Free Energy Gradient Method Research Articles

Chirality of Alanine Molecules in Water Solvent: A Theoretical Perspective

Sequential quantum mechanics/molecular mechanics (QM/MM) calculations combining the average solvent electrostatic configuration (ASEC) and the free energy gradient method are employed to locate minimum structures of α- and β-alanine in a water environment. Herein, we study the solvation effects in the nuclear magnetic resonance (NMR) spectroscopy, vibrational circular dichroism (VCD) spectroscopy, and electronic circular dichroism (ECD) spectroscopy of dl-α-alanine and β-alanine molecules. Our results point out that the ASEC-FEG (average solvent electrostatic configuration with the free energy gradient) method is a suitable approach for finding equilibrium structures of the alanine molecules in aqueous solution. Its accuracy is checked by comparing the optimized structures with those reached by the polarizable continuum model (PCM) and via experimental data. NMR parameters and vibrational and electronic UV-vis spectra are computed with a remarkable agreement with their corresponding experimental values.

Free energy gradient for understanding the stability and properties of neutral and charged L-alanine molecule in water

Amino acids exhibit their most important properties in aqueous environment in physiological conditions. These properties are related to their structural changes in water. Although several studies have been performed earlier for obtaining the structure of alanine in a solvent environment, an explicit consideration of the solvent molecular system is still in need. This work uses a Free Energy Gradient method to obtain the structures of alanine with an explicit consideration of the water environment. This is combined with a QM/MM method. Next, the electronic and vibrational properties of L-Alanine in water solution at different pH scales are obtained. The equilibrium structures of L-alanine are obtained in its neutral, anionic and cationic form. A systematic study of the solute-solvent hydrogen bonds was performed to predict the stability of neutral and charged L-alanine molecules. Quantum mechanical calculations were also performed to obtain the infrared spectrum, pH induced changes and to predict NMR parameters such as chemical shifts, magnetic shieldings and spin-spin coupling constants.

Solvation Structures and Deactivation Pathways of Luminescent Isothiazole-Derived Nucleobases: tzA, tzG, and tzI.

The photophysical relaxation pathways of tzA, tzG, and tzI luminescent nucleobases were investigated with the MS-CASPT2 quantum-chemical method and double-ζ basis sets (cc-pVDZ) in gas and condensed phases (1,4-dioxane and water) with the sequential Monte Carlo/CASPT2 and free energy gradient (FEG) methods. Solvation shell structures, in the ground and excited states, were examined with the pairwise radial distribution function (G(r)) and solute-solvent hydrogen-bond networks. Site-specific hydrogen bonding analysis evidenced relevant changes between both electronic states. The three luminescent nucleobases share a common photophysical pattern, summarized as the lowest-lying 1(ππ*) bright state that is populated directly after the absorption of radiation and evolves barrierless to the minimum energy structure, from where the excess of energy is released by fluorescence. From the 1(ππ*)min region, the conical intersection with the ground state ((ππ*/GS)CI) is not accessible due to the presence of high energetic barriers. By combining the present results with those reported earlier by us for the pyrimidine fluorescent nucleobases, we present a comprehensive description of the photophysical properties of this important class of new fluorescent nucleosides.

The influence of geometry relaxation in solution on the first hyperpolarizability of mesoionic compounds

Theoretical results for the linear and nonlinear properties of mesoionic compounds in solution are presented. The electronic properties in solvents were determined by carrying out Sequential QM/MM calculations by means of the average solvent electrostatic configuration (ASEC) and the Free Energy Gradient (FEG) methods. The results illustrate the role played by geometry relaxation in the electronic properties of mesoionic rings in environments. It is found that environment-induced geometric changes impact on the molecular electronic structure of the mesoionic ring. MP2/aug-ccpVDZ results for the first hyperpolarizability obtained in solution are substantially smaller than the gas phase results.

