The ability of complexes of hard and labile metal ions with one or more open coordination sites to capture phosphates with high affinity and selectivity directly in water at neutral pH and release them under acidic conditions is evaluated with Gadolinium- 2,2',2''-(((nitrilotris(ethane-2,1-diyl))tris(azanediyl))tris(carbonyl))tris(4-oxo-4H-pyran-3-olate) (Gd-TREN-MAM). This model lanthanide complex has two open coordination sites that, at neutral pH, are filled with water molecules. In water at neutral pH, Gd-TREN-MAM binds phosphate with high affinity (K = 1.3 × 10) via the formation of a ternary complex in which one phosphate replaces both inner-sphere water molecules. The formation of this complex is highly pH-dependent; the phosphate is completely released from Gd-TREN-MAM below pH 2. Because the Gd ion remains complexed by its ligand, even under strong acidic conditions, Gd-TREN-MAM can be used at least 10 times in a pH-based recycling scheme that enables the catch and release of one phosphate per cycle. Gd-TREN-MAM is highly selective for phosphate over other anions of environmental concerns, including HCO, HCO, CHCO, SO, NO, NO, BrO, AsO, F, Cl, and Br and, to a lesser extent, ClO. The development of such receptors that bind phosphate reversibly in a pH-dependent manner opens the possibility to design catch-and-release systems for the purification of surface waters.
We discuss and review the strategies of metal-based receptors targeting phosphate.
Magnetic resonance imaging (MRI) has emerged over the years as one of the preferred modalities for medical diagnostic and biomedical research. It has the advantage over other imaging modalities such as positron emission tomography and X-ray of affording high resolution three-dimensional images of the body without using harmful radiation. The use of contrast agents has further expanded this technique by increasing the contrast between regions where they accumulate and background tissues. As MRI most often measures the relaxation rate of water throughout the body, contrast agents function by modulating the intensity of the water signal either via improved relaxation or via saturation transfer to selected exchangeable proton. Among the growing class of MRI contrast agents, a subset of them called "smart" contrast agents function as responsive probes. Their ability to increase or decrease their signal intensity is modulated by the presence of an analyte. These probes offer the unique ability to image the distribution of an analyte in vivo, thereby opening new possibilities for diagnostics and for elucidating the role of specific analytes in various pathologies or biological processes. A number of different strategies can be exploited to design responsive MRI contrast agents. The majority of contrast agents are based on Gd complexes. These complexes can be rendered responsive in either of two ways: either by modulating the number of inner-sphere water molecules, q, or via modulating the rotational correlation time, τ, of the contrast agent upon substrate binding. The longitudinal relaxivity increases with the number of inner-sphere water molecules. Gd complexes can be rendered responsive if they contain a recognition moiety that can bind to both the open coordination site of Gd and to the analyte. When the recognition moiety leaves the lanthanide ion to bind to the analyte, q increases and therefore so does the relaxivity. The dependence of relaxivity on rotational correlation time is more complex and more pronounced at lower magnetic fields. In general, slower tumbling macromolecules have longer rotational correlation times and higher relaxivities. Analyte-triggered formation of macromolecules thus also increases relaxivity. Such macromolecules can either be analyte-templated supramolecular assemblies, or analyte-enhanced protein-contrast agent complexes. Chemical Exchange Saturation Transfer (CEST) agents are a newer class of contrast agents that offer the possibility of multifrequency and thus ratiometric imaging, which in turn enables quantitative mapping of the concentration of an analyte in vivo under conditions where the concentration of the contrast agent is not known. Such agents can be rendered responsive if the analyte changes the number of exchangeable proton(s), its exchange rate, or its chemical shift. All of these approaches have been successfully employed for detecting and imaging both copper and zinc, including in vivo. Magnetic Iron Oxide Nanoparticles (MIONs) are powerful MRI transverse relaxation a...
Two thulium-based ParaCEST responsive contrast agents, Tm-DOTAm-py and Tm-DOTAm-βAla-py, have been synthesized and evaluated for imaging copper and zinc. Unusual for responsive MRI contrast agents, both agents display a complete on/off response in the presence of transition metals. Both complexes function as paraCEST agents in the absence of copper and zinc, with the positively charged Tm-DOTAm-py being more sensitive than the neutrally charged Tm-DOTAm-βAla-py. In each case, the CEST signal arises from amide protons rather than from a water molecule coordinated to Tm3+ ions. Upon binding to Cu+, Cu2+, or Zn2+, the exchange rate of the amide protons increases substantially, resulting in a complete loss of the CEST signal. This efficient mode of action along with the lack of inner-sphere water molecules both in the presence and absence of transition metals was confirmed by 1/T1 NMRD profiles, 17O NMR measurements, and molecular modelling simulations. Neither complex is selective for copper over zinc. Both form either a 1 : 1 TmL : Cu+ or a 2 : 1 TmL : Cu2+ and TmL : Zn2+ complexes with binding affinities comparable to that of other responsive MRI contrast agents and sensitivity comparable to that of other CEST contrast agents.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.