A single‐molecule reaction cascade: First‐principles molecular dynamics simulation

The success of mechanochemistry is continued with the targeted organic synthesis of functional nano‐scale devices. In the present theoretical study, first principles molecular dynamics simulations are performed for a recently synthesized three‐ring system that functions as a molecular reaction cascade. Mechanochemical and photochemical reaction conditions are investigated. The system was designed in a way that three bonds would break consecutively in mechanochemical and sonochemical setups. We succeeded to simulate the reaction mechanisms with first‐principles molecular dynamics simulations and discuss the stereochemistry.     

Molecular Mechanism of a Hotdog‐Fold Acyl‐CoA Thioesterase

Thioesterases are enzymes that hydrolyze thioester bonds between a carbonyl group and a sulfur atom. They catalyze key steps in fatty acid biosynthesis and metabolism, as well as polyketide biosynthesis. The reaction molecular mechanism of most hotdog‐fold acyl‐CoA thioesterases remains unknown, but several hypotheses have been put forward in structural and biochemical investigations. The reaction of a human thioesterase (hTHEM2), representing a thioesterase family with a hotdog fold where a coenzyme A moiety is cleaved, was simulated by quantum mechanics/molecular mechanics metadynamics techniques to elucidate atomic and electronic details of its mechanism, its transition‐state conformation, and the free energy landscape of the process. A single‐displacement acid‐base‐like mechanism, in which a nucleophilic water molecule is activated by an aspartate residue acting as a base, was found, confirming previous experimental proposals. The results provide unambiguous evidence of the formation of a tetrahedral‐like transition state. They also explain the roles of other conserved active‐site residues during the reaction, especially that of a nearby histidine/serine pair that protonates the thioester sulfur atom, the participation of which could not be elucidated from mutation analyses alone.     

van der Waals interactions are critical in Car–Parrinello molecular dynamics simulations of porphyrin–fullerene dyads

The interplay between electrostatic and van der Waals (vdW) interactions in porphyrin‐C₆₀ dyads is still under debate despite its importance in influencing the structural characteristics of such complexes considered for various applications in molecular photovoltaics. In this article, we sample the conformational space of a porphyrin‐C₆₀ dyad using Car–Parrinello molecular dynamics simulations with and without empirical vdW corrections. Long‐range vdW interactions, which are poorly described by the commonly used density functional theory functionals, prove to be essential for a proper dynamics of the dyad moieties. Inclusion of vdW corrections brings porphyrin and C₆₀ close together in an orientation that is in agreement with experimental observations. The structural differences arising from the vdW corrections are shown to be significant for several properties and potentially less important for others. Additionally, our Mulliken population analysis reveals that contrary to the common belief, porphyrin is not the primary electron donating moiety for C₆₀. In the considered dyad, fullerene's affinity for electrons is primarily satisfied by charge transfer from the amide group of the linker. However, we show that in the absence of another suitable bound donor, C₆₀ can withdraw electrons from porphyrin if it is sufficiently close. © 2015 Wiley Periodicals, Inc.     

A comparative study of O2, CO,and NO binding to iron–porphyrin

Minimum-energy structures of O₂, CO, and NO iron–porphyrin (FeP) complexes, computed with the Car–Parrinello molecular dynamics, agree well with the available experimental data for synthetic heme models. The diatomic molecule induces a 0.3–0.4 Å displacement of the Fe atom out of the porphyrin nitrogen (N_p) plane and a doming of the overall porphyrin ring. The energy of the iron–diatomic bond increases in the order Fe(SINGLE BOND)O₂ (9 kcal/mol) < Fe(SINGLE BOND)CO (26 kcal/mol) < Fe(SINGLE BOND)NO (35 kcal/mol). The presence of an imidazole axial ligand increases the strength of the Fe(SINGLE BOND)O₂ and Fe(SINGLE BOND)CO bonds (15 and 35 kcal/mol, respectively), with few structural changes with respect to the FeP(CO) and FeP(O₂) complexes. In contrast, the imidazole ligand does not affect the energy of the Fe(SINGLE BOND)NO bond, but induces significant structural changes with respect to the FeP(NO) complex. Similar variations in the iron–imidazole bond with respect to the addition of CO, O₂, and NO are also discussed. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 69: 31–35, 1998     

