A Combined Experimental and Quantum Chemical Study on the Putative Protonophoric Activity of Thiocyanate

¹ Institut für Biochemie, Otto-von-Guericke-Universität Magdeburg
² Laboratorio de Quimica Computacional Teorica, Universidad de la Habana
³ Institut für Organische Chemie, Technische Universität Dresden

^* To whom correspondence should be addressed. E-mail: peter.schoenfeld{at}medizin.uni-magdeburg.de.

Submitted on January 4, 2005
Revised on February 18, 2005
Accepted on 2 June 2005

	Abstract

Inhibition of gastric acid secretion by thiocyanate is explained by a protonophoric mechanism, assuming that thiocyanate induces a H+ back flux from the acidic gastric lumen into the parietal cells of gastric mucosa. Protonophoric activity of thiocyanate was examined by swelling measurements using rat liver mitochondria, and theoretically by quantum chemical methods. Mitochondria suspended in K-thiocyanate medium plus nigericin (a H/K-exchanger) swelled when the medium-pH was acidic, indicating that SCN- initiates a transfer of H+ across the inner membrane. To rationalize the protonophoric activity of thiocyanate, we considered the dehydra-tion of SCN- to be critical for transmembranal H+ transfer. For modelling this process, various hydrate clusters of SCN- and Cl- were generated and optimized by density functional theory (DFT) at the B3-LYP/6-311++G(d,p) level. The cluster hydration energy was lower for SCN- than for Cl-. The total Gibbs free energies of hydration of the ions were estimated by a hybrid supermolecule-continuum approach based on DFT. The calculated hydration energies also led to the conclusion that SCN- is less efficiently solvated than Cl-. Due to the more easy removal of the hydration shell of SCN- relative to Cl-, SCN- is favoured in going across the membrane giving rise to the protonophoric activity.

Key Words: cluster hydration energies, density functional theory, hydrate structures, polarizable continuum model, thiocyanate, total hydration energies.