High-affinity and selective detection of pyrophosphate in water by a resorcinarene salt receptor.

Ngong Kodiah Beyeh,John F Trant,Robin H A Ras,Isabel Díez,Andrew I Feig,Kari Rissanen,S Maryamdokht Taimoory,Daniel Meister

doi:10.1039/c7sc05167k

Abstract

Pyrophosphate (PPi) is a byproduct of DNA and RNA synthesis, and abnormal levels are indicative of disease. We report the high-affinity binding of PPi in water by N-alkyl ammonium resorcinarene chloride receptors. Experimental analysis using 1H and 31P NMR, isothermal titration calorimetry, mass spectrometry, and UV-vis spectroscopy all support exceptional selectivity of these systems for PPi in water. The measured affinity of K1 = 1.60 × 107 M-1 for PPi is three orders of magnitude larger than that observed for binding to another phosphate, ATP. This exceptional anion-binding affinity in water is explored through a detailed density functional theory computational study. These systems provide a promising avenue for the development of future innovative medical diagnostic tools.

Highlights

Considerable effort is continuously being invested in developing receptors to detect biologically relevant ions under physiological conditions.[1]
Pyrophosphate (PPi) is a byproduct of DNA and RNA synthesis, and abnormal levels are indicative of disease
This is due to a combination of factors including: (1) the tighter complex of PPi@OH-C3-NAR, (2) the formation of additional H-bonds between host and guest in PPi@OH-C3-NARCl due to the presence of the upper-rim hydroxyls, and (3) the stronger and larger number of other types of noncovalent interactions; together these factors all lead to an improved t and complementarity between the anionic PPi and the cationic cavitand in PPi@OHC3-NARCl rather than PPi@Cy-NAR

Summary

Introduction

Considerable effort is continuously being invested in developing receptors to detect biologically relevant ions under physiological conditions.[1]. The binding interactions between the NARCl receptors and the three phosphate anions were quanti ed through a series of ITC experiments in H2O (Fig. 2f, S10 and S11†).

Results

Conclusion