugate acid. In solution chemistry. the proton is transferred to the base. The equilibrium constant for this dissociation reaction is known as a dissociation constant.knowledge of the pKa values. an acid is a substance that dissociates in aqueous solution. boric acid (B(OH)3) produces H3O+ as if it were a . For example. regardless of the solvent. the conjugate base is A− and the conjugate acid is the hydronium ion. accepting a proton and forming the conjugate acid SH+.

K is dimensionless since activity is dimensionless. in a medium of high ionic strength. where possible. Similarly. Variation of pKa of acetic acid with ionic strength Since activity is the product of concentration and activity coefficient (γ) the definition could also be written as where [HA] represents the concentration of HA and Γ is a quotient of activity coefficients. metal ion hydrolysis causes ions such as [Al(H2O)6]3+ to behave as weak acids:[9] [Al(H2O)6]3+ +H2O [Al(H2O)5(OH)]2+ + H3O+. Activities of the products of dissociation are placed in the numerator. [edit] Equilibrium constant An acid dissociation constant is a particular example of an equilibrium constant. dissociation constants are determined. activities of the reactants are placed in the denominator. that is.[7] but it has been confirmed by Raman spectroscopy that this is due to the hydrolysis equilibrium:[8] B(OH)3 + 2 H2O B(OH)4− + H3O+. To avoid the complications involved in using activities. in water. HA and its conjugate base A−. HA + H2O A− + H3O+ can be defined by[10] the thermodynamic equilibrium constant. K where {A} is the activity of the chemical species A etc.proton donor. For the specific equilibrium between a monoprotic acid. under conditions in which Γ can be . See activity coefficient for a derivation of this expression.

approximately 55 mol·dm−3. This is the definition in common use. the medium might be a solution of 0. Furthermore. and its conjugate base. Nevertheless it is not unusual.[11] pKa is defined as −log10 Ka.[12] Although Ka appears to have the dimension of concentration it must in fact be dimensionless or it would not be possible to take its logarithm. When published constants refer to an ionic strength other than the one required for a particular application. as shown for acetic acid in the illustration above. Note. [H2O]. AH. from which the following conclusions can be drawn. they may be adjusted by means of specific ion theory (SIT) and other theories. The illusion is the result of omitting the constant term [H2O] from the defining expression.assumed to be always constant. "Ka = 300 M". a unit of molar concentration). A−. with the difference between the pH and the pKa of the acid After rearranging the expression defining Ka. one obtains This is a form of the Henderson–Hasselbalch equation. and putting pH = −log10[H+]. On dividing K by the constant terms and writing [H+] for the concentration of the hydronium ion the expression is obtained. however. in all but the most concentrated solutions it can be assumed that the concentration of water. particularly in texts relating to biochemical equilibria. for example. . to see a value quoted with a dimension as. [edit] Monoprotic acids Variation of the % formation of a monoprotic acid.1 M sodium nitrate or 3 M potassium perchlorate (1 M = 1 mol·dm−3.[10] For example. is constant. that all published dissociation constant values refer to the specific ionic medium used in their determination and that different values are obtained with different conditions.

though buffering is weak outside the range pKa ± 1. estimated from thermodynamic quantities. All acids with a pKa value of less than −2 are more than 99% dissociated at pH 0 (1 M acid). If the pH is known. The buffer region extends over the approximate range pKa ± 2.[3] An example of a strong acid is hydrochloric acid. In practice the mixture can be created by dissolving the acid in water. regardless of their pKa values. The pKa of the acid must be less than two units different from the target pH. • • In water. Hydrochloric acid is said to be "fully dissociated" in aqueous solution because the amount of undissociated acid is imperceptible. Conversely. When the pKa 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. and adding the requisite amount of strong acid or base. A buffer solution of a desired pH can be prepared as a mixture of a weak acid and its conjugate base. Likewise.[13] The concentration of undissociated acid in a 1 mol·dm−3 solution will be less than 0.3 in water. the pH at half-neutralization is numerically equal to pKa. At pKa ± 1. measurable pKa values range from about −2 for a strong acid to about 12 for a very weak acid (or strong base). [A−]/[HA] = 10 or 1/10.01% of the concentrations of the products of dissociation. since log(1) =0. which has a pKa value. the ratio may be calculated. all bases with a pKa value larger than the upper limit are more than 99% protonated at all attainable pH values and are classified as strong bases.• At half-neutralization [A−]/[HA] = 1. This is known as solvent leveling since all such acids are brought to the same level of being strong acids. when pH = pKa. of −9. HCl. See also: Acid#Monoprotic acids [edit] Polyprotic acids % species' formation as a function of pH . the concentration of HA is equal to the concentration of A−. This ratio is independent of the analytical concentration of the acid.

