Rationalising the Geometric Variation between the A and B Monomers in the 1.9 Å Crystal Structure of Photosystem II

Density functional theory calculations are reported on a set of models of the water‐oxidising complex (WOC) of photosystem II (PSII), exploring structural features revealed in the most recent (1.9 Å resolution) X‐ray crystallographic studies of PSII. Crucially, we find that the variation in the Mn–Mn distances seen between the A and B monomers of this crystal structure can be entirely accounted for, in the low oxidation state (LOS) paradigm, by consideration of the interplay between two hydrogen‐bonding interactions involving proximate amino acid residues with the oxo bridges of the WOC, that is, His337 with O3 (which leads to a general elongation in the Mn–Mn distances between Mn1, Mn2 and Mn3) and Arg357 with O2 (which results in a specific elongation of the Mn2?Mn3 distance).     

Resolving the Differences Between the 1.9 Å and 1.95 Å Crystal Structures of Photosystem II: A Single Proton Relocation Defines Two Tautomeric Forms of the Water‐Oxidizing Complex

Great progress has been made in characterizing the water‐oxidizing complex (WOC) in photosystem II (PSII) with the publication of a 1.9 Å resolution X‐ray diffraction (XRD) and recently a 1.95 Å X‐ray free‐electron laser (XFEL) structure. However, these achievements are under threat because of perceived conflicts with other experimental data. For the earlier 1.9 Å structure, lack of agreement with extended X‐ray absorption fine structure (EXAFS) data led to the notion that the WOC suffered from X‐ray photoreduction. In the recent 1.95 Å structure, Mn photoreduction is not an issue, but poor agreement with computational models which adopt the ‘high’ oxidation state paradigm, has again resulted in criticism of the structure on the basis of contamination with lower S states of the WOC. Here we use DFT modeling to show that the distinct WOC geometries in the 1.9 and 1.95 Å structures can be straightforwardly accounted for when the Mn oxidation states are consistent with the ‘low’ oxidation state paradigm. Remarkably, our calculations show that the two structures are tautomers, related by a single proton relocation.     

On Ammonia Binding to the Oxygen‐Evolving Complex of Photosystem II: A Quantum Chemical Study

A recent EPR study (M. Perrez Navarro et al., Proc. Natl. Acad. Sci.­ 2013 , 110, 15561) provided evidence that ammonia binding to the oxygen‐evolving complex (OEC) of photosystem II in its S₂ state takes place at a terminal‐water binding position (W1) on the “dangler” manganese center Mn_A. This contradicted earlier interpretations of ¹⁴N electron‐spin‐echo envelope modulation (ESEEM) and extended X‐ray absorption fine‐structure (EXAFS) data, which were taken to indicate replacement of a bridging oxo ligand by an NH₂ unit. Here we have used systematic broken‐symmetry density functional theory calculations on large (ca. 200 atom) model clusters of an extensive variety of substitution patterns and core geometries to examine these contradictory pieces of evidence. Computed relative energies clearly favor the terminal substitution pattern over bridging‐ligand arrangements (by about 20–30 kcal mol^?1) and support W1 as the preferred binding site. Computed ¹⁴N EPR nuclear‐quadrupole coupling tensors confirm previous assumptions that the appreciable asymmetry may be accounted for by strong, asymmetric hydrogen bonding to the bound terminal NH₃ ligand (mainly by Asp61). Indeed, bridging NH₂ substitution would lead to exaggerated asymmetries. Although our computed structures confirm that the reported elongation of an Mn–Mn distance by about 0.15 Å inferred from EXAFS experiments may only be reproduced by bridging NH₂ substitution, it seems possible that the underlying EXAFS data were skewed by problems due to radiation damage. Overall, the present data clearly support the suggested terminal NH₃ coordination at the W1 site. The finding is significant for the proposed mechanistic scenarios of OEC catalysis, as this is not a water substrate site, and effects of this ammonia binding on catalysis thus must be due to more indirect influences on the likely substrate binding site at the O5 bridging‐oxygen position.     

A Z‐Scheme‐Inspired Photobioelectrochemical H2O/O2 Cell with a 1 V Open‐Circuit Voltage Combining Photosystem II and PbS Quantum Dots

A biohybrid photobioanode mimicking the Z‐scheme has been developed by functional integration of photosystem II (PSII) and PbS quantum dots (QDs) within an inverse opal TiO₂ architecture giving rise to a rather negative water oxidation potential of about ?0.55 V vs. Ag/AgCl, 1 m KCl at neutral pH. The electrical linkage between both light‐sensitive entities has been established through an Os‐complex‐modified redox polymer (P_Os), which allows the formation of a multi‐step electron‐transfer chain under illumination starting with the photo‐activated water oxidation at PSII followed by an electron transfer from PSII through P_Os to the photo‐excited QDs and finally to the TiO₂ electrode. The photobioanode was coupled to a novel, transparent, inverse‐opal ATO cathode modified with an O₂‐reducing bilirubin oxidase for the construction of a H₂O/O₂ photobioelectrochemical cell reaching a high open‐circuit voltage of about 1 V under illumination.     

Thiazole‐Based γ‐Building Blocks as Reverse‐Turn Mimetic to Design a Gramicidin S Analogue: Conformational and Biological Evaluation

This paper describes the ability of a new class of heterocyclic γ‐amino acids named ATCs (4‐amino(methyl)‐1,3‐thiazole‐5‐carboxylic acids) to induce turns when included in a tetrapeptide template. Both hybrid Ac‐Val‐(R or S)‐ATC‐Ile‐Ala‐NH₂ sequences were synthesized and their conformations were studied by circular dichroism, NMR spectroscopy, MD simulations, and DFT calculations. It was demonstrated that the ATCs induced highly stable C₉ pseudocycles in both compounds promoting a twist turn and a reverse turn conformation depending on their absolute configurations. As a proof of concept, a bioactive analogue of gramicidin S was successfully designed using an ATC building block as a turn inducer. The NMR solution structure of the analogue adopted an antiparallel β‐pleated sheet conformation similar to that of the natural compound. The hybrid α,γ‐cyclopeptide exhibited significant reduced haemotoxicity compared to gramicidin S, while maintaining strong antibacterial activity.     

Total Synthesis of Potent Antitumor Agent (−)‐Lasonolide A: A Cycloaddition‐Based Strategy

A detailed account of the enantioselective total synthesis of (?)‐lasonolide A is described. Our initial synthetic route to the