complexes part9

Spectroscopy and change transfer complexation
Absorption Spectroscopy in the visible and ultraviolet regions of the spectrum is commonly used to investigate electron donor-acceptor or charge transfer complexation. When iodine is analyzed in a noncomplexing solvent such CCl4, a curve is obtained with a single peak at about 520 nm. The solution is violet. A solution of iodine in benzene exhibits a maximum shift to 475 nm, and a new peak of consider¬ably higher intensity for the charge-shifted band appears at 300 nm. A solution of iodine in diethyl ether shows a still greater shift to lower wavelength, these solutions are red to brown. Their curves are shown in Figure 11-13. In benzene and ether, iodine is the electron acceptor and the organic solvent is the donor; in CCl4, no complex is formed. The shift toward the ultra¬violet region becomes greater as the electron donor solvent becomes a stronger electron-releasing agent. The complexation. constant, K, can be obtained by use of visible and ultraviolet Spectroscopy.
Protein binding
Protein binding (PB) plays an important role in the pharmacokinetics and pharmacodynamics of a drug. The extent of PB in the plasma or tissue controls the volume of distribution and affects both hepatic and renal clearance. In many cases, the free drug concentration, rather than the total concentration in plasma, is correlated to the effect. Drug displacement from drug-protein complex can occur by direct competition of two drugs for the same binding site and is important with drugs that are highly bound (>95%), for which a small displacement of bound drug can greatly increase the free drug concentration in the plasma. In order to measure free fraction or PB of a drug, ultrafiltration (UF), ultracentrifugation, equilibrium dialysis (ED), chromatogra-phy, spectrophotometry, electrophoresis, etc. have been used. Essential methodologic aspects of PB study include the selection of assay procedures, devices, and materials. The most commonly used method for PB measurement is ED, which is believed to be less susceptible to experimental artifacts. However, it is time consuming and is not suitable for unstable compounds because it requires substantial equilibration time (3-24 hr) depending on drugs, membrane materials, and devices. Many researchers have used UF centrifugal devices for PB measurement. UF is a simple and rapid method in which centrifugation forces the buffer containing free drugs through the size exclusion mem¬brane and achieves a fast separation of free from protein-bound drug. However, the major disadvantage of this method is nonspe¬cific binding of drugs on filter membranes and plastic devices. When the drug binds extensively to the filtration membrane, the ultrafiltrate concentration may deviate from the true free con¬centration.