Photogeneration of reactive intermediates

Bond cleavage and formation are key steps in chemistry and biochemistry. The present work investigates the generation of diphenylmethyl cations (Ph2CH+) via photoinduced bond cleavage of diphenylmethyl derivatives with a cationic or neutral leaving group. The resulting Ph2CH+ cations and its numerous derivatives serve as reference electrophiles for one of the most extensive reactivity scales covering 40 orders of magnitude. In chapter 1, the focus is on the initial bond cleavage of diphenylmethyltriphenylphosphonium ions (Ph2CH−PPh3+) exhibiting a cationic leaving group. With the help of state-of-the-art quantum chemical and quantum dynamical methods, the reaction mechanism of the bond cleavage is revealed. Using a reduced model system, the potential energy surfaces can be calculated at the ONIOM level of theory along specially designed reactive coordinates. Two competing reaction channels emerge: a homolytic one in the S1 state and a heterolytic one in the ground state. They are connected via an energetically accessible conical intersection which makes an efficient generation of the observed Ph2CH+ cations feasible. In contradiction with the experiment in polar or moderately polar solvents, quantum dynamical calculations for the isolated molecule reveal the formation of Ph2CH• radicals. While electrostatic solvent effects are negligible in this system, dynamic solvent effects emerge as being essential to explain the molecular mechanism. Two methods with increasing complexity to describe the dynamic impact of the solvent environment are developed. The first approach, the dynamic continuum ansatz, treats the environment implicitly. It uses Stokes’ law and the dynamic viscosity of the solvent in combination with quantum chemically and dynamically evaluated quantities to obtain the decelerating force exerted on the dissociating fragments. The ansatz does not require any fitting of parameters. The second method, the QD/MD approach, is based on an explicit treatment of the solvent surrounding. It combines molecular dynamics (MD) simulations of the reactant in a box of solvent molecules with quantum dynamics (QD) calculations of the reactant’s dynamics. In this way, a more detailed microscopic picture of the molecular process can be derived taking into account individual arrangements of the solvent. Both methods unveil the crucial impact of the solvent cage on the bond cleavage mechanism. It hinders the free dissociation in the S1 state and guides the molecular system to the conical intersection. QD simulations including the non-adiabatic coupling around the conical intersection show the formation of Ph2CH+ within ∼400 fs which compares well with the initial rise of the cation absorption in the experiment. Chapter 2 deals with the position of the counterion X– in the ion pairs Ph2CH−PPh3+ X–, PhCH2−PPh3+ X–, and (p-CF3-C6H4)CH2−PPh3+ X– in solution with X– being Cl–, Br–, BF4–, and SbF6–. These structures are essential to clarify the role of oxidizable counterions like e.g. Cl– during the initial bond cleavage in dichloromethane. The structures determined quantum chemically in dichloromethane show a similar counterion position than in the crystal. They are confirmed by the good accordance of the calculated and measured 1H NMR shifts. The C(α)–H···X– hydrogen bonds account for the pronounced counterion-dependent 1H NMR shifts of the C(α)–H in CD2Cl2. The strong downfield shift of the signals increases according to SbF6– < BF4– << Br– < Cl–. The last part (chapter 3) focuses on the secondary processes within a few picoseconds to several nanoseconds after the C-Cl bond cleavage in diphenylmethylchloride in solution. Initially, the neutral leaving group Cl leads mainly to the formation of radical pairs; only a minor fraction of ion pairs is generated in the beginning. A combined Marcus-Smoluchowski model is used to simulate the interplay between geminate recombination, diffusional separation, and electron transfer of the radical and ion pair populations. The distance-dependent rates of the three processes together with broad distance-dependent population distributions faithfully reproduce the spectroscopically observed dynamics. The majority of Ph2CH+ cations is generated via electron transfer from the radical pairs. The detailed understanding of the secondary processes shows that a high Ph2CH+ cation yield can be expected if the radicals within a pair stay nearby for a long time to achieve an efficient electron transfer and if the resulting ions are separated fast to prevent geminate recombination

