Macrocyclic Chelates Bridged by a Diaza-Crown Ether: Towards Multinuclear Bimodal Molecular Imaging Probes

Gaoji Wang,Goran Angelovski

doi:10.3390/molecules25215019

Abstract

Bridged polymacrocyclic ligands featured by structurally different cages offer the possibility of coordinating multiple trivalent lanthanide ions, giving rise to the exploitation of their different physicochemical properties, e.g., multimodal detection for molecular imaging purposes. Intrigued by the complementary properties of optical and MR-based image capturing modalities, we report the synthesis and characterization of the polymetallic Ln(III)-based chelate comprised of two DOTA-amide-based ligands (DOTA—1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) bridged via 1,10-diaza-18-crown-6 (DA18C6) motif. The DOTA-amide moieties and the DA18C6 were used to chelate two Eu(III) ions and one Tb(III) ion, respectively, resulting in a multinuclear heterometallic complex Eu2LTb. The bimetallic complex without Tb(III), Eu2L, displayed a strong paramagnetic chemical exchange saturation transfer (paraCEST) effect. Notably, the luminescence spectra of Eu2LTb featured mixed emission including the characteristic bands of Eu(III) and Tb(III). The advantageous features of the complex Eu2LTb opens new possibilities for the future design of bimodal probes and their potential applicability in CEST MR and optical imaging.

Highlights

In modern medicine, magnetic resonance imaging (MRI) is recognized as the method of choice for non-radiative and non-invasive imaging of soft body tissues [1,2,3]
Conventional MRI exploits the magnetic properties of water proton’s spins to generate signal. It suffers from intrinsic insensitivity, which often requires the administration of contrast agents (CAs)
One of the recently introduced MRI strategies is based on the chemical exchange saturation transfer (CEST) effect, which possesses specific advantages over the conventional T1 -weighted MRI

Summary

Introduction

Magnetic resonance imaging (MRI) is recognized as the method of choice for non-radiative and non-invasive imaging of soft body tissues [1,2,3]. Conventional MRI exploits the magnetic properties of water proton’s spins to generate signal. It suffers from intrinsic insensitivity, which often requires the administration of contrast agents (CAs). These mainly paramagnetic Ln(III)-based complexes improve specificity of the MRI scans through various contrast-generating mechanisms [3]. One of the recently introduced MRI strategies is based on the chemical exchange saturation transfer (CEST) effect, which possesses specific advantages over the conventional T1 -weighted MRI. The principle of CEST detection is based on the selective saturation of the pool of protons that are in slow to intermediate exchange rate on the NMR time-scale, with bulk water pool. The chemical exchange of the pre-saturated CEST proton pool with the Molecules 2020, 25, 5019; doi:10.3390/molecules25215019 www.mdpi.com/journal/molecules

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