# Henderson–Hasselbalch equation

In chemistry and biochemistry, the Henderson–Hasselbalch equation

${\ce {pH}}={\ce {p}}K_{{\ce {a}}}+\log _{10}\left({\frac {[{\ce {Base}}]}{[{\ce {Acid}}]}}\right)$ relates the pH of a chemical solution of a weak acid to the numerical value of the acid dissociation constant, Ka, of acid and the ratio of the concentrations, ${\frac {[{\ce {Base}}]}{[{\ce {Acid}}]}}$ of the acid and its conjugate base in an equilibrium.

$\mathrm {{\underset {(acid)}{HA}}\leftrightharpoons {\underset {(base)}{A^{-}}}+H^{+}}$ For example, the acid may be acetic acid

$\mathrm {CH_{3}CO_{2}H\leftrightharpoons CH_{3}CO_{2}^{-}+H^{+}}$ The Henderson–Hasselbalch equation can be used to estimate the pH of a buffer solution by approximating the actual concentration ratio as the ratio of the analytical concentrations of the acid and of a salt, MA.

The equation can also be applied to bases by specifying the protonated form of the base as the acid. For example, with an amine, $\mathrm {RNH_{2}}$ $\mathrm {RNH_{3}^{+}\leftrightharpoons RNH_{2}+H^{+}}$ ## Derivation, assumptions and limitations

A simple buffer solution consists of a solution of an acid and a salt of the conjugate base of the acid. For example, the acid may be acetic acid and the salt may be sodium acetate. The Henderson–Hasselbalch equation relates the pH of a solution containing a mixture of the two components to the acid dissociation constant, Ka of the acid, and the concentrations of the species in solution.

To derive the equation a number of simplifying assumptions have to be made. (pdf)

Assumption 1: The acid, HA, is monobasic and dissociates according to the equations

${\ce {HA <=> H^+ + A^-}}$ $\mathrm {C_{A}=[A^{-}]+[H^{+}][A^{-}]/K_{a}}$ $\mathrm {C_{H}=[H^{+}]+[H^{+}][A^{-}]/K_{a}}$ CA is the analytical concentration of the acid and CH is the concentration the hydrogen ion that has been added to the solution. The self-dissociation of water is ignored. A quantity in square brackets, [X], represents the concentration of the chemical substance X. It is understood that the symbol H+ stands for the hydrated hydronium ion. Ka is an acid dissociation constant.

The Henderson–Hasselbalch equation can be applied to a polybasic acid only if its consecutive pK values differ by at least 3. Phosphoric acid is such an acid.

Assumption 2. The self-ionization of water can be ignored. This assumption is not, strictly speaking, valid with pH values close to 7, half the value of pKw, the constant for self-ionization of water. In this case the mass-balance equation for hydrogen should be extended to take account of the self-ionization of water.

$\mathrm {C_{H}=[H^{+}]+[H^{+}][A^{-}]/K_{a}+K_{w}/[H^{+}]}$ However, the term $\mathrm {K_{w}/[H^{+}]}$ can be omitted to a good approximation.

Assumption 3: The salt MA is completely dissociated in solution. For example, with sodium acetate

$\mathrm {Na(CH_{3}CO_{2})\rightarrow Na^{+}+CH_{3}CO_{2}^{-}}$ the concentration of the sodium ion, [Na+] can be ignored. This is a good approximation for 1:1 electrolytes, but not for salts of ions that have a higher charge such as magnesium sulphate, MgSO4, that form ion pairs.

Assumption 4: The quotient of activity coefficients, $\Gamma$ , is a constant under the experimental conditions covered by the calculations.

The thermodynamic equilibrium constant, $K^{*}$ ,

$K^{*}={\frac {[{\ce {H+}}][{\ce {A^-}}]}{[{\ce {HA}}]}}\times {\frac {\gamma _{{\ce {H+}}}\gamma _{{\ce {A^-}}}}{\gamma _{HA}}}$ is a product of a quotient of concentrations ${\frac {[{\ce {H+}}][{\ce {A^-}}]}{[{\ce {HA}}]}}$ and a quotient, $\Gamma$ , of activity coefficients ${\frac {\gamma _{{\ce {H+}}}\gamma _{{\ce {A^-}}}}{\gamma _{HA}}}$ . In these expressions, the quantities in square brackets signify the concentration of the undissociated acid, HA, of the hydrogen ion H+, and of the anion A; the quantities $\gamma$ are the corresponding activity coefficients. If the quotient of activity coefficients can be assumed to be a constant which is independent of concentrations and pH, the dissociation constant, Ka can be expressed as a quotient of concentrations.

$K_{a}=K^{*}/\Gamma ={\frac {[{\ce {H+}}][{\ce {A^-}}]}{[{\ce {HA}}]}}$ Rearrangement of this expression and taking logarithms provides the Henderson–Hasselbalch equation

${\ce {pH}}={\ce {p}}K_{{\ce {a}}}+\log _{10}\left({\frac {[{\ce {A^-}}]}{[{\ce {HA}}]}}\right)$ ## Application to bases

The equilibrium constant for the protonation of a base, B,

+ H+

is an association constant, Kb, which is simply related to the dissociation constant of the conjugate acid, BH+.

$\mathrm {pK_{a}=\mathrm {pK_{w}} -\mathrm {pK_{b}} }$ The value of $\mathrm {pK_{w}}$ is ca. 14 at 25°C. This approximation can be used when the correct value is not known. Thus, the Henderson–Hasselbalch equation can be used, without modification, for bases.

## Biological applications

With homeostasis the pH of a biological solution is maintained at a constant value by adjusting the position of the equilibria

${\ce {HCO3-}}+\mathrm {H^{+}} \rightleftharpoons {\ce {H2CO3}}\rightleftharpoons {\ce {CO2}}+{\ce {H2O}}$ where $\mathrm {HCO_{3}^{-}}$ is the bicarbonate ion and $\mathrm {H_{2}CO_{3}}$ is carbonic acid. However, the solubility of carbonic acid in water may be exceeded. When this happens carbon dioxide gas is liberated and the following equation may be used instead.

$\mathrm {[H^{+}][HCO_{3}^{-}]} =\mathrm {K^{m}[CO_{2}(g)]}$ $\mathrm {CO_{2}(g)}$ represents the carbon dioxide liberated as gas. In this equation, which is widely used in biochemistry, $K^{m}$ is a mixed equilibrium constant relating to both chemical and solubility equilibria. It can be expressed as

$\mathrm {pH} =6.1+\log _{10}\left({\frac {[\mathrm {HCO} _{3}^{-}]}{0.0307\times P_{\mathrm {CO} _{2}}}}\right)$ where [HCO
3
]
is the molar concentration of bicarbonate in the blood plasma and PCO2 is the partial pressure of carbon dioxide in the supernatant gas.

## History

In 1908, Lawrence Joseph Henderson derived an equation to calculate the hydrogen ion concentration of a bicarbonate buffer solution, which rearranged looks like this:

[H+] [HCO3] = K [CO2] [H2O]

In 1909 Søren Peter Lauritz Sørensen introduced the pH terminology, which allowed Karl Albert Hasselbalch to re-express Henderson's equation in logarithmic terms, resulting in the Henderson–Hasselbalch equation.