Differences in the Active Site of Water Oxidation among Photosynthetic Organisms

The site of biological water oxidation is highly conserved across photosynthetic organisms, but differences of unidentified structural and electronic origin exist between taxonomically discrete clades, revealed by distinct spectroscopic signatures of the oxygen-evolving Mn₄CaO₅ cluster and variations in active-site accessibility. Comparison of atomistic models of a native cyanobacterial form (<i>Thermo­synecho­coccus vulcanus</i>) and a chimeric spinach-like form of photosystem II allows us to identify the precise atomic-level differences between organisms in the vicinity of the manganese cluster. Substitution of cyanobacterial D1-Asn87 by higher-plant D1-Ala87 is the principal discriminating feature: it drastically rearranges a network of proximal hydrogen bonds, modifying the local architecture of a water channel and the interaction of second coordination shell residues with the manganese cluster. The two variants explain species-dependent differences in spectroscopic properties and in the interaction of substrate analogues with the oxygen-evolving complex, enabling assignment of a substrate delivery channel to the active site

Functional Water Networks in Fully Hydrated Photosystem II

Water channels and networks within photosystem II (PSII) of oxygenic photosynthesis are critical for enzyme structure and function. They control substrate delivery to the oxygen-evolving center and mediate proton transfer at both the oxidative and reductive endpoints. Current views on PSII hydration are derived from protein crystallography, but structural information may be compromised by sample dehydration and technical limitations. Here, we simulate the physiological hydration structure of a cyanobacterial PSII model following a thorough hydration procedure and large-scale unconstrained all-atom molecular dynamics enabled by massively parallel simulations. We show that crystallographic models of PSII are moderately to severely dehydrated and that this problem is particularly acute for models derived from X-ray free electron laser (XFEL) serial femtosecond crystallography. We present a fully hydrated representation of cyanobacterial PSII and map all water channels, both static and dynamic, associated with the electron donor and acceptor sides. Among them, we describe a series of transient channels and the attendant conformational gating role of protein components. On the acceptor side, we characterize a channel system that is absent from existing crystallographic models but is likely functionally important for the reduction of the terminal electron acceptor plastoquinone QB. The results of the present work build a foundation for properly (re)evaluating crystallographic models and for eliciting new insights into PSII structure and function

A Hierarchy of Methods for the Energetically Accurate Modeling of Isomerism in Monosaccharides

The performance of different wave-function-based and density functional theory (DFT) methods was evaluated with respect to the prediction of relative energies for gas-phase monosaccharide isomers. A test set of 58 structures was employed, representing all forms of isomerism encountered in d-aldohexoses. The set was built from eight hexopyranose epimers by deriving subsets of isomers that include hydroxymethyl rotamers, anomers, ring conformers, furanose, and open-chain forms. Each subset of isomers spans a different energy range and involves various stereoelectronic effects. Reference energy values were obtained with coupled-cluster calculations extrapolated to the complete basis set limit, CCSD­(T)/CBS. The tested CBS-extrapolated ab initio methods include various types of Møller–Plesset (MP) perturbation theory and the localized paired natural orbital coupled electron pair approach (LPNO-CEPA). Extensive benchmarking of DFT methods was carried out with 31 functionals. The results allow us to establish a hierarchy of methods that forms a reference guide for further computational studies. Among wave-function-based methods, LPNO-CEPA proved indistinguishable from CCSD­(T), offering a promising alternative for a reference method that can be applied to larger systems. MP2 and SCS-MP2 follow closely, surpassing SOS-MP2 and MP3. The <i>m</i>PW2PLYP-D double hybrid and the Minnesota M06-2X hybrid meta-GGA are the best performing density functionals and are directly competitive with wave-function-based ab initio methods. Among the remaining functionals, B3PW91, TPSSh, <i>m</i>PW1PW91, and PBE0 yield the best results on average, while PBE is the best general-purpose GGA functional, surpassing meta-GGAs and several hybrids such as B3LYP. The choice of method strongly depends on the type of isomerism that needs to be considered, since many DFT methods perform well for purely conformational isomerism, but most of them fail to describe ring versus open-chain isomerism, where LYP-based GGA functionals perform particularly poorly