Photogeneration of reactive intermediates

Bond cleavage and formation are key steps in chemistry and biochemistry. The present work investigates the generation of diphenylmethyl cations (Ph2CH+) via photoinduced bond cleavage of diphenylmethyl derivatives with a cationic or neutral leaving group. The resulting Ph2CH+ cations and its numerous derivatives serve as reference electrophiles for one of the most extensive reactivity scales covering 40 orders of magnitude. In chapter 1, the focus is on the initial bond cleavage of diphenylmethyltriphenylphosphonium ions (Ph2CH−PPh3+) exhibiting a cationic leaving group. With the help of state-of-the-art quantum chemical and quantum dynamical methods, the reaction mechanism of the bond cleavage is revealed. Using a reduced model system, the potential energy surfaces can be calculated at the ONIOM level of theory along specially designed reactive coordinates. Two competing reaction channels emerge: a homolytic one in the S1 state and a heterolytic one in the ground state. They are connected via an energetically accessible conical intersection which makes an efficient generation of the observed Ph2CH+ cations feasible. In contradiction with the experiment in polar or moderately polar solvents, quantum dynamical calculations for the isolated molecule reveal the formation of Ph2CH• radicals. While electrostatic solvent effects are negligible in this system, dynamic solvent effects emerge as being essential to explain the molecular mechanism. Two methods with increasing complexity to describe the dynamic impact of the solvent environment are developed. The first approach, the dynamic continuum ansatz, treats the environment implicitly. It uses Stokes’ law and the dynamic viscosity of the solvent in combination with quantum chemically and dynamically evaluated quantities to obtain the decelerating force exerted on the dissociating fragments. The ansatz does not require any fitting of parameters. The second method, the QD/MD approach, is based on an explicit treatment of the solvent surrounding. It combines molecular dynamics (MD) simulations of the reactant in a box of solvent molecules with quantum dynamics (QD) calculations of the reactant’s dynamics. In this way, a more detailed microscopic picture of the molecular process can be derived taking into account individual arrangements of the solvent. Both methods unveil the crucial impact of the solvent cage on the bond cleavage mechanism. It hinders the free dissociation in the S1 state and guides the molecular system to the conical intersection. QD simulations including the non-adiabatic coupling around the conical intersection show the formation of Ph2CH+ within ∼400 fs which compares well with the initial rise of the cation absorption in the experiment. Chapter 2 deals with the position of the counterion X– in the ion pairs Ph2CH−PPh3+ X–, PhCH2−PPh3+ X–, and (p-CF3-C6H4)CH2−PPh3+ X– in solution with X– being Cl–, Br–, BF4–, and SbF6–. These structures are essential to clarify the role of oxidizable counterions like e.g. Cl– during the initial bond cleavage in dichloromethane. The structures determined quantum chemically in dichloromethane show a similar counterion position than in the crystal. They are confirmed by the good accordance of the calculated and measured 1H NMR shifts. The C(α)–H···X– hydrogen bonds account for the pronounced counterion-dependent 1H NMR shifts of the C(α)–H in CD2Cl2. The strong downfield shift of the signals increases according to SbF6– < BF4– << Br– < Cl–. The last part (chapter 3) focuses on the secondary processes within a few picoseconds to several nanoseconds after the C-Cl bond cleavage in diphenylmethylchloride in solution. Initially, the neutral leaving group Cl leads mainly to the formation of radical pairs; only a minor fraction of ion pairs is generated in the beginning. A combined Marcus-Smoluchowski model is used to simulate the interplay between geminate recombination, diffusional separation, and electron transfer of the radical and ion pair populations. The distance-dependent rates of the three processes together with broad distance-dependent population distributions faithfully reproduce the spectroscopically observed dynamics. The majority of Ph2CH+ cations is generated via electron transfer from the radical pairs. The detailed understanding of the secondary processes shows that a high Ph2CH+ cation yield can be expected if the radicals within a pair stay nearby for a long time to achieve an efficient electron transfer and if the resulting ions are separated fast to prevent geminate recombination

Two cooperative binding sites sensitize PI(4,5)P2 recognition by the tubby domain

Phosphoinositides (PIs) are lipid signaling molecules that operate by recruiting proteins to cellular membranes via PI recognition domains. The dominant PI of the plasma membrane is phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. One of only two PI(4,5)P2 recognition domains characterized in detail is the tubby domain. It is essential for targeting proteins into cilia involving reversible membrane association. However, the PI(4,5)P2 binding properties of tubby domains have remained enigmatic. Here, we used coarse-grained molecular dynamics simulations to explore PI(4,5)P2 binding by the prototypic tubby domain. The comparatively low PI(4,5)P2 affinity of the previously described canonical binding site is underpinned in a cooperative manner by a previously unknown, adjacent second binding site. Mutations in the previously unknown site impaired PI(4,5)P2-dependent plasma membrane localization in living cells and PI(4,5)P2 interaction in silico, emphasizing its importance for PI(4,5)P2 affinity. The two-ligand binding mode may serve to sharpen the membrane association-dissociation cycle of tubby-like proteins that underlies delivery of ciliary cargo

Lipid Fingerprints and Cofactor Dynamics of Light-Harvesting Complex II in Different Membranes