The Controlled Formation and Cleavage of an Intramolecular d8–d8 Pt–Pt Interaction in a Dinuclear Cycloplatinated Molecular “Pivot‐Hinge”

The bis(diphenylphosphino)methane (dppm)‐bridged dinuclear cycloplatinated complex {[Pt(L)]₂(μ‐dppm)}²⁺ (Pt₂ ? dppm; HL: 2‐phenyl‐6‐(1H‐pyrazol‐3‐yl)‐pyridine) demonstrates interesting reversible “pivot‐hinge”‐like intramolecular motions in response to the protonation/deprotonation of L. In its protonated “closed” configuration, the two platinum(II) centers are held in position by intramolecular d⁸–d⁸ Pt–Pt interaction. In its deprotonated “open” configuration, such Pt–Pt interaction is cleaved. To further understand the mechanism behind this hingelike motion, an analogous dinuclear cycloplatinated complex, {[Pt(L)]₂(μ‐dchpm)}²⁺ (Pt₂ ? dchpm) with bis(dicyclohexylphosphino)methane (dchpm) as the bridging ligand, was synthesized. From its protonation/deprotonation responses, it was revealed that aromatic π–π interactions between the phenyl moieties of the μ‐dppm and the deprotonated pyrazolyl rings of L was essential to the reversible cleavage of the intramolecular Pt–Pt interaction in Pt₂ ? dppm. In the case of Pt₂ ? dchpm, spectroscopic and spectrofluorometric titrations as well as X‐ray crystallography indicated that the distance between the two platinum(II) centers shrank upon deprotonation, thus causing a redshift in its room‐temperature triplet metal–metal‐to‐ligand charge‐transfer emission from 614 to 625 nm. Ab initio calculations revealed the presence of intramolecular hydrogen bonding between the deprotonated and negatively charged 1‐pyrazolyl‐N moiety and the methylene CH and phenyl C–H of the μ‐dppm. The “open” configuration of the deprotonated Pt₂ ? dppm was estimated to be 19 kcal mol^?1 more stable than its alternative “closed” configuration. On the other hand, the open configuration of the deprotonated Pt₂ ? dchpm was 6 kcal mol^?1 less stable than its alternative closed configuration.     

CPMD Simulation of a Bimolecular Chemical Reaction: Nucleophilic Attack of a Disulfide Bond under Mechanical Stress

Previous single‐molecule atomic force microscopy (AFM) experiments showed a change in the reactivity of a bimolecular substitution reaction with a definite force acting on a protein containing disulfide bonds. Using Car–Parrinello molecular dynamics (CPMD) simulations, we analyse the relevant reaction pathways for the breaking of a disulfide bond in the presence of nucleophiles.     

Conservation of Orbital Symmetry can be Circumvented in Mechanically Induced Reactions

In first‐principles molecular dynamics simulations of the mechanically induced ring‐opening of substituted benzocyclobutene we observe both con‐ and disrotatory ring‐opening reactions. We show that this finding does not contradict the fundamental principle that the orbitals develop continuously in time. However, it constitutes an exception from the principle of the conservation of orbital symmetry and thus is indeed an exception from the Woodward–Hoffmann rules. In contrast, the ring‐opening of unsubstituted cyclobutene proceeds in a conrotatory fashion. This shows that the breaking of the Woodward–Hoffmann rules is significantly facilitated by the substituents.     

