Calculations of Molecular Surface Area Changes with Docking of Host and Guest and Applications to Cyclodextrin Inclusion

Abstract

A method for calculations of molecular surface area changes with the docking of host and guest is developed and applied to the estimation of the structures and binding constants of cyclodextrin inclusion systems. Each molecule of the host and guest is regarded to consist of hydrophilic and hydrophobic groups. The change ΔS in water-accessible surface area with the docking of these host and guest molecules is divided into four terms: ΔSoo(HG), ΔSow(HG), ΔSwo(HG), and ΔSww(HG). For instance, ΔSoo(HG) stands for the change in host hydrophobic surface area by overlapping with guest hydrophobic surface area. When a guest molecule is moved along the symmetry axis of cyclodextrin, the structure of the complex having the maximum ΔSoo(HG) value is close to its crystal structure. Thus, we can estimate the “solution” structure of the complex from the maximum ΔSoo(HG) value. Using this method, we predict the solution structures of six cyclodextrin inclusion systems. Furthermore, we find that the logarithm of the 1:1 binding constant is linear with the maximum ΔSoo(HG) value for 11 systems including α-, β-, and γ-cyclodextrins and aliphatic and aromatic guest molecules. The present results would be applied to other cyclodextrin inclusion systems and protein−ligand systems.

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

“…The NMR chemical shift method has been employed for binding constant determination of surfactants and CDs. [8][9][10] Very recently, it has been demonstrated that applications of this method require a special attention to references of chemical shifts. [11][12][13] The internal reference method is superior to the external one in several points, but it is often difficult to find any inert reference.…”

“…Because the volume magnetic susceptibility of the sample solution depends on the concentration of an added substance, this effect on the chemical shift must be corrected. [10][11][12][13] NMR data, such as NOE cross-peaks, vicinal spin-spin coupling constants, and chemical shifts generally provide information on rather detailed solution structures. The relationship between chemical shifts and structures remains almost unexplored for CD inclusion complexes.…”

Stoichiometric and microenvironmental effects on hydrolysis of propantheline and oxyphenonium bromides in cyclodextrin solutions

“…A HyperChem (Hypercube, Inc.) package modeling software and our own software16 were also used for molecular modeling. The data analysis was carried out on a Dell Precision 610 personal computer.…”

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

“…[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. 16,17) The effect of protonation and chain length on complexation between a-CD and a,w-diaminoalkanes was investigated by NMR diffusion measurements.…”

“…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. [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.…”