7104
J. Phys. Chem. B 2008, 112, 7104–7110
Stabilization of Amino Acid Zwitterions with Varieties of Anionic Species: The Intrinsic Mechanism Gang Yang,†,‡ Yuangang Zu,*,† Chengbu Liu,‡ Yujie Fu,† and Lijun Zhou† Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry UniVersity, Harbin 150040, P. R. China, and Institute of Theoretical Chemistry, Shandong UniVersity, Jinan 250100, P. R. China ReceiVed: October 28, 2007; ReVised Manuscript ReceiVed: February 9, 2008; In Final Form: March 19, 2008
With high-level ab initio theoretical methods, varieties of novel anions (two monoanions and dianions with two binding sites) were explored to stabilize the glycine zwitterions. Unlike the malonic and oxalic dianions (J. Am. Chem. Soc. 2005, 127, 13098.), the presently found anions are self-stable and widely available, ensuring the direct and convenient applications to stabilize the zwitterions. Some of the complexes formed with the anions and glycine zwitterions have very large vertical dissociation energies (>500.0 kJ mol-1), implying that the contained anions can be used to stabilize much more unstable zwitterions than the glycine zwitterions. Further studies revealed that the stabilization effects are closely related with the proton-capturing capacities of the anions. In order to stabilize the glycine zwitterions, the proton affinity (PA) of the anionic species should fall within the range of 1567.0-1983.6 kJ mol-1 and, meanwhile, the proton-affinity differences of the two binding sites (∆PA) should be less than 104.2 kJ mol-1. The present results can be used to direct the efficient designs of the stabilizers to other amino acid zwitterions as well as other types of zwitterions. In addition, the density functional theory was used and compared with the default MP2 theory, with the details given in the discussions. 1. Introduction For amino acids in aqueous solutions, the zwitterionic structures predominate over the neutral structures within a wide range of pH.1,2 The zwitterions are usually present in form of NH3+-CHR-COO-, with the carboxyl deprotonated and one of the nitrogen atoms protonated. However, the situations are totally different in gas phase. The millimeter wave spectroscopy experiments3 and the measurements of substituent effects on gas-phase basicities1 suggested that glycine in gas phase does not exist in the zwitterionic form. The latter ab initio calculations indicate that the zwitterionic form of glycine is not even a local minimum on the potential energy surface, and that the gas-phase glycine is exclusively the nonionic tautomers.4–7 Zwitterions play an important role in varieties of biological processes.8 The electric fields of zwitterionic structures are the driving force that determines the function and activity of amino acids, peptides, or proteins. In addition, many drugs are present in the form of zwitterionic structures forming strong electrostatic interactions with the protein receptors.9 Due to the instabilities of amino acid zwitterions in gas phase, the direct experimental evidence of their behavior is lacking, and therefore numerous attempts were made to stabilize the gas-phase zwitterions.4,7,10–14 The ab initio calculations at MP2/DZP++//HF/DZP theoretical level4 revealed that two water molecules can stabilize the glycine zwitterion sufficiently to render it geometrically stable. Besides the addition of water molecules, metalation10,11 and protonation12 are another two conventional ways to stabilize the amino acid zwitterioins. Recently, Gutowski et al.7 attached an excess electron on the glycine zwitterion, making it a local minimum on the potential energy surface. The most striking results, we * Corresponding author. E-mail:
[email protected]. Fax: 00860451-82102082. † Northeast Forestry University. ‡ Shandong University.
