Enhancement of anion binding in lanthanide optical sensors.

In the design of molecular sensors, researchers exploit binding interactions that are usually defined in terms of topology and charge complementarity. The formation of complementary arrays of highly cooperative, noncovalent bonding networks facilitates protein-ligand binding, leading to motifs such as the "lock-and-key". Synthetic molecular sensors often employ metal complexes as key design elements as a way to construct a binding site with the desired shape and charge to achieve target selectivity. In transition metal complexes, coordination number, structure and ligand dynamics are governed primarily by a combination of inner-sphere covalent and outer-sphere noncovalent interactions. These interactions provide a rich variable space that researchers can use to tune structure, stability, and dynamics. In contrast, lanthanide(III)-ligand complex formation and ligand-exchange dynamics are dominated by reversible electrostatic and steric interactions, because the unfilled f shell is shielded by the larger, filled d shell. Luminescent lanthanides such as terbium, europium, dysprosium, and samarium display many photophysical properties that make them excellent candidates for molecular sensor applications. Complexes of lanthanide ions act as receptors that exhibit a detectable change in metal-based luminescence upon binding of an anion. In our work on sensors for detection of dipicolinate, the unique biomarker of bacterial spores, we discovered that the incorporation of an ancillary ligand (AL) can enhance binding constants of target anions to lanthanide ions by as much as two orders of magnitude. In this Account, we show that selected ALs in lanthanide/anion systems greatly improve sensor performance for medical, planetary science, and biodefense applications. We suggest that the observed anion binding enhancement could result from an AL-induced increase in positive charge at the lanthanide ion binding site. This effect depends on lanthanide polarizability, which can be established from the ionization energy of Ln(3+) → Ln(4+). These results account for the order Tb(3+) > Dy(3+) > Eu(3+) ≈ Sm(3+). As with many lanthanide properties, ranging from hydration enthalpy to vaporization energy, this AL-induced enhancement shows a large discrepancy between Tb(3+) and Eu(3+) despite their similarity in size, a phenomenon known as the "gadolinium break". This discrepancy, based on the unusual stabilities of the Eu(2+) and Tb(4+) oxidation states, results from the half-shell effect, as both of these ions have half-filled 4f-shells. The high polarizability of Tb(3+) explains the extraordinarily large increase in the binding affinity of anions for terbium compared to other lanthanides. We recommend that researchers consider this AL-induced enhancement when designing lanthanide-macrocycle optical sensors. Ancillary ligands also can reduce the impact of interfering species such as phosphate commonly found in environmental and physiological samples.