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

in which a complex A_xB_y breaks down into x A subunits and y B subunits, the dissociation constant is defined

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

Additional recommended knowledge

Don't let static charges disrupt your weighing accuracy

What is the Sensitivity of my Balance?

Recognize and detect the effects of electrostatic charges on your balance

Protein-Ligand binding

The dissociation constant is commonly used to describe the affinity between a ligand (L) (such as a drug) and a protein (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 (C) can be described by a two-state process

the corresponding dissociation constant is defined

where [P], [L] and [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 [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 [C], equals the concentration of protein with no ligand bound [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 (μM) 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 pK_a, which is defined as:

pK_a = − log₁₀K_a

These pK_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 = [H ⁺ ][OH ⁻ ]

(The concentration of water 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.

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 pK values they are designated by indices: pK₁, pK₂, pK₃ and so on. For amino acids, the pK₁ constant refers to its carboxyl (-COOH) group, pK₂ refers to its amino (-NH₃) group and the pK₃ is the pK value of its side chain.

References

1. ^ Livnah O, Bayer EA. et al (1993). "Three-dimensional structures of avidin and the avidin-biotin complex". Proc Natl Acad Sci USA. 90 (11): 5076-5080. PMID 8506353.
2. ^ Johnson RJ, McCoy JG. et al (2007). "Inhibition of Human Pancreatic Ribonuclease by the Human Ribonuclease Inhibitor Protein". J. Mol. Biol retrieved ahead of print. PMID 17350650.

See also

• K_i Database
• Acid
• pH