title: Lipophilicity of morphine microspecies and their contribution to the lipophilicity profile.
abstract: The complete set of experimental microscopic partition coefficients of morphine was determined for the first time for any compound. The acid-base microequilibria were characterized by combining pH-potentiometry and deductive methods using auxiliary compounds of reduced complexity. The results show around three times as many non-charged than zwitterionic microspecies in aqueous solution. Partition of the individual microspecies was mimicked by model compounds of the closest possible similarity, then correction factors were determined and introduced. Thus the intrinsic partition coefficients of all the microspecies could be quantitated, including the non-charged and the zwitterionic ones. The non-charged microspecies is 1070 times as lipophilic as its zwitterionic protonation isomer. Their contribution ratio to the overall lipophilicity is 3090. The lipophilicity profile of morphine was expressed, calculated and depicted in terms of species-specific lipophilicities over the entire pH range.
authors: Semmelweis University, Department of Pharmaceutical Chemistry, Research Group of Drugs of Abuse and Doping Agents, Hungarian Academy of Sciences, Hőgyes E. u. 9., H-1092 Budapest, Hungary. mazakk@gytk.sote.hu
authors: Károly
authors: K
authors: Mazák
authors: Béla
authors: B
authors: Noszál
mesh_terms: D000465:Algorithms; D000701:Analgesics, Opioid / Q000737:chemistry*; D000838:Anions / Q000737:chemistry; D002412:Cations / Q000737:chemistry; D003061:Codeine / Q000031:analogs & derivatives / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D009020:Morphine / Q000737:chemistry*; D009022:Morphine Derivatives / Q000737:chemistry*; D011199:Potentiometry
chemical_list: D000701:Analgesics, Opioid; D000838:Anions; D002412:Cations; D009022:Morphine Derivatives; D009020:Morphine; D003061:Codeine