An Unusual Phase Transition Driven by Vibrational Entropy Changes in a Hybrid Organic–Inorganic Perovskite

The driving forces for the phase transitions of ABX₃ hybrid organic–inorganic perovskites have been limited to the octahedral tilting, order–disorder, and displacement. Now, a complex structural phase transition has been explored in a HOIP, [CH₃NH₃][Mn(N₃)₃], based on structural characterizations and ab initio lattice dynamics calculations. This unusual first‐order phase transition between two ordered phases at about 265 K is primarily driven by changes in the collective atomic vibrations of the whole lattice, along with concurrent molecular displacements and an unusual octahedral tilting. A significant entropy difference (4.35 J K^?1 mol^?1) is observed between the low‐ and high‐temperature structures induced by such atomic vibrations, which plays a main role in driving the transition. This finding offers an alternative pathway for designing new ferroic phase transitions and related physical properties in HOIPs and other hybrid crystals.     

Protonation-induced stereoisomerism in nicotine: Conformational studies using classical (AMBER) and <Emphasis Type="Italic">ab initio</Emphasis> (Car–Parrinello) molecular dynamics

A variety of biologically active small molecules contain prochiral tertiary amines, which become chiral centers upon protonation. S-nicotine, the prototypical nicotinic acetylcholine receptor agonist, produces two diastereomers on protonation. Results, using both classical (AMBER) and ab initio (Car–Parrinello) molecular dynamical studies, illustrate the significant differences in conformational space explored by each diastereomer. As is expected, this phenomenon has an appreciable effect on nicotines energy hypersurface and leads to differentiation in molecular shape and divergent sampling. Thus, protonation induced isomerism can produce dynamic effects that may influence the behavior of a molecule in its interaction with a target protein. We also examine differences in the conformational dynamics for each diastereomer as quantified by both molecular dynamics methods.     

Ab-Initio Molecular Dynamics Simulation of Condensed-Phase Reactivity: The Electrolysis of Amino Acids and Peptides

Electrolysis is a potential candidate for a quick method of wastewater cleansing. However, it is necessary to know what compounds might be formed from bioorganic matter. We want to know if there are toxic intermediates and if it is possible to influence the product formation by the variation in initial conditions. In the present study, we use Car–Parrinello molecular dynamics to simulate the fastest reaction steps under such circumstances. We investigate the behavior of amino acids and peptides under anodic conditions. Such highly reactive situations lead to chemical reactions within picoseconds, and we can model the reaction mechanisms in full detail. The role of the electric current is to discharge charged species and, hence, to produce radicals from ions. This leads to ultra-fast radical reactions in a bulk environment, which can also be seen as redox reactions as the oxidation states change. In the case of amino acids, the educts can be zwitterionic, so we also observe complex acid–base chemistry. Hence, we obtain the full spectrum of condensed-phase chemistry.     

Significant Cation Effects in Carbon Dioxide–Ionic Liquid Systems

Carbon dioxide–ionic liquid systems are of great current interest, and significant efforts have been made lately to understand the intermolecular interactions in these systems. In general, all the experimental and theoretical studies have concluded so far that the main solute–solvent interaction takes effect through the anion, and the cation has no, or only a secondary role in solvation. In this theoretical approach it is shown that this view is unfounded, and evidence is provided that, similarly to the benzene–CO₂ system, dispersion interactions are present between the solute and the cation. Therefore, this defines a novel site for tailoring solvents to tune CO₂ solubility.     

