Proton Transfer In Malonaldehyde Research Articles

Nuclear-Electronic Orbital Quantum Mechanical/Molecular Mechanical Real-Time Dynamics.

Simulating the nuclear-electronic quantum dynamics of large-scale molecular systems in the condensed phase is key for studying biologically and chemically important processes such as proton transfer and proton-coupled electron transfer reactions. Herein, the real-time nuclear-electronic orbital time-dependent density functional theory (RT-NEO-TDDFT) approach is combined with a hybrid quantum mechanical/molecular mechanical (QM/MM) strategy to enable the accurate description of coupled nuclear-electronic quantum dynamics in the presence of heterogeneous environments such as solvent or proteins. The densities of the electrons and quantum protons are propagated in real time, while the other nuclei are propagated classically on the instantaneous electron-proton vibronic surface. This approach is applied to phenol bound to lysozyme, intramolecular proton transfer in malonaldehyde, and nonequilibrium excited-state intramolecular proton transfer in o-hydroxybenzaldehyde. These examples illustrate that the RT-NEO-TDDFT framework, coupled with an atomistic representation of the environment, allows the simulation of condensed-phase systems that exhibit significant nuclear quantum effects.

Electronic Born-Oppenheimer approximation in nuclear-electronic orbital dynamics.

Within the nuclear-electronic orbital (NEO) framework, the real-time NEO time-dependent density functional theory (RT-NEO-TDDFT) approach enables the simulation of coupled electronic-nuclear dynamics. In this approach, the electrons and quantum nuclei are propagated in time on the same footing. A relatively small time step is required to propagate the much faster electronic dynamics, thereby prohibiting the simulation of long-time nuclear quantum dynamics. Herein, the electronic Born-Oppenheimer (BO) approximation within the NEO framework is presented. In this approach, the electronic density is quenched to the ground state at each time step, and the real-time nuclear quantum dynamics is propagated on an instantaneous electronic ground state defined by both the classical nuclear geometry and the nonequilibrium quantum nuclear density. Because the electronic dynamics is no longer propagated, this approximation enables the use of an order-of-magnitude larger time step, thus greatly reducing the computational cost. Moreover, invoking the electronic BO approximation also fixes the unphysical asymmetric Rabi splitting observed in previous semiclassical RT-NEO-TDDFT simulations of vibrational polaritons even for small Rabi splitting, instead yielding a stable, symmetric Rabi splitting. For the intramolecular proton transfer in malonaldehyde, both RT-NEO-Ehrenfest dynamics and its BO counterpart can describe proton delocalization during the real-time nuclear quantum dynamics. Thus, the BO RT-NEO approach provides the foundation for a wide range of chemical and biological applications.

Nonadiabatic Dynamics of Hydrogen Tunneling with Nuclear-Electronic Orbital Multistate Density Functional Theory.

Proton transfer reactions play a critical role in many chemical and biological processes. The development of computationally efficient approaches to describe the quantum dynamics of proton transfer, which often involves hydrogen tunneling, is challenging. Herein, the nuclear-electronic orbital multistate density functional theory (NEO-MSDFT) method is combined with both Ehrenfest and surface hopping nonadiabatic dynamics methods to describe hydrogen tunneling. The NEO-MSDFT method treats the transferring hydrogen nucleus quantum mechanically on the same level as the electrons and incorporates both static and dynamical correlation by mixing localized NEO-DFT solutions with a nonorthogonal configuration interaction scheme. The other nuclei are propagated on the NEO-MSDFT vibronic surfaces during the Ehrenfest or surface hopping dynamics. These methods are applied to proton transfer in malonaldehyde as a prototypical hydrogen tunneling system. The inclusion of vibronically nonadiabatic effects is found to significantly impact the proton transfer time and tunneling dynamics. This approach is applicable to a wide range of other proton transfer reactions.

Analytical gradients for nuclear–electronic orbital multistate density functional theory: Geometry optimizations and reaction paths

Hydrogen tunneling plays a critical role in many biologically and chemically important processes. The nuclear-electronic orbital multistate density functional theory (NEO-MSDFT) method was developed to describe hydrogen transfer systems. In this approach, the transferring proton is treated quantum mechanically on the same level as the electrons within multicomponent DFT, and a nonorthogonal configuration interaction scheme is used to produce delocalized vibronic states from localized vibronic states. The NEO-MSDFT method has been shown to provide accurate hydrogen tunneling splittings for fixed molecular systems. Herein, the NEO-MSDFT analytical gradients for both ground and excited vibronic states are derived and implemented. The analytical gradients and semi-numerical Hessians are used to optimize and characterize equilibrium and transition state geometries and to generate minimum energy paths (MEPs), for proton transfer in the deprotonated acetylene dimer and malonaldehyde. The barriers along the resulting MEPs are lower when the transferring proton is quantized because the NEO-MSDFT method inherently includes the zero-point energy of the transferring proton. Analysis of the proton densities along the MEPs illustrates that the proton density can exhibit symmetric or asymmetric bilobal character associated with symmetric or slightly asymmetric double-well potential energy surfaces and hydrogen tunneling. Analysis of the contributions to the intrinsic reaction coordinate reveals that changes in the C-O bond lengths drive proton transfer in malonaldehyde. This work provides the foundation for future reaction path studies and direct nonadiabatic dynamics simulations of a wide range of hydrogen transfer reactions.

Direct Dynamics with Nuclear-Electronic Orbital Density Functional Theory.

Direct dynamics simulations of chemical reactions typically require the selection of a method for generating the potential energy surfaces and a method for the dynamical propagation of the nuclei on these surfaces. The nuclear-electronic orbital (NEO) framework avoids this Born-Oppenheimer separation by treating specified nuclei on the same level as the electrons with wave function methods or density functional theory (DFT). The NEO approach is particularly applicable to proton, hydride, and proton-coupled electron transfer reactions, where the transferring proton(s) and all electrons are treated quantum mechanically. In this manner, the zero-point energy, density delocalization, and anharmonicity of the transferring protons are inherently and efficiently included in the energies, optimized geometries, and dynamics.This Account describes how various NEO methods can be used for direct dynamics simulations on electron-proton vibronic surfaces. The strengths and limitations of these approaches are discussed, and illustrative examples are presented. The NEO-DFT method can be used to simulate chemical reactions on the ground state vibronic surface, as illustrated by the application to hydride transfer in C4H9+. The NEO multistate DFT (NEO-MSDFT) method is useful for simulating ground state reactions in which the proton density becomes bilobal during the dynamics, a characteristic of hydrogen tunneling, as illustrated by proton transfer in malonaldehyde. The NEO time-dependent DFT (NEO-TDDFT) method produces excited electronic, vibrational, and vibronic surfaces. The application of linear-response NEO-TDDFT to H2 and H3+, as well as the partially and fully deuterated counterparts, shows that this approach produces accurate fundamental vibrational excitation energies when all nuclei and all electrons are treated quantum mechanically. Moreover, when only specified nuclei are treated quantum mechanically, this approach can be used to optimize geometries on excited state vibronic surfaces, as illustrated by photoinduced single and double proton transfer systems, and to conduct adiabatic dynamics on these surfaces. The real-time NEO-TDDFT method provides an alternative approach for simulating nonequilibrium nuclear-electronic dynamics of such systems. These various NEO methods can be combined with nonadiabatic dynamics methods such as Ehrenfest and surface hopping dynamics to include the nonadiabatic effects between the quantum and classical subsystems. The real-time NEO-TDDFT Ehrenfest dynamics simulation of excited state intramolecular proton transfer in o-hydroxybenzaldehyde illustrates the power of this type of combined approach. The field of multicomponent quantum chemistry is in the early stages, and the methods discussed herein provide the foundation for a wide range of promising future directions to be explored. An appealing future direction is the expansion of the real-time NEO-TDDFT method to describe the dynamics of all nuclei and electrons on the same level. Direct dynamics simulations using NEO wave function methods such as equation-of-motion coupled cluster or multiconfigurational approaches are also attractive but computationally expensive options. The further development of NEO direct dynamics methods will enable the simulation of the nuclear-electronic dynamics for a vast array of chemical and biological processes that extend beyond the Born-Oppenheimer approximation.

A simplistic computational procedure for tunneling splittings caused by proton transfer

In this manuscript, we present an approach for computing tunneling splittings for large amplitude motions. The core of the approach is a solution of an effective one-dimensional Schrödinger equation with an effective mass and an effective potential energy surface composed of electronic and harmonic zero-point vibrational energies of small amplitude motions in the molecule. The method has been shown to work in cases of three model motions: nitrogen inversion in ammonia, single proton transfer in malonaldehyde, and double proton transfer in the formic acid dimer. In the current work, we also investigate the performance of different DFT and post-Hartree–Fock methods for prediction of the proton transfer tunneling splittings, quality of the effective Schrödinger equation parameters upon the isotopic substitution, and possibility of a complete basis set (CBS) extrapolation for the resulting tunneling splittings.

Density functional tight binding-based free energy simulations in the DFTB+ program.

The timescale problem-in which high barriers on the free energy surface trap molecular dynamics simulations in local energy wells-is a key limitation of current reactive MD simulations based on the density functional tight binding (DFTB) potential. Here, we report a new interface between the DFTB+ software package and the PLUMED library for performing DFTB-based free energy calculations. We demonstrate the performance of this interface for 3 archetypal rare-event chemical reactions, (i) intramolecular proton transfer in malonaldehyde, (ii) bowl inversion in corannulene, and (iii) oxygen diffusion on graphene. Using third-order DFTB in conjunction with metadynamics (with/without multiple walkers) and well-tempered metadynamics, we report here free energies of activation (ΔG‡ ) of 13.1 ± 0.4, 48.2 ± 1.7, and 52.0 ± 6.2 kJ mol-1 , respectively, for these processes. In each case, our DFTB free energy barriers and local minima compare favorably with previous literature results, demonstrating the utility of the DFTB+ - PLUMED interface. © 2018 Wiley Periodicals, Inc.

Visualization of the Intrinsic Reaction Coordinate and Global Reaction Route Map by Classical Multidimensional Scaling.

A classical multidimensional scaling (CMDS) method is employed to visualize an intrinsic reaction coordinate (IRC) and a global reaction route map consisting of the equilibrium minima and transition state structures connected by the IRC network. As demonstrations, the method was applied to the IRCs of the intramolecular proton transfer in malonaldehyde and the SN2 reaction of OH- + CH3F → CH3OH + F-, which are both well described by two principal coordinates. Next, the method was applied to the global reaction route map of the Au5 cluster; the resulting map shows appropriate positions of five minima and 14 transition states in a reduced 2- or 3-dimensional coordinate space successfully.

Autocorrelation of electronic wave-functions: a new approach for describing the evolution of electronic structure in the course of dynamics

ABSTRACTWe introduce a new approach for analysing changes in electronic structure in the course of ab initio molecular dynamics simulations. The analysis is based on the time autocorrelation function of the many-body electronic wave-function. The approach facilitates the interpretation of dynamical events that may not be easily revealed by consideration of nuclear configurations alone. We apply the method to several illustrative examples: the shared proton vibration in the F−(H2O) complex, representing changes in strength of non-covalent interactions; proton transfer in the water dimer cation, as an example for chemical reactions in weakly bound systems; and the intramolecular proton transfer in malonaldehyde. In all cases, we observe distinct features in the time autocorrelation function when chemical changes occur. The autocorrelation function serves as an effective reaction coordinate, incorporating all degrees of freedom, including electronic ones. The method is also sensitive to changes in the electronic wave-function not accompanied by significant nuclear motions.

Implementation of replica-exchange umbrella sampling in GAMESS

In GAMESS-US quantum chemistry package, both replica-exchange molecular dynamics (REMD) and the umbrella sampling (US) methods are available. However, prior to this work, the replica-exchange umbrella sampling (REUS) method, combining REMD and US, was not implemented. REUS affords a more efficient conformational sampling than the conventional US method and is often used in MD simulations. We implemented REUS in GAMESS-US and improved some routines of the existing REMD code. A density-functional tight-binding REMD (DFTB-REMD) simulation of alanine deca-peptide and a DFTB-MD REUS simulation of proton transfer in malonaldehyde were performed. The results of DFTB-MD REUS simulations performed with three different simulation packages were compared to validate our GAMESS-US implementation.

Kinetic isotope effects and how to describe them.

We review several methods for computing kinetic isotope effects in chemical reactions including semiclassical and quantum instanton theory. These methods describe both the quantization of vibrational modes as well as tunneling and are applied to the ⋅H + H2 and ⋅H + CH4 reactions. The absolute rate constants computed with the semiclassical instanton method both using on-the-fly electronic structure calculations and fitted potential-energy surfaces are also compared directly with exact quantum dynamics results. The error inherent in the instanton approximation is found to be relatively small and similar in magnitude to that introduced by using fitted surfaces. The kinetic isotope effect computed by the quantum instanton is even more accurate, and although it is computationally more expensive, the efficiency can be improved by path-integral acceleration techniques. We also test a simple approach for designing potential-energy surfaces for the example of proton transfer in malonaldehyde. The tunneling splittings are computed, and although they are found to deviate from experimental results, the ratio of the splitting to that of an isotopically substituted form is in much better agreement. We discuss the strengths and limitations of the potential-energy surface and based on our findings suggest ways in which it can be improved.

A global reaction route mapping-based kinetic Monte Carlo algorithm.

We propose a new on-the-fly kinetic Monte Carlo (KMC) method that is based on exhaustive potential energy surface searching carried out with the global reaction route mapping (GRRM) algorithm. Starting from any given equilibrium state, this GRRM-KMC algorithm performs a one-step GRRM search to identify all surrounding transition states. Intrinsic reaction coordinate pathways are then calculated to identify potential subsequent equilibrium states. Harmonic transition state theory is used to calculate rate constants for all potential pathways, before a standard KMC accept/reject selection is performed. The selected pathway is then used to propagate the system forward in time, which is calculated on the basis of 1st order kinetics. The GRRM-KMC algorithm is validated here in two challenging contexts: intramolecular proton transfer in malonaldehyde and surface carbon diffusion on an iron nanoparticle. We demonstrate that in both cases the GRRM-KMC method is capable of reproducing the 1st order kinetics observed during independent quantum chemical molecular dynamics simulations using the density-functional tight-binding potential.

Muon-Substituted Malonaldehyde: Transforming a Transition State into a Stable Structure by Isotope Substitution.

Isotope substitutions are usually conceived to play a marginal role on the structure and bonding pattern of molecules. However, a recent study [Angew. Chem. Int. Ed. 2014, 53, 13706-13709; Angew. Chem. 2014, 126, 13925-13929] further demonstrates that upon replacing a proton with a positively charged muon, as the lightest radioisotope of hydrogen, radical changes in the nature of the structure and bonding of certain species may take place. The present report is a primary attempt to introduce another example of structural transformation on the basis of the malonaldehyde system. Accordingly, upon replacing the proton between the two oxygen atoms of malonaldehyde with the positively charged muon a serious structural transformation is observed. By using the ab initio nuclear-electronic orbital non-Born-Oppenheimer procedure, the nuclear configuration of the muon-substituted species is derived. The resulting nuclear configuration is much more similar to the transition state of the proton transfer in malonaldehyde rather than to the stable configuration of malonaldehyde. The comparison of the "atoms in molecules" (AIM) structure of the muon-substituted malonaldehyde and the AIM structure of the stable and the transition-state configurations of malonaldehyde also unequivocally demonstrates substantial similarities of the muon-substituted malonaldehyde to the transition state.

New QM/MM implementation of the DFTB3 method in the gromacs package.

The approximate density-functional tight-binding theory method DFTB3 has been implemented in the quantum mechanics/molecular mechanics (QM/MM) framework of the Gromacs molecular simulation package. We show that the efficient smooth particle-mesh Ewald implementation of Gromacs extends to the calculation of QM/MM electrostatic interactions. Further, we make use of the various free-energy functionalities provided by Gromacs and the PLUMED plugin. We exploit the versatility and performance of the current framework in three typical applications of QM/MM methods to solve biophysical problems: (i) ultrafast proton transfer in malonaldehyde, (ii) conformation of the alanine dipeptide, and (iii) electron-induced repair of a DNA lesion. Also discussed is the further development of the framework, regarding mostly the options for parallelization.

1P128 DFTBおよびREUSを用いたマロンアルデヒドのプロトン移動計算(06.電子状態,ポスター,日本生物物理学会年会第51回(2013年度))

1P128 DFTBおよびREUSを用いたマロンアルデヒドのプロトン移動計算(06.電子状態,ポスター,日本生物物理学会年会第51回(2013年度))

Intramolecular proton transfer in malonaldehyde: Accurate multilayer multi-configurational time-dependent Hartree calculations

Full-dimensional (multilayer) multi-configurational time-dependent Hartree calculations studying the intramolecular proton transfer in malonaldehyde based on a recent potential energy surface (PES) [Wang et al., J. Chem. Phys. 128, 224314 (2008)] are presented. The most accurate calculations yield a ground state tunneling splitting of 23.8 cm(-1) and a zero point energy of 14,678 cm(-1). Extensive convergence tests indicate an error margin of the quantum dynamics calculations for the tunneling splitting of about 0.2 cm(-1). These results are to be compared with the experimental value of the tunneling splitting of 21.58 cm(-1) and results of Monte Carlo calculations of Wang et al. on the same PES which yielded a zero point energy of 14,677.9 cm(-1) with statistical errors of 2-3 cm(-1) and a tunneling splitting of 21.6 cm(-1). The present data includes contributions resulting from the vibrational angular momenta to the tunneling splitting and the zero point energy of 0.2 cm(-1) and 2.4 cm(-1), respectively, which have been computed using a perturbative approach.

The proton transfer reaction in malonaldehyde derivatives: Substituent effects and quasi-aromaticity of the proton bridge

The proton transfer in malonaldehyde and in some of its derivatives have been considered in order to study the interrelation between the reaction barrier and the π-delocalization in the quasi-ring. A set of simple and mostly common substituents having different properties in resonance effect according to values of substituents constants were chosen in order to simulate the influence of substitution in position 2 or in position 1 (or 3) of malonaldehyde on the quasi-aromaticity and H-bonding. The following substituents have been taken into consideration: NO, NO 2, CN, CHO, F, H, CH 3, OCH 3, OH, and NH 2. Our results show that when the substituent is attached at position 2 of the quasi-ring, the resonance effect predominates over the field/inductive effect which leads to changes in H-bonding and quasi-aromaticity of the ring motif, while in the case of 1(3) substitution the field/inductive effect is significantly more effective influencing the HB strength, and thus, the proton transfer barrier. Somehow counterintuitively, for the 1(3) substituted systems, the most stable isomer is the one having the weakest HB and lower aromaticity. The reason for this surprising behaviour is discussed.

A novel parametrization scheme for classical and quantum mechanical simulations of large, floppy molecular systems

We present an algorithm aimed at efficiently representing analytical full dimensional ab initio potential energy surfaces for floppy molecular systems. By introducing a new set of coordinates, we can define large amplitude displacements in one or more dimensions. Then, we use a general representation of the full dimensional potential energy surface based on a Taylor-like series expansion. Classical and quantum mechanical Path Integral Monte Carlo simulations on proton transfer in malonaldehyde and strong hydrogen bond in picolinic acid N-oxide establish the accuracy of our analytical representation and of our interpolating schemes.

Proton transfer in malonaldehyde: From reaction path to Schrödinger’s Cat

Proton transfer in the chelated form of malonaldehyde is commonly supposed to occur between two tautomers, across a transition state involving changes of the chemical bonding. We show that this view is in conflict with rotational spectra. The molecule is better thought of as a superposition of indistinguishable and non-separable C s tautomers and proton tunneling is totally decoupled from the other degrees of freedom. Double minimum potential functions are determined from experiments and ab initio calculations.

Excited-State Intramolecular Proton Transfer: A Survey of TDDFT and RI-CC2 Excited-State Potential Energy Surfaces

TDDFT and RI-CC2 calculations have been performed on the excited-state intramolecular proton transfer in malonaldehyde, o-hydroxybenzaldehyde, salicylic acid, 7-hydroxy-1-indanone, and 2-(2'-hydroxyphenyl)benzothiazole. Vertical and adiabatic excitation energies have been computed for the npi and pipi states. Overall, we have found that both RI-CC2 and TDDFT methods are good candidates for the description of ESIPT potential energy surfaces. Proton transfer (PT) curves have been computed for both excited states. An essentially barrierless and very shallow energy profile has been found for the pi pi* state. For the n pi* state the keto minimum is more pronounced than for the pi pi* state and, depending on the case, energy barriers ranging from values <0.1 eV up to 0.5 eV were found. From the computed PT curves we conclude that extended crossing regions between the two excited states will occur.