complexes part 12

Dynamic dialysis
A kinetic method for deter¬mining the concentrations of bound drug in a protein solu¬tion was developed. This method is favored in recent years because it is relatively rapid, economical in terms of the amount of pro¬tein required, and readily applied to the study of competitive inhibition of protein binding. The method, known as dynamic dialysis, is based on the rate of disappearance of drug from a dialysis cell that is proportional to the concentration of unbound drug. The appa¬ratus consists of a 400-mL jacketed (temperature-controlled) beaker into which 200 mL of buffer solution is placed. A cellophane dialysis bag containing 7 mL of drug or drug-protein solution is suspended in the buffer solution. Both solutions are stirred continuously. Samples of solution exter¬nal to the dialysis sac are removed periodically and analyzed spectrophotometrically, and an equivalent amount of buffer solution is returned to the external solution. The dialysis pro¬cess follows the rate law
 where [Dt] is the total drug concentration, [Df], is the concen¬tration of free or unbound drug in the dialysis sac, –d[Dt]/dt is the rate of loss of drug from the sac, and k is the first-order rate constant representative of the diffusion process.
Hydrophobic interaction
Hydrophobic "bonding," is actually not bond formation at all, but rather the tendency of hydrophobic molecules or hydrophobic parts of molecules to avoid water because they are not readily accommodated in the hydrogen-bonding structure of water. Large hydropho¬bic species such as proteins avoid the water molecules in an aqueous solution insofar as possible by associating into micelle-like structures with the nonpolar por¬tions in contact in the inner regions of the "micelles," the polar ends facing the water molecules. This attraction of hy¬drophobic species, resulting from their unwelcome reception in water, is known as hydrophobic bonding, or, better, hy¬drophobic interaction. It involves Van der Waals forces, hy¬drogen bonding of water molecules in a three-dimensional structure, and other interactions. Hydrophobic interaction is favored thermodynamically because of an increased disorder or entropy of the water molecules that accompanies the as¬sociation of the nonpolar molecules, which squeeze out the water.