Photophysics of Emissive tzC[Isothiazolo‐Cytidine] and tzU[Isothiazolo‐Uridine] Pyrimidine Analogues

AbstractThe tzC and tzU emissive properties were investigated with the MS‐CASPT2 method and CASSCF/CASPT2 protocol, with inclusion of solvent effects with the aid of the PCM and Sequential QM/MM, the Free Energy Gradient methods. Theoretical vertical emission energies and Stokes shifts, using the ASEC‐FEG method, are in a good agreement with the experimental data, within the expected accuracy of CASPT2 method. Their emissive properties can be understood in analogy to the photophysical behaviour of the canonical uracil and cytosine pyrimidine nucleobases, for which the twisting of the C5C6 bond is the key for understanding their ultrashort radiationless decay times. For both tzC and tzU, the computed photophysical deactivation pathway, shows that the bright state goes directly to a minimum structure on its potential energy hypersurface , from where no conical intersection with the ground state can be reached, due to the steric hindrance of the C5C6 position, which forms the bridge between the rings in both molecules. Solvent effects place the conical intersection in higher energy region, reinforcing their emissive nature.

Microscopic Origin of Different Hydration Patterns of para-Nitrophenol and Its Anion: A Study Combining Multiconfigurational Calculations and the Free-Energy Gradient Method.

A theoretical study of the solvatochromic shifts of para-nitrophenol ( pNP) and para-nitrophenolate anion ( pNP-) in aqueous solution is presented using a QM/MM methodology with molecular dynamics simulation. The optimized structures in aqueous solution are obtained using both the polarizable continuum and the free-energy gradient methods. For pNP, the calculated redshifts at the CASPT2 (12,10) level are, respectively, 0.71 and 0.94 eV, in good agreement with the experimental ones (0.80-0.83 eV), whereas for pNP-, they are small. The difference between the solvatochromic shifts of pNP and pNP- is calculated as 0.71 eV in good agreement with the experimental one (0.79-0.81 eV). Finally, these shifts are understood in terms of the solvent effect on the solute structure, accurately calculated by the present theoretical treatment.

First hyperpolarizability of isomers of pyridinium N-phenoxide betaine dye in solution using the ASEC-FEG method

The linear and nonlinear properties of isomeric forms of pyridinium-N-phenoxide betaine dye were investigated in protic and aprotic solvents using atomistic simulations. We employed the sequential Quantum Mechanics/Molecular Mechanics (S-QM/MM) and the free energy gradient (FEG) methods to optimize the geometry of each isomer in chloroform, acetonitrile, methanol and water. The results show a complex dependence of the first hyperpolarizability with respect to the solvent nature and isomeric form, with a marked effect of conformational changes for para-betaine. Large contrasts of the first hyperpolarizability show a clear distinction between isomeric forms in solution that could be experimentally detected.

Zwitterionization of glycine in water environment: Stabilization mechanism and NMR spectral signatures.

At physiological conditions, myriads of biomolecules (e.g., amino acids, peptides, and proteins) exist predominantly in the zwitterionic structural form and their biological functions will result in these conditions. However these geometrical structures are inaccessible energetically in the gas phase, and at this point, stabilization of amino-acids in physiological conditions is still under debate. In this paper, the electronic properties of a glycine molecule in the liquid environment were studied by performing a relaxation of the glycine geometry in liquid water using the free energy gradient method combined with a sequential quantum mechanics/molecular mechanics approach. A series of Monte Carlo Metropolis simulations of the glycine molecule embedded in liquid water, followed by only a quantum mechanical calculation in each of them were carried out. Both the local and global liquid environments were emphasized to obtain nuclear magnetic resonance (NMR) parameters for the glycine molecule in liquid water. The results of the equilibrium structure in solution and the systematic study of the hydrogen bonds were used to discard the direct proton transfer from the carboxyl group to the ammonium group of the glycine molecule in water solution. The calculations of the Density Functional Theory (DFT) were performed to study the polarization of the solvent in the parameters of nuclear magnetic resonance of the glycine molecule in liquid water. DFT calculations predicted isotropic chemical changes on the H, C, N, and O atoms of glycine in liquid water solution which agree with the available experimental data.

