The Hydration Shell of Ions

Ions in solutions are not free. Each is surrounded by a shell of water molecules, called a hydration shell, held by the attraction of the water dipoles to the charged ion. For cations, the oxygen end of water dipoles point toward the center of a cation, maximizing the ion-dipole interaction.

Look at the orientation of water molecules in this computer simulation of the first hydration shell of Na⁺. What would be the orientation of water molecules in the first hydration shell of Cl^-?

The hydration shell is dynamic. Since there are no covalent bonds, water molecules come and go from the inner shell in picoseconds! The water molecules do not sacrifice many hydrogen bonds, even near the ion, so the packing combines partial dipole orientation with positions compatible with preserving water-water hydrogen bonds.

Computer simulation of the flickering inner and outer hydration shells of Na⁺. The water molecules in the inner shell are relatively firmly bound, followed by a more loosely bound outer shell. In thermodynamic terms, the outer shell of the sodium ion "owns" 7 to 14 water molecules at any instant. This accounts for the fact that the activity coefficient of Na⁺ in a 100 mM aqueous solution of NaCl is 0.77.

Negatively charged ions binds water molecules with the positive end of the water dipole pointed at the center of the anion. Chloride is by far the most abundant physiological anion.

Energy minimized model of chloride anion. Recent molecular dynamics calculations show that the inner shell is not rigid and that the water molecules in the inner shell exchange hydrogen bonds with waters in both the inner and outer shells in picoseconds.

Ion Hydration Energies Are Large

How strong are the interactions between ions and water molecules? The hydration energy of an ion tells us the strength of ion-dipole interactions with water. The hydration energy is the stabilization gained by orienting water molecules appropriately in the intense local field of the ion. Click here for a table of ion properties.

Inner hydration shell of K⁺. Eight oxygen atoms are coordinated to the potassium ion. The coordination geometry can be described as a twisted cube. Four oxygens are arranged in a square on top and bottom. The squares are rotated slightly with respect to each, thereby forming a twisted cube. Toggle space filling.

Magnesium is essential for life. It acts as a metallo-coenzyme in more than 300 phosphate transfer reactions and thus has a critical role in the transfer and utilization of energy within cells. Mg²⁺ is also required for the folding of RNA into stable tertiary structures. Magnesium is ideally suited for neutralizing the negative charges of backbone phosphates in RNA, for two reasons. First, it is the most abundant intracellular multivalent cation. Second, it has the highest charge density of all biologically available ions, owing to its relatively small ionic radius (0.6 Å).

Mg²⁺ exhibits octahedral coordination. The divalent cation has a very tightly bound inner shell of six water molecules and a relatively tightly bound second shell containing 12 to 14 water molecules. Toggle space-filling model.

Hydration of Charged Groups in Proteins and Nucleic Acids

The hydration energies of charged groups in proteins and nucleic acids are also large. The interaction differs from the hydration of ions in two ways:

1. Charged groups in proteins and nucleic acids are hydrogen bonded to water molecules.
2. The number of water molecules in the first hydration shell depends in part on steric clashes with the surface of the macromolecule.

All charged groups in proteins and nucleic acids are either hydrogen bond acceptors or donors. For example, the only negatively charged groups found in these macromolecules are either carboxylate (proteins) or phosphate (nucleic acids), both of which are hydrogen bond acceptors. Key regulatory proteins may also contain one or more phosphate groups which are posttranslation modifications; protein phosphate groups bear two negative charges at physiological pH and thus create a localized negative potential that is greater than that of carboxylate anions. Positively charged groups occur only in proteins and are hydrogen bond donors. The importance of charged groups for structure and function will be covered in detail in later tutorials.

As an example, let's consider the interaction of a K⁺ ion with a protein side-chain carboxyl group (–CH₂COO^-). First, the negative charge of the carboxlyate is delocalized (-0.5 on each oxygen atom). This weakens the charge-charge interaction. Second, the hydration energy of carboxylate groups amounts to -60 kJ/mol with smaller values for a shielded carboxylate group. In order for a K⁺ ion to bind tightly to the carboxylate group, both would need to shed part of their inner hydration shell.

Binding of K⁺ to a protein side-chain carboxyl group. Toggle space filling.

This model comes from a neutron diffraction study of a protein crystal and shows ordered water molecules around the carboxylate and a K⁺ ions. The bond between the side chain and the protein backbone is shown in green.

The K⁺ must lose at least one water molecule from its inner hydration shell in order to make van der Waals contact with one of the O atoms of the carboxylate anion. Thus, the charge-charge interaction comes at a cost of partial dehydration of both the carboxylate and K⁺ ions. However, the coulombic interaction between the two ions would be weaker if both ions retained their full inner hydration shells, since the distance between charges would then be 6 to 8 Å, instead of the 2.85 Å seen here.

Let's turn now to an exquisite example of ion-dipole interactions involving K⁺ and uncharged oxygen atoms in a protein.