Nitrate (NO3−) pollution poses a critical environmental threat by contaminating water resources and disrupting the global nitrogen cycle. The electrochemical nitrate reduction reaction (NO3RR) in alkaline media offers a dual solution: mitigating nitrate contamination while enabling sustainable ammonia (NH3) production. However, the scarcity of free protons (H+) at high pH hampers efficient NO3−-to-NH3 conversion. Here, we report a sub-stoichiometric covalent organic framework PEPy-2CHO-TTA, synthesized by microwave-assisted [4 + 3 + 2] polycondensation strategy, which retains pendant unreacted aldehyde groups oriented toward the pore channels. This framework-intrinsic integration of polar aldehyde functionalities enhances water uptake and promotes the formation of a structured hydration network within the pores, enabling localized proton transfer that overcomes proton deficiency under alkaline conditions. As a result, PEPy-2CHO-TTA COF achieves a Faradaic efficiency (FE) exceeding 95% and an NH3 yield rate of 5.87 mg h−1 cm−2 which is among the highest reported for metal-free or metal-based porous electrocatalysts. Isotope labelling using K15NO3 confirms that the produced ammonia originates exclusively from nitrate reduction. DFT calculations reveal a multi-step eight-electron reduction pathway with the NO-to-NHO transformation as the potential-determining step. This work introduces a new design paradigm for COF electrocatalysts, where pendant aldehydes within the framework serve as molecular handles for water-mediated proton transport, enabling efficient nitrate reduction under alkaline conditions, without external acidification or metal catalysts.

Accurate modeling of the dynamic structures of ribonucleic acid (RNA) molecules is essential for understanding their biological roles. However, such modeling remains challenging due to limitations in current force fields. This study critically evaluates three RNA force fields, HB-CUFIX, AMBER-χOL3, and AMBER-ROC, comparing their performance against experimental nuclear magnetic resonance and small-angle x-ray scattering data for single-stranded oligonucleotides. Using enhanced sampling techniques, specifically Unified Free Energy Dynamics, we exhaustively sampled the conformational space of tetramer and hexamer RNA sequences, achieving a detailed and thermodynamically converged view of their structural dynamics. Our findings reveal that HB-CUFIX outperforms AMBER-χOL3 and AMBER-ROC, providing near-experimental accuracy in capturing sequence-dependent structural preferences. In particular, HB-CUFIX accurately predicts low energy states for the AAAA and CCCC sequences, favoring A-form helical conformations, while the UUUU sequence adopts an extended, heterogeneous structure. The mixed GACC sequence displays a predominantly A-form helix with flexible terminal residues. These results highlight the significant role of sequence in dictating RNA conformational spaces, which are driven by base stacking interactions and covalent geometry. We also emphasize the importance of enhanced sampling, particularly methods that can handle large numbers of collective variables, in evaluating RNA force fields, as traditional brute-force Molecular dynamics fails to capture the conformational diversity of flexible RNAs. Our study provides a reliable tool for RNA structure prediction and dynamic analysis, supporting future advancements in RNA-targeted research and therapeutic design.

Developing a low-cost, robust, and high-performance electrocatalyst capable of efficiently performing both the oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER) under both basic and acidic conditions is a major challenge. This area of research has attracted much attention in recent decades due to its importance in energy storage and conversion. Herein, we report the synthesis of two imine-linked isoindigo-based covalent organic networks I-TTA and I-TG (I=Isoindigo, TTA=4,4′,4′′-(1,3,5-triazine-2,4,6-triyl)-trianiline, TG=triamino-guanidinium hydrochloride salt). By introducing two amine core units with different planarity, such as triazine and ionic guanidinium units, we control the morphology, crystallinity, and corresponding electrocatalytic properties of the materials. The combination of isoindigo dialdehyde with a planar triazine core, leads to the formation of thin, highly crystalline, planar two dimensional (2D) nanosheets covalent organic framework (COF), I-TTA whereas its combination with ionic non-planar guanidinium core leads to an amorphous covalent organic polymer (COP), I-TG with a fibrous morphology. The sheet-like crystalline I-TTA COF shows better electrocatalytic activity compared to the amorphous fibrous I-TG COP. I-TTA exhibits a current density of 10 mA cm−2 at an overpotential of ~134 mV for HER (in 0.5 M H2SO4) and ~283 mV for OER (in 1 M KOH). The electrocatalytic activity of the I-TTA COF in the OER exceeds that of other metal-free COFs. The catalytic activity is maintained even after 24 hours of chronoamperometry and 500 cycles of cyclic voltammetry (CV) at high scan rates.

