Mendeleev Communications Electronic Version, Issue 2, 2000 (pp. 43–82) Stabilization of the glycine zwitterionic form by complexation with Na+ and Cl–: an ab initio study Ruslan M. Minyaev,* Andrei G. Starikov and Vladimir I. Minkin Institute of Physical and Organic Chemistry, Rostov State University, 344090 Rostov-on-Don, Russian Federation. Fax: +7 863 228 5667; e-mail: minyaev@ipoc.rsu.ru DOI: 10.1070/MC2000v010n02ABEH001259 Ab initio [MP2(full)/6-31G**] calculations predict that the glycine zwitterionic form bridged with NaCl is more stable than the isomeric complexes of the neutral forms.The zwitterionic form of amino acids dominates in the aqueous media of biological systems.1 Gas phase experimental data2–4 and numerous ab initio calculations4–9 show that the simplest amino acid glycine exists only in the neutral forms 1, 2 and 3, whereas the zwitterionic form 4 is not observed; that is, it does not correspond to a minimum on the potential energy surface (PES).Both theoretical and experimental studies2–8 point to the crucial role of medium effects on the existence and stability of the zwitterionic form of glycine. Recent ab initio calculations predict that the glycine zwitterionic form can be stabilised, i.e., corresponds to the minimum on the PES, when it forms an H-bonded cluster with at least two water molecules.5,6 At the same time, it is well known1 that in biological systems amino acids form salts and various complexes with alkali metals (Na+, K+),9,10 copper (Cu+)11,12 or other ions,1,13 which stabilise the zwitterionic form.Here, we report on ab initio [MP2(full)/6-31G**]14 calculations of glycine complexes 5–7 with the cation Na+, complexes 8–10 with the anion Cl– and complexes 11–13 with undissociated sodium chloride. Our results indicate that only complexation of a glycine molecule simultanuously with the two counterions Na+ and Cl– results in the stabilization of zwitterionic form 13 relative to isomeric complexes 11, 12 formed by neutral glycine.According to the MP2(full)/6-31G** calculations, all structures 5–13 correspond to minima (l = 0, hereafter l designates the number of hessian negative eigenvalues at a given stationary point) on the PES. Various other possible structures of the complexes have also been studied but have been found to correspond to the stationary points with l � 1.Therefore, they are not considered here. The calculated molecular structures, geometries and energy parameters of complexes 5–13 are given in Figure 1 and Table 1. The counterions Na+ and Cl– stabilise glycine zwitterionic forms 7 and 10, respectively, i.e., calculations predict the correspondence to local minima on the PESs. However, complex 7 is less stable than the neutral form of glycine 5 and 6, and anionic complex 10 is less stable than 8, 9.Only the cooperative influence of the two counterions makes the zwitterionic form 13 preferred in energy (0.5 kcal mol–1) as compared to the most stable complex of the neutral form of glycine 11. Accounting for ZPE makes the zwitterionic form less stable than the neutral form 11 by 0.5 kcal mol–1.The same tendency is observed for relative enthalpy, whereas the behaviour of the relative free energy (DG) coincides with that of the relative free energy (DE). The complexation energy of 13 calculated without accounting for a basis set superposition error (BSSE)15 is 32.9 kcal mol–1. We will compare it with the value 32.4 kcal mol–1 for the complexation energy of the neutral form 11 (in both cases, complexation energies are estimated as the difference {Etot(13 or 11) – – [Etot(1) + Etot(NaCl)]}, where Etot is the total energy of 13, 11, 1 or NaCl, respectively). Note that the C1-structure of 13 is skewed toward a helical form (see Figure 1).The geometric parameters of glycine forms 1 and 2 are markedly changed under complexation with NaCl: all valent bonds participating in interactions with Na and Cl are elongated by ~0.03 Å, as is the NaCl N O O H H H H H N O O H H H H H N O O H H H H H N O O H H H H H 1, Cs 2, C1 3, C1 4 N O O H H H H H N O O H H H H H N O O H H H H H 5, C1 6, Cs 7, Cs Na+ Na+ Na+ N O O H H H H H N O O H H H H H N O O H H H H H 8, Cs 9, C1 10, C1 Cl– Cl– Cl– N O O H H H H H N O O H H H H H N O O H H H H H 11, Cs 12, C1 13, C1 Na Cl Cl– Na Cl Na+ N 2.010 2.466 99.9 2.245 1.24 1 112.1 178.6 1.006 C C O O Cl Na 1.314 1.517 122.0 116.0 1.447 11, Cs O C O N C Na Cl 1.011 1.012 1.466 1.089 2.480 1.522 0.997 1.232 1.321 2.244 2.452 N Na Cl O C O C 1.253 1.543 1.490 1.275 1.066 1.960 2.572 2.374 2.385 12, C1 13, C1 Figure 1 Geometry parameters of glycine complexes with NaCl 11, 12 and 13, as calculated by the MP2(full)/6-31G** method. Bond lengths and angles are given in angström units and degrees, respectively.Mendeleev Communications Electronic Version, Issue 2, 2000 (pp. 43–82) distance increased on 0.1 Å. It should be noted that the electric dipole moment of the zwitterionic form of complex 13 (3.84 D) is smaller than that of 11 (6.83 D) and 12 (5.10 D) by a factor of about two.This fact testifies to a partial screening of the charges on the NH3 + and CO2 – groups in the complex. In conclusion, the calculations show that the counterions not only stabilise the zwitterionic form of glycine but also convert it to the dominating form in the complex with NaCl. Obviously, the zwitterionic form of glycine in biological systems is stabilised by interactions with both water molecules and counterions. The cooperative medium effect can increase the zwitterionic stability.This work was supported by the Russian Foundation for Basic Research (grant no. 98-03-33169a). V. I. 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H. van Lenthe, Chem.Rev., 1994, 94, 1873. aEtot and DE are the total and relative energies (1 a.u. = 627.5095 kcal mol–1); DEZPE is the relative energy including a harmonic zero-point correction; DH is the relative enthalpy; DG is the relative free energy; w1 is the smallest vibration frequency. bThermochemistry data are given at T = 298.15 K and P = 1 atm. Table 1 Ab initio MP2(full)/6-31G** data for the structures of 5–13.a Structure Etot/a.u. DE/kcal mol–1 DEZPE/kcal mol–1 DHb/kcal mol–1 DGb/kcal mol–1 w1/cm–1 5, C1 –445.40111 0 0 0 0 85 6, Cs –445.39513 3.75 2.94 3.04 4.84 80 7, Cs (ZW) –445.39686 2.67 2.80 2.80 2.51 102 8, C1 –743.36694 0 0 0 0.48 43, C1 –743.36631 0.39 1.34 1.16 0 34 10, C1 (ZW) –743.36347 2.18 2.71 2.44 1.62 80 11, Cs –905.26099 0.50 0 0 2.84 41 12, C1 –905.25422 4.75 4.73 4.70 6.82 40 13, C1 (ZW) –905.26178 0 0.47 0.01 0 92 Received: 29th December 1999; Com. 99/1585