Quantitative investigation of the interactions between inositol-tris(phosphates) and polyamines

Abstract

Inositol-phosphates (IPs) provide particularly favourable stereochemistry for the formation of complexes with polyammonium salts which may exist in their biological environment. In the present work we report the study of the complexation of spermine by four inositol tris(phosphates) differing by the position of the phosphate groups i.e.D-myo-inositol-1,2,6-tris(phosphate)[Ins(1,2,6)P₃], (±)-myo-inositol-4,5,6-tris(phosphate)[Ins(4,5,6)P₃], (±)-myo-inositol-1,3,5-tris(phosphate)[Ins(1,3,5)P₃] or by the configuration of the hydroxyls: (±)-chiro-inositol-1,2,6-tris(phosphate)[chiro-Ins(1,2,6)P₃]. The complexation study of various linear or macrocyclic polyamines such as spermidine, dioctadecylamidoglycyl spermine (DOGS) and the A₆27C6-1 with Ins(1,2,6)-P₃, are also included. All the studies have been carried out at 25 °C in a 0.1 mol dm^–3 tetramethylammonium toluene-p-sulfonate medium (Me₄NOTs). By performing ³¹P NMR titrations, the protons of the complexes have been precisely localized and, therefore, the stepwise complexation constants could be unambiguously calculated. The constants of the spermine–IP complexes tend to be linearly related to the basicity of the phosphate groups, which, itself depends on the position of the phosphates around the myo-inositol ring. The highest stabilities are achieved for the IPs carrying three vicinal phosphates. As expected, the electrostatic forces govern the stability of the complexes since the number of charges, the negative charge density of the IP and the local dielectric constant largely influence the strength of the interaction. Spermine and spermidine form with the IP's complexes which are stable enough to play a major biological role.