Analytical Chemistry (journal)

Physics

Organic chemistry

Chemistry

Conformational isomerism

Valinomycin

Ionophore

Molecule

Membrane

Biochemistry

Membrane transport

Diffusion

Crystallography

Thermodynamics

Ion transporter

The Journal of Physical Chemistry Letters

Valinomycin is a macrocyclic ionophore that transports K+ across hydrophobic membranes. Its function depends on selectivity, capture, transport, and release of the ion. While thermodynamics clearly indicate that valinomycin binds K+ preferentially over all other alkali ions, characterizing the capture/transport/release of K+ by valinomycin at the molecular level remains a challenge. The bracelet-like structure of valinomycin-K+ (K+VM) has the ion completely enveloped, facilitating transport through the cell membrane. We report that hydration by a single water molecule, (K+VM)(H2O), produces three different conformers, identified by infrared spectroscopy and supporting computational studies. For two minor conformers, the water prevents the ionophore from closing, a conformation that would inhibit diffusion through the membrane. However, the dominant conformer encloses both the ion and the water, replicating the bracelet-like K+VM and arguably enhancing diffusion through the membrane. This potential for active participation of water in transport through the hydrophobic cellular membrane has never been previously considered.

Rethinking Ion Transport by Ionophores: Experimental and Computational Investigation of Single Water Hydration in Valinomycin-K<sup>+</sup> Complexes

Rethinking Ion Transport by Ionophores: Experimental and Computational Investigation of Single Water Hydration in Valinomycin-K+ Complexes

Rethinking Ion Transport by Ionophores: Experimental and Computational Investigation of Single Water Hydration in Valinomycin-K⁺ Complexes