Plant light-harvesting complex II (LHCII) is the key antenna complex for plant photosynthesis. We present coarse-grained molecular dynamics simulations of monomeric and trimeric LHCII in a realistic thylakoid membrane environment based on the Martini force field. The coarse-grained protein model has been optimized with respect to atomistic reference simulations. Our simulations provide detailed insights in the thylakoid lipid fingerprint of LHCII which compares well with experimental data from membrane protein purification. Comparing the monomer and trimeric LHCII reveals a stabilizing effect of trimerization on the chromophores as well as the protein. Moreover, the average chromophore distance shortens in the trimer leading to stronger excitonic couplings. When changing the native thylakoid environment to a model membrane the protein flexibility remains constant, whereas the chromophore flexibility is reduced. Overall, the presented LHCII model lays the foundation to investigate the μs dynamics of this key antenna protein of plants

Molecular dynamics simulations in photosynthesis

Photosynthesis is regulated by a dynamic interplay between proteins, enzymes, pigments, lipids, and cofactors that takes place on a large spatio-temporal scale. Molecular dynamics (MD) simulations provide a powerful toolkit to investigate dynamical processes in (bio)molecular ensembles from the (sub)picosecond to the (sub)millisecond regime and from the Å to hundreds of nm length scale. Therefore, MD is well suited to address a variety of questions arising in the field of photosynthesis research. In this review, we provide an introduction to the basic concepts of MD simulations, at atomistic and coarse-grained level of resolution. Furthermore, we discuss applications of MD simulations to model photosynthetic systems of different sizes and complexity and their connection to experimental observables. Finally, we provide a brief glance on which methods provide opportunities to capture phenomena beyond the applicability of classical MD

Running in the Family : Molecular Factors controlling Spin Crossover of Iron(II) Complexes with Schiff‐base like Ligands

Tailoring of spin state energetics of transition metal complexes and even the correct prediction of the resulting spin state is still a challenging task, both for the experimentalist and the theoretician. Apart from the complexity in the solid state imposed by packing effects, molecular factors of the spin state ordering are required to be identified and quantified on equal rights. In this work we experimentally record the spin states and SCO energies within an eight-member substitution-series of N4O2 ligated iron(II) complexes both in the solid state (SQUID magnetometry and single-crystal X-ray crystallography) and in solution (VT-NMR). The experimental survey is complemented by exhaustive theoretical modelling of the molecular and electronic structure of the open-chain N4O2 family and its macrocyclic N6 congeners through density-functional theory methods. Ligand topology is identified as the leading factor defining ground-state multiplicity of the corresponding iron(II) complexes. Invariably the low-spin state is sterically trapped in the macrocycles, whereas subtle substitution effects allow for a molecular fine tuning of the spin state in the open-chain ligands. Factorization of computed relative SCO energies holds promise for directed design of future SCO systems

Martini 3 Coarse-Grained Model for Type III Deep Eutectic Solvents:Thermodynamic, Structural, and Extraction Properties

Deep eutectic solvents (DESs) are a more environmentally friendly, cost-effective, and recyclable alternative for ionic liquids. Since the number of possible deep eutectic solvents is very large, there are needs for effective methods to predict the physicochemical nature of possible new deep eutectic solvents that are not met by the currently available models. Here, we have built coarse-grained models for a few well-known and actively studied deep eutectic solvents using the recently published Martini 3 force field. Molecular dynamics simulations demonstrate that our models predict the properties of these particular DESs with an acceptable accuracy, and they are capable of capturing known liquid-liquid extraction processes as well as morphological shape changes of surfactant aggregates. Our coarse-grained approach is novel in the study of DESs, opening new possibilities for rapid screening of new DESs and their properties

An Allosteric Pathway in Copper, Zinc Superoxide Dismutase Unravels the Molecular Mechanism of the G93A Amyotrophic Lateral Sclerosis-Linked Mutation

Several different mutations of the protein copper, zinc superoxide dismutase (SOD1) produce the neurodegenerative disorder amyotrophic lateral sclerosis (ALS). The molecular mechanism by which the diverse mutations converge to a similar pathology is currently unknown. The electrostatic loop (EL) of SOD1 is known to be affected in all of the studied ALS-linked mutations of SOD1. In this work, we employ a multiscale simulation approach to show that this perturbation corresponds to an increased probability of the EL detaching from its native position, exposing the metal site of the protein to water. From extensive atomistic and coarse-grained molecular dynamics (MD) simulations, we identify an allosteric pathway that explains the action of the distant G93A mutation on the EL. Finally, we employ quantum mechanics/molecular mechanics MD simulations to show that the opening of the EL decreases the Zn(II) affinity of the protein. As the loss of Zn(II) is at the center of several proposed pathogenic mechanisms in SOD1-linked ALS, the structural effect identified here not only is in agreement with the experimental data but also places the opening of the electrostatic loop as the possible main pathogenic effect for a significant number of ALS-linked SOD1 mutations