equilibrium H3PO4 H2PO4− HPO42− H2PO4− + H+ pKa value pKa1 = 2. The smaller the difference. Phosphoric acid.% species formation calculated with the program HySS for a 10 millimolar solution of citric acid. H3VO4. whereas vanadic . the vanadium is octahedral.20 PO43− + H+ pKa3 = 12. The species distribution diagram shows that the concentrations of the two ions are maximum at pH 5. In the case of VO2+ (aq).5. the two equilibria are H2A HA− HA− + H+ A2− + H+ it can be seen that the second proton is removed from a negatively charged species.[15] For example. H3PO4. for a diprotic acid. H2A.15 HPO42− + H+ pKa2 = 7. as in this example. pKa2 = 4. Polyprotic acids are acids that can lose more than one proton.40. In general. pKa1=3. that is the cause of the trend noted above.5 and salts of HPO42− may be crystallised from solution by adjustment of pH to about 10. is an example of a polyprotic acid as it can lose three protons.5 and 10. etc. The constant for dissociation of the first proton may be denoted as Ka1 and the constants for dissociation of successive protons as Ka2. as do the values for vanadic acid. solutions of citric acid are buffered over the whole range of pH 2. When an exception to the rule is found it indicates that a major change in structure is occurring.[14] In fact salts of H2PO4− may be crystallised from solution by adjustment of pH to about 5.13. When the difference between successive pK values is less than about four there is overlap between the pH range of existence of the species in equilibrium. pKa3=6. it is true that successive pK values increase (Pauling's first rule). Phosphoric acid values (above) illustrate this rule. Since the proton carries a positive charge extra work is needed to remove it. The case of citric acid is shown at the right. 6-coordinate. each species may be considered as an acid in its own right.5 to 7.76.37 When the difference between successive pK values is about four or more. the more the overlap.

defined as AH. the pH is given by pI values for amino acids are listed at Proteinogenic amino acid#Chemical properties. so [H+]2 = K1K2 Therefore. A-.92 pKa4 = 13. the isoelectric point can be obtained directly from the pK values. of concentrations of positively charged species is equal to the weighted sum of concentrations of negatively charged species. There are two dissociation equilibria to consider. AH2+ AH AH + H+. When more than two charged species are in equilibrium with each other a full speciation calculation may be needed.60 pKa3 = 7. This is the basis for an explanation of why pKa1 > pKa2 for vanadium(V) oxoacids. [AH][H+] = K1[AH2+] A. AH2+. weighted by charge value. is equal to the concentration of the negatively charged species. In the case that there is one species of each type. taking cologarithms.27 H3VO4 + H+ + 2H2O pKa1 = 4.2 H2VO4− + H+ HVO42− + H+ VO43− + H+ [edit] Isoelectric point Main article: isoelectric point For substances in solution the isoelectric point (pI) is defined as the pH at which the sum.+ H+. 4-coordinate.acid is tetrahedral. equilibrium [VO2(H2O)4]+ H3VO4 H2VO4− HVO42− pKa value pKa2 = 2. Take the example of glycine. [A-][H+] = K2[AH] Substitute the expression for [AH] into the first equation [A-][H+]2 = K1K2[AH2+] At the isoelectric point the concentration of the positively charged species. The equilibrium constant for the equilibrium 2 H2O is given by OH− + H3O+ . [edit] Water self-ionization Main article: Self-ionization of water Water has both acidic and basic properties.

