Molecular Recognition of Inositol 1,4,5-Trisphosphate and Model Compounds in Aqueous Solution by Ditopic Zn²⁺ Complexes Containing Chiral Linkers

Abstract

We report on molecular recognition of inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)), an important intracellular second messenger, and some related model compounds, cyclohexanediol bisphosphate derivatives (CDP(2)), by ditopic Zn(2+) complexes containing chiral linkers ((S,S)- and (R,R)-11) in aqueous solution at physiological pH. A crystal structure analysis of (S,S)-11 indicated that the distance between two Zn(2+) ions (6.8 A) is suitable for accommodating two phosphate groups at the 4- and 5-positions of Ins(1,4,5)P(3) and two phosphate groups of trans-1,2-CDP(2). (1)H NMR, (31)P NMR, potentiometric pH, and isothermal calorimetric titration data indicate that (S,S)-11 forms 1:1 complexes with (S,S)- and (R,R)-1,2-CDP(2) at pH 7.4 and 25 degrees C. The apparent 1:1 complexation constants (log K(app)) for (S,S)-11-(S,S)-1,2-CDP(2) and (S,S)-11-(R,R)-1,2-CDP(2) (K(app) = [(S,S)-11-1,2-CDP(2) complex]/[(S,S)-11][1,2-CDP(2)] (M(-1))) were determined to be 7.6 +/- 0.1 and 7.3 +/- 0.1, respectively, demonstrating that both enantiomers of 11 bind to chiral trans-1,2-CDP(2) to almost the same extent. The log K(app) value of 6.3 was obtained for a 1:1 complex of (S,S)-11 with cis-1,3-CDP(2), while a small amount of 2:1 (S,S)-11-cis-1,3-CDP(2) was detected, as evidenced by electrospray ionization mass spectrometry (ESI-MS). In contrast, 11 formed several complexes with trans-1,4-CDP(2). On the basis of isothermal titration calorimetry data for (S,S)- and (R,R)-11 with Ins(1,4,5)P(3), it was concluded that 11 forms a 2:1 complex with Ins(1,4,5)P(3), in which the first molecule of 11 binds to the 4- and 5-phosphates of Ins(1,4,5)P(3) and the second molecule of 11 binds to the 1- and 5-phosphates.

Isothermal titration calorimetry for chiral chemistry

“…20 They showed that the binding of amino acids to the chiral-metal selector is an entropy-driven process. 22 Isothermal titration calorimetry, in this case, provided a good means of calculating the number of ligands that were bonded, as well as the number of bonding sites. An additional example is the work of the Vincent L. Pecoraro group who measured the interactions of chiral Gd (III) hydrophobic complexes with enantiomers of phenylalanine.…”

“…Yet another example is the work of Shin Aoki and coworkers that described the design and synthesis of some chiral ditopic zinc complexes (S,S) and (R,R) Zn 2 L 6 ( Figure 5A) and examined their complexation with cyclohexanediol bisphosphate derivatives ( Figure 5B). 22 Isothermal titration calorimetry, in this case, provided a good means of calculating the number of ligands that were bonded, as well as the number of bonding sites.…”

“…The solid lines represent the best fit, obtained by using a two binding site model(Figure 8from Kitamura et al22 ) B, Isothermal titration calorimetry results for the complex formation of Ins(1,4,5)P 3 with (S,S)-Zn 2 L 6 (▪) and (R,R)-Zn 2 L 6 (▫).…”

Design, synthesis and evaluation of a tripodal receptor for phosphatidylinositol phosphates

“…Anslyn 9 , 10 , Ahn 11 , Yoon 12 , 13 , Aoki 14 , 15 and Best 16 have previously reported receptors for inositol phosphates such as IP 3 based on scaffolds substituted with phosphate-recognition moieties such as guanidinium, alkyl ammonium or imidazolium groups as well as zinc(II) complexes. While these receptors have shown high affinity and, in some cases, good selectivity for specific IPs (mainly IP 3 ), their binding to PIPs (i.e.…”

Supramolecular Complexes Formed by the Self-assembly of Hydrophobic Bis(Zn²⁺-cyclen) Complexes, Copper, and Di- or Triimide Units for the Hydrolysis of Phosphate Mono- and Diesters in Two-Phase Solvent Systems (Cyclen=1,4,7,10-Tetraazacyclododecane)

“…[12][13][14][15][16][17][18][19][20][21] There are few examples of supramolecular phosphatases formed by a multicomponent self-assembly, although some artificial models of naturally occurring dinuclear metalloenzymes that hydrolyze phosphate monoester such as alkaline phosphatase (AP) have been reported. [22][23][24][25][26][27][28][29] It has been established that the complexation of Zn 2+ -macrocyclic polyamine complexes with organic anions provides unique modules for molecular recognition, [30][31][32][33][34] the sensing of biorelevant molecules, 35,36) catalysts for asymmetric synthesis, 37) and three-dimensional (3D) molecular assembly. [38][39][40][41][42][43][44][45] We recently reported on the preparation of a supramolecular complex 4, formed by the 4 : 4 : 4 assembly of a dimeric zinc(II) complex having a 2,2′-bipyridyl (bpy) linker 1 (Zn 2 L 1 ), 36) a dianion of cyanuric acid (CA), and copper(II) ion (Cu 2+ ) in an aqueous solution 46) (Chart 1).…”