Transport Processes at α‐Quartz–Water Interfaces: Insights from First‐Principles Molecular Dynamics Simulations

Car–Parrinello molecular dynamics (CP–MD) simulations are performed at high temperature and pressure to investigate chemical interactions and transport processes at the α‐quartz–water interface. The model system initially consists of a periodically repeated quartz slab with O‐terminated and Si‐terminated (1000) surfaces sandwiching a film of liquid water. At a temperature of 1000 K and a pressure of 0.3 GPa, dissociation of H₂O molecules into H⁺ and OH^? is observed at the Si‐terminated surface. The OH^? fragments immediately bind chemically to the Si‐terminated surface while Grotthus‐type proton diffusion through the water film leads to protonation of the O‐terminated surface. Eventually, both surfaces are fully hydroxylated and no further chemical reactions are observed. Due to the confinement between the two hydroxylated quartz surfaces, water diffusion is reduced by about one third in comparison to bulk water. Diffusion properties of dissolved SiO₂ present as Si(OH)₄ in the water film are also studied. We do not observe strong interactions between the hydroxylated quartz surfaces and the Si(OH)₄ molecule as would have been indicated by a substantial lowering of the Si(OH)₄ diffusion coefficient along the surface. No spontaneous dissolution of quartz is observed. To study the mechanism of dissolution, constrained CP–MD simulations are done. The associated free energy profile is calculated by thermodynamic integration along the reaction coordinate. Dissolution is a stepwise process in which two Si? O bonds are successively broken. Each bond breaking between a silicon atom at the surface and an oxygen atom belonging to the quartz lattice is accompanied by the formation of a new Si? O bond between the silicon atom and a water molecule. The latter loses a proton in the process which eventually leads to protonation of the oxygen atom in the cleaved quartz Si? O bond. The final solute species is Si(OH)₄.     

Magnetic Properties of a Terbium–[1]Ferrocenophane Complex: Analogies between Lanthanide–Ferrocenophane and Lanthanide–Bis‐phthalocyanine Complexes

A rare example of an organometallic terbium single‐ion magnet is reported. A Tb³⁺–[1]ferrocenophane complex displays a larger barrier to magnetization reversal than its isostructural Dy³⁺ analogue, which is reminiscent of trends observed for lanthanide–bis‐phthalocyanine complexes. Detailed ab initio calculations support the experimental observations and suggest a significantly larger ground‐state stabilization for the non‐Kramers ion Tb³⁺ in the Tb complex than for the Kramers‐ion Dy³⁺ in the Dy complex.     

Lewis Acids as Activators in CBS‐Catalysed Diels–Alder Reactions: Distortion Induced Lewis Acidity Enhancement of SnCl4

The effect of several Lewis acids on the CBS catalyst (named after Corey, Bakshi and Shibata) was investigated in this study. While ²H NMR spectroscopic measurements served as gauge for the activation capability of the Lewis acids, in situ FT‐IR spectroscopy was employed to assess the catalytic activity of the Lewis acid oxazaborolidine complexes. A correlation was found between the Δδ(²H) values and rate constants k_DA, which indicates a direct translation of Lewis acidity into reactivity of the Lewis acid–CBS complexes. Unexpectedly, a significant deviation was found for SnCl₄ as Lewis acid. The SnCl₄–CBS adduct was much more reactive than the Δδ(²H) values predicted and gave similar reaction rates to those observed for the prominent AlBr₃–CBS adduct. To rationalize these results, quantum mechanical calculations were performed. The frontier molecular orbital approach was applied and a good correlation between the LUMO energies of the Lewis acid–CBS–naphthoquinone adducts and k_DA could be found. For the SnCl₄–CBS–naphthoquinone adduct an unusual distortion was observed leading to an enhanced Lewis acidity. Energy decomposition analysis with natural orbitals for chemical valence (EDA‐NOCV) calculations revealed the relevant interactions and activation mode of SnCl₄ as Lewis acid in Diels–Alder reactions.     

Insights into the dynamics of evaporation and proton migration in protonated water clusters from Large‐scale Born–Oppenheimer direct dynamics

Large‐scale on‐the‐fly Born–Oppenheimer molecular dynamics simulations using recent advances in linear scaling electronic structure theory and trajectory integration techniques have been performed for protonated water clusters around the magic number (H₂O)_nH⁺, for n = 20 and 21. Besides demonstrating the feasibility and efficiency of the computational approach, the calculations reveal interesting dynamical details. Elimination of water molecules is found to be fast for both cluster sizes but rather insensitive to the initial geometry. The water molecules released acquire velocities compatible with thermal energies. The proton solvation shell changes between the well‐known Eigen and Zundel motifs and is characterized by specific low‐frequency vibrational modes, which have been quantified. The proton transfer mechanism largely resembles that of bulk water but one interesting variation was observed. © 2012 Wiley Periodicals, Inc.     

