Conformation-Dependent Binding of Diheptanoylphosphatidylcholine by Cyclodextrins As Revealed by Proton Nuclear Magnetic Resonance

Abstract

The complex formation of 1 mmol kg -1 diheptanoylphosphatidylcholine (DHPC) with Rand γ-cyclodextrins (CD) in deuterium oxide solutions has been investigated by proton nuclear magnetic resonance. With the addition of CD, the variations in proton chemical shifts of DHPC and in vicinal coupling constants of the glycerol C1H 2 -C2H protons allow us to estimate the equilibrium constant and stoichiometry of complexation and to image the three-dimensional structures of their complexes. The addition of R-CD causes an increase of the trans conformer (T) of DHPC and a decrease of the gauche + conformer (G + ), whereas the addition of γ-CD results in the reverse changes. From the dependence of the chemical shift of a DHPC proton on the CD concentration, we estimate the equilibrium formation macroconstants K 1 and K 2 of 1:1 and 1:2 complexations of DHPC and CD. In contrast with the case for single-chain surfactants, the K 1 value for R-CD is smaller than that for γ-CD and the K 2 value for γ-CD is smaller than K 1 for γ-CD. The equilibrium microconstants of CD complexation of the three rotamers G + , G -(gauche -), and T of DHPC are also estimated from the concentration dependence of vicinal coupling constants. Predominant binary complexes of R-CD and γ-CD are composed of the Gform and the G + form, respectively. The T of the three conformers of DHPC tends most easily to form the ternary complex with R-CD and γ-CD. There seems to be almost no distinction between the 1-and 2-heptanoyl chains of DHPC for binding to the R-CD cavity. The inclusion of DHPC into the γ-CD cavity induces magnetic nonequivalence of the terminal methyl protons of chains 1 and 2. It is likely that DHPC is bound from the side of secondary hydroxyl groups of γ-CD. The threedimensional structures of major complexes are proposed on the basis of the magnitude of chemical-shift variation of each proton of DHPC and CD. The intermediate methylene groups of DHPC are located near the center of an R-CD cavity, whereas the two terminal methyl groups of DHPC are deeply penetrated into a γ-CD cavity. The above results are discussed in relation to the hemolysis of erythrocytes, one of the serious toxicities of CD caused when it was added in foods and pharmaceuticals.

Proton NMR Study of α-Cyclodextrin Inclusion of Short-Chain Surfactants

“…For doublechain surfactants, more stoichiometries must be taken into consideration. 20,29,30 The present work on single-and short-chain surfactants provides the basis for determining the stoichiometries, binding constants, and the structures of complexes for these more complicated systems. 5,20,29,30 …”

Formation of a Unique 1:2 Calcium-Calixquinone Complex in Aqueous Media

“…Determination of binding constants using chemical shifts in NMR spectra is one of the conventional methods. 37,42,43 In the case of this system, the constants were too high to estimate accurately using NMR titration data. However, the relatively good fit result on the basis of the model assuming 1:1 and 1:2 complexes is significant in understanding the complexation behavior although it should be kept in mind that the absolute values of the best-fit parameters are not very reliable ( Figure S5 in Supporting Information C).…”

“…(11). 37 The method used for curve fitting of NMR titration data is the same as that for UVvisible spectrophotometric titration data.…”

Molecular Motions of .ALPHA.-Cyclodextrin on a Dodecyl Chain Studied by Molecular Dynamics Simulations

“…This CD cavity, therefore, can accommodate surfactants very well. Complex formation between surfactants and CD has been extensively investigated by electrochemical, 9,10) surface chemical, 11,12) NMR, [13][14][15][16][17][18] crystallographic, 19,20) and computational methods. [21][22][23] The solution structures of complexes of CD with surfactants and related compounds are estimated from ROESY spectra and chemical shifts and compared with molecular mechanics and molecular surface area calculations.…”

“…[21][22][23] The solution structures of complexes of CD with surfactants and related compounds are estimated from ROESY spectra and chemical shifts and compared with molecular mechanics and molecular surface area calculations. [6][7][8][14][15][16][17][21][22][23][24] Recently, on the basis of intensity data of intermolecular ROESY cross-peaks, we determined rather detailed solution structures of a-CD complexes with propanol, 24) hexyltrimethylammonium, octyltrimethylammonium, 16) and dodecyltrimethylammonium (DTAB) bromides. 17) It was suggested that an a-CD molecule complexed with a surfactant molecule moves more extensively on the alkyl chain, as the alkyl chain becomes longer.…”