Metal ion complexation modulates gas-phase acidity of amino acids and their membrane diffusion properties: a combined DFT–MD study

Advances in computational methods, such as density functional theory (DFT) calculations combined with molecular dynamics (MD) simulations, have enabled chemists to gain more precise insights into molecular behavior at the microscopic level. DFT methods allow detailed examination of interactions between species, such as alkali metal ions and amino acids, and enable evaluation of how these ions influence the gas-phase acidity of amino acids. MD simulations, in turn, provide insight into how amino acid–metal ion complex formation affects interactions with biological membranes. This study aims to identify periodic trends in how alkali metal ions affect the gas-phase acidity of amino acids such as aspartic acid, glutamic acid, asparagine, glutamine, and cysteine. Importantly, the work is not limited to alkali metal ion complexation; we also investigate the influence of Zn²⁺ as a representative transition metal ion on the gas-phase acidity of these amino acids. This comparison allows us to systematically distinguish between the effects of alkali and transition metal ions. In addition, we investigate how amino acid–metal ion complexation affects membrane interactions and diffusion behavior. For this purpose, a dipalmitoylphosphatidylcholine (DPPC) bilayer was used as a membrane model, and molecular dynamics simulations were performed using GROMACS to gain mechanistic insight into these processes.