Cryosurgery represents a transformative approach in the treatment of resistant tumors, utilizing extreme cold to selectively ablate malignant tissue. However, the clinical success of this technique is constrained by the limited ability of current imaging techniques to differentiate effectively between cancerous and healthy tissues with high spatial resolution. To overcome this challenge, we present a nanoscale Covalent Organic Framework, nTG-DFP-COF, specifically designed to enhance fluorescence-guided cryo-imaging. This framework exhibits a unique temperature-dependent luminescence, that results in enhanced fluorescence emission under cryogenic conditions, enabling precise tissue differentiation during surgical procedures. Engineered for biocompatibility and water dispersibility, nTG-DFP-COF demonstrates minimal cytotoxicity and exceptional specificity toward cancer cells. Comprehensive in vitro, in vivo, and ex vivo evaluations confirm its structural stability and functional efficacy under cryogenic conditions. This innovation not only enhances the precision and safety of cryosurgical procedures but also advances the integration of diagnostic and therapeutic functionalities into a unified platform. By substantially improving tumor targeting accuracy, the use of nTG-DFP-COF will reduce the need for repeat surgeries, facilitate faster recovery, and minimize healthcare costs, thus setting a new standard in oncologic imaging and intervention.

Visual sensing of humidity and temperature by solids plays an important role in the everyday life and in industrial processes. Due to their hydrophobic nature, most covalent organic framework (COF) sensors often exhibit poor optical response when exposed to moisture. To overcome this challenge, the optical response is set out to improve, to moisture by incorporating H-bonding ionic functionalities into the COF network. A highly sensitive COF, consisting of guanidinium and diformylpyridine linkers (TG-DFP), capable of detecting changes in temperature and moisture content is fabricated. The hydrophilic nature of the framework enables enhanced water uptake, allowing the trapped water molecules to form a large number of hydrogen bonds. Despite the presence of non-emissive building blocks, the H-bonds restrict internal bond rotation within the COF, leading to reversible fluorescence and solid-state optical hydrochromism in response to relative humidity and temperature.

Computational quantum chemistry can be more than just numerical experiments when methods are specifically adapted to investigate chemical concepts. One important example is the development of energy decomposition analysis (EDA) to reveal the physical driving forces behind intermolecular interactions. In EDA, typically the interaction energy from a good-quality density functional theory (DFT) calculation is decomposed into multiple additive components that unveil permanent and induced electrostatics, Pauli repulsion, dispersion, and charge-transfer contributions to noncovalent interactions. Herein, we formulate, implement, and investigate decomposing the forces associated with intermolecular interactions into the same components. The resulting force decomposition analysis (FDA) is potentially useful as a complement to the EDA to understand chemistry, while also providing far more information than an EDA for data analysis purposes such as training physics-based force fields. We apply the FDA based on absolutely localized molecular orbitals (ALMOs) to analyze interactions of water with sodium and chloride ions as well as in the water dimer. We also analyze the forces responsible for geometric changes in carbon dioxide upon adsorption onto (and activation by) gold and silver anions. We also investigate how the force components of an EDA-based force field for water clusters, namely MB-UCB, compare to those from force decomposition analysis.

The generation of reference data for deep learning models is challenging for reactive systems, and more so for combustion reactions due to the extreme conditions that create radical species and alternative spin states during the combustion process. Here, we extend intrinsic reaction coordinate (IRC) calculations with ab initio MD simulations and normal mode displacement calculations to more extensively cover the potential energy surface for 19 reaction channels for hydrogen combustion. A total of ∼290,000 potential energies and ∼1,270,000 nuclear force vectors are evaluated with a high quality range-separated hybrid density functional, ωB97X-V, to construct the reference data set, including transition state ensembles, for the deep learning models to study hydrogen combustion reaction.

We report a new deep learning message passing network that takes inspiration from Newton's equations of motion to learn interatomic potentials and forces. With the advantage of directional information from trainable force vectors, and physics-infused operators that are inspired by Newtonian physics, the entire model remains rotationally equivariant, and many-body interactions are inferred by more interpretable physical features. We test NewtonNet on the prediction of several reactive and non-reactive high quality ab initio data sets including single small molecules, a large set of chemically diverse molecules, and methane and hydrogen combustion reactions, achieving state-of-the-art test performance on energies and forces with far greater data and computational efficiency than other deep learning models.