535 13.734 14. HB+.680 13.997 13. this expression may be replaced by The self-ionization constant of water. to form the conjugate acid.+ H+ At high pH a second dissociation may take place. forming a zwitter ion . as is usually the case. is thus just a special case of an acid dissociation constant. Another example of an amphoteric molecule is the bicarbonate ion HCO3− that is the conjugate base of the carbonic acid molecule H2CO3 in the equilibrium H2CO3 + H2O HCO3− + H3O+ but also the conjugate acid of the carbonate ion CO32− in (the reverse of) the equilibrium HCO3− + OH− CO32− + H2O. [edit] Bases Historically. As pH increases the acid dissociates according to NH3+CHRCO2H NH3+CHRCO2.943 14. .87 °C. NH3+CHRCO2NH2CHRCO2.396 13.167 13. the concentration of water can be assumed to be constant. pKw values for pure water[16] T/°C 0 5 10 15 20 25 30 35 40 45 50 pKw 14.When. the equilibrium constant Kb for a base has been defined as the association constant for protonation of the base.262 From these data it can be deduced that Kw = 10−14 at 24. 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. Carbonic acid equilibria are important for acid-base homeostasis in the human body. depending on pH. [edit] Amphoteric substances An amphoteric substance is one that can act as an acid or as a base. NH3+CHRCO2-.830 13. NH2CHRCO2H NH3+CHRCO2- At pH less than about 5 both the carboxylate group and the amino group are protonated. is amphoteric because it may either be protonated or deprotonated.346 14. Water (above) is amphoteric.+ H+ Thus the zwitter ion. At that temperature both hydrogen and hydroxide ions have a concentration of 10−7 mol dm−3. Kw. B.535 14.

In water.[20] Solvent Solvent properties at 25 °C Donor number[19] Dielectric constant[19] . making it a good solvent for ionic species.B + H2O HB+ + OH− Using similar reasoning to that used before Kb is related to Ka for the conjugate acid. it follows. capable of forming hydrogen bonds. Thus. [edit] Acidity in nonaqueous solutions A solvent will be more likely to promote ionization of a dissolved acidic molecule in the following circumstances. making it a strong Lewis base. 2. but it is done here because pKb values can be found in the older literature.[17] so pKb ~ 14 − pKa. therefore Substitution of the expression for [OH−] into the expression for Kb gives When Ka.[19] 1. that pKb = pKw − pKa. [edit] Temperature dependence All equilibrium constants vary with temperature according to the van 't Hoff equation[18] R is the gas constant and T is the absolute temperature . but for endothermic reactions (ΔH is positive) K increases with temperature. In aqueous solutions at 25 °C. In effect there is no need to define pKb separately from pKa.9965. (the standard enthalpy change. It has a high donor number. it has a high dielectric constant (relative permittivity). the concentration of the hydroxide ion. is related to the concentration of the hydrogen ion by Kw = [H+] [OH−]. pKa values of organic compounds are often obtained using the aprotic solvents dimethyl sulfoxide (DMSO)[19] and acetonitrile (ACN). taking cologarithms. pKw is 13. It is a protic solvent. [OH−]. Kb and Kw are determined under the same conditions of temperature and ionic strength. ΔH . is negative) K decreases with temperature. 3. for exothermic reactions.