Improved Segmented All-Electron Relativistically Contracted Basis Sets for the Lanthanides

Improved versions of the segmented all-electron relativistically contracted (SARC) basis sets for the lanthanides are presented. The second-generation SARC2 basis sets maintain efficient construction of their predecessors and their individual adaptation to the DKH2 and ZORA Hamiltonians, but feature exponents optimized with a completely new orbital shape fitting procedure and a slightly expanded f space that results in sizable improvement in CASSCF energies and in significantly more accurate prediction of spin–orbit coupling parameters. Additionally, an extended set of polarization/correlation functions is constructed that is appropriate for multireference correlated calculations and new auxiliary basis sets for use in resolution-of-identity (density-fitting) approximations in combination with both DFT and wave function based treatments. Thus, the SARC2 basis sets extend the applicability of the first-generation DFT-oriented basis sets to routine all-electron wave function-based treatments of lanthanide complexes. The new basis sets are benchmarked with respect to excitation energies, radial distribution functions, optimized geometries, orbital eigenvalues, ionization potentials, and spin–orbit coupling parameters of lanthanide systems and are shown to be suitable for the description of magnetic and spectroscopic properties using both DFT and multireference wave function-based methods

What Can We Learn from a Biomimetic Model of Nature’s Oxygen-Evolving Complex?

A recently reported synthetic complex with a Mn₄CaO₄ core represents a remarkable structural mimic of the Mn₄CaO₅ cluster in the oxygen-evolving complex (OEC) of photosystem II (Zhang et al., <i>Science</i> <b>2015</b>, 348, 690). Oxidized samples of the complex show electron paramagnetic resonance (EPR) signals at <i>g</i> ≈ 4.9 and 2, similar to those associated with the OEC in its <i>S</i>₂ state (<i>g</i> ≈ 4.1 from an <i>S</i> = ⁵/₂ form and <i>g</i> ≈ 2 from an <i>S</i> = ¹/₂ form), suggesting similarities in the electronic as well as geometric structure. We use quantum-chemical methods to characterize the synthetic complex in various oxidation states, to compute its magnetic and spectroscopic properties, and to establish connections with reported data. Only one energetically accessible form is found for the oxidized “<i>S</i>₂ state” of the complex. It has a ground spin state of <i>S</i> = ⁵/₂, and EPR simulations confirm it can be assigned to the <i>g</i> ≈ 4.9 signal. However, no valence isomer with an <i>S</i> = ¹/₂ ground state is energetically accessible, a conclusion supported by a wide range of methods, including density matrix renormalization group with full valence active space. Alternative candidates for the <i>g</i> ≈ 2 signal were explored, but no low-spin/low-energy structure was identified. Therefore, our results suggest that despite geometric similarities the synthetic model does not mimic the valence isomerism that is the hallmark of the OEC in its <i>S</i>₂ state, most probably because it lacks a coordinatively flexible oxo bridge. Only one of the observed EPR signals can be explained by a structurally intact high-spin one-electron-oxidized form, while the other originates from an as-yet-unidentified rearrangement product. Nevertheless, this model provides valuable information for understanding the high-spin EPR signals of both the <i>S</i>₁ and <i>S</i>₂ states of the OEC in terms of the coordination number and Jahn–Teller axis orientation of the Mn ions, with important consequences for the development of magnetic spectroscopic probes to study <i>S</i>-state intermediates immediately prior to O–O bond formation

On the Magnetic and Spectroscopic Properties of High-Valent Mn₃CaO₄ Cubanes as Structural Units of Natural and Artificial Water-Oxidizing Catalysts