Electronic structure and absorption spectra of fluorescent nucleoside analogues.

This work presents a systematic investigation of the electronic and conformational properties of five new fluorescent nucleobases belonging to the alphabet based on the isothiazole[4,3-d]pyrimidine molecule, very recently synthesized. This is of particular importance in the characterization of the main electronic aspects of these fluorescent nucleosides. The solvent effects of 1,4-dioxane and water were included combining the Sequential Monte Carlo/CASPT2 and the Free Energy Gradient (FEG) methods. For comparison, the Polarizable Continuum method was also used. The geometries of all compounds were optimized in solvent with the largest effects observed in water using the average solvent electrostatic configuration (ASEC) and the FEG approaches. Statistical analysis of the solute-solvent hydrogen bonds is performed and their effect on the absorption spectra analyzed. The dipole moments were calculated and the value obtained from the ASEC-FEG method in water follows the same trend as the natural canonical bases (adenine → uracil → guanine → cytosine). The theoretical results for the absorption spectra obtained from CASPT2(18,13) calculations using the geometries obtained with the ASEC-FEG procedure are in very good agreement with the experimental data. A detailed elucidation of the main aspects of the absorption spectra of the five new fluorescent nucleoside analogues is successfully attempted.

Temperature and Stress Dependence of Mobility of Screw Dislocation in BCC Iron

The Peierls stress and barrier of a screw dislocation in body-centered cubic iron at finite temperature is investigated by using the free energy gradient method. The Peierls barrier is shown to decrease from 12 to 5 meV per unit length of the Burgers vector with increasing temperature from 0 to 400 K. The entropy term of the Peierls barrier is estimated to be 0.2kB. The Peierls stress also decreases from 900 to 400 MPa with increasing temperature from 0 to 300 K. The change in the Peierls stress due to the entropic effect is larger than that of the Peierls barrier because of thermal softening.

Elucidating the structure of merocyanine dyes with the ASEC-FEG method. Phenol blue in solution.

The electronic structure of phenol blue (PB) was investigated in several protic and aprotic solvents, in a wide range of dielectric constants, using atomistic simulations. We employed the sequential QM/MM and the free energy gradient methods to optimize the geometry of PB in each solvent at the MP2/aug-cc-pVTZ level. The ASEC mean field is used to include the ensemble average of the solute-solvent interaction into the molecular hamiltonian, both for the geometry optimization and for the calculations of the electronic properties. We found that the geometry of PB changes considerably, from a polyene-like structure in nonpolar solvents to a cyanine-like in water. Moreover, and quite interestingly, in protic solvents with higher dielectric constant than water, the structure of the molecule is less affected and lies in an intermediate state. The results illustrate the important role played by hydrogen bonds in the conformation of merocyanine dyes.

Theoretical and experimental procedure for scaling-up RDF gasifiers: The Gibbs Gradient Method

The thermodynamic Model “Gibbs Free Energy Gradient Method” (GMM), published on the Vol. 90 (2011) of this Journal and validated with literature data, is now applied to the simulation of an experimental campaign realized at the ENEA Research Centre of Trisaia (Italy). The GMM well reproduces the experimental results of steam gasification of refuse-derived fuel (RDF) obtained on two laboratory and pilot scale rotary kilns.Consequently, the experimental syngas composition is put in relation to the main process parameters through a new approach incorporating the GMM for identifying a reliable correlation between the extent of reactions and the gasifier temperature. This correlation appears independent from the scale of the rotary kiln and the residence time in the investigated range of variables. On this basis, the GMM is adapted to become a tool for designing industrial gasifiers starting from experimental data since the required final composition of the syngas and the required performances may be obtained by designing a gasification zone operating at the temperature calculated by the proposed method. It is believed that this procedure is extendable to other geometries and different type of apparatus by studying and including the effect of other parameters.