Acetonitrile 14 Dimethylsulfoxide 30 Water 18 37 47 78 DMSO is widely used as an alternative to water because it has a lower dielectric constant than water.1 23.51 12. so.62 7. and is less polar and so dissolves non-polar.5 0.6 strong 3.72 12.[26] Other acidity functions have been proposed for non-aqueous media. It has a measurable pKa range of about 1 to 30. for superacid media and its modified version H− for superbasic media. HCl + CH3CO2H acid + base Cl− + CH3C(OH)2+ conjugate base + conjugate acid Compare this reaction with what happens when acetic acid is dissolved in the more acidic solvent pure sulfuric acid[25] H2SO4 + CH3CO2H HSO4− + CH3C(OH)2+ The unlikely geminal diol species CH3C(OH)2+ is stable in these environments.6 29.8 18. This is because acetic acid is a much weaker base than water.4-Dinitrophenol Benzoic acid Acetic acid Phenol BH+ B + H+ Pyrrolidine Triethylamine Proton sponge Pyridine Aniline ACN DMSO water 8.[27] .0 18.0 19. For example.53 3.4 10. hydrophobic substances more easily.1 21. Acetonitrile is less basic than DMSO.1 5. Some pKa values at 25 °C for acetonitrile (ACN)[21][22][23] and dimethyl sulfoxide (DMSO)[24] are shown in the following tables.9 16.62 3.14 18. H0. and.51 11.4 10.82 9. For aqueous solutions the pH scale is the most convenient acidity function.9 4. hydrogen chloride is a weak acid when dissolved in acetic acid. in general.5 12. the most notable being the Hammett acidity function.2 4. pKa values of acids HA A− + H+ p-Toluenesulfonic acid 2.56 10.66 5.4 Ionization of acids is less in an acidic solvent than in water. Values for water are included for comparison.99 11. acids are weaker and bases are stronger in this solvent.2 9.756 9.

a universal. solvent-independent. A pKa value obtained in a mixed solvent cannot be used directly for aqueous solutions.[30] In the example shown at the right. For example. such as the well-known acetic acid dimer. since there is no known way to compare the standard states of two different solvents. Homoconjugation enhances the protondonating power of toluenesulfonic acid in acetonitrile solution by a factor of nearly 800.Dimerization of a carboxylic acid In aprotic solvents. but pKa values obtained in a given mixed solvent can be compared to each other. because water forms stronger hydrogen bonds to the conjugate base than does the acid. homoconjugation does not occur. These facts are obscured by the omission of the solvent from the expression that is normally used to define pKa. The same is true of pKa values obtained in a particular nonaqueous solvent such a DMSO.[29] When a compound has limited solubility in water it is common practice (in the pharmaceutical industry. −3 for m = 2 and < −10 for m = 3. giving relative acid strengths. may be formed by hydrogen bonding. As of 2008. in which the compound is more soluble. oligomers. the standard state of water:dioxane 9:1 is precisely that solvent mixture. [edit] Mixed solvents pKa of acetic acid in dioxane/water mixtures. X: the . has the effect of enhancing the acidity of acids. [edit] Factors that affect pKa values Pauling's second rule states that the value of the first pKa for acids of the formula XOm(OH) n is approximately independent of n and X and is approximately 8 for m = 0. An acid may also form hydrogen bonds to its conjugate base. with no added solutes. the pKa value rises steeply with increasing percentage of dioxane as the dielectric constant of the mixture is decreasing. scale for acid dissociation constants has not been developed. lowering their effective pKa values.[28] In aqueous solutions.[15] This correlates with the oxidation state of the central atom. To obtain the pKa value for use with aqueous solutions it has to be extrapolated to zero co-solvent concentration from values obtained from various co-solvent mixtures. This process. for example) to determine pKa values in a solvent mixture such as water/dioxane or water/methanol. The reason for this is that when the solvent is in its standard state its activity is defined as one. by stabilizing the conjugate base. Data at 25 °C from Pine et al. 2 for m = 1. known as homoconjugation.

