Premium
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
Author(s) -
Kitagishi Hiroaki,
Saito Mai,
Mao Qiyue,
Kiriyama Akiko,
Negi Shigeru,
Kano Koji
Publication year - 2019
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201900983
Subject(s) - chemistry , supramolecular chemistry , cyclodextrin , porphyrin , nuclear magnetic resonance spectroscopy , aqueous medium , spectroscopy , inclusion compound , stereochemistry , aqueous solution , intermolecular force , proton nmr , chemical shift , crystallography , organic chemistry , molecule , crystal structure , physics , quantum mechanics
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‐O 13 CH 3 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.