Issue 27, 2019

Rational design and implementation of a cucurbit[8]uril-based indicator-displacement assay for application in blood serum

Abstract

In this study, we report the first supramolecular indicator-displacement assay (IDA) based on cucurbit[n]uril (CBn) hosts that is operational in blood serum. Rational design principles for host–guest chemosensing in competitively binding media were derived through detailed mathematical simulations. It was shown that currently known CBn-based chemosensing ensembles are not suited for use in highly competitive matrices such as blood serum. Conversely, the simulations indicated that a combination of cucurbit[8]uril (CB8) and an ultra-high affinity dye would be a promising IDA reporter pair for the detection of Alzheimer's drug memantine in blood serum. Therefore, a novel class of [2.2]paracyclophane-derived indicator dyes for the host CB8 was developed that possesses one of the highest host–guest affinities (Ka > 1012 M−1 in water) known in supramolecular host–guest chemistry, and which provides a large Stokes shift (up to 200 nm). The novel IDA was then tested for the detection of memantine in blood serum in a physiologically relevant sub- to low micromolar concentration range.

Graphical abstract: Rational design and implementation of a cucurbit[8]uril-based indicator-displacement assay for application in blood serum

Supplementary files

Article information

Article type
Edge Article
Submitted
09 fev 2019
Accepted
31 may 2019
First published
04 iyn 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2019,10, 6584-6593

Rational design and implementation of a cucurbit[8]uril-based indicator-displacement assay for application in blood serum

S. Sinn, E. Spuling, S. Bräse and F. Biedermann, Chem. Sci., 2019, 10, 6584 DOI: 10.1039/C9SC00705A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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