A photoluminescence study of the deprotonation of tertiary amine local anesthetics : dibucaine HCl

Bibliography: pages [135]-137.The work in this thesis has focused on the effect of dibucaine, a tertiary amine local anesthetic, on excitable biological membranes. The technique of low temperature (77K) photoluminescence was utilized to investigate several studies. The first of these involves the emissive properties of the incorporated chromophore, the lowest-lying radiative electronic state of the chromophore, and the molecular conformation of the dibucaine opiate. The dibucaine molecule is capable of existing in three different forms. As to which form is dominant (neutral, monoprotonated, and diprotonated) depends upon the pH of the aqueous environment, with each species capable of demonstrating unique luminescence emission and phosphorescence lifetimes. The second study using low temperature (77K) photoluminescence involves the introduction of the dibucaine species into hydrophobic media (water-fearing environments). The hydrophobic surroundings consist initially of straight-chain alcohols (a simple hydrophobic model), and subsequently, of long-chain multiform surfactant molecules (an enhanced hydrophobic model). With an aqueous pH value close to that of physiological pH, both the neutral and charged (protonated) species of the anesthetic may interact with the membrane surface and/or membrane-bound proteins. The chemical structure of the protonated form of anesthetic closely resembles that of hydrophobic ion species which are known to bind strongly to lipid membranes. Here, the membrane surface was modified by the binding of the anesthetic which may constitute a mechanism for anesthesia. The neutral species of anesthetic partitions readily into the inner hydrophobic domain and perturbs the lipid membrane bilayer. Critical regions of an excitable membrane are expanded by the incorporation of the anesthetic and interfere with the action current. As to which species of anesthetic, or perchance both, promotes the opiate effect of anesthesia is still uncertain, as is the mechanism. Although, the breaking and formation of hydrogen bonds and hydrophobic interactions appear to lend credence to axonal inhibition. Dibucaine was used as a luminescence probe at the molecular level, in order to study its protonation-deprotonation dynamics in aqueous/hydrophobic environments (membrane models). These studies may offer some insight into opiate drug transport within the excitable membrane and the mechanism of anesthesia.M.S. (Master of Science