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

作者：Kitamura Masanori; Nishimoto Hiroyuki; Aoki Keita; Tsukamoto Masato; Aoki Shin^*

来源：Inorganic Chemistry, 2010, 49(11): 5316-5327.

DOI：10.1021/ic1004038

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 (CDP2), by ditopic Zn2+ 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 Zn2+ ions (6.8 angstrom) 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-CDP2. H-1 NMR, P-31 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-CDP2 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-CDP2 and (S,S)-11-(R,R)-1,2-CDP2 (K-app=[(S,S)-11-1,2-CDP2 complex]/[(S,S)-11][1,2-CDP2] (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-CDP2 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-CDP2, while a small amount of 2:1 (S,S)-11 cis-1,3-CDP2 was detected, as evidenced by electrospray ionization mass spectrometry (ESI-MS). In contrast, 11 formed several complexes with trans-1,4-CDP2. 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.

• 出版日期2010-6-7