Aqueous solutions of alkyl/alkaline metal and halide ions play a crucial functional role in biological systems such as proteins, membranes, and nucleic acids and for interfacial chemistry in geomedia and in the atmosphere. We present the MB-UCB many-body force field for monovalent and divalent ions that includes polarization, charge penetration to describe the short-range permanent electrostatics accurately, as well as a model for charge transfer to better describe the quantum mechanical potential energy surface and its components obtained from the absolutely localized molecular orbital energy decomposition analysis (ALMO-EDA). We find that the MB-UCB force field is in very good agreement with a validation suite of ion-ion and ion-water cluster data, exhibiting overall better cancellation of errors among energy components, unlike the case for other many-body potentials that do not utilize an EDA scheme. However, limitations in the functional form for the classical many-body energy components do limit the best achievable accuracy through complete cancellation of error and warrant further study.

The dynamics and spectroscopy ofN-methyl-acetamide (NMA) and trialanine in solution are characterized from molecular dynamics simulations using different energy functions, including a conventional point charge (PC)-based force field, one based on a multipolar (MTP) representation of the electrostatics, and a semiempirical DFT method. For the 1D infrared spectra, the frequency splitting between the two amide-I groups is 10 cm-1from the PC, 13 cm-1from the MTP, and 47 cm-1from self-consistent charge density functional tight-binding (SCC-DFTB) simulations, compared with 25 cm-1from experiment. The frequency trajectory required for the frequency fluctuation correlation function (FFCF) is determined from individual normal mode (INM) and full normal mode (FNM) analyses of the amide-I vibrations. The spectroscopy, time-zero magnitude of the FFCFC(t= 0), and the static component Δ02from simulations using MTP and analysis based on FNM are all consistent with experiments for (Ala)3. Contrary to this, for the analysis excluding mode-mode coupling (INM), the FFCF decays to zero too rapidly and for simulations with a PC-based force field, the Δ02is too small by a factor of two compared with experiments. Simulations with SCC-DFTB agree better with experiment for these observables than those from PC-based simulations. The conformational ensemble sampled from simulations using PCs is consistent with the literature (including PII, β, αR, and αL), whereas that covered by the MTP-based simulations is dominated by PIIwith some contributions from β and αR. This agrees with and confirms recently reported Bayesian-refined populations based on 1D infrared experiments. FNM analysis together with a MTP representation provides a meaningful model to correctly describe the dynamics of hydrated trialanine.

Many pairwise additive force fields are in active use for intrinsically disordered proteins (IDPs) and regions (IDRs), some of which modify energetic terms to improve the description of IDPs/IDRs but are largely in disagreement with solution experiments for the disordered states. This work considers a new direction—the connection to configurational entropy—and how it might change the nature of our understanding of protein force field development to equally well encompass globular proteins, IDRs/IDPs, and disorder-to-order transitions. We have evaluated representative pairwise and many-body protein and water force fields against experimental data on representative IDPs and IDRs, a peptide that undergoes a disorder-to-order transition, for seven globular proteins ranging in size from 130 to 266 amino acids. We find that force fields with the largest statistical fluctuations consistent with the radius of gyration and universal Lindemann values for folded states simultaneously better describe IDPs and IDRs and disorder-to-order transitions. Hence, the crux of what a force field should exhibit to well describe IDRs/IDPs is not just the balance between protein and water energetics but the balance between energetic effects and configurational entropy of folded states of globular proteins.

Nonreactive force fields are defined by perturbations of electron density that are relatively small, whereas chemical reactivity involves wholesale electronic rearrangements that make and break bonds. Thus, reactive force fields are incredibly difficult to develop compared to nonreactive force fields, yet at the same time, they fill a critical need when ab initio molecular dynamics methods are not affordable. We introduce a new reactive force field model for water that combines modified nonbonded terms of the ReaxFF model and its embedding in the electrostatic interactions described by our recently introduced coarse-grained electron model (C-GeM). The ReaxFF/C-GeM force field is characterized for many energetic and dissociative water properties for water clusters, structure, and dynamical properties under ambient conditions in the condensed phase, as well as the temperature dependence of density and water diffusion, with very good agreement with experiment. The ReaxFF/C-GeM force field should be more transferable and more broadly applicable to a range of reactive systems involving both proton and electron transfer in the condensed phase.

