Ein großräumiger Cyclophan‐Wirt zur Einschlußkomplexierung von Steroiden und [m.n]Paracyclophanen

Abstract

Gallensäure‐Derivate, Corticoide und Androgene werden in D2O/CD3OD (1 : 1) von dem Wirt 1, der durch zwei Naphthylphenylmethan‐Einheiten charakterisiert ist, gebunden. Bei der Einschlußkomplexierung von [m.n]Paracyclophanen wird eine Vierfachstapelung von Benzolringen beider Bindungspartner beobachtet.

Steroids in Molecular Recognition

“…Carlson and Jorgensen showed by Monte Carlo liquid-phase simulations that the complex between 113 and cholic acid ( 2 ) is strongly disfavored compared to the complexes of steroids lacking the 12α-HO group, since the latter becomes deeply buried inside the cyclophane cavity and cannot be stabilized neither by the apolar host nor by solvation. Similar conclusions had previously been drawn from Corey−Pauling−Koltun (CPK) molecular model examinations . The difference in stability of 2 kcal mol -1 between the complexes formed by lithocholic acid ( 83 ) and deoxycholic acid ( 82 ) with host 113 provides an impressive example for a binding selectivity in aqueous solution that does not originate from differences in attractive host−guest interactions but rather from energetically unfavorable, complexation-induced polar functional group desolvation.…”

“…While the cyclodextrins are known to rather unspecifically complex a broad range of apolar substrates including steroids (section III), the first artificial hosts for steroids were only reported some 10 years ago. Since then, a very limited number of novel synthetic steroid receptors have appeared in the literature. − Except for some steroid-recognizing polymers , obtained by molecular imprinting, so far all artificial receptors have been based on cyclophanes ,− (including calixarenes − ), a major class of macrocyclic hosts comprising bridged aromatic systems. Thereby, a few macrocycles have been shown to recognize polar steroids by means of multiple H-bonding in both apolar organic solvents 214-216 and in the solid state, while the others bind in aqueous or alcoholic solutions, − taking advantage of hydrophobic desolvation and dispersion forces besides electrostatic donor−acceptor interactions. − …”

“…Since then, a very limited number of novel synthetic steroid receptors have appeared in the literature. [214][215][216][217][218][219][220][221][222][223][224][225][226][227][228][229] Except for some steroid-recognizing polymers 230,232 obtained by molecular imprinting, 231 so far all artificial receptors have been based on cyclophanes 39,[233][234][235] (including calixarenes [236][237][238] ), a major class of macrocyclic hosts comprising bridged aromatic systems. Thereby, a few macrocycles have been shown to recognize polar steroids by means of multiple H-bonding in both apolar organic solvents [214][215][216] and in the solid state, 217 while the others bind in aqueous or alcoholic solutions, [218][219][220][221][222][223][224][225][226][227][228][229] taking advantage of hydrophobic desolvation and dispersion forces besides electrostatic donor-acceptor interactions.…”

Binding Site Optimisation for Artificial Enzymes by Diffusion NMR of Small Molecules

“…This agrees well with the presence of a binding equilibrium between H‐Arg‐Arg‐OH and the TSA 2 . The measured diffusion coefficients of the H‐Arg‐Arg‐OH were plotted against the concentration of the TSA, and the binding constant K a was calculated using the non‐linear least squares fitting 27, 28. The estimated value of K a was found to be 86±15 L M −1 ( D′ pep =3.24±0.07×10 −10 m 2 s −1 ).…”

“…The diffusion coefficients were determined from Equation (7) using T 1 / T 2 utility of XwinNMR. The Associate program, which employs the non‐linear least squares Levenberg–Marquardt method to fit parameters to equilibrium complexation models, was used to determine the binding constant K a 27, 28…”