Fumaric acid Maleic acid proton sponge With organic acids inductive effects and mesomeric effects affect the pKa values.7. The diketone 2. pKa for HClO is 7. In aromatic compounds. and to distinguish between inductive and mesomeric effects. A simple example is provided by the effect of replacing the hydrogen atoms in acetic acid by the more electronegative chlorine atom.0. conjugation with the aromatic ring as a whole greatly increases the stability of the deprotonated form. so successive pKa values decrease in the series 4. 2.higher the oxidation state the stronger the oxyacid. The electron-withdrawing effect of the substituent makes ionisation easier.8. Ascorbic acid is an example of this effect. A plot of log Ka against σ is a straight line with intercept log Ka0 and slope ρ. ρ is a property of the unsubstituted compound and σ has a particular value for each substituent. Ka0 is the dissociation constant when the substituent is hydrogen. such as phenol.4-pentanedione (acetylacetone) is also a weak acid because of the keto-enol equilibrium. Hammett originally[33] formulated the relationship with data from benzoic acid with different substiuents in the ortho.[34][35] Alcohols do not normally behave as acids in water. for HClO2 is 2. This is an example of a linear free energy relationship as log Ka is proportional to the standard fee energy change.1. for HClO3 is −1 and HClO4 is a strong acid.[32] log Ka = log Ka0 + ρσ. . This and other studies allowed substituents to be ordered according to their electron-withdrawing or electron-releasing power.[31] The Hammett equation. but the presence of a double bond adjacent to the OH group can substantially decrease the pKa by the mechanism of keto-enol tautomerism.2.positions: some numerical values are in Hammett equation.and para.3 and 0. provides a general expression for the effect of substituents. 2 or 3 chlorine atoms are present.7 when 0. For example. 1. Ka is the dissociation constant of a substituted compound. which have an OH substituent.

It is one of the strongest amine bases known.4-but-2-enedioic acid (see cis-trans isomerism).1. is changed by water to Me2NH > MeNH2 > Me3N > NH3. the two carboxyl groups are always far apart. This favors the formation of the maleate H+. Fumaric acid is (E)-1.Structural effects can also be important. the entropy terms are calculated from the experimental values of pKa and ΔH and zero ionic strength. R is the gas constant and T is the absolute temperature. For example. The high basicity is attributed to the relief of strain upon protonation and strong internal hydrogen bonding. Me3N > Me2NH > MeNH2 > NH3.[37][38] Effects of the solvent and solvation should be mentioned also in this section. in water. Free energy is made up of an enthalpy term and an entropy term. Note that pKa= −log Ka and 2. When both the standard enthalpy change and acid dissociation constant have been determined. methylamines are stabilized to about the same extent by hydration. The difference between fumaric acid and maleic acid is a classic example.[7] .0 and 4. has a pKa value of 12. 1.708 pKa (1 kJ·mol−1 = 1000 Joules per mole).303 ≈ ln 10. i. Fumaric acid has pKa values of approximately 3. Relative stabilization of methylammonium ions thus decreases with the number of methyl groups explaining the order of water basicity of methylamines.e. the expected (by electronic effects of methyl substituents) and observed in gas phase order of basicity of methylamines. It turns out. At 25 °C ΔG in kJ·mol−1 = 5.[36] Proton sponge.isomer (maleic acid) a strong intramolecular hydrogen bond is formed with the nearby remaining carboxyl group. a trans isomer. the standard entropy change is easily calculated from the equation above. The data were critically selected and refer to 25 °C Acids Compound Equilibrium pKa ΔG /kJ·mol−1 ΔH /kJ·mol−1 —TΔS /kJ·mol−1 . (Z)-1. corresponding methylammonium cations always utilize all the available protons for donor NH-OH2 bonding. Hence. In the following table.8-bis(dimethylamino)naphthalene. In the trans isomer.5 and 6. so hydrogen bonding is not observed. N-HOH. interaction and only occasionally just one more donor bond. these influences are more subtle than that of a dielectric medium mentioned above. though the calorimetric method is preferable. and it opposes the removal of the second proton from that species.5.[39] [edit] Thermodynamics An equilibrium constant is related to the standard Gibbs energy change for the reaction. whereas maleic acid is the corresponding cis isomer. By contrast. In stark contrast. maleic acid has pKa values of approximately 1. so for an acid dissociation constant ΔG = −RT ln Ka.5. regardless of the number of methyl groups. NH-OH2.4-but-2-enedioic acid. Neutral methylamine molecules are hydrogen-bonded to water molecules mailnly through one acceptor. The reason for this large difference is that when one proton is removed from the cis.[7] ΔG = ΔH − TΔS The standard enthalpy change can be determined by calorimetry or by using the van 't Hoff equation.

