Zwitterionic Forms Of Glycine Research Articles

Molecular interactions of 2′-deoxyguanosine 5′-monophosphate with glycine in aqueous media probed via concentration and pH dependent Raman spectroscopic investigations and DFT study

In order to gain insights into nucleotide-protein interaction, the molecular interaction of glycine (Gly) with 2'-deoxyguanosine 5'-monophosphate (dGMP) was monitored in aqueous media through Raman spectroscopic measurements and density functional theory (DFT) calculations. Raman spectra of dGMP, glycine and their binary mixtures (dGMP + Gly) in aqueous media at 10 different concentrations corresponding to the dGMP : Gly molar ratios varying from 1 : 1 to 1 : 10 were recorded in the fingerprint region 2000-400 cm(-1). Raman spectra of the dGMP : Gly mixture with a molar ratio of 1 : 3 in aqueous media at 10 different pH values starting from 1 to 10 at an interval of 1 were also recorded. The DFT calculations were performed on dGMP, glycine and their various complexes with varying number of H(2)O molecules in gas phase as well as in solvation using hybrid functional B3LYP employing the high level basis set 6-311+G(d,p). The variations in the observed spectral features were explained in terms of calculated optimized structures of dGMP, glycine and their various complexes with water molecules and a good spectra-structure correlation was obtained. Raman spectra of glycine in 1.2 M aqueous solution were also recorded at three pH values, 2, 6 and 10, and the subtle differences in the spectral features were correlated with the calculated Raman spectra of protonated, deprotonated and zwitterionic forms of glycine. The results also give experimental evidence rather convincingly that the zwitterionic and protonated forms of glycine are formed at pH = 6 and 2, respectively, but even at pH = 10, deprotonated glycine is not formed. An important aspect of this study is the monitoring of the interaction of dGMP with the zwitterionic form of glycine giving insightful details regarding the binding site.

A theoretical investigation of the relative stability of hydrated glycine and methylcarbamic acid—from water clusters to interstellar ices

We have theoretically investigated how the low-energy conformers of the neutral and the zwitterionic forms of glycine as well as methylcarbamic acid are stabilized by the presence water. The MP2/6-311++G(d,p) method was utilized to conduct calculations on glycine and methylcarbamic acid in both isolated clusters and in clusters embedded in the conductor-like polarizable continuum model (C-PCM), where the clusters explicitly contain between one and ten water molecules. The neutral forms of glycine and methylcarbamic acid were found to have similar hydration energies, whereas the neutral methylcarbamic acid was determined to be approximately 32 kJ mol(-1) more stable than the neutral glycine in the isolated clusters and 30 kJ mol(-1) more stable in the C-PCM embedded clusters. Both the number and strength of the hydrogen bonding interactions between water and the zwitterions drive the stability. This lowers the relative energy of the glycine zwitterion from 50 kJ mol(-1) above neutral glycine, when there are two water molecules in the clusters to 11 kJ mol(-1) below for the clusters containing ten water molecules. For the methylcarbamic acid clusters with two water molecules, the zwitterion is 51 kJ mol(-1) higher in energy than the neutral form, but it remains 13 kJ mol(-1) above the neutral methylcarbamic acid in the clusters containing ten water molecules. When the bulk water environment is simulated by the C-PCM calculations, we find both the methylcarbamic acid and glycine zwitterionic forms have similar energies at 20 kJ mol(-1) above the neutral methylcarbamic acid energy and 10 kJ mol(-1) lower than the neutral glycine energy. Although neither methylcarbamic acid nor glycine have been detected in the interstellar medium yet, our findings indicate that methylcarbamic acid is the more stable product from methylamine and carbon dioxide reactions in a water ice. This suggests that methylcarbamic acid likely plays a role in the intermediate steps if glycine is formed in the interstellar medium.

