The Hofmeister series or lyotropic series is a classification of ions in order of their lyotrophic properties, which is the ability to salt out or salt in proteins. [1] [2] The effects of these changes were first worked out by Franz Hofmeister, who studied the effects of cations and anions on the solubility of proteins. [3]
Highly charged ions interact strongly with water, breaking hydrogen bonds and inducing electrostatic structuring of nearby water, [4] and are thus called "structure-makers" or "kosmotropes". [5] Conversely, weak ions can disrupt the structure of water, and are thus called "structure-breakers" or "chaotropes". [5] The order of the tendency of ions to make or break water structure is the basis of the Hofmeister series.
Hofmeister discovered a series of salts that have consistent effects on the solubility of proteins and (it was discovered later) on the stability of their secondary and tertiary structure. Anions appear to have a larger effect than cations, [6] and are usually ordered
(kosmotropic) : (chaotropic)
(This is a partial listing; many more salts have been studied.) The order of cations is usually given as
(chaotropic) : (kosmotropic)
When oppositely charged kosmotropic cations and anions are in solution together, they are attracted to each other, rather than to water, and the same can be said for chaotropic cations and anions. [5] Thus, the preferential associations of oppositely charged ions can be ordered as:
kosmotrope-kosmotrope > kosmotrope-water > water-water > chaotrope-water > chaotrope-chaotrope [5]
Combining kosmotropic anions with kosmotropic cations reduces the kosmotropic effect of these ions because they are pairing to each other too strongly to be structuring water. [5] Kosmotropic anions do not readily pair with chaotropic cations. The combination of kosmotropic anions with chaotropic cations is the best ion combination to stabilize proteins. [4]
The mechanism of the Hofmeister series is not entirely clear, but does not seem to result from changes in general water structure, instead more specific interactions between ions and proteins and ions and the water molecules directly contacting the proteins may be more important. [7] Simulation studies have shown that the variation in solvation energy between the ions and the surrounding water molecules underlies the mechanism of the Hofmeister series. [8] [9] A quantum chemical investigation suggests an electrostatic origin to the Hofmeister series. [10] This work provides site-centred radial charge densities of the ions' interacting atoms (to approximate the electrostatic potential energy of interaction), and these appear to quantitatively correlate with many reported Hofmeister series for electrolyte properties, reaction rates and macromolecular stability (such as polymer solubility, and virus and enzyme activities).
Early members of the series increase solvent surface tension and decrease the solubility of nonpolar molecules ("salting out"); in effect, they strengthen the hydrophobic interaction. By contrast, later salts in the series increase the solubility of nonpolar molecules ("salting in") and decrease the order in water; in effect, they weaken the hydrophobic effect. [11] [12]
The "salting out" effect is commonly exploited in protein purification through the use of ammonium sulfate precipitation. [13] However, these salts also interact directly with proteins (which are charged and have strong dipole moments) and may even bind specifically (e.g., phosphate and sulfate binding to ribonuclease A).
Ions that have a strong "salting in" effect such as I− and SCN− are strong denaturants, because they salt in the peptide group, and thus interact much more strongly with the unfolded form of a protein than with its native form. Consequently, they shift the chemical equilibrium of the unfolding reaction towards unfolded protein. [14]
The denaturing of proteins by an aqueous solution containing many types of ions is more complicated as all the ions can act, according to their Hofmeister activity, i.e., a fractional number specifying the position of the ion in the series (given previously) in terms of its relative efficiency in denaturing a reference protein.
