Transport of the highly charged myo-inositol hexakisphosphate molecule across the red blood cell membrane: a phase transfer and biological study

Bioorg Med Chem. 2002 Sep;10(9):2825-34. doi: 10.1016/s0968-0896(02)00162-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Octanol
  • Biological Transport
  • Blood / metabolism
  • Diffusion
  • Erythrocyte Membrane / metabolism*
  • Humans
  • Membranes, Artificial
  • Oxygen / metabolism
  • Phytic Acid / pharmacokinetics*
  • Quaternary Ammonium Compounds / chemical synthesis
  • Quaternary Ammonium Compounds / pharmacokinetics*
  • Structure-Activity Relationship
  • Water

Substances

  • Membranes, Artificial
  • Quaternary Ammonium Compounds
  • Water
  • Phytic Acid
  • 1-Octanol
  • Oxygen