The Mn­(IV)₃CaO₄ cubane is a structural motif present in the oxygen-evolving complex (OEC) of photosystem II and in water-oxidizing Mn/Ca layered oxides. This work investigates the magnetic and spectroscopic properties of two recently synthesized complexes and a series of idealized models that incorporate this structural unit. Magnetic interactions, accessible spin states, and ⁵⁵Mn isotropic hyperfine couplings are computed with quantum chemical methods and form the basis for structure–property correlations. Additionally, the effects of oxo-bridge protonation and one-electron reduction are examined. The calculated properties are found to be in excellent agreement with available experimental data. It is established that all synthetic and model Mn­(IV)₃CaO₄ cubane complexes have the same high-spin <i>S</i> = ⁹/₂ ground state. The magnetic coupling conditions under which different ground spin states can be accessed are determined. Substitution of Mn­(IV) magnetic centers by diamagnetic ions [e.g., Ge­(IV)] allows one to “switch off” specific spin sites in order to examine the magnetic orbitals along individual Mn–Mn exchange pathways, which confirms the predominance of ferromagnetic interactions within the cubane framework. The span of the Heisenberg spin ladder is found to correlate inversely with the number of protonated oxo bridges. Energetic comparisons for protonated models show that the tris-μ-oxo bridge connecting only Mn ions in the cubane has the lowest proton affinity and that the average relaxation energy per additional proton is on the order of 18 kcal·mol^–1, thus making access to ground states other than the high-spin <i>S</i> = ⁹/₂ state in these cubanes unlikely. The relevance of these cubanes for the OEC and synthetic oxides is discussed

Convergence of QM/MM and Cluster Models for the Spectroscopic Properties of the Oxygen-Evolving Complex in Photosystem II

The latest crystal structure of photosystem II at 1.9 Å resolution, which resolves the topology of the Mn₄CaO₅ oxygen evolving complex (OEC) at atomistic detail, enables a better correlation between structural features and spectroscopic properties than ever before. Building on the refined crystallographic model of the OEC and the protein, we present combined quantum mechanical/molecular mechanical (QM/MM) studies of the spectroscopic properties of the natural catalyst embedded in the protein matrix. Focusing on the S₂ state of the catalytic cycle, we examine the convergence of not only structural parameters but also of the intracluster magnetic interactions in terms of exchange coupling constants and of experimentally relevant ⁵⁵Mn, ¹⁷O, and ¹⁴N hyperfine coupling constants with respect to QM/MM partitioning using five QM regions of increasing size. This enables us to assess the performance of the method and to probe second sphere effects by identifying amino acid residues that principally affect the spectroscopic properties of the OEC. Comparison between QM-only and QM/MM treatments reveals that whereas QM/MM models converge quickly to stable values, the QM cluster models need to incorporate significantly larger parts of the second coordination sphere and surrounding water molecules to achieve convergence for certain properties. This is mainly due to the sensitivity of the QM-only models to fluctuations in the hydrogen bonding network and ligand acidity. Additionally, a hydrogen bond that is typically omitted in QM-only treatments is shown to determine the hyperfine coupling tensor of the unique Mn­(III) ion by regulating the rotation plane of the ligated D1-His332 imidazole ring, the only N-donor ligand of the OEC

Benzonitrile Adducts of Terminal Diarylphosphido Complexes: Preparative Sources of “RuPR₂”

