We report on a macrocyclic platform based on an 18-membered macrocycle that forms kinetically highly inert paramagnetic complexes and possesses an excellent outlook for the development of bioresponsive paraCEST(parama...We report on a macrocyclic platform based on an 18-membered macrocycle that forms kinetically highly inert paramagnetic complexes and possesses an excellent outlook for the development of bioresponsive paraCEST(paramagnetic chemical exchange saturation transfer)contrast agents.The investigated europium(III)chelate is non-hydrated and contains four amide groups,each possessing two paramagnetically shifted proton resonances distant from bulk water.The X-ray crystal structure and solution studies indicate that the metal ion is ten-coordinated,being directly bound to the six N atoms of the macrocycle and the four amide O atoms of the pendant arms.The complex presents an excellent inertness with respect to dissociation,being stable under a variety of harsh conditions,including highly acidic and basic media or elevated temperatures.The amide protons are in slow-to-intermediate exchange with bulk water,which gives rise to the generation of a strong CEST effect at low probe concentration and saturation powers(~25%at 5 mM,B_(1)=5μT,37°C).We demonstrate the potential of this platform for mapping pH in its microenvironment and foresee potential for the development of diverse paraCEST probes and sensors.展开更多
基金the German Academic Exchange Service(DAAD)for the Ph.D.fellowship.D.E.-G.and C.P.-I.thank Ministerio de Economía y Competitividad(CTQ2016-76756-P)Xunta de Galicia(ED431B 2017/59 and ED431D 2017/01)for generous financial support.M.Z.thanks the research support of the German Research Foundation(DFG,grant ZA 814/2-1)European Union’s Horizon 2020 research and innovation programme(Grant Agreement No.667510).Open Access funding provided by the Max Planck Society.
文摘We report on a macrocyclic platform based on an 18-membered macrocycle that forms kinetically highly inert paramagnetic complexes and possesses an excellent outlook for the development of bioresponsive paraCEST(paramagnetic chemical exchange saturation transfer)contrast agents.The investigated europium(III)chelate is non-hydrated and contains four amide groups,each possessing two paramagnetically shifted proton resonances distant from bulk water.The X-ray crystal structure and solution studies indicate that the metal ion is ten-coordinated,being directly bound to the six N atoms of the macrocycle and the four amide O atoms of the pendant arms.The complex presents an excellent inertness with respect to dissociation,being stable under a variety of harsh conditions,including highly acidic and basic media or elevated temperatures.The amide protons are in slow-to-intermediate exchange with bulk water,which gives rise to the generation of a strong CEST effect at low probe concentration and saturation powers(~25%at 5 mM,B_(1)=5μT,37°C).We demonstrate the potential of this platform for mapping pH in its microenvironment and foresee potential for the development of diverse paraCEST probes and sensors.
