Valinomycin-proton interaction in low-polarity media

Valinomycin is shown to form a stable complex with protons in the form of H3O+ ions. Using 1H and 13C nuclear magnetic resonance (NMR), Fourier transform (FT) infrared spectroscopy, and ab initio-density functional theory (DFT) quantum mechanical calculations, it is shown that H3O+, produced by hydrogen bis(1,2-dicarbollyl) cobaltate (HDCC) in the presence of water, interacts with valinomycin in 1,1,2,2-tetrachloroethane-d2 to give a relatively stable complex. The equilibrium constant K of the complex formation was derived from chemical shifts in 1H-NMR, its value being 5.9. The proton affinity constant estimated from this value taking into account HDCC dissociation is 10(5.3), i.e., high enough to be relevant under physiological conditions. Under suitable conditions there is a fast exchange of H3O+ between valinomycin molecules, the exchange correlation time being of the order of 10(-4) s. The instantaneous structure of the complex is slightly asymmetric, the H3O+ ion being strongly hydrogen-bonded to three of the six ester carbonyl groups and weekly bound to the residual ones by electrostatic interactions. This asymmetry is averaged by fast reorientation and displacement of H3O+ so that the molecule appears to be symmetric in the time window of NMR. The results indicate that valinomycin could serve as a carrier for proton transfer across a biological membrane.