Quantum chemistry in the form of density functional theory (DFT) calculations is a powerful numerical experiment for predicting intermolecular interaction energies. However, no chemical insight is gained in this way beyond predictions of observables. Energy decomposition analysis (EDA) can quantitatively bridge this gap by providing values for the chemical drivers of the interactions, such as permanent electrostatics, Pauli repulsion, dispersion, and charge transfer. These energetic contributions are identified by performing DFT calculations with constraints that disable components of the interaction. This review describes the second-generation version of the absolutely localized molecular orbital EDA (ALMO-EDA-II). The effects of different physical contributions on changes in observables such as structure and vibrational frequencies upon complex formation are characterized via the adiabatic EDA. Example applications include red- versus blue-shifting hydrogen bonds; the bonding and frequency shifts of CO, N binf? einf? and BF bound to a [Ru(II)(NH3)5]2 +moiety; and the nature of the strongly bound complexes between pyridine and the benzene and naphthalene radical cations. Additionally, the use of ALMO-EDA-II to benchmark and guide the development of advanced force fields for molecular simulation is illustrated with the recent, very promising, MB-UCB potential.

To study intermolecular interactions involving radicals at the correlated level, the energy decomposition analysis scheme for second-order MoÌ•ller-Plesset perturbation theory based on absolutely localized molecular orbitals (ALMO-MP2-EDA) is generalized to unrestricted and restricted open-shell MP2. The benefit of restricted open-shell MP2 is that it can provide accurate binding energies for radical complexes where density functional theory can be error-prone due to delocalization errors. As a model application, the open-shell ALMO-MP2-EDA is applied to study the first solvation step of halogenated benzene radical cations, where both halogen- A nd hydrogen-bonded isomers are possible. We determine that the lighter halogens favor the hydrogen-bonded form, while the iodine-substituted species prefers halogen bonding due to larger polarizability and charge transfer at the halogen. As a second application, relevant to the activation of CO2 in photoelectrocatalysis, complexes of CO2 - · interacting with both pyridine and imidazole are analyzed with ALMO-MP2-EDA. The results reveal the importance of charge transfer into the Ï∗ orbital of the heterocycle in controlling the stability of the carbamate binding mode, which is favored for pyridine but not for imidazole.

The nucleophilic substitution reaction [Cl-CH3-Br]- is used for a comparative study of several reactive molecular dynamics schemes in the gas phase and in solution. Multi surface adiabatic reactive MD (MS-ARMD) and multi-state valence bond (MS-VALBOND) use empirical force fields to allow bond-breaking and bond-formation in dynamics studies. As a third alternative, machine learning is used to obtain a reactive force field from training a neural network. The focus of the present work is on highlighting differences of the parametrisation strategy and the associated computational cost and parametrization effort, as well as discussing the transferability and the ease with which the methods can be applied to a given chemical reaction. All methods are able to fit the reference data with R2 = 0.99 or better. Free energy barrier heights in the gas phase from all three methods for the SN2 reaction compare to within 3.5 kcal mol1 for the forward and to within 0.6 kcal mol1 for the reverse reaction. For the reaction in solution only the MS-ARMD and MS-VALBOND approaches can be used as training a NN for this would be computationally extremely prohibitive. Overall, MS-VALBOND yields the best results compared to experiment with differences in the barrier heights of 1 kcal mol1 for the reaction in solution. Potential improvements for all three methods are discussed and aim to guide computational investigation of chemical reactions applying these three methods.

Given the piecewise approach to modeling intermolecular interactions for force fields, they can be difficult to parametrize since they are fit to data like total energies that only indirectly connect to their separable functional forms. Furthermore, by neglecting certain types of molecular interactions such as charge penetration and charge transfer, most classical force fields must rely on, but do not always demonstrate, how cancellation of errors occurs among the remaining molecular interactions accounted for such as exchange repulsion, electrostatics, and polarization. In this work we present the first generation of the (many-body) MB-UCB force field that explicitly accounts for the decomposed molecular interactions commensurate with a variational energy decomposition analysis, including charge transfer, with force field design choices that reduce the computational expense of the MB-UCB potential while remaining accurate. We optimize parameters using only a single water molecule and water cluster data up through pentamers, with no fitting to condensed phase data, and we demonstrate that high accuracy is maintained when the force field is subsequently validated against conformational energies of larger water cluster data sets, radial distribution functions of the liquid phase, and the temperature dependence of thermodynamic and transport water properties. We conclude that MB-UCB is comparable in performance to MB-Pol but is less expensive and more transferable by eliminating the need to represent short-ranged interactions through large parameter fits to high order polynomials.