419 11. Last.147† 13.855 27.49 11.261 41.76 35.9 39.06 /kJ·mol−1 B + H+ 9.5 54.266 H2A = Maleic acid H2A HA− H3A = Citric acid H3A H2A− HA2− H3A = Boric acid H3A = Phosphoric acid H3A H3A H2A− HA2− HA− = Hydrogen sulfate H2A = Oxalic acid HA− H2A HA− † ‡ ΔG = 2.27 24.9 38.645 55.34 B + H+ 10.79 17.60 4.78 24. but.35 HA + H+ 2.725 12.6 9. which orders .8205 5. which determines that ΔG is positive.76 A3− + H+ 6.72 43.40 −3.20 1.128 HA2− + H+ 4.13 B = Methylamine HB+ B = Triethylamine HB+ The first point to note is that.23 −3.00 44. the standard free energy change for the dissociation reaction is also positive.087 80. Second.90 7.15 31.245 51.07 2.422 18.49 33.351 H+ + A− 9.38 13.85 39.HA = Acetic acid H2A+ = GlycineH+ HA H2A+ HA H+ + A− 4.4 13.56‡ 9.148 HA2− + H+ 7.420 55.74 11.756 27.36 7.10 −3.509 52.80 −8.303RT pKa = ΔG Computed here.60 16.00 −22.41 4.00 3.176 36.237 H2A− + H+ 2. Ions in aqueous solution tend to orient the surrounding water molecules.92 H+ + A2− 6. when ΔH is negative −TΔS is the dominant factor.40 H2A− + H+ 9.78 HA− + H+ 1.00 27. from ΔH and ΔG values supplied in the citation.26 37.35 A2− + H+ HA− + H+ A2− + H+ 1.92 20.27 H2A− + H+ 3.825 10. some reactions are exothermic and some are endothermic.95 B + H+ 10. when pKa is positive. the entropy contribution is always unfavourable (ΔS < 0) in these reactions.27 4.20 A3− + H+ 12.351 −0.99 1. using —TΔS — ΔH Conjugate acids of bases Compound B = Ammonia Equilibrium HB+ pKa ΔH /kJ·mol−1 —TΔS 0.

The solution is then titrated with a strong base until all the protons have been removed. [edit] Experimental determination A calculated titration curve of oxalic acid titrated with a solution of sodium hydroxide See also: Determination of equilibrium constants The experimental determination of pKa values is commonly performed by means of titrations. so the entropy again decreases. On the second ionization of the same acid. using the method of least squares. Therefore the buffer regions will be centered at about pH 1. the end-point would not be noticeable. When this is so.3. The equilibrium constants are found by fitting calculated pH values to the observed values. Between the two buffer regions there is an end-point. where the pH rises by about two units. or equivalence point. The buffer regions carry the information necessary to get the pKa values as the concentrations of acid and conjugate base change along a buffer region. A solution of the compound in the medium is acidified with a strong acid to the point where the compound is fully protonated. < Note that the standard free energy change for the reaction is for the changes from the reactants in their standard states to the products in their standard states.the solution and decreases the entropy. the solution is not buffered and the pH rises steeply on addition of a small amount of .[40] The ionization of a neutral acid involves formation of two ions so that the entropy decreases (ΔS 0). This end-point is not sharp and is typical of a diprotic acid whose buffer regions overlap by a small amount: pKa2 − pKa1 is about three in this example.27. Oxalic acid has pKa values of 1.27 and 4. This will ensure that pKa remains invariant during the titration.[41] A typical procedure would be as follows.[42] The total volume of added strong base should be small compared to the initial volume of titrand solution in order to keep the ionic strength nearly constant.) The second end-point begins at about pH 6. At each point in the titration pH is measured using a glass electrode and a pH meter.3 and pH 4. The contribution of an ion to the entropy is the partial molar entropy which is often negative.3 and is sharp. (If the difference in pK values were about two or less. there are now three ions and the anion has a charge. This indicates that all the protons have been removed. especially for small or highly charged ions. The free energy change at equilibrium is zero since the chemical potentials of reactants and products are equal at equilibrium. in a medium of high ionic strength and at constant temperature. A calculated titration curve for oxalic acid is shown at the right.

can be used with normal water and 1 H NMR spectra can be used with non-aqueous media. . However. Aqueous solutions with normal water cannot be used for 1H NMR measurements but heavy water. which is where self-ionization of water becomes important.[52][53][54] The isoelectric point of a given molecule is a function of its pK values.[22] These may involve absorbance or fluorescence measurements.strong base. or either of the internal -NH. because the Nernst equation breaks down at such low pH values. A new buffer region begins at about pH 11 (pKw − 3). The pKa values for dissociation of spermine protonated at one or other of the sites are examples of microconstants. which is used in gel electrophoresis. They cannot be determined directly by means of pH. for example.[51] and is key to understanding disorders such as acid-base imbalance. 13C NMR data. Many applications exist in biochemistry. absorbance. This permits a technique called isoelectric focusing.[48] the design of these solutions depends on a knowledge of the pKa values of their components.[49][50] Buffering is an essential part of acid base physiology including acid-base homeostasis. with absorbance measurements the Beer-Lambert law is assumed to apply. pH measurements. Important buffer solutions include MOPS. but may be calculated using theoretical methods. spectrophotometric methods are frequently used. must be used instead. In both cases the measured quantity is assumed to be proportional to the sum of contributions from each photo-active species. such as those of 31P can be measured. To determine pK values of less than about 2 or more than about 11 spectrophotometric[43] or NMR[11][44] measurements may be used instead of. however. which provides a solution with pH 7.groups.[45] When the glass electrode cannot be employed.[55] which is used for separation of proteins by 2-D gel polyacrylamide gel electrophoresis. Other chemical shifts. the pKa values of proteins and amino acid side chains are of major importance for the activity of enzymes and the stability of proteins. the site of protonation is very important for biological function. fluorescence or NMR measurements. [edit] Micro-constants spermine A base such as spermine has a few different sites where protonation can occur. and tricine. as with non-aqueous solutions.2. Buffer solutions are used extensively to provide solutions at or near the physiological pH for the study of biochemical reactions. It is very difficult to measure pH values of less than two in aqueous solution with a glass electrode. In this example the first proton can go on the terminal -NH2 group.[47] Protein pKa values cannot always be measured directly. Nevertheless. so different molecules have different isoelectric points. D2O.[46] [edit] Applications and significance A knowledge of pKa values is important for the quantitative treatment of systems involving acid– base equilibria in solution. so mathematical methods have been developed for the determination of microconstants. as proton exchange is fast on the NMR time-scale. or combined with. The quantities measured with NMR are time-averaged chemical shifts. the pH does not continue to rise indefinitely.