Spectroscopic fingerprints of toroidal nuclear quantum delocalization via ab initio path integral simulations

We investigate the quantum‐mechanical delocalization of hydrogen in rotational symmetric molecular systems. To this purpose, we perform ab initio path integral molecular dynamics simulations of a methanol molecule to characterize the quantum properties of hydrogen atoms in a representative system by means of their real‐space and momentum‐space densities. In particular, we compute the spherically averaged momentum distribution n(k) and the pseudoangular momentum distribution n(k_θ). We interpret our results by comparing them to path integral samplings of a bare proton in an ideal torus potential. We find that the hydroxyl hydrogen exhibits a toroidal delocalization, which leads to characteristic fingerprints in the line shapes of the momentum distributions. We can describe these specific spectroscopic patterns quantitatively and compute their onset as a function of temperature and potential energy landscape. The delocalization patterns in the projected momentum distribution provide a promising computational tool to address the intriguing phenomenon of quantum delocalization in condensed matter and its spectroscopic characterization. As the momentum distribution n(k) is also accessible through Nuclear Compton Scattering experiments, our results will help to interpret and understand future measurements more thoroughly. © 2012 Wiley Periodicals, Inc.     

Quantum‐Transport Characteristics of a p–n Junction on Single‐Layer TiS3

By using density functional theory and non‐equilibrium Green′s function‐based methods, we investigated the electronic and transport properties of a TiS₃ monolayer p–n junction. We constructed a lateral p–n junction on a TiS₃ monolayer using Li and F adatoms. An applied bias voltage caused significant variability in the electronic and transport properties of the TiS₃ p–n junction. In addition, the spin‐dependent current–voltage characteristics of the constructed TiS₃ p–n junction were analyzed. Important device characteristics were found, such as negative differential resistance and rectifying diode behaviors for spin‐polarized currents in the TiS₃ p–n junction. These prominent conduction properties of the TiS₃ p–n junction offer remarkable opportunities for the design of nanoelectronic devices based on a recently synthesized single‐layered material.     

Nature of hydration shells of a polyoxy‐anion with a large cationic centre: The case of iodate ion in water

The structural nature of the solvation shells of an iodate ion, which is known to be a polyoxy‐anion with a large cationic centre, is investigated by means of Born–Oppenheimer molecular dynamics (BOMD) simulations using BLYP and the dispersion corrected BLYP‐D3 functionals. The iodate ion is found to have two distinct solvation regions around the positively charged iodine (iodine solvation shell or ISS) and the negatively charged oxygens (oxygen solvation shell or OSS). We have looked at the spatial, orientational, and hydrogen bond distributions of water in the two solvation regions. It is found that the water orientational profile in the ISS is typical of a cation hydration shell. The hydrogen bonded structure of water in the OSS is found to be very similar to that of the bulk water structure. Thus, the iodate ion essentially behaves like a positively charged iodine ion in water as if there is no anionic part. This explains why the cationic character of the iodate ion was prominently seen in earlier studies. The arrangement of water molecules in the two solvation shells and in the intervening regions around the iodate ion is further resolved by looking at structural cross‐correlations. The electronic properties of the solvation shells are also looked at by calculating the solute–solvent orbital overlap and dipole moments of the solute and solvation shell water. We have also performed BOMD simulations of iodate ion‐water clusters at experimentally relevant conditions. The simulation results are found to be in agreement with experimental results. © 2018 Wiley Periodicals, Inc.