Carboxylate vibrational spectroscopy as a probe of ion binding site structure and properties

We report vibrational spectra and density functional theory (DFT) calculations for aminopolycarboxylate chelators and small lanthanide binding peptides bound to series of alkaline earth metals and lanthanides. The asymmetric stretching transitions of the carboxylate groups which directly mediate ion binding interactions in these molecules is known to respond sensitively to the identity of the bound ion, reporting on both the electrostatic environment in the binding pocket and the deformation of the host scaffold by the binding interaction. Though the sensitivity of these transitions to guest ion is similar in most cases, we find that the carboxylate stretching transitions in some chelators display markedly different sensitivity. We explore the provenance of this behavior and discuss potential applications for inferring binding site properties from the infrared spectra.

The ion binding structures central to biological signaling pathways share many common traits, but the ion-binding-initiated conformational cascades that drive signaling are not fully understood. Characterization of binding site architectures often remains limited to static crystallographic structures, and large gaps remain in knowledge of the conformational sequences leading from ion binding to downstream signal transduction. To address this deficiency, we deploy infrared methods that provide both time resolution and structural sensitivity to better understand the factors that drive ion recognition.