Inframolecular acid–base studies of the tris and tetrakis myo-inositol phosphates including the 1,2,3-trisphosphate motif

Insight into the protonation and K(I)-interaction of the inositol 1,2,3-trisphosphate as provided by 31P NMR and theoretical calculations

“…The results (Table 4 and Fig. 4) are similar to those previously reported in 0.2 M KCl at 37°C by Dozol et al [12] (also included in Table 4). Some slight to moderate differences between them can be explained by the formation, under metal ion excess, of [K x (H y L)] (6ÀxÀy)À species.…”

“…Nevertheless, they are very close to those obtained by potentiometry under identical experimental conditions [4]. The previously reported data in 0.2 M KCl at 37.0°C were 9.37(3), 17.05(3), and 22.48(3) for the first three protonations as determined by 31 P NMR titrations [12]. The influence of K(I) interaction can explain the observed difference with the values in 0.15 M NMe 4 Cl: 9.27(3), 16.71(5), and 21.94(8), respectively.…”

“…It produces a structural distortion in (1a5e) L 6À and (1a5e) HL 5À , leading the carbon ring to become closer to a boat conformation. This could be the reason for the slight experimental shift in the H5 NMR signal starting from pH 7-8 [12], where HL 5À becomes the principal form of Ins(1,2,3)P 3 [4]. From a structural point of view, 1a5e state seems to have a more suitable geometry to establish phosphate-HO hydrogen bonds, supporting again this conformation as the most stable for low protonated Ins(1,2,3)P 3 .The average intramolecular hydrogen bond distance (X O-H ) for the species shown in Fig.…”

“…There are few studies focusing on the protonation state at an inframolecular level and/or the intrinsic 0022-2860/$ -see front matter Ó 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.molstruc.2010.11.050 metal complexation properties of myo-inositol phosphates [9][10][11][12]. In particular for Ins(1,2,3)P 3 , a molecule whose biological function is still controversial, some information regarding the intrinsic acid-base properties has been reported [12], although the data were acquired in the presence of large amounts of K(I), which substantially interacts with this ligand in weakly acid to basic media [4].…”

Determination of microscopic acid?base parameters from NMR?pH titrations

“…Since pH influences the binding of inositol phosphates (IPs) to Ins(1,4,5)P 3 receptors [142], Spiess and co-workers have used 31 P NMR-pH titrations to determine microconstant for a large number of IPs and their analogues. In the pH range 2-12, each group coordinates one proton, giving rise to biprotic [143] and triprotic [74,114,144,145,146,147,148] microequilibrium systems. The microconstants and interactivity parameters indicate that hydrogen bonding and hydration are the main factors to determine the basicity of individual phosphate groups.…”