Novel lithocholaphanes: Syntheses, NMR, MS, and molecular modeling studies

Novel head-to-head lithocholaphanes 6 and 11 have been synthesized via precursors 1–5 and 7–10 with overall good yields, and characterized by 1H, 13C, and 15N NMR spectroscopy, ESI-TOF mass spectrometry, thermal analysis, and molecular modeling. In addition, the binding abilities of 6 and 11 towards alkali metal cations have been investigated via competitive complexation studies using equimolar mixtures of Li+, Na+, K+, and Rb+-cations, and cholaphanes 6 and 11. The formation of cation–cholaphane adducts was detected by ESI-TOF mass spectrometry. The trends in these comparative binding studies are nicely reproduced theoretically with PM3 energetically optimized structures of 6 and 11 and their interaction energies with alkali metal cations calculated by molecular mechanics. Cholaphane 11 possessing a peptoid type structural fragment, –(CH2CONHCH2CH2)2O–, as a coordination sphere, shows binding tendency towards lithium and sodium cations, whereas 6 possessing an ester type, –(CH2OCOCH2)2O–, moiety and a bigger cavity size than 11, shows merely a tendency towards bigger alkali metal cations, potassium and rubidium.