Supramolecular Complexation in Biological Media: NMR Study on Inclusion of an Anionic Tetraarylporphyrin into a Per-O-Methylated β-Cyclodextrin Cavity in Serum, Blood, and Urine

Abstract

The supramolecular complexation of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) with heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TMCD) has been known to be highly specific in aqueous media. In this study, we have used NMR spectroscopy to reveal that this supramolecular system also works even in biologically crowded media such as serum, blood, and urine. A ¹³ C-labeled heptakis(2,3,6-tri-O-methyl-¹³ C)-β-cyclodextrin (¹³ C-TMCD) was synthesized and studied using one-dimensional (1D) HMQC spectroscopy in serum and blood. The 1D HMQC spectrum of ¹³ C-TMCD showed clear signals due to the 2-, 3-, and 6-O¹³ CH₃ groups, whose chemical shifts changed upon addition of TPPS due to quantitative formation of the ¹³ C-TMCD/TPPS=2/1 inclusion complex in such biological media. The ¹ H NMR signals of non-isotope-labeled TPPS included by ¹³ C-TMCD were detected using the ¹³ C-filtered ROESY technique. A pharmacokinetic study of ¹³ C-TMCD and its complex with TPPS was carried out in mice using the 1D HMQC method. The results indicated that (1) 1D HMQC is an effective technique for monitoring the inclusion phenomena of ¹³ C-labeled cyclodextrin in biological media and (2) the intermolecular interaction between ¹³ C-TMCD and TPPS is highly selective even in contaminated media like blood, serum, and urine.

Keywords: NMR; biological media; cyclodextrin; porphyrin; supramolecular chemistry.