At high salt concentrations lysozyme protein aggregation obeys the Hofmeister series originally observed by Hofmeister in the 1870s, but at low salt concentrations electrostatic interactions rather than ion dispersion forces affect protein stability resulting in the series being reversed. [15] [5] However, at high concentrations of salt, the solubility of the proteins drop sharply and proteins can precipitate out, referred to as "salting out". [16]
Ion binding to carbolylic surface groups of macromolecules can either follow the Hofmeister series or the reversed Hofmeister series depending on the pH. [17]
The concept of Hofmeister ionicity Ih has been invoked by Dharma-wardana et al. [18] where it is proposed to define Ih as a sum over all ionic species, of the product of the ionic concentration (mole fraction) and a fractional number specifying the "Hofmeister strength" of the ion in denaturing a given reference protein. The concept of ionicity (as a measure of the Hofmeister strength) used here has to be distinguished from ionic strength as used in electrochemistry, and also from its use in the theory of solid semiconductors. [19]
The stability of metal ion protein binding, which affects the properties of metal cofactor-containing proteins in solution, is reflected by the Irving-Williams series. [20]
Ionic bonding is a type of chemical bonding that involves the electrostatic attraction between oppositely charged ions, or between two atoms with sharply different electronegativities, and is the primary interaction occurring in ionic compounds. It is one of the main types of bonding, along with covalent bonding and metallic bonding. Ions are atoms with an electrostatic charge. Atoms that gain electrons make negatively charged ions. Atoms that lose electrons make positively charged ions. This transfer of electrons is known as electrovalence in contrast to covalence. In the simplest case, the cation is a metal atom and the anion is a nonmetal atom, but these ions can be more complex, e.g. molecular ions like NH+
4 or SO2−
4. In simpler words, an ionic bond results from the transfer of electrons from a metal to a non-metal to obtain a full valence shell for both atoms.
In chemistry, a salt or ionic compound is a chemical compound consisting of an ionic assembly of positively charged cations and negatively charged anions, which results in a neutral compound with no net electric charge. The constituent ions are held together by electrostatic forces termed ionic bonds.
Solvation describes the interaction of a solvent with dissolved molecules. Both ionized and uncharged molecules interact strongly with a solvent, and the strength and nature of this interaction influence many properties of the solute, including solubility, reactivity, and color, as well as influencing the properties of the solvent such as its viscosity and density. If the attractive forces between the solvent and solute particles are greater than the attractive forces holding the solute particles together, the solvent particles pull the solute particles apart and surround them. The surrounded solute particles then move away from the solid solute and out into the solution. Ions are surrounded by a concentric shell of solvent. Solvation is the process of reorganizing solvent and solute molecules into solvation complexes and involves bond formation, hydrogen bonding, and van der Waals forces. Solvation of a solute by water is called hydration.
An electrolyte is a medium containing ions that are electrically conductive through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon dissolving, the substance separates into cations and anions, which disperse uniformly throughout the solvent. Solid-state electrolytes also exist. In medicine and sometimes in chemistry, the term electrolyte refers to the substance that is dissolved.
A chaotropic agent is a molecule in water solution that can disrupt the hydrogen bonding network between water molecules. This has an effect on the stability of the native state of other molecules in the solution, mainly macromolecules by weakening the hydrophobic effect. For example, a chaotropic agent reduces the amount of order in the structure of a protein formed by water molecules, both in the bulk and the hydration shells around hydrophobic amino acids, and may cause its denaturation.
Ion chromatography is a form of chromatography that separates ions and ionizable polar molecules based on their affinity to the ion exchanger. It works on almost any kind of charged molecule—including small inorganic anions, large proteins, small nucleotides, and amino acids. However, ion chromatography must be done in conditions that are one pH unit away from the isoelectric point of a protein.
In chemistry, a counterion is the ion that accompanies an ionic species in order to maintain electric neutrality. In table salt the sodium ion is the counterion for the chloride ion and vice versa.
In chemistry, a non-covalent interaction differs from a covalent bond in that it does not involve the sharing of electrons, but rather involves more dispersed variations of electromagnetic interactions between molecules or within a molecule. The chemical energy released in the formation of non-covalent interactions is typically on the order of 1–5 kcal/mol. Non-covalent interactions can be classified into different categories, such as electrostatic, π-effects, van der Waals forces, and hydrophobic effects.
Co-solvents are defined as kosmotropic (order-making) if they contribute to the stability and structure of water-water interactions. In contrast, chaotropic (disorder-making) agents have the opposite effect, disrupting water structure, increasing the solubility of nonpolar solvent particles, and destabilizing solute aggregates. Kosmotropes cause water molecules to favorably interact, which in effect stabilizes intramolecular interactions in macromolecules such as proteins.