Efficient Computational Research Protocol to Survey Free Energy Surface for Solution Chemical Reaction in the QM/MM Framework: The FEG-ER Methodology and Its Application to Isomerization Reaction of Glycine in Aqueous Solution.

In solution chemical reaction, we often need to consider a multidimensional free energy (FE) surface (FES) which is analogous to a Born-Oppenheimer potential energy surface. To survey the FES, an efficient computational research protocol is proposed within the QM/MM framework; (i) we first obtain some stable states (or transition states) involved by optimizing their structures on the FES, in a stepwise fashion, finally using the free energy gradient (FEG) method, and then (ii) we directly obtain the FE differences among any arbitrary states on the FES, efficiently by employing the QM/MM method with energy representation (ER), i.e., the QM/MM-ER method. To validate the calculation accuracy and efficiency, we applied the above FEG-ER methodology to a typical isomerization reaction of glycine in aqueous solution, and reproduced quite satisfactorily the experimental value of the reaction FE. Further, it was found that the structural relaxation of the solute in the QM/MM force field is not negligible to estimate correctly the FES. We believe that the present research protocol should become prevailing as one computational strategy and will play promising and important roles in solution chemistry toward solution reaction ergodography.

Combining ab initio multiconfigurational and Free Energy Gradient methods to study the π–π* excited state structure and properties of uracil in water

The Free Energy Gradient method is used to obtain the π–π* excited state structure of uracil in aqueous environment. The geometry calculations are made at the CASSCF level. The CASPT2 method is employed to calculate absorption and emission energies of uracil in gas and in aqueous solution. An average discrete electrostatic model is used to include the solvent effect. The results for the calculated absorption and emission transitions are found in good agreement with experiment both in gas phase and in water. The solvent effect on the Stokes shift is also calculated in good agreement with experiment. These agreements lend additional credence to the structures obtained for the lowest π–π* excited state.

Peierls Barrier of Screw Dislocation in bcc Iron at Finite Temperature

The Peierls barrier of a screw dislocation in body-centered cubic iron at finite temperature is investigated by using the free energy gradient method. By using the empirical potential, the Peierls barrier is shown to decrease from 11.7 to 6.9meV per unit length of the Burgers vector with temperature increasing from 0 to 300K. The entropy term of the Peierls barrier is estimated to be 0.19 kB, and the change of free energy, which is an entropic effect, is found to strongly depend on the local atomic configuration. [doi:10.2320/matertrans.M2014170]

Electronic Properties of Water in Liquid Environment. A Sequential QM/MM Study Using the Free Energy Gradient Method

There is a continuous search for theoretical methods that are able to describe the effects of the liquid environment on molecular systems. Different methods emphasize different aspects, and the treatment of both the local and bulk properties is still a great challenge. In this work, the electronic properties of a water molecule in liquid environment is studied by performing a relaxation of the geometry and electronic distribution using the free energy gradient method. This is made using a series of steps in each of which we run a purely molecular mechanical (MM) Monte Carlo Metropolis simulation of liquid water and subsequently perform a quantum mechanical/molecular mechanical (QM/MM) calculation of the ensemble averages of the charge distribution, atomic forces, and second derivatives. The MP2/aug-cc-pV5Z level is used to describe the electronic properties of the QM water. B3LYP with specially designed basis functions are used for the magnetic properties. Very good agreement is found for the local properties of water, such as geometry, vibrational frequencies, dipole moment, dipole polarizability, chemical shift, and spin-spin coupling constants. The very good performance of the free energy method combined with a QM/MM approach along with the possible limitations are briefly discussed.

