Novel permethylated beta-cyclodextrin derivatives appended with chromophores as efficient fluorescent sensors for the molecular recognition of bile salts

J Org Chem. 2007 Oct 26;72(22):8227-34. doi: 10.1021/jo071131m. Epub 2007 Oct 3.

Abstract

Two novel permethylated beta-cyclodextrin (PM-beta-CD) derivatives, i.e., 6I-O-(1-naphtholxy)-2I,31-di-O-methylhexakis(2II-VII,3II-VII,6II-VII-tri-O-methyl)-beta-cyclodextrin (1) and 6I-O-(8-hydroxyquinoline)-2I,31-di-O-methylhexakis(2II-VII,3II-VII,6II-VII- tri-O-methyl)-beta-cyclodextrin (2), were synthesized in satisfactory yields, and their inclusion modes, complex-induced fluorescent behaviors, binding ability, and selectivity for bile salts of biological relevance (cholic acid sodium salt, CA; deoxycholic acid sodium salt, DCA; glycochoic acid sodium salt, GCA; taurocholic acid sodium salt, TCA) were investigated by the circular dichroism, 2D NMR, steady-state, and time-resolved fluorescent spectra. The results obtained from induced circular dichroism and ROESY spectra show that the chromophore groups of 1 and 2 reside in the central cavity of PM-beta-CD, and are expelled to the region of narrow torus rim upon complexation with bile guests, which presents the binding mode of cooperative inclusion. The transfer of the chromophore groups from the central cavity to the more hydrophobic torus rim leads to the remarkable increase of fluorescent intensities and longer fluorescent lifetimes of hosts 1 and 2 upon gradual addition of bile salts, which is importantly distinct from the molecular recognition of the chromophore-modified beta-CD species with bile salts. Interestingly, hosts 1 and 2 present much stronger binding ability for bile guests than PM-beta-CD. Differing from native beta-CD, all the PM-beta-CDs are more prone to include bile salts with longer tails, such as GCA and TCA. Their corresponding binding ability and molecular selectivity are closely discussed from the viewpoints of difference of cavity size/shape between beta-CD and PM-beta-CD, effect of substituent groups, and structures of bile guests, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bile Acids and Salts / chemistry*
  • Carbohydrate Conformation
  • Fluorescence
  • Fluorescent Dyes* / chemical synthesis
  • Fluorescent Dyes* / chemistry
  • Magnetic Resonance Spectroscopy / methods
  • Methylation
  • Naphthalenes* / chemical synthesis
  • Naphthalenes* / chemistry
  • Quinones* / chemical synthesis
  • Quinones* / chemistry
  • Sensitivity and Specificity
  • Spectrometry, Fluorescence
  • beta-Cyclodextrins* / chemical synthesis
  • beta-Cyclodextrins* / chemistry

Substances

  • 6I-O-(1-naphtholxy)-2I,31-di-O-methylhexakis(2II-VII,3II-VII,6II-VII-tri-O-methyl)-beta-cyclodextrin
  • 6I-O-(8-hydroxyquinoline)-2I,31-di-O-methylhexakis(2II-VII,3II-VII,6II-VII- tri-O-methyl)-beta-cyclodextrin
  • Bile Acids and Salts
  • Fluorescent Dyes
  • Naphthalenes
  • Quinones
  • beta-Cyclodextrins
  • betadex