Published: July 12, 2011 r2011 American Chemical Society 10147 dx.doi.org/10.1021/jp202850s | J. Phys. Chem. B 2011, 115, 10147–10153 ARTICLE pubs.acs.org/JPCB Microsolvation of Lysine by Water: Computational Study of Stabilized Zwitterion Tae-Kyu Hwang, Ga-Young Eom, Min-Seo Choi, Sung-Woo Jang, Ju-Young Kim, and Sungyul Lee* Department of Applied Chemistry, Kyung Hee University, Kyungki 446-701, South Korea Yonghoon Lee* Department of Chemistry, Mokpo National University, Muan-gun, Jeonnam 534-729, South Korea Bongsoo Kim* Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejon 305-701, South Korea I. INTRODUCTION Effects of solvation on the structures and reactivity of amino acids, both canonical 1À12 and zwitterionic, 10,13À20 have been under intensive study. One of the most intriguing questions concerning the solvation is: What are the effects of solvation on the relative stability of canonical and zwitterionic conformers? This has been addressed for a number of amino acids by examin- ing the relative stability of these two forms as a function of the number of microsolvating water molecules. 1À20 It is now agreed that the transition from a canonical conformer to a zwitterionic conformer starts with four to five water molecules 1,21,22 and the zwitterion is clearly preferable with more than seven water molecules. 23 Lysine (Lys) is the amino acid with a very basic side chain, which is second only to arginine. Although the canonical form of Lys is only observed in the gas phase, the presence of the strongly basic side chain may render different structural features of Lys. For example, a single cation may stabilize the Lys zwitterion, as it was observed that the stability of the zwitter- ionic form relative to the nonzwitterionic form of aliphatic amino acids is directly related to proton affinity. 24,25 The pre- sence of the amino group in the side chain may also give distinct effects of solvation on the relative stability of canonical vs zwitterionic conformers of Lys. Microsolvating water mol- ecules, for example, may interact with this basic amino group, influencing the proton transfer process from the carboxyl group. This structural feature may also allow the zwitterio- nic conformers of Lys to be stabilized under the influence of fewer water molecules than are ordinarily observed in other amino acids. In the present work, we examine LysÀ(H 2 O) n (n = 2, 3), predicting that the zwitterionic Lys becomes quasidegenerate with the canonical forms as a result of the solvating effects of three water molecules. We also study the canonical T zwitterion pathways to show that the two lowest energy zwitterionic and canonical conformers of LysÀ(H 2 O) 3 are not interconnected by direct routes. Because each of the two forms is kinetically correlated with other higher energy conformers of LysÀ(H 2 O) 3 , we suggest that both of them may be observed in jet-cooled low temperature gas phase. II. COMPUTATIONAL METHODS We employ the density functional theories (B3LYP 26,27 and wB97XD 28 ) with the 6-311++G* and the MP2/aug-cc-pvdz methods, as implemented in the GAUSSIAN 03 set of programs. 29 Received: March 28, 2011 Revised: July 6, 2011 ABSTRACT: We present calculations for LysÀ(H 2 O) n (n = 2, 3) to examine the effects of microsolvating water on the relative stability of the zwitterionic vs canonical forms of Lys. We calculate the structures, energies, and Gibbs free energies of the conformers at the B3LYP/6-311++G(d,p), wB97XD/6-311++G(d,p), and MP2/ aug-cc-pvdz levels of theory, finding that three water molecules are required to stabilize the Lys zwitterion. By calculating the barriers of the canonical T zwitterionic pathways of LysÀ(H 2 O) 3 conformers, we suggest that both forms of LysÀ(H 2 O) 3 may be observed in low temperature gas phase.