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Reversible anion binding to lanthanide complexes in aqueous solution has emerged as an effective method for anion sensing. Through careful design of the organic ligand, luminescent lanthanide complexes capable of binding biologically relevant anions in a bidentate or monodentate manner can be realized. While single-crystal X-ray diffraction analyses and NMR spectroscopy have revealed the structural geometry of several host-guest complexes, the challenge remains in designing preorganized lanthanide receptors with enhanced anion selectivity for broader applications in diagnostics and bioimaging. To address this challenge, innovative and complementary methods to investigate host-anion binding geometry are becoming increasingly important. Herein, we demonstrate the combined use of Eu L 3 -edge extended X-ray absorption fine structure (EXAFS) and electron paramagnetic resonance (EPR) spectroscopy to elucidate the binding of nucleoside phosphates (ATP, ADP, and AMP) to a cationic lanthanide complex. We establish that ATP unequivocally binds the lanthanide center in a bidentate manner in water, while ADP adopts both bidentate and monodentate modes, and AMP binds in a monodentate manner. This interdisciplinary approach provides deeper insight into lanthanide host-guest chemistry in solution, laying the groundwork for designing emissive probes that undergo specific anion-induced structural changes and elicit desired optical responses upon binding.

Synthetic anion receptors are increasingly being explored for the transport of anions across lipid membranes because of their potential therapeutic applications. A considerable amount of research focuses on the transport of chloride, whereas the transmembrane transport of inorganic phosphate has not been reported to date, despite the biological relevance of this anion. Here we present a calix[4]pyrrole with a bisurea strap that functions as a receptor and transporter for H 2 PO 4 - , relying on the formation of eight hydrogen bonds and efficient encapsulation of the anion. Using a phosphate-sensitive lanthanide probe and 31 P NMR spectroscopy, we demonstrate that this receptor can transport phosphate into vesicles by H 2 PO 4 - /Cl - antiport, H 2 PO 4 - uniport, and Cs + /H 2 PO 4 - symport mechanisms. This first example of inorganic phosphate transport by a neutral receptor opens perspectives for the future development of transporters for various biological phosphates.

Bambusurils are macrocyclic molecules that are known for their high binding affinity and selectivity toward anions. Here, we present the preparation of two bambusurils bearing fluorinated substituents and one carboxylic function. These monofunctionalized bambusurils were conjugated with crown ether and cholesterol units. The resulting conjugates were successfully tested in liquid-liquid extraction of inorganic salts and chloride/bicarbonate transport across lipid bilayers.

We present here a series of thermoresponsive glycopolymers in the form of poly( N -isopropylacrylamide) -co- (2-[β-manno[oligo]syloxy] ethyl methacrylate)s. These copolymers were prepared from oligo-β-mannosyl ethyl methacrylates that were synthesized through enzymatic catalysis, and were subsequently investigated with respect to their aggregation and phase behavior in aqueous solution using a combination of 1 H NMR spectroscopy, dynamic light scattering, cryogenic transmission electron microscopy (TEM), and small-angle X-ray scattering (SAXS). The thermoresponsive glycopolymers were prepared by conventional free radical copolymerization of different mixtures of 2-(β-manno[oligo]syloxy)ethyl methacrylates (with either one or two saccharide units) and N -isopropylacrylamide (NIPAm). The results showed that below the lower critical solution temperature (LCST) of poly(NIPAm), the glycopolymers readily aggregate into nanoscale structures, partly due to the presence of the saccharide moieties. Above the LCST of poly(NIPAm), the glycopolymers rearrange into a heterogeneous mixture of fractal and disc/globular aggregates. Cryo-TEM and SAXS data demonstrated that the presence of the pendant β-mannosyl moieties in the glycopolymers induces a gradual conformational change over a wide temperature range. Even though the onset of this transition is not different from the LCST of poly(NIPAm), the gradual conformational change offers a variation of the temperature-dependent properties in comparison to poly(NIPAm), which displays a sharp coil-to-globule transition. Importantly, the compacted form of the glycopolymers shows a larger colloidal stability compared to the unmodified poly(NIPAm). In addition, the thermoresponsiveness can be conveniently tuned by varying the sugar unit-length and the oligo-β-mannosyl ethyl methacrylate content.

Tyrosine sulfation is a post-translational modification that enhances protein-protein interactions and may identify druggable sites in the extracellular space. The G protein-coupled receptor CXCR4 is a prototypical example with three potential sulfation sites at positions 7, 12, and 21. Each receptor sulfotyrosine participates in specific contacts with its chemokine ligand in the structure of a soluble, dimeric CXCL12:CXCR4(1-38) complex, but their relative importance for CXCR4 binding and activation by the monomeric chemokine remains undefined. NMR titrations with short sulfopeptides showed that the tyrosine motifs of CXCR4 varied widely in their contributions to CXCL12 binding affinity and site specificity. Whereas the Tyr21 sulfopeptide bound the same site as in previously solved structures, the Tyr7 and Tyr12 sulfopeptides interacted nonspecifically. Surprisingly, the unsulfated Tyr7 peptide occupied a hydrophobic site on the CXCL12 monomer that is inaccessible in the CXCL12 dimer. Functional analysis of CXCR4 mutants validated the relative importance of individual CXCR4 sulfotyrosine modifications (Tyr21 > Tyr12 > Tyr7) for CXCL12 binding and receptor activation. Biophysical measurements also revealed a cooperative relationship between sulfopeptide binding at the Tyr21 site and CXCL12 dimerization, the first example of allosteric behavior in a chemokine. Future ligands that occupy the sTyr21 recognition site may act as both competitive inhibitors of receptor binding and allosteric modulators of chemokine function. Together, our data suggests that sulfation does not ubiquitously enhance complex affinity and that distinct patterns of tyrosine sulfation could encode oligomer selectivity, implying another layer of regulation for chemokine signaling.

The design and synthesis of a diketopiperazine based anion receptor bearing two dipicolylamino arms complexed to zinc(II) ions is described. This receptor is readily prepared from the dipeptide precursor by a microwave-assisted intramolecular cyclization reaction. Upon addition of zinc(II), the receptor binds di- and triphosphate ions with high affinity and selectivity in aqueous solution, as determined by using a fluorescent indicator displacement assay.