the pKa of the protonated ligand must be known. This technique is used for the purification of weak acids and bases. it behaves as a weak acid. along with the solubility product of iron hydroxide.[65] [edit] Values for common substances There are multiple techniques to determine the pKa of a chemical. Data presented here were taken at 25 °C in water. acting as a Lewis base.1 units of each other. The design of a universal indicator requires a mixture of indicators whose adjacent pKa values differ by about two. In acidbase extraction. in that case. the ligand may be polyprotic. For example ionization of any compound will increase the solubility in water. such a species is more soluble in organic solvents having a low dielectric constant than it is in water. the metal ion is subject to hydrolysis. Another example occurs in chemical oceanography:[64] in order to quantify the solubility of iron(III) in seawater at various salinities. In addition. the ligand may also undergo protonation reactions. L. the pKa values for the formation of the iron(III) hydrolysis products Fe(OH)2+.[58] Knowledge of pKa values is important for the understanding of coordination complexes. all pKa values must be known.[59] Assessing the hazard associated with an acid or base may require a knowledge of pKa values. In strongly alkaline solutions. above. in which the ligand loses a proton. the efficiency of extraction of a compound into an organic phase.[60] For example. hydrogen cyanide is a very toxic gas. Ingestion of cyanide by mouth is potentially fatal. because of the reaction with cytochrome c oxidase. the concentration of the electrically neutral species is maximised. In practice. In pharmacology ionization of a compound alters its physical behaviour and macro properties such as solubility and lipophilicity (log p). so the pK values for the hydrolysis reactions must also be known.[57] A pH indicator is a weak acid or weak base that changes colour in the transition pH range. leading to some discrepancies between different sources. so that their transition pH ranges just overlap. that is. on the other hand. The buffer capacity[56] of a simple buffer solution is largest when pH = pKa. say. Hydrogen cyanide is a weak acid in aqueous solution with a pKa of about 9. Well measured values are typically within 0. independently of pH. This is exploited in drug development to increase the concentration of a compound in the blood by adjusting the pKa of an ionizable group. so the formation of a complex in aqueous solution could be represented symbolically by the reaction [M(H2O)n]m+ +LH [M(H2O)n−1L](m−1)+ + H3O+ To determine the equilibrium constant for this reaction.Buffer solutions also play a key role in analytical chemistry.[3][66] More values can be found in thermodynamics. with a ligand. such as an ether. However. is very hazardous because all the cyanide is in its acid form. humic acids are important components of natural waters. An acidic solution. Compared with an aqueous solution. They are used whenever there is a need to fix the pH of a solution at a particular value. above pH 11. the pH of a buffer solution is relatively insensitive to the addition of a small amount of strong acid or strong base. can be optimised by adjusting the pH of the aqueous phase using an appropriate buffer. Fe(OH)2+ and Fe(OH)3 were determined. acting as a Lewis acid.[62][63] for example. In environmental science acid–base equilibria are important for lakes[61] and rivers. because the cyanide ion inhibits the iron-containing enzyme cytochrome c oxidase. At the optimum pH. which are formed by the interaction of a metal ion. it follows that sodium cyanide is "fully dissociated" so the hazard due to the hydrogen cyanide gas is much reduced. Mm+. but decrease the lipophilicity. for example EDTA4− can accept four protons. . which is approximately pKa ± 1.

86 4.5 8.29 3.87 9.17 B + H+ H2A− + H+ 2.53 4.21 3.751 3.204 4.65 BH+ + H+ 4.99 4.htm .17 11.mpcfaculty.57 H3A = Arsenic acid H3A H2A− HA2− HA = Benzoic acid HA = Butanoic acid H2A = Chromic acid HA HA H2A HA− B = Codeine HA = Cresol HA = Formic acid HA = Hydrofluoric acid HA = Hydrocyanic acid HA = Hydrogen selenide BH+ HA HA HA HA HA HA = Hydrogen peroxide (90%) HA HA = Lactic acid HA = Propionic acid HA = Phenol H2A = L-(+)-Ascorbic Acid HA HA HA H2A HA− http://www.7 3.22 HA2− + H+ 6.Chemical Name B = Adenine Equilibrium BH22+ BH+ pKa 9.98 A3− + H+ H+ + A− H+ + A− HA− + H+ A2− + H+ B + H+ H+ + A− H+ + A− H+ + A− H+ + A− H+ + A− H+ + A− H+ + A− H+ + A− H+ + A− HA− + H+ A2− + H+ 11.17 10.98 6.17 11.82 0.