Effects of external ions on the energetics of proton transfer in hydrogen-bonded systems modelling a membrane-active drug–receptor interaction

Abstract

Ab initio(3-21G) molecular orbital calculations were performed on model systems HCO^–₂⋯⁺HNH₂CH₃, CH₃CO^–₂⋯⁺HNH₂CH₃ and H₂PO^–₄⋯⁺HNH₂CH₃ to investigated the hydrogen bonds and proton transfer between the amine part of antiarrhythmics and polar groups of the cardiac membrane. The effect of specific complexation of the anionic part of those complexes by cations H⁺, Li⁺ and Na⁺ was also investigated. For the isolated systems two-minima potential functions (at R_O⋯N= 2.75 Å) were found. The most stable minimum corresponds to the neutral O—H⋯N bond. The coordination of small cations caused dramatic changes in the stability of two H-bonded structures. The most stable minima on the proton potential curves of the systems containing cations correspond to the charged O^–⋯⁺HN structures.