In chemistry, a salt bridge is a combination of two non-covalent interactions: hydrogen bonding and ionic bonding. Ion pairing is one of the most important noncovalent forces in chemistry, in biological systems, in different materials and in many applications such as ion pair chromatography. It is a most commonly observed contribution to the stability to the entropically unfavorable folded conformation of proteins. Although non-covalent interactions are known to be relatively weak interactions, small stabilizing interactions can add up to make an important contribution to the overall stability of a conformer. Not only are salt bridges found in proteins, but they can also be found in supramolecular chemistry. The thermodynamics of each are explored through experimental procedures to access the free energy contribution of the salt bridge to the overall free energy of the state.
Tetramethylammonium hydroxide (TMAH or TMAOH) is a quaternary ammonium salt with molecular formula N(CH3)4+ OH−. It is commonly encountered in form of concentrated solutions in water or methanol. TMAH in solid state and its aqueous solutions are all colorless, but may be yellowish if impure. Although TMAH has virtually no odor when pure, samples often have a strong fishy smell due to presence of trimethylamine which is a common impurity. TMAH has several diverse industrial and research applications.
Franz Hofmeister was an early protein scientist, and is famous for his studies of salts that influence the solubility and conformational stability of proteins. In 1902, Hofmeister became the first to propose that polypeptides were amino acids linked by peptide bonds, although this model of protein primary structure was independently and simultaneously conceived by Emil Fischer.
Hexafluorophosphate is an anion with chemical formula of [PF6]−. It is an octahedral species that imparts no color to its salts. [PF6]− is isoelectronic with sulfur hexafluoride, SF6, and the hexafluorosilicate dianion, [SiF6]2−, and hexafluoroantimonate [SbF6]−. In this anion, phosphorus has a valence of 5. Being poorly nucleophilic, hexafluorophosphate is classified as a non-coordinating anion.
Protein precipitation is widely used in downstream processing of biological products in order to concentrate proteins and purify them from various contaminants. For example, in the biotechnology industry protein precipitation is used to eliminate contaminants commonly contained in blood. The underlying mechanism of precipitation is to alter the solvation potential of the solvent, more specifically, by lowering the solubility of the solute by addition of a reagent.
In chemistry, ion association is a chemical reaction whereby ions of opposite electric charge come together in solution to form a distinct chemical entity. Ion associates are classified, according to the number of ions that associate with each other, as ion pairs, ion triplets, etc. Ion pairs are also classified according to the nature of the interaction as contact, solvent-shared or solvent-separated. The most important factor to determine the extent of ion association is the dielectric constant of the solvent. Ion associates have been characterized by means of vibrational spectroscopy, as introduced by Niels Bjerrum, and dielectric-loss spectroscopy.
Salting in refers to the effect where increasing the ionic strength of a solution increases the solubility of a solute, such as a protein. This effect tends to be observed at lower ionic strengths.
Chaotropicity describes the entropic disordering of lipid bilayers and other biomacromolecules which is caused by substances dissolved in water. According to the original usage and work carried out on cellular stress mechanisms and responses, chaotropic substances do not necessarily disorder the structure of water.
Lyotropy refers to concentration-dependent physical effects in solutions and often more specifically to ion-specific behavior in aqueous solutions.
Polysulfobetaines are zwitterionic polymers that contain a positively charged quaternary ammonium and a negatively charged sulfonate group within one constitutional repeat unit. In recent years, polysulfobetaines have received increasing attention owing to their good biotolerance and ultralow-fouling behavior towards surfaces. These properties are mainly referred to a tightly bound hydration layer around each zwitterionic group, which effectively suppresses protein adsorption and thus, improves anti-fouling behavior. Therefore, polysulfobetaines have been typically employed as ultrafiltration membranes, blood-contacting devices, and drug delivery materials.
An ion network is an interconnected network or structure composed of ions in a solution. The term "ion network" was coined by Cho and coworkers in 2014. The notion of extended ion aggregates in electrolyte solutions, however, can be found in an earlier report. The ion network is particularly relevant in high-salt solutions where ions can aggregate and interact strongly and it has been investigated in an increasing number of research and review articles.
