Molecular recognition of inositol 1,4,5-trisphosphate and model compounds in aqueous solution by ditopic Zn(2+) complexes containing chiral linkers

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.