Neutral vs Zwitterionic Glycine Forms at the Water/Silica Interface: Structure, Energies, and Vibrational Features from B3LYP Periodic Simulations

B3LYP periodic calculations with a triple-xi-polarized Gaussian basis set have been used to study adsorption of glycine on a hydroxylated silica surface (2.2 OH/nm2) model derived from the (001) surface of edingtonite. The simulation envisages glycine adsorbed either as a gas-phase molecule or when microsolvated by up to five H20 molecules. Both neutral and zwitterionic forms of glycine have been considered and their structural, energetic, and spectroscopic vibrational features compared internally and with experiments. As a gas phase glycine sticks in its neutral form at the silica surface, the zwitterion being highly unstable and with transition-state character. When glycine is microsolvated at the silica interface, two H20 molecules render the zwitterion population comparable to that of the neutral form whereas with four H2O molecules the neutral glycine population is wiped out in favor of the zwitterion. With four H20 molecules the most stable structure shows no direct contact between glycine and the silica surface, H20 acting as a mediator via H-bond interactions. The B3LYP energies and structural data were also supported by comparing the scaled harmonic vibrational features with literature FTIR data of glycine adsorbed on an amorphous silica surface either from the gas phase or in water solution.

Nature of Glycine and Its α-Carbon Radical in Aqueous Solution: A Theoretical Investigation.

Quantum chemistry calculations and classical molecular dynamics simulations have been used to examine the equilibria in solution between the neutral and zwitterionic forms of glycine and also of the glycyl radical. The established preference (by 30 kJ mol(-1)) for the zwitterion of glycine was confirmed by both the quantum chemical calculations and the classical molecular dynamics simulations. The best agreement with experiment was derived from thermodynamic integration calculations of explicitly solvated systems, which gives a free energy difference of 36.6 ± 0.6 kJ mol(-1). In contrast, for the glycyl radical in solution, the neutral form is preferred, with a calculated free energy difference of 54.8 ± 0.6 kJ mol(-1). A detailed analysis of the microsolvation environments of each species was carried out by evaluating radial distribution functions and hydrogen bonding patterns. This analysis provides evidence that the change in preference between glycine and glycyl radical is due to the inherent gas-phase stability of the neutral α-carbon radical rather than to any significant difference in the solvation behavior of the constituent species.

A novel quantum mechanical/molecular mechanical approach to the free energy calculation for isomerization of glycine in aqueous solution

The free energy change associated with the isomerization reaction of glycine in water solution has been studied by a hybrid quantum mechanical/molecular mechanical (QM/MM) approach combined with the theory of energy representation (QM/MM-ER) recently developed. The solvation free energies for both neutral and zwitterionic form of glycine have been determined by means of the QM/MM-ER simulation. The contributions of the electronic polarization and the fluctuation of the QM solute to the solvation free energy have been investigated. It has been found that the contribution of the density fluctuation of the zwitterionic solute is estimated as -4.2 kcal/mol in the total solvation free energy of -46.1 kcal/mol, while that of the neutral form is computed as -3.0 kcal/mol in the solvation free energy of -15.6 kcal/mol. The resultant free energy change associated with the isomerization of glycine in water has been obtained as -7.8 kcal/mol, in excellent agreement with the experimental data of -7.3 or -7.7 kcal/mol, implying the accuracy of the QM/MM-ER approach. The results have also been compared with those computed by other methodologies such as the polarizable continuum model and the classical molecular simulation. The efficiency and advantage of the QM/MM-ER method has been discussed.

A theoretical study of solvent effects on the conformational equilibria of neutral glycine in aqueous solution

In this work conformational equilibrium of neutral glycine in solution is systematically investigated by using DFT and MP2 methods combined with solvent continuum models. A systematic exploration of the potential energy surface and full geometry optimizations for several conformers have been carried out in the gas phase and aqueous solution at the MP2/6-31+G** and B3LYP/6-31+G** levels. Zero-point and thermal contributions to the free energy have been obtained at the B3LYP level. Both theoretical levels lead to very similar results, in geometrical and energetic terms, both in the gas phase and in solution. Solvent effects play an important role on the conformational equilibria of neutral glycine; so the absolute free energy minimum in solution is not the same as in the gas phase. The changes found when passing from gas phase to aqueous solutions can have important consequences also on the tautomeric equilibrium between the neutral and zwitterionic forms of glycine.

An integrated effective fragment—polarizable continuum approach to solvation: Theory and application to glycine

A new discrete/continuum solvation model has been developed by combining the effective fragment potential (EFP) for the discrete part and the polarizable continuum model (PCM) for the continuum part. The usefulness of this model is demonstrated by applying it to the calculation of the relative energies of the neutral and zwitterionic forms of glycine. These calculations were performed by treating glycine with ab initio wave functions. Water clusters were treated with both ab initio and EFP methods for comparison purposes, and the effect of the continuum was accounted for by the PCM model. The energy barrier connecting the zwitterionic and neutral three-water clusters was also examined. The computationally efficient EFP/PCM model gives results that are in close agreement with the much more expensive full ab initio/PCM calculation. The use of methods that account for electron correlation is necessary to obtain accurate relative energies for the isomers of glycine.

A direct-dynamics study of the zwitterion-to-neutral interconversion of glycine in aqueous solution

The mechanism of interconversion between the neutral and zwitterionic forms of glycine in aqueous solution is studied theoretically. It is argued that indirect transfer via a water bridge is a plausible alternative to the generally assumed direct transfer mechanism. The argument is based on model calculations in which the system glycine-water is represented by a 1:6 supermolecule embedded in a dielectric continuum. Optimized geometries and vibrational frequencies are obtained at the Hartree–Fock level with a 6-31G* basis set, and at the second-order Mo/ller–Plesset frozen-core level with the 6-31+G* basis set for the neutral and zwitterionic forms, and for their transition state. At both levels the energetics are corrected by single-point quadratic configuration interaction calculations, including single and double substitutions with frozen-core inner-shell orbitals. Both models reproduce the observed endothermicity of the transfer better than models that use only a limited number of discrete water molecules without a continuum and models solely based on the continuum approximation. In the optimized structures of this complex and of complexes with fewer water molecules, one of the water molecules always bridges the two functional groups. In the 1:6 complex, two of the other water molecules form hydrogen bonds with the amino hydrogens, two others with the carboxyl oxygens, and the sixth water molecule forms a bridge between the two water molecules attached to the amino group. The interaction of this supermolecule with the bulk solvent is treated by means of the Onsager model. The transition state calculated with the two models implies that the mechanism of interconversion is concerted transfer of two protons along the amino–water–carboxyl bridge. The dynamics calculations are performed with a multidimensional instanton model that includes solvent reorganization. For both models the calculated transfer rate constants are about an order of magnitude larger than the observed rate constants, indicating that the indirect mechanism can easily account for the observed dynamics. These results confirm the plausibility of the indirect mechanism of proton transfer via a water bridge in aqueous solutions of glycine.

A combined discrete/continuum solvation model: Application to glycine

A new solvation model that combines discrete and continuum descriptions of the solvent has been developed. The discrete solvent molecules are represented by effective fragment potentials (EFP), while the continuum is represented by the Onsager model. This (EFP+Onsager) model has been applied to the relative stabilities of the neutral and zwitterionic forms of glycine. Other supermolecule-continuum calculations were also performed, using quantum mechanical discrete waters and the isodensity polarizable continuum model (IPCM) or solvation model 5.42R (SM5.42R) for the continuum. It is shown that the Onsager model provides a poor description of the solvent in the supermolecule-continuum calculations. On the other hand, more sophisticated models can predict the correct energy order of the glycine isomers. Thus, the development of mixed methods that combine sophisticated continuum models with the discrete EFP model appear to be promising.

Computed molecular surface electrostatic potentials of the nonionic and zwitterionic forms of glycine, histidine, and tetracycline

Computed molecular surface electrostatic potentials of the nonionic and zwitterionic forms of glycine, histidine, and tetracycline

Computed molecular surface electrostatic potentials of the nonionic and zwitterionic forms of glycine, histidine, and tetracycline

Three different procedures (HF/STO-3G, HF/3-21G, and B3P86/6-31+G**) were used to compute the electrostatic potentials on the molecular surfaces of glycine, histidine, tetracycline, and their zwitterions. These surface potentials were characterized in terms of a group of statistically defined quantities, which include the average deviation, the positive and negative average potentials, variances and extremes, and a balance parameter. The results were found to be qualitatively reasonably independent of the computational procedure. The zwitterions have much greater internal charge separations than the nonionic forms, although this is progressively diluted as the system increases in size. The statistical properties of the surface potentials permitted the determination of the solvation energetics of both the nonionic forms and the zwitterions. © 2000 John Wiley & Sons, Inc. Int J Quant Chem 80: 1216–1223, 2000

Potential Energy Function for Intramolecular Proton Transfer Reaction of Glycine in Aqueous Solution

An analytical potential function of the glycine−water system, which can describe not only a reactive potential energy surface but also the interaction energy with water, has been proposed, by the empirical valence bond method with the exchange matrix element improved by Chang and Miller to reproduce an ab initio molecular orbital (MO) surface with high accuracy. The fitted potential function can reproduce satisfactorily the Born−Oppenheimer adiabatic surface obtained by ab initio MO calculations. Further, by molecular dynamics (MD) simulation and the free energy perturbation theory, we have presented the average of the interaction energy of glycine with water and the free energy profile of its intramolecular proton transfer reaction along the intrinsic reaction coordinate. It has been found that the zwitterionic form of glycine is much more stable than the neutral form, which is consistent with the result of Clementi et al. We obtained the free energy change of the reaction and that of activation to be 8....

Experimental determinations of diffusion coefficients in dilute aqueous solution using the method of hydrodynamic stability.

Diffusion coefficients were experimentally determined in dilute aqueous solution at 25 +/- 0.1 degrees C, ionic strength 0.5 M, using Taylor's method of hydrodynamic stability. The methodology described is accurate enough to show significant differences in diffusion coefficients between the various ionic forms of the same species as a function of degree of ionization. In Taylor's method, diffusion coefficients were measured by allowing two solutions of differing solute concentration to contact in a capillary tube, forming a stable, measurable concentration gradient. The solute diffusion coefficient is a function of the gradient, the solution viscosity, the solution density, and some capillary dimensions. Viscosity was maintained constant across experiments and values of sufficient accuracy were available in the literature. Solution densities were measured with a tuning fork densimeter. Compounds studied were o-aminobenzoic acid, benzoate anion, the four forms of phosphate and citrate, and the zwitterionic forms of glycine, diglycine, and triglycine. Based on the results for the four forms of phosphate and citrate, experimental diffusivity values vary with the ionic state of the diffusant, presumably because of the altered state of hydration as charge varies. For the glycine series, the diffusivity showed an unexpected dependency on molecular weight (size).

X-ray photoelectron and infrared spectroscopy of glycine adsorbed upon copper

Glycine adsorbed on polycrystalline copper has been studied by angle-dependent X-ray photoelectron spectroscopy, XPS(θ), and infrared reflection absorption spectroscopy, IRAS. At −50°C the molecule adsorbs with its molecular identity intact. Upon heating to 30°C the glycine molecule slowly decomposes on the copper surface. The adsorbate held at −50°C is compared with a thin film of glycine, which is known to be zwitterionic. The binding energy shifts, the intensity ratios in the N(1 s), C(1 s), and O(1 s)XPS(θ) spectra, and the infrared spectra of the adsorbate show that the glycine molecule coordinates with both the nitrogen and the two oxygen atoms to the copper surface. The amino group exists as an −NH 2 group in the adsorbate rather than as an −NH 3 +, which is the case in the zwitterionic form of glycine. This result is in contrast with the molecular orientation of glycine on hydrophilic gold, silicon, and highly oriented pyrolytic graphite (HOPG).

Monte Carlo simulation studies of the solvation of ions. 2. Glycine zwitterion

A Monte Carlo (MC) simulation has been carried out on the zwitterionic form of glycine in water, using TIP4P potentials for water and analogous potentials for the solute. In the conformation considered an intramolecular H bond between one of the carboxyl oxygens and one of the ammonium hydrogens is present, that prevents an intermolecular H bond with solvent for both atoms. As in the case of the solvation of the individual ions, analysis of the water structure around the solute suggests four types of water: (a) those tightly bound to the oxygens of the carboxyl group; (b) those tightly bound to the hydrogens of the ammonium group; (c) hydrophobically bound waters near the methylene group and (d) bulk waters. An enthalpy of solvation of −70 kcal/mol is calculated, in reasonable agreement with the experimental value.

The acid dependent dissociation of glycinatocopper(II) ion: Evidence for zwitterion reactivity

The dissociation of glycinatocopper(II) ion has been observed by stopped-flow spectrophotometry at 675 nm between pH 1.5 and 2.9 to follow the rate law kobs = k−1+kH[H+] with k−1 = 41±19 s−1 and kH = (7.6±1.1)×103M−1, s−1 at 25°C. The results indicate, Through application of the principle of microscopic reversibility, that the zwitterionic form of glycine cannot be ignored in the kinetics of the complex formation reaction.