Reaction path optimization and vibrational frequency analysis via ab initio QM/MM free energy gradient (FEG) method: application to isomerization process of glycine in aqueous solution

For the purpose to explore reaction paths accurately for chemical reaction systems in solution, we have proposed the free energy gradient (FEG) method combined with ab initio QM/MM–MD calculation, i.e., the ab initio QM/MM–FEG method. For demonstration, the method has been applied to the isomerization reaction of glycine in aqueous solution, i.e., the intramolecular proton transfer reaction from zwitterion (ZW) to the neutral form (NF). Including the solvent effect explicitly by the ab initio QM/MM–FEG method, those stable-state structures were found different from those obtained in gas phase and by an implicit dielectric continuum model at the same ab initio QM level. Additionally, by the vibration frequency analysis with the “free energy (FE)” hessian in solution, the calculated vibrational frequencies were in good agreement with the experimental ones in the range from low to middle frequency of ZW. Furthermore, the FE of activation from ZW to NF was found in very good agreement with not only the estimation by the Car-Parrinello MD method but also by the previous experimental one. It is concluded that the ab initio QM/MM–FEG method is promising and should provide a better description of chemical reaction systems in solution in comparison with a number of conventional approaches by using the mean field approximations.

The Gibbs Free Energy Gradient Method for RDF gasification modelling

Starting from an equilibrium model for gasification, this research group has devised a new mathematical model, the so called Gibbs Free Energy Gradient Method Model (GMM). This model permits to bypass the semi-qualitative view, typical of equilibrium models, which assume very restrictive hypotheses such as equilibrium state for all the reactions involved in gasification process, complete conversion of carbon matter, gasification products in gas phase only. GMM model overcomes these limitations providing a quantitative point of view, even though the hypothesis of no tar production affects both models.GMM model has been applied to RDF gasification, supplying reliable results in the gasification process analysis. Model computations in terms of gas yield, gas composition, low heating value and H2 yield, have been compared with literature results, showing that computed data are in good agreement with experimental ones.

A minimal implementation of the AMBER–GAUSSIAN interface for ab initio QM/MM‐MD simulation

For applying to a number of theoretical methodologies based on an ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics method connecting AMBER9 with GAUSSIAN03, we have developed an AMBER-GAUSSIAN interface (AG-IF), which can be one of the simplest architectures. In the AG-IF, only a few subroutines addition is necessary to retrieve the QM/MM energy and forces, obtained by GAUSSIAN, for solving a set of Newtonian equations of motion in AMBER. It is, therefore, easy to be modified for individual applications since AG-IF utilizes most of those functions originally equipped not only in AMBER but also in GAUSSIAN. In the present minimal implementation, only AMBER is modified, whereas GAUSSIAN is left unchanged. Moreover, a different method of calculating electrostatic forces of MM atoms interacting with QM region is proposed. Using the AG-IF, we also demonstrate three examples of application: (i) the QM versus MM comparison in the radial distribution function, (ii) the free energy gradient method, and (iii) the charge from interaction energy and forces.

On the Importance of Lennard–Jones Parameter Calibration in QM/MM Framework: Reaction Path Tracing via Free Energy Gradient Method for Ammonia Ionization Process in Aqueous Solution

Abstract The free energy gradient (FEG) method combined with the QM/MM–MD calculation has realized full-atomic structural optimization of the solute NH3–H2O molecule pair in aqueous solution, exploring successful tracing of the reaction path on the free energy surface from the neutral state (H3N–H2O) to the ionized (H4+N–O−H) through the transition state (H3N···H+···O−H). To reproduce accurately the structural change of the hydrated molecule pair, the LJ parameter calibration in the QM/MM nonelectrostatic interaction was essential for four kinds of QM solute species, i.e., OH−, H2O, NH3, and NH4+, treated in the NDDO-SSRP framework with the ab initio quality. Two linear interpolations of these calibrated LJ parameters optimized at the NSS and ISS were utilized in the path-dependent FEG calculation, as is common in the free energy perturbation treatment. After including the effects of the intramolecular entropic contribution and quantum tunneling, the free energies of activation and reaction were satisfactorily estimated to be 13.8 and 9.8 kcal mol−1 (1 kcal = 4.184 kJ), respectively. It is expected that far more agreement with the experimental values should be reasonably attained if the QM region were extended to three surrounding water molecules to take in the electron delocalization effect adequately.