think, are from the contributions of Kass.13 He stabilized the glycine zwitterionic structure with the oxalic and malonic dianions (-O2CCO2- and -O2CCH2CO2-, respectively). As he reported, neither of the oxalate and malonate dianions can exist independently in gas phase; instead, they will spontaneously lose an electron due to their negative electron binding energies.15 Accordingly, these two anionic stabilizers are more important to the theoretical researches rather than the practical uses. In this work, self-stable anionic species were explored to stabilize the amino acid zwitterionic structures. These anionic species should be ubiquitous and thus can be put into use directly and conveniently. On such basis, an in-depth study was carried out to research into the stabilizing mechanisms of anionic species of the amino acid zwitterions, which we believe is of great help to the stabilizations of other types of zwitterions as well as other amino acid zwitterions. 2. Computational Details 2.1. Theoretical Methods. All the calculations were performed under Gaussian 98 and 03 packages.16,17 The B3LYP and MP2 theoretical methods were employed: MP2 level of theory is the default and was used throughout except when specified, while B3YLP density functional level of theory only appears in Section 3.5 to clarify the B3LYP and MP2 differences in treating the anion-stabilized glycine zwitterions. In accordance with ref 13, the Aug-CC-pVDZ basis set18 was used for all the elements except P, S, Cl, Br, and I. The relativistic effects play significant roles in the Br and I elements, and accordingly their inner electrons are represented with the LanL2DZ effective core potentials (ECP), with the valence electrons described by LanL2DZ basis sets. The P, S, and Cl elements were treated the same way as Br and I, with the reasons provided in the Supporting Information. The natural bond orbital (NBO) pro-
10.1021/jp710394f CCC: $40.75 2008 American Chemical Society Published on Web 05/15/2008
Stabilization of Amino Acid Zwitterions
J. Phys. Chem. B, Vol. 112, No. 23, 2008 7105
SCHEME 1: Two Types of Anionic Species used to Stabilize the Amino Acid Zwitterions
gram,19 as implemented in Gaussian 98, was used to obtain the Wiberg bond indices (bond orders), which are a measure of bond strengths.20 To take into account the solvent effects, the self-consistent isodensity polarizable continuum model (SCI-PCM) of selfconsistent reaction field (SCRF)21 was employed. The reliabilities of this solvation model have been convinced by the previous studies, including the treatments of amino acids.22–24 2.2. Vertical Dissociation Energy. As shown in Scheme 1, the anionic stabilizers (AnS) can be two monoanions (e.g., Br+ I-) or dianions with double binding sites (e.g., SO42-). Through the interactions with the binding sites of certain anionic stabilizers, the glycine zwitterions (GZw) can be stabilized and thus form the GZw-AnS complexes. The vertical dissociation energy (VDE) was calculated with the equation below:25
VDE ) E(GZw) + E(AnS) - E(GZw-AnS)
(1)
where the energies of the GZw and AnS species were obtained on the geometries of GZw-AnS complexes. 2.3. Proton Affinity. As to the different anionic species (AnS), their proton-capturing capabilities may show differences, which was estimated with the proton affinity (PA).26
PA ) E(AnSH+) - E(AnS)
(2)
Here, AnSH+ stands for the protonated structure of the anionic species AnS. When the binding sites A and B are not identical, the proton affinities of these two binding sites will show differences (∆PA):
|∆PA| ) |∆PA(A) - PA(B) |
(3)
where PA(A) and PA(B) stand for the proton affinities of binding sites A and B, respectively. 3. Results and Discussion 3.1. Two Monoanions as the Stabilizers. The vertical dissociation energies (VDE) of the GZw-AnS complexes, proton affinities (PA) of the anionic stabilizers as well as the differences of the proton affinities between the A and B binding sites (∆PA) are given in Table 1. It can be found that two same halide anions can stabilize the glycine zwitterions, and the optimized GZw-2X– complexes are shown in Figure 1 (X ) F, Cl, Br or I). Their VDEs increase in the order 366.4 kJ mol-1 in GA01 (2I–) < 442.3 kJ mol-1 in GA03 (2Br–) < 508.2 kJ mol-1 in GA07 (2Cl–) < 517.9 kJ mol-1 in GA16 (2F–). This indicates that the halide anions with smaller atomic numbers have larger VDEs and thus can better stabilize the glycine zwitterions. Two unequal halide anions were also tried, and the theoretical results (Table 1 and Figure S6) showed that they are all successful stabilizers to the glycine zwitterions except the case with the F- and I- anions in GA09. As the geometryoptimization process goes on, the GA09 complex is gradually
TABLE 1: Vertical Dissociation Energies (VDE) of the GZw-AnS Complexes, Proton Affinities (PA) of the Anionic Stabilizers, as well as the Differences of the Proton Affinities between the A and B Binding Sites (∆PA)a GA01 GA02 GA03 GA04 GA05 GA06 GA07 GA08 GA09b GA10 GA11 GA12 GA13 GA14 GA15 GA16 GA17b GA18 GA19 GA20 GA21b GA22b GA23b GA24b GA25b
stabilizer
VDE
PA
∆PA
2IBr- + I2BrCl- + ICl- + Br(SCH2CHdCHCH2S)22ClCl-/SHF- + IF- + Br(OOCCHdCHCOO)2(OOCH2COO)2F- + Cl(OOCCOO)2SO422F(OCH2CH)CHCOS)2o-C6H4O22HPO32F-/OH(OCH2CHdCHCOO)2(OCH2CHdCHCH2O)2SO32CO32O22-
366.4 404.5 442.3 439.2 475.8 408.7 508.2 489.3
1653.7 1716.8 1728.8 1780.7 1793.5 1799.1 1806.5 1839.3