Dehydrohalogenation of secondary diarylphosphine ruthenium complexes in the presence of benzonitrile yields stable, isolable nitrile adducts of the formula [Ru­(η⁵-indenyl)­(PAr₂)­(NCPh)­(PPh₃)], in which the terminal phosphido ligand is pyramidal at P and contains a stereochemically active lone pair. Unlike the analogous carbonyl adducts [Ru­(η⁵-indenyl)­(PAr₂)­(CO)­(PPh₃)], these benzonitrile complexes behave as masked sources of the highly reactive planar phosphido complexes [Ru­(η⁵-indenyl)­(PAr₂)­(PPh₃)], which contain a RuPAr₂ π bond. This is illustrated by the addition (or cycloaddition) reactions of the benzonitrile adducts with dihydrogen, methyl iodide, and 1-hexene, as well as their thermal decomposition via orthometalation of the PPh₃ ligand. Enthalpies of CO vs NCPh dissociation from the [Ru­(η⁵-indenyl)­(PR₂)­(PPh₃)] fragments (R = alkyl, aryl) have been calculated, as has the trajectory of addition of H₂ to the model planar phosphido complex [Ru­(η⁵-indenyl)­(PMe₂)­(PMe₃)]. The latter study shows the intermediacy of an η²-H₂ adduct, [Ru­(η⁵-indenyl)­(PAr₂)­(η²-H₂)­(PPh₃)], in the formation of [RuH­(η⁵-indenyl)­(HPMe₂)­(PMe₃)], a further indication of the importance of the variable binding modes of the terminal phosphido ligand in this system

Benzonitrile Adducts of Terminal Diarylphosphido Complexes: Preparative Sources of “RuPR₂”

Dehydrohalogenation of secondary diarylphosphine ruthenium complexes in the presence of benzonitrile yields stable, isolable nitrile adducts of the formula [Ru­(η⁵-indenyl)­(PAr₂)­(NCPh)­(PPh₃)], in which the terminal phosphido ligand is pyramidal at P and contains a stereochemically active lone pair. Unlike the analogous carbonyl adducts [Ru­(η⁵-indenyl)­(PAr₂)­(CO)­(PPh₃)], these benzonitrile complexes behave as masked sources of the highly reactive planar phosphido complexes [Ru­(η⁵-indenyl)­(PAr₂)­(PPh₃)], which contain a RuPAr₂ π bond. This is illustrated by the addition (or cycloaddition) reactions of the benzonitrile adducts with dihydrogen, methyl iodide, and 1-hexene, as well as their thermal decomposition via orthometalation of the PPh₃ ligand. Enthalpies of CO vs NCPh dissociation from the [Ru­(η⁵-indenyl)­(PR₂)­(PPh₃)] fragments (R = alkyl, aryl) have been calculated, as has the trajectory of addition of H₂ to the model planar phosphido complex [Ru­(η⁵-indenyl)­(PMe₂)­(PMe₃)]. The latter study shows the intermediacy of an η²-H₂ adduct, [Ru­(η⁵-indenyl)­(PAr₂)­(η²-H₂)­(PPh₃)], in the formation of [RuH­(η⁵-indenyl)­(HPMe₂)­(PMe₃)], a further indication of the importance of the variable binding modes of the terminal phosphido ligand in this system

Alkene Insertions into a Ru–PR₂ Bond

An unusually broad series of discrete alkene insertion reactions has provided the opportunity to examine the mechanism(s) of this fundamental carbon–heteroatom bond-forming process. Ethylene, electron-rich and electron-poor (activated) alkenes all react with the Ru–P double bond in Ru­(η⁵-indenyl)­(PCy₂)­(PPh₃) to form κ²-ruthenaphosphacyclo­butanes. Thermal decomposition of these metallacycles in solution, via alkene deinsertion and β-hydride elimination, is particularly favored for electron-rich alkenes, and hydride-containing decomposition products are implicit intermediates in the observed isomerization of 1-hexene. Kinetic studies, including a Hammett analysis of the insertion reactions of para-substituted styrenes, suggest that two distinct inner-sphere pathways operate for the insertion of electron-rich versus activated alkenes. DFT analyses have identified one pathway involving simple cycloaddition via a four-centered transition state and another that proceeds through an η²-alkene intermediate. Such an intermediate was observed spectroscopically during formation of the ethylene metallacycle, but not for substituted alkenes. We propose that “pre-polarized”, activated alkenes participate in direct cycloaddition, while rate-determining η²-adduct formation is necessary for the activation of electron-rich alkenes toward migratory insertion into the Ru–P bond