In this work, we have developed an anisotropic polarizable model for the AMOEBA force field that is derived from electrostatic fitting on a gas phase water molecule as the primary approach to improve the many-body polarization model. We validate our approach using small to large water cluster benchmark data sets and ambient liquid water properties and through comparisons to a variational energy decomposition analysis breakdown of molecular interactions for water and water-ion trimer systems. We find that the accounting of anisotropy polarization for a single water molecule demonstrably improves the description of the many-body polarization energy in all cases. This study provides a proof of principle for extending our protocol for developing a general purpose anisotropic polarizable force field for other biological and material functional groups to better describe complex and asymmetric environments for which accurate polarization models are most needed.

The implementation, validation, and application of the multi-state VALBOND method for transition-metal-containing and hypervalent molecules are presented. This approach is particularly suited for molecules with unusual shapes and systems that need to be described by a superposition of resonance structures, each of which satisfies the octet rule. The implementation is based on the original VALBOND force field and allows us to smoothly switch between resonance structures, each of which can be characterized by its own force field, including varying charge distributions and coupling terms between the states. The implementation conserves total energy for simulations in the gas phase and in solution and is applied to a number of topical systems. For the small hypervalent molecule ClF3, the barrier for pseudorotation is found to be 4.3 kcal/mol, which compares favorably with the experimentally measured value of 4.8 kcal/mol. A transition-metal-containing complex, cisplatin, is characterized by six resonance states, for which the vibrational spectrum is found to be in good agreement with experiment. Finally, umbrella sampling simulations of the SN2 reaction BrMe + Cl- Br- + MeCl in solution yield a barrier height of 24.6 kcal/mol, in good agreement with experiment (24.7 kcal/mol).

The conversion of nitric oxide (NO) into nitrate (NO3 −) by dioxygenation protects cells from lethal NO. Starting from NO-bound heme, the first step in converting NO into benign NO3 − is the ligand exchange reaction FeNO+O2→FeO2+NO, which is still poorly understood at a molecular level. For wild-type (WT) truncated hemoglobin N (trHbN) and its Y33A mutant, the calculated barriers for the exchange reaction differ by 1.5 kcal mol−1, compared with 1.7 kcal mol−1 from experiment. It is directly confirmed that the ligand exchange reaction is rate-limiting in trHbN and that entropic contributions account for 75 % of the difference between the WT and the mutant. Residues Tyr 33, Phe 46, Val 80, His 81, and Gln 82 surrounding the active site are expected to control the reaction path. By comparison with electronic structure calculations, the transition state separating the two ligand-bound states was assigned to a 2A state.

The transfer of charge at the molecular level plays a fundamental role in many areas of chemistry, physics, biology and materials science. Today, more than 60 years after the seminal work of R. A. Marcus, charge transfer is still a very active field of research. An important recent impetus comes from the ability to resolve ever faster temporal events, down to the attosecond time scale. Such a high temporal resolution now offers the possibility to unravel the most elementary quantum dynamics of both electrons and nuclei that participate in the complex process of charge transfer. This review covers recent research that addresses the following questions. Can we reconstruct the migration of charge across a molecule on the atomic length and electronic time scales? Can we use strong laser fields to control charge migration? Can we temporally resolve and understand intramolecular charge transfer in dissociative ionization of small molecules, in transition-metal complexes and in conjugated polymers? Can we tailor molecular systems towards specific charge-transfer processes? What are the time scales of the elementary steps of charge transfer in liquids and nanoparticles? Important new insights into each of these topics, obtained from state-of-the-art ultrafast spectroscopy and/or theoretical methods, are summarized in this review.

Structural characterization of the copper-coordination shell is important in catalysis and biology. Cu-containing domains are prevalent in biological systems and play important roles in oxidation and electron transport process. Here, the solution structure, solvent organization, and dynamics around aqueous [Cu(II)(Imidazole)4] were characterized using atomistic simulations. Asymmetric axial water coordination around the metal atom was found which agrees with results from Minuit X-ray absorption near-edge structure (MXAN) experiments. The simulations reveal that exchange of the axial water occurs on the 25 to 50 ps time scale and is facilitated by and coupled to the flexibility of the copper-out of plane motion relative to the nitrogen atoms. Both concerted and stepwise water exchange of the two axially coordinated water molecules with first-shell water molecules are observed. The results suggest that axial access of a copper center can be fine-tuned by the degree of flexibility of its first coordination sphere. (Figure Presented).

Nitric oxide binding and unbinding from myoglobin (Mb) is central to the function of the protein. By using reactive molecular dynamics (MD) simulations, the dynamics following NO dissociation were characterized in both time and space. Ligand rebinding can be described by two processes on the 10 ps and 100 ps timescale, which agrees with recent optical and X-ray absorption experiments. Explicitly including the iron out-of-plane (Fe-oop) coordinate is essential for a meaningful interpretation of the data. The proposed existence of an “Fe-oop/NO-bound” state is confirmed and assigned to NO at a distance of approximately 3 Å away from the iron atom. However, calculated XANES spectra suggest that it is diffcult to distinguish between NO close to the heme-Fe and positions further away in the primary site. Another elusive state, with Fe−ON coordination, was not observed experimentally because it is masked by the energetically more favorable but dissociative4A state in this region, which makes the Fe−ON local minimum unobservable in wild-type Mb. However, suitable active-site mutations may stabilize this state.

We apply two recently developed computational methods, DFTB3 and VALBOND, to study copper oxidation/reduction processes in solution and protein. The properties of interest include the coordination structure of copper in different oxidation states in water or in a protein (plastocyanin) active site, the reduction potential of the copper ion in different environments, and the environmental response to copper oxidation. The DFTB3/MM and VALBOND simulation results are compared to DFT/MM simulations and experimental results whenever possible. For a copper ion in aqueous solution, DFTB3/MM results are generally close to B3LYP/MM with a medium basis, including both solvation structure and reduction potential for Cu(II); for Cu(I), however, DFTB3/MM finds a two-water coordination, similar to previous Born-Oppenheimer molecular dynamics simulations using BLYP and HSE, whereas B3LYP/MM leads to a tetrahedron coordination. For a tetraammonia copper complex in aqueous solution, VALBOND and DFTB3/MM are consistent in terms of both structural and dynamical properties of solvent near copper for both oxidation states. For copper reduction in plastocyanin, DFTB3/MM simulations capture the key properties of the active site, and the computed reduction potential and reorganization energy are in fair agreement with experiment, especially when the periodic boundary condition is used. Overall, the study supports the value of VALBOND and DFTB3(/MM) for the analysis of fundamental copper redox chemistry in water and protein, and the results also help highlight areas where further improvements in these methods are desirable.

The solvent dynamics in Fe-tris-bipyridine [Fe(bpy)3]2+ upon electronic excitation (oxidation) and subsequent relaxation is followed on the picosecond time scale by using atomistic simulations. Starting from the low spin (LS) Fe(II)LS state the transition to the excited Fe(III) 1,3MLCT (metal-to-ligand charge transfer) state decreases the water coordination in immediate proximity of the central iron atom. This readjustment of the solvent shell occurs on the subpicosecond time scale. Full relaxation of the water environment would occur on the 10 ps time scale which is, however, never reached as the lifetime of the 1,3MLCT state is only 200 fs. Further relaxation toward the long-lived (665 ps) [Fe(II)HS(bpy)3] high spin (HS) state does not change the degree of solvation. The results support a model in which the change in the degree of solvation is driven by electronic effects (charge redistribution) and not by structural changes (change in bond lengths). Furthermore, the results are consistent with recent combined X-ray emission (XES) and X-ray diffusion (XDS) scattering experiments which provided evidence for a reduced solvent density upon excitation of the [Fe(II)LS(bpy)3] initial state. However, the time scale for water exchange dynamics is faster than that found in the experiments.

Following chemical reactions in atomistic detail is one of the most challenging aspects of current computational approaches to chemistry. In this chapter the application of adiabatic reactive MD (ARMD) and its multistate version (MS-ARMD) are discussed. Both methods allow to study bond-breaking and bond-forming processes in chemical and biological processes. Particular emphasis is put on practical aspects for applying the methods to investigate the dynamics of chemical reactions. The chapter closes with an outlook of possible generalizations of the methods discussed.

The solvent dynamics around fluorinated acetonitrile is characterized by 2-dimensional infrared spectroscopy and atomistic simulations. The lineshape of the linear infrared spectrum is better captured by semiempirical (density functional tight binding) mixed quantum mechanical/molecular mechanics simulations, whereas force field simulations with multipolar interactions yield lineshapes that are significantly too narrow. For the solvent dynamics, a relatively slow time scale of 2 ps is found from the experiments and supported by the mixed quantum mechanical/molecular mechanics simulations. With multipolar force fields fitted to the available thermodynamical data, the time scale is considerably faster - on the 0.5 ps time scale. The simulations provide evidence for a well established CF-HOH hydrogen bond (population of 25%) which is found from the radial distribution function g(r) from both, force field and quantum mechanics/molecular mechanics simulations.