Nanomolar Binding of Steroids to Cucurbit[n]urils: Selectivity and Applications.
Cucurbit[n]urils (CBn, n = 7, 8) serve as artificial receptors for steroids (21 tested), including the hormones testosterone and estradiol as well as steroidal drugs. Fluorescence displacement titrations and isothermal titration calorimetry (ITC) provided up to nanomolar binding affinities in aqueous solution for these hydrophobic target molecules, exceeding the values of known synthetic receptors. Remarkable binding selectivities, even for homologous steroid pairs, were investigated in detail by NMR, X-ray crystal diffraction, ITC, and quantum chemical calculations. Notably, the CBn•steroid complexes are stable in water and buffers, in artificial gastric acid, and even in blood serum. Numerous applications have been demonstrated, which range from the solubility enhancement of the steroids in the presence of the macrocycles (up to 100 times, for drug delivery) and the principal component analysis of the fluorescence responses of different CBn•reporter dye combinations (for differential sensing of steroids) to the real-time monitoring of chemical conversions of steroids as substrates (for enzyme assays).
Department of Life Sciences and Chemistry, Jacobs University Bremen , Campus Ring 1, 28759 Bremen, Germany.
Alexandra I
AI
Lazar
Institute of Nanotechnology, Karlsruhe Institute of Technology (KIT) , Hermann-von-Helmholtz Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
Frank
F
Biedermann
Department of Life Sciences and Chemistry, Jacobs University Bremen , Campus Ring 1, 28759 Bremen, Germany.
Kamila R
KR
Mustafina
Department of Life Sciences and Chemistry, Jacobs University Bremen , Campus Ring 1, 28759 Bremen, Germany.
Khaleel I
KI
Assaf
Department of Life Sciences and Chemistry, Jacobs University Bremen , Campus Ring 1, 28759 Bremen, Germany.
Andreas
A
Hennig
Department of Life Sciences and Chemistry, Jacobs University Bremen , Campus Ring 1, 28759 Bremen, Germany.
Werner M
WM
Nau
D001952:Bridged-Ring Compounds / Q000737:chemistry* / Q000378:metabolism*; D002151:Calorimetry; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D013256:Steroids / Q000378:metabolism; D013816:Thermodynamics
D001952:Bridged-Ring Compounds; D013256:Steroids