Transport of the highly charged myo-inositol hexakisphosphate molecule across the red blood cell membrane: a phase transfer and biological study.
To address the problem of delivering highly charged small molecules, such as phytic acid (InsP(6) or IHP), across biological membranes, we investigated an approach based on a non-covalent interaction between transport molecule(s) and IHP. Thus, we synthesized a collection of compounds containing IHP ionically bound to lipophilic (but non-lipidic) ammonium or poly-ammonium cations. First, we assessed the ability of these water-soluble salts to cross a biological membrane by measuring the partition coefficients between human serum and 1-octanol. In view of the ability of IHP to act as potent effector for oxygen release, the O(2)-hemoglobin dissociation curves were then measured for the most efficient salts on whole blood. From both the biological and the physical properties of IHP-ammonium salts we determined that cycloalkylamines (or poly-amines) were the best transport molecules, especially cycloheptyl- and cyclooctylamine. Indeed, the octanol/serum partition coefficient of IHP undecacyclooctylammonium salt, is superior to 1, which is very favorable for potential uptake into the red blood cell membrane. A qualitative correlation was found between the partitioning experiments and the biological evaluations performed on whole blood.
Vincent
Stéphane P
SP
Laboratoire de Chimie Supramoléculaire, ISIS-Université Louis Pasteur CNRS, 4 rue Blaise Pascal, 67000 Strasbourg, France.
Lehn
Jean-Marie
JM
Lazarte
Jaime
J
Nicolau
Claude
C
D020003:1-Octanol; D001692:Biological Transport; D001769:Blood / Q000378:metabolism; D004058:Diffusion; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006801:Humans; D008567:Membranes, Artificial; D010100:Oxygen / Q000378:metabolism; D010833:Phytic Acid / Q000493:pharmacokinetics*; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D014867:Water
D008567:Membranes, Artificial; D000644:Quaternary Ammonium Compounds; D014867:Water; D010833:Phytic Acid; D020003:1-Octanol; D010100:Oxygen