SMALL-MOLECULE ANALOGS OF PHOSPHOLIPID METAL-ION BINDING-SITES - POTENTIOMETRIC AND SPECTROSCOPIC STUDIES OF MG(II) AND CA(II) COMPLEXES OF CYCLOHEXANE-1,2,4-TRIOL TRISPHOSPHATES

Studies on the Mg(II) and Ca(II) complexes of four diastereomeric cyclohexane-1,2,4-triol trisphosphates were conducted using H-1 NMR, P-31 NMR, and calcium ion selective electrode (ISE) titrations. Based on the trends in Mg(II) and Ca(II) ion affinity, the 2,4-phosphate groups were concluded to be the primary determinants of the metal ion binding behavior of the 1,2,4-trisphosphates. Results from the proton and metal ion binding studies of the 1,2,4-trisphosphates indicate that the 1,2,4-trisphosphates satisfy two of the criteria as analogs of phospholipid-metal ion binding sites: (1) anionic groups which interact in metal ion binding, and (2) metal ion affinity constants determined by both ISE and P-31 NMR titrations are comparable to the metal ion affinity observed for phosphatidylserine vesicles. In particular, the all-cis trisphosphate diastereomer, (+/-)-(1R, 2S, 4S)-cyclohexane-1,2,4-triol trisphosphate, is the only 1,2,4-trisphosphate to exhibit a higher affinity for Ca(II) ion than Mg(II) ion. A higher Ca(II) ion affinity than Mg(II) ion affinity is characteristic of the behavior observed for phosphatidylserine vesicles or monolayers. (C) 1994 Academic Press, Inc.