Reactive Dynamics and Spectroscopy of Hydrogen Transfer from Neural Network-Based Reactive Potential Energy Surfaces

The in silico exploration of chemical, physical and biological systems requires accurate and efficient energy functions to follow their nuclear dynamics at a molecular and atomistic level. Recently, machine learning tools gained a lot of attention in the field of molecular sciences and simulations and are increasingly used to investigate the dynamics of such systems. Among the various approaches, artificial neural networks (NNs) are one promising tool to learn a representation of potential energy surfaces. This is done by formulating the problem as a mapping from a set of atomic positions $\mathbf{x}$ and nuclear charges $Z_i$ to a potential energy $V(\mathbf{x})$. Here, a fully-dimensional, reactive neural network representation for malonaldehyde (MA), acetoacetaldehyde (AAA) and acetylacetone (AcAc) is learned. It is used to run finite-temperature molecular dynamics simulations, and to determine the infrared spectra and the hydrogen transfer rates for the three molecules. The finite-temperature infrared spectrum for MA based on the NN learned on MP2 reference data provides a realistic representation of the low-frequency modes and the H-transfer band whereas the CH vibrations are somewhat too high in frequency. For AAA it is demonstrated that the IR spectroscopy is sensitive to the position of the transferring hydrogen at either the OCH- or OCCH$_3$ end of the molecule. For the hydrogen transfer rates it is demonstrated that the O-O vibration is a gating mode and largely determines the rate at which the hydrogen is transferred between the donor and acceptor. Finally, possibilities to further improve such NN-based potential energy surfaces are explored. They include the transferability of an NN-learned energy function across chemical species (here methylation) and transfer learning from a lower level of reference data (MP2) to a higher level of theory (pair natural orbital-LCCSD(T))

Transfer-Learned Potential Energy Surfaces: Towards Microsecond-Scale Molecular Dynamics Simulations in the Gas Phase at CCSD(T) Quality

The rise of machine learning has greatly influenced the field of computational chemistry, and that of atomistic molecular dynamics simulations in particular. One of its most exciting prospects is the development of accurate, full-dimensional potential energy surfaces (PESs) for molecules and clusters, which, however, often require thousands to tens of thousands of ab initio data points restricting the community to medium sized molecules and/or lower levels of theory (e.g. DFT). Transfer learning, which improves a global PES from a lower to a higher level of theory, offers a data efficient alternative requiring only a fraction of the high level data (on the order of 100 are found to be sufficient for malonaldehyde). The present work demonstrates that even with Hartree-Fock theory and a double-zeta basis set as the lower level model, transfer learning yields CCSD(T)-level quality for H-transfer barrier energies, harmonic frequencies and H-transfer tunneling splittings. Most importantly, finite-temperature molecular dynamics simulations on the sub-microsecond time scale in the gas phase are possible and the infrared spectra determined from the transfer learned PESs are in good agreement with experiment. It is concluded that routine, long-time atomistic simulations on PESs fulfilling CCSD(T)-standards become possible

a case study

Computer simulations have become increasingly popular in many different areas over the years, owing mainly to more effective and cheaper machines. In many cases, the trend seems to be that computer simulations are replacing experiments, at least in areas in which experiments are very difficult (expensive) or impossible. One such area is that of attempting to foresee what will happen in the future. Such analyses are very important for a durable construction such as a repository for spent nuclear fuel, for example. In the modelling effort, several computer codes are used and input data are often used without scrutiny. However, this work shows that even the rather simple task of calculating the solubility of a solid phase in a given water is encumbered with the effects of different uncertainties. These uncertainties may make the calculated solubility vary by several orders of magnitude. Thus the input to the more complex codes, simulating processes in connection with the repository, will also be affected. This report presents some computer programs for uncertainty and sensitivity analysis of solubility calculations. They are then illustrated by numerical simulations and estimation of uncertainty intervals for a case at the Äspö site in Sweden. Some of the input data treated as uncertain parameters are the stability constants for the reactions between the metal ion concerned and the elements present in the selected water or the rock. Stability constants and the enthalpies and entropies of reaction for the thoriumwater-acetylacetone-phosphate system have been determined experimentally. In addition to the values determined for these entities, uncertainty intervals are also estimated. A complexing mechanism for the thorium-phosphates at pH 8 is also suggested.researc

Simulations of proton transfer processes using reactive force fields

Within this thesis we presented the development of reactive force fields that are ca- pable to describe the dynamics of proton and hydrogen atom transfer processes. The presented implementation in CHARMM overcomes the limitation that bond break- ing and formation cannot be investigated by conventional classical MD simulations. Derived from high-level ab initio calculations this approach combines the accuracy of such calculations with the speed of MD simulations. The high-quality force fields of the prototype systems are comparable to high-level ab initio calculations in terms of structure and energy barriers. The PESs of proton transfer reactions are extremely sensitive with respect to the chemical environment. Nevertheless one is always able to classify the PT under investigation into symmetric and asymmetric PES. We de- veloped a series of parameter sets that are not only able to describe symmetric and asymmetric correctly but also can accommodate to different locations of energetic minima and barriers. The chosen three-dimensional potential energy functions have shown to be quite flexible and transferable in characterizing PT reactions in quite diverse chemical systems. The morphing transformation of MMPT force field param- eter, starting from one of our prototype systems to develop a new force field for a new molecular system which exhibits a similar topology in the PES along the proton reac- tion coordinates, has been shown to be successfully applicable in various examples. Energy scaling has been employed to investigate the effect on the proton transfer os- cillation in NH+ 4 · · ·NH3. New parameters through morphing have been developed for protonated diglyme, as well as for double proton transfer in 2PY2HP and for as- partic acid and water as model system for PT reactions in the active site of bacterial ferredoxin I. We applied the MMPT force field to investigate the vibrational infrared spectra of proton-bound species and explored the relationship of infrared spectra for protonated water dimer and protonated diglyme. The results for protonated water dimer compared well with other high-level calculations. Besides the further system- atic development of the morphing approach one can also employ the force field in combination with Feynman path integral methods. The MMPT force field could be a viable alternative to lower level quantum mechanical methods because the accuracy of the force field is only limited by the initial determination of the underlying PES for the PT of interest

Atomistic simulations of proton transport in the gas and condensed phases : spectroscopy, reaction kinetics and grotthuss mechanism

The empirical force field method of Molecular Mechanics with Proton Transfer (MMPT) follows concepts from a QM/MM scheme which treats the proton transfer (PT) process in its full dimensionality while improving on three important aspects of the problem: speed, accuracy, and versatility. Recent applications focused on the computation of infrared signatures for the shared proton between a donor and an acceptor atom. This was complemented and supported by recent experiments. Both conventional molecular dynamics and more advanced ring polymer molecular dynamics (RPMD) simulations were carried out to characterize the energetics, dynamics and spectroscopy of transferring protons in systems including formic acid dimer and protonated oxalate. The simulations were found reproducing infrared spectra in good agreement with experimental results. Moreover, the primary kinetic isotope effects (KIEs) of intramolecular hydrogen transfer are determined in both classical molecular dynamics (MD) and quantum simulations with the MMPT force fields. For classical simulations, the parametric potential energy surfaces (PESs) were refined with zero point vibrational effects (ZPVEs) considered, which effectively leads to the reduction of reaction barrier heights for the corresponding systems such as malondialdehyde and acetylacetone. With ZPVE introduced, the effective barrier heights are different between the isotope unsubstituted and substituted systems. That led to the chemical contributions into the primary kinetic isotope effects. In addition to classical simulations, the nuclear quantum effects (NQEs) are explicitly included in the path integral simulations based on the same empirical potential surfaces. With the inclusion of NQEs, simulation results lead to the increase of KIE values at 250 K by a factor of 2.5~3.0 compared to those from classical MD simulations. Rather than performing proton transfer within a priori defined reaction motif, in this thesis work, MMPT was extensively developed to be capable of delocalizing and treating diffusive proton transport in both gas and condensed phases. This became possible by combining the MMPT force field with multi-surface adiabatic reactive molecular dynamics (MS-ARMD), which leads to the new multi-state MMPT (MS-MMPT) method. In this method, a global potential energy for proton transports is built by mixing multiple potential energy surfaces, each of which corresponds to an oscillatory PT reaction. That enables, for instance, all hydrogen atoms in a water bulk with excess protons to equally participate into the transfer reactions within the force field framework. The integrated MS-MMPT method was applied to performing proton diffusion simulations for [H2O]nH+ clusters at the gas phase and bulk systems with the periodic boundary condition. Results were compared with both experiments and simulations using other established methods

Zinc(ii) complex of (Z)-4-((4-Nitrophenyl)Amino)Pent-3-en-2-one, a potential antimicrobial agent: synthesis, characterization, antimicrobial screening, DFT calculation and docking study

Herein, the synthesis and characterizations of (Z)-4-((4-nitrophenyl)amino)pent-3-en-2-one (HL) ligand and its Zn(II) complex are reported. The compounds were characterized using elemental and thermogravimetric (TGA) analysis, electrochemical studies, FTIR, UV-Vis, 1H and 13C{H}NMR, HRMS, and PXRD techniques. Antimicrobial activity was screened on some Gram-positive and Gram-negative bacteria. DFT predictions were achieved using B3LYP, ωB97XD and M06-2X functional with 6-31+G(d,p) and LANL2DZ basis sets for nonmetallic and metallic atoms, respectively. The therapeutic potentials of the compounds were evaluated based on protein binding affinity, ADME/T and drug-likeness properties. The experimental results revealed the formation of a complex in which two ligands coordinated to the zinc ion in a tetrahedral arrangement through their carbonyl and amino groups. The antimicrobial study showed that the complex possesses higher antimicrobial activity than free ligand and the control (Streptomycin). B3LYP emerged as the best performing functional having yielded the best IR spectra and geometrical parameters relative to the experimental data. The density functional theory (DFT) predictions revealed that the complex is more active than the ligand, and its formation is thermodynamically feasible and exothermic. The docking results revealed that the binding affinities of the compounds are in agreement with the in-vitro data, and they possess drug-like properties

Zinc(II) complex of (Z)-4-((4-nitrophenyl)amino)pent-3-en-2-one, a potential antimicrobial agent: synthesis, characterization, antimicrobial screening, DFT calculation and docking study

Herein, the synthesis and characterizations of (Z)-4-((4-nitrophenyl)amino)pent-3-en-2-one (HL) ligand and its Zn(II) complex are reported. The compounds were characterized using elemental and thermogravimetric (TGA) analysis, electrochemical studies, FTIR, UV-Vis, 1H and 13C{H}NMR, HRMS, and PXRD techniques. Antimicrobial activity was screened on some Gram-positive and Gram-negative bacteria. DFT predictions were achieved using B3LYP, ωB97XD and M06-2X functional with 6-31+G(d,p) and LANL2DZ basis sets for nonmetallic and metallic atoms, respectively. The therapeutic potentials of the compounds were evaluated based on protein binding affinity, ADME/T and drug-likeness properties. The experimental results revealed the formation of a complex in which two ligands coordinated to the zinc ion in a tetrahedral arrangement through their carbonyl and amino groups. The antimicrobial study showed that the complex possesses higher antimicrobial activity than free ligand and the control (Streptomycin). B3LYP emerged as the best performing functional having yielded the best IR spectra and geometrical parameters relative to the experimental data. The density functional theory (DFT) predictions revealed that the complex is more active than the ligand, and its formation is thermodynamically feasible and exothermic. The docking results revealed that the binding affinities of the compounds are in agreement with the in-vitro data, and they possess drug-like properties