DFT Study of the Effects of Halogen Anions on the Stability of Alanine Zwitterion

Abstract

Alanine is the most abundant and important amino acid found in proteins, and is present on both the interior and exterior surface of proteins in contact with water. The structure of alanine has been studied both experimentally and theoretically by many researchers. Using a highpressure mass spectrometer (HPMS) and ab initio calculations, Wu et al. showed that certain organic ammonium ions are able to stabilize the zwitterionic structure of amino acids. Amino acids in aqueous solutions also exist in the zwitterionic form over a wide range of pH. However, they do not exist in the zwitterionic form in the gas phase. Zwitterions play an important role in variety of biological reactions. The electric fields of zwitterionic structures serve as the driving force that determines the activity of amino acids, peptides, and proteins. In particular, many drugs are present in their zwitterionic form and exhibit strong electrostatic interactions with protein receptors. Because of the instability of amino acid zwitterions in the gas phase, direct experimental evidence of their behavior is lacking; therefore, numerous attempts were made to stabilize gas-phase zwitterions. On the basis of ab initio calculations, Jensen et al. reported that two water molecules can stabilize the glycine zwitterion. Metalation and protonation also stabilize the amino acid zwitterions. Kass stabilized the zwitterionic glycine using oxalic and malonic dianions, which cannot exist independently in the gas phase. He also examined the utility of self-stabilized anionic species to stabilize amino acid zwitterionic structures. On the basis of this finding, and as continuation of our studies on organic radicals and alanine radical cations, we report the effects of halogen anions on the stability of the alanine zwitterion in this paper. All theoretical calculations on structures considered in this study were carried out with the Gaussian 09 series of programs. The relativistic effects play important roles in the Br and I elements, and accordingly their electrons near the nuclei are represented with the LanL2DZ basis set containing effective core potential (ECP). In accordance with ref 13, F and Cl elements were treated the same method as Br and I. DFT calculations were evaluated at the B3LYP level, and ab initio calculations were performed using the MP2 level of theory. Equilibrium geometries of each structures were fully optimized without any restriction on symmetries. Vibration frequencies were also calculated to confirm whether all the stationary points correspond to the true minima. The stationary structures were obtained by verifying if the harmonic frequencies for the local minimum were real. In this study, halogen anions (X = F−, Cl−, Br−, and I−) were used as the anionic stabilizer for zwitterionic alanine in the gas phase. Through interactions with binding sites of halogen anionic stabilizers (2X−), alanine zwitterions (AZW) can be stabilized and form AZW–2X− complexes. The dissociation energy (DE) of the AZW–2X− complexes were estimated using the following equation: