DISSOCIATION CONSTANT

In chemistry and biochemistry, a 'dissociation constant' is a specific type of equilibrium constant that measures the propensity of a larger object to separate (dissociate) reversibly into smaller components, as
when a complex falls apart into its component molecules, or when a salt splits up
into its component ions. The dissociation constant is usually denoted $K\_\{d\}$ and is the inverse
of the affinity constant. In the special case of salts, the dissociation constant can also be called an ionization constant.
For a general reaction
:$$
mathrm{A}_{x}mathrm{B}_{y}
ightleftharpoons xmathrm{A} + ymathrm{B}

in which a complex $mathrm\{A\}\_\{x\}mathrm\{B\}\_\{y\}$ breaks down into ''x'' A
subunits and ''y'' B subunits, the dissociation constant is defined
:$$
K_{d} = rac{[A]^x imes [B]^y}{[A_x B_y]}

where [A], [B], and [A_xB_y] are the concentrations of A, B, and the
complex A_xB_y, respectively.

Contents

Protein-Ligand binding

Another notation

Dissociation constant of water

Acid base reactions

References

See also

Protein-Ligand binding

The dissociation constant is commonly used to describe the affinity between a ligand ('$mathrm\{L\}$') (such as a drug) and a protein ('$mathrm\{P\}$') i.e. how tightly a ligand binds to a particular protein. Ligand-protein affinities are influenced by non-covalent intermolecular interactions between the two molecules such as hydrogen bonding, electrostatic interactions , hydrophobic and Van der Waals forces.
The formation of a ligand-protein complex ('$mathrm\{C\}$') can be described by a two-state process
:$$
mathrm{C}
ightleftharpoons mathrm{P} + mathrm{L}

the corresponding dissociation constant is defined
:$$
K_{d} = rac{left[ mathrm{P}
ight] left[ mathrm{L}
ight]}{left[ mathrm{C}
ight]}

where ['$mathrm\{P\}$'], ['$mathrm\{L\}$'] and ['$mathrm\{C\}$'] represent the concentrations of the protein, ligand and complex, respectively.
The dissociation constant has molar units (M), which correspond to the concentration of ligand ['$mathrm\{L\}$'] at which the binding site on a particular protein is half occupied, i.e. the concentration of ligand, at which the concentration of protein with ligand bound ['$mathrm\{C\}$'], equals the concentration of protein with no ligand bound ['$mathrm\{P\}$']. The smaller the dissociation constant, the more tightly bound the ligand is, or the higher the affinity between ligand and protein. For example, a ligand with a nanomolar (nM) dissociation constant binds more tightly to a particular protein than a ligand with a micromolar ($mu$M) dissociation constant.
Sub-nanomolar dissociation constants as a result of non-covalent binding interactions between two molecules are rare. Nevertheless, there are some important exceptions. Biotin and avidin bind with a dissociation constant of roughly $10^\{-15\}$ M = 1 fM = 0.000001 nM.^[1]
While ribonuclease inhibitor proteins may also bind to ribonuclease with a similar $10^\{-15\}$ M affinity.^[2]
The dissociation constant for a particular ligand-protein interaction can change significantly with solution conditions (e.g. temperature, pH and salt concentration). The effect of different solution conditions is to effectively modify the strength of any intermolecular interactions holding a particular ligand-protein complex together.
Drugs can produce harmful side effects through interactions with proteins for which they were not meant to or designed to interact. Therefore much pharmaceutical research is aimed at designing drugs that bind to only their target proteins with high affinity (typically 0.1-10 nM) or at improving the affinity between a particular drug and its ''in-vivo'' protein target.

Another notation

A dissociation constant $K\_\{a\}$ is sometimes expressed by its p$K\_\{a\}$, which is defined as:
:$$
mathrm{p}K_{a} = -log_{10}{K_{a}}

These p$K\_\{a\}$'s are mainly used for covalent dissociations (i.e., reactions in which chemical
bonds are made or broken) since such dissociation constants can vary greatly.

Dissociation constant of water

As a frequently used special case, the dissociation constant of water is often expressed as K_w:
$K\_w\; =\; [mbox\{H\}^+]\; [mbox\{OH\}^-]$
(The concentration of water $left[\; mbox\{H\}\_2mbox\{O\}$
ight] is not included in the definition
of $k\_\{w\}$, for reasons described in the article equilibrium constant.
The value of K_w varies with temperature, as shown in the table below. This variation must be taken into account when making precise measurements of quantities such as pH.

'Water temperature'	'Kw ★ 10-14'	'pKw'
0°C	0.1	14.92
10°C	0.3	14.52
18°C	0.7	14.16
25°C	1.2	13.92
30°C	1.8	13.75
50°C	8.0	13.10
60°C	12.6	12.90
70°C	21.2	12.67
80°C	35	12.46
90°C	53	12.28
100°C	73	12.14

Acid base reactions

For the deprotonation of acids, ''K'' is known as ''K''_a, the acid dissociation constant. Stronger acids, for example sulfuric or phosphoric acid, have larger dissociation constants; weaker acids, like acetic acid, have smaller dissociation constants. A molecule can have several acid dissociation constants. In this regard, that is depending on the number of the protons they can give up, we define ''monoprotic'', ''diprotic'' and ''triprotic'' acids. The first (e.g. acetic acid or ammonium) have only one dissociable group, the second (carbonic acid, bicarbonate, glycine) have two dissociable groups and the third (e.g. phosphoric acid) have three dissociable groups. In the case of multiple p''K'' values they are designated by indices: p''K''₁, p''K''₂, p''K''₃ and so on. For amino acids, the p''K''₁ constant refers to its carboxyl (-COOH) group, p''K''₂ refers to its amino (-NH₃) group and the p''K''₃ is the p''K'' value of its side chain.
$H\_3\; B$
ightleftharpoons H ^ + + H_2 B ^ - qquad K_1 = {[H ^ +] cdot [H_2 B ^ -] over [H_3 B]} qquad pK_1 = - log K_1
$H\_2\; B\; ^\; -$
ightleftharpoons H ^ + + H B ^ {-2} qquad K_2 = {[H ^ +] cdot [H B ^{-2}] over [H_2 B^ -]} qquad pK_2 = - log K_2
$H\; B\; ^\{-2\}$
ightleftharpoons H ^ + + B ^{-3} qquad K_3 = {[H ^ +] cdot [ B ^ {-3}] over [H B ^ {-2}]} qquad pK_3 = - log K_3

References

1. Three-dimensional structures of avidin and the avidin-biotin complex, Livnah O, Bayer EA. ''et al'', , , Proc Natl Acad Sci USA., 1993
2. Inhibition of Human Pancreatic Ribonuclease by the Human Ribonuclease Inhibitor Protein, Johnson RJ, McCoy JG. ''et al'', , , J. Mol. Biol, 2007

See also

★ ''K''_i Database

★ Acid