Study of the stepwise deprotonation reactions of glyphosate and the corresponding pKa values in aqueous solution.

Glyphosate (N-(phosphonomethyl)glycine) (Gph) is a herbicide that is broadly used in several countries. Its application to eliminate weeds may have the undesired effect of diminishing the metallic cations found in the soil (e.g., Ni(2+) and Zn(2+)), due to a complexation reaction that depends on the soil's pH. To better understand the molecular structures of glyphosate that are involved in such a complexation reaction, we have studied all possible glyphosate conformations in aqueous solution that may be involved in deprotonation reactions in the pH range from 2 to 11 using the polarizable continuum method (PCM). We have also compared direct (or absolute) methods to calculate pKa values, the cluster-continuum model and the proton-exchange scheme, using different thermodynamic cycles. The best result was achieved when using a proton-exchange scheme, which was able to properly reproduce three glyphosate experimental pKa values predicted for the glyphosate structures and conformations previously determined.

Specific rotation of monosaccharides: a global property bringing local information.

Carbohydrates generally occur in several conformations that may differ among themselves by energy values that are smaller than the accuracy of the most sophisticated theoretical methods used to determine them. In addition, the preferential orientations of the hydroxyl groups of these molecules cannot be identified by any experimental technique. Therefore, a method that is able to validate the absolute conformations (i.e., consisting of the orientations of the hydroxyl groups) of carbohydrates would be helpful to improve our knowledge about monosaccharides. SR has been used for this purpose, and here, we present a test to measure the specific rotation (SR) ability of a molecule that possesses not only many conformations, but also four adjacent chiral centers. The results show that the final SR value is a weighted average of a global property (obtained for each conformation), and the latter by its turn is influenced by each chiral center in a multi chiral system. By comparing the SR values calculated for the most abundant anomers of xylopyranose with those of the corresponding monochiral analogs obtained by saturation of three different chiral centers each time, the influence of each center on the global property is confirmed.

Polarimetry as a tool for the study of solutions of chiral solutes.

Optical rotation of aqueous solutions of D-levoglucosan was studied experimentally in the 0.03-4.0 mol L(-1) concentration range and a nonlinear concentration dependence of specific optical rotation (SR) was revealed. Discontinuities observed in the concentration plot of SR (at 0.1, 0.3, 0.5, 1.0, and 2.0 mol L(-1)) are well correlated with those found by static and dynamic light scattering and identify concentration ranges in which different solution domains (supramers) may exist. The average SR experimental value for a D-levoglucosan aqueous solution ([α]D(28) -58.5±8.7 deg dm(-1) cm(-3) g(-1)) was found to be in good agreement with values obtained by theoretical calculation (TD-DFT/GIAO) of SR for 15 different conformers revealed by conformational sampling at the PCM/B3LYP/6-311++G(2d,2p)//B3LYP/6-31+G(d,p) level, which were shown to be strongly affected by the solvation microenvironment (0, 1, 2, and 3 explicit solvent molecules considered) due to local geometrical changes induced in the solute molecule. This exceptionally high sensitivity of SR makes polarimetry a unique method capable of sensing changes in the structure of supramers detected in this study.

The anomeric effect: the dominance of exchange effects in closed-shell systems.

The origin of the anomeric effect has remained an open question. After Mo demonstrated that hyperconjugation is not responsible for the anomeric effect [Y. Mo, Nature Chem., 2010, 2, 666.], electrostatic interactions and Pauli repulsions have been at the center of this debate. In this work, the total energies of the most stable rotamers of the equatorial and axial anomers of fluoro, hydroxyl, cyano and amino groups in cyclohexane and 2-substituted tetrahydropyran rings are decomposed into their fundamental kinetic, electrostatic and exchange components. In this partitioning scheme, the differences in the total energies among the most stable rotamers of each anomer correlate very well with the differences in the exchange components, revealing that the anomeric effect has no electrostatic origin. Indeed, the anomeric effect is dominated by the exchange energy. This proposal for the origin of the anomeric effect brings new insights that, once incorporated, may improve qualitative chemical models. Implications of this new proposal for the origin of the anomeric effect on geometric parameters and solvation are also discussed.

Specific rotation as a property to validate monosaccharide conformations.

Specific rotation ([α](D)) values were calculated for the 15 conformations of xylopyranose that are the most stable in the gas phase and in aqueous solution. The effects of different theoretical descriptions and the medium on the geometry of the conformers and the [α](D) values are evaluated. Differences in [α](D) values found for the same conformer in all descriptions used were smaller than those found between any two different conformers in the same description. The difference between [α](D) values is prominent, even for two conformations that are distinguished from each other only by the orientation of one secondary hydroxyl group. This finding suggests that [α](D) values may potentially be used in the validation of monosaccharide conformations that are theoretically sampled.

Conformational study of methylphosphocholine: a prototype for phospholipid headgroups in membranes.

Phospholipid bilayers constitute the largest structural component of cell membranes, in which choline phospholipids are abundant. In this study, through a theoretical sampling on a methylphosphocholine (MePC) potential energy surface, a set of conformers was selected as a prototype for the membrane phospholipid head. We performed a detailed conformational study of such a prototype, both as an isolated moiety and in a solvated system. We used the polarizable continuum model (PCM) to account for solvation effects. We used a quantum-mechanical methodology based on density functional theory (DFT) and the 6-31G(d,p) basis set for the calculations. Through this methodology we were able to obtain a set of conformations that presented a mirror-image pattern, in good agreement with the experimental geometric values for the different phosphocholine derivatives. Potential curves for the main parameters of the dihedral space of MePC were obtained and are provided to guide future force-field parameterizations.

The (alpha-1,6) glycosidic bond of isomaltose: a tricky system for theoretical conformational studies.

Stable conformations of beta-isomaltose (alpha-D-glucopyranosyl-(1-->6)-beta-D-glucose) in gas-phase and aqueous solution are investigated in this study using quantum mechanical calculations. Conformational maps are calculated at HF/6-31G(d,p) level and lower energy structures are sampled in the most stable regions. Entropic and thermal corrections are considered and the Boltzmann population is obtained for conformers that are representative of the 18 most stable regions found on the potential energy surface. B3LYP/6-31+G(d,p) and B3LYP/6-311+G(2d,2p) calculations are used in conformational samplings. Solvation effects are considered through the polarizable continuum model approach. Hydroxymethyl group orientations are investigated for the most stable conformers. The influence of electronic correlation and solvation on the glycosidic linkage preference (TG, GT, and GG) and hydroxymethyl group orientation (tg, gt, and gg) are discussed. Heteronuclear spin coupling constants ((3)J(C,H)) along the glycosidic linkage are calculated and comparison with other theoretical results and experiments is used to validate the obtained structures.

A quantum mechanical strategy to investigate the structure of liquids: the cases of acetonitrile, formamide, and their mixture.

A computational strategy based on quantum mechanical (QM) calculations and continuum solvation models is used to investigate the structure of liquids (either neat liquids or mixtures). The strategy is based on the comparison of calculated and experimental spectroscopic properties (IR-Raman vibrational frequencies and Raman intensities). In particular, neat formamide, neat acetonitrile, and their equimolar mixture are studied comparing isolated and solvated clusters of different nature and size. In all cases, the study seems to indicate that liquids, even when strongly associated, can be effectively modeled in terms of a shell-like system in which clusters of strongly interacting molecules (the microenvironments) are solvated by a polarizable macroenvironment represented by the rest of the molecules. Only taking into proper account both these effects can a correct picture of the liquid structure be achieved.

The Optical Rotation of Glucose Prototypes: A Local or a Global Property?

In this work, we present a quantum-mechanical study of the optical rotation (OR) of model systems representing glucose prototypes with one and two chiral centers. The ONIOM method is used to evaluate the property and to analyze its local or global character. Different ONIOM partitions are tested and compared to better appreciate differences and similarities between mono- and bichiral prototypes. The local versus global character of OR is investigated and compared to other properties such as energies and nuclear magnetic shieldings, which have been deeply studied in previous applications of the ONIOM method.

A theoretical study of glucose mutarotation in aqueous solution.

In this work the mechanism of glucose mutarotation is investigated in aqueous solution considering the most likely pathways proposed from experimental work. Two mechanisms are studied. The first involves an intramolecular proton transfer as proposed by textbooks of organic chemistry, and the second uses one solvent water molecule to assist proton transfer. Both mechanisms are studied in the gas phase and in aqueous solution with the help of a polarizable continuum model, which is adopted to introduce the electrostatic nonspecific influence of bulk solvent. The structures are fully characterized through the calculation of the corresponding vibrational frequencies. The rate coefficients for each mechanism are calculated following transition-state theory in both the gas phase and in aqueous solution. Values computed for the water-assisted pathway in the continuum solvent agree best with the experimental results.

Parametrizing PCM to obtain solvation free energies from group contributions.

A parametrization methodology for evaluating the solvation free energy, using the polarizable continuum model implemented in Gamess software, is presented in a formulation which makes use of a group contribution conception to construct the cavities. The systems studied include alkanes, alcohols, aldehydes and ketones embeded in a continuous medium simulating the water as the solvent. For each family, the CH2, OH, and C=O moieties of atoms are put together in single spheres forming a group. The cavities are constructed in two different ways, one for the electrostatic component and the other for nonelectrostatic contributions, i.e., the cavitation, dispersion, and repulsion components of free energy of solvation. A multivariate analysis is performed to obtain an assembly of variables, for each homologous series, able to give the results which are close to experiment. The analysis is addressed in order to (i) compare the theoretical free energy of solvation with the experimental trends of the solutes in aqueous media, when the chain is increased, (ii) compare the behavior of each component of free energy with the increasing CH2 number, (iii) investigate the influence of the oxygen atom on the components, and (iv) quantify the relative contribution of each component to the final free energy of solvation for some homologous series.

On the generalized valence bond description of the anomeric and exo-anomeric effects: an ab initio conformational study of 2-methoxytetrahydropyran.

An ab initio conformational study of the alpha- and beta-glycosidic C1-O1 bonds has been carried out on the axial and equatorial forms of 2-methoxytetrahydropyran (2-MTHP) at the HF/6-31G(d,p) and GVB-PP/6-31G(d,p) levels of calculation. Six conformers of 2-MTHP were fully optimized at both levels. The calculations have shown that the conformer containing the (+sc) orientation around the axial C1-O1 bond is the most stable one and is favored over that bearing the (-sc) arrangement about the equatorial C1-O1 bond by 1.39 (HF) and 1.52 (GVB-PP)kcal/mol. The potential energy surfaces for rotating about the axial and equatorial C1-O1 bonds were constructed at the HF and GVB-PP levels. For each form of 2-MTHP the HF and GVB-PP potential curves exhibit similar profiles. This shows that both methods provide similar descriptions for the position of the conformational minima and for the values and location of the rotational barriers. In addition to the conformational study, a discussion concerning the nature of the chemical bond in acetal fragments and the origin of the anomeric and exo-anomeric effects is presented in terms of optimized non-orthogonal GVB orbitals of 2-MTHP. The intramolecular factors that respond for the order of stability and conformational changes in bond lengths of the conformers of 2-MTHP are examined in light of the GVB description. The problems associated with the use of the NBOs (natural bond orbitals) to analyze chemical bonding in the acetal fragments are discussed, and the choice for the GVB-PP description is justified.

Density functional study of the optical rotation of glucose in aqueous solution.

Optical rotation values were calculated for the eight most abundant structures of glucose in aqueous solution, following the TD-DFT/GIAO approach for the property and the PCM description for the solvent. The results show that all alpha structures give a large positive contribution to the OR property, while the beta structures give both positive and negative contributions. The good agreement of the calculated OR, obtained as a Boltzmann average of the property of the eight conformers, with experimental data proves the validity of the quantum-mechanical approach and of the solvent modelization.

Ab initio conformational maps for disaccharides in gas phase and aqueous solution.

Ab initio conformational maps for beta-lactose in both the gas phase and in aqueous solution have been constructed at the HF/6-31G(d,p) level of calculation. The results of the gas-phase ab initio calculations allow us to conclude that a rigid conformational map is able to predict the regions of the minima in the potential energy surface of beta-lactose, in full agreement with those found in the relaxed conformational map. The solvation effects do not give rise to any new local minimum in the potential energy surface of beta-lactose, but just change the relative Boltzmann populations of the conformers found in the gas-phase calculations. The values obtained for heteronuclear spin coupling constant (3J(H,C)), using the seven most stable conformers in solution are in good agreement with the available experimental values. This is a good indication that ab initio rigid conformational maps can be reliably used to sort the most stable conformers of beta-lactose.