Cell-impermeable ligands

Receptors have three important properties (1) they are activated in response to specific ligands, (2) they conduct ions through the otherwise impermeable cell membrane, and (3) they select among different ions. 

Allen MC, Gale PA, Hunter AC, Lloyd A, Hardy SP (2000) Membrane impermeant antioestrogens discriminate between ligand- and voltage-gated cation channels in NG108-15 cells. Biochim Biophys Acta 1509(1—2) 229—236... 

Normally, in the resting state, the channel is impermeable to ions. When a ligand binds to the receptor, it becomes activated and opens a channel to a diameter of about 6.5 A (6.5 x 10" °m).This action allows the migration of, for example, extracellular sodium ions to the interior of the cell. A cascade of further changes then proceed within the cell to amplify the signal. 

Water is an essential part in the biomacromolecular system, which is mainly responsible for the structure and functions of nucleic acids, proteins, and other constituents of cell [136-138]. Both proteins and DNA are generally hydrated. It is well known that the conformation of DNA is sensitive to hydration, and presence of salts and ligand molecules [112, 138]. The nucleic acids have three levels of water structure. About 12 water molecules per nucleotide are involved in the primary hydration shell [107, 112, 137, 138]. The water molecules present in the primary shell are impermeable to cations and do not form ice on freezing. The secondary level is permeable to cations and forms ice on freezing and third level is the completely disordered, so-called bulk water. Several theoretical studies have been carried out on the level of hydration on DNA bases, base pairs, base stacks, and double helical DNA [107, 121, 131, 139]. Both the experimental and molecular simulation studies have clearly brought out the importance of hydration in DNA and RNA structures [140-147]. 

The inactivity of chromium(III) in cellular short term assay systems is probably due to the fact that cell membranes appear to be quite impermeable to most chromium(III) complexes. However, it appears that heterocyclic aromatic ligands facilitate uptake of chromium(III) into cells since c -dichlorobis(2,2 -bipyridine)chromium(III), ciy-di-chlorobis(l, 10-phenanthroline)chromium(III) and cis -oxalatobis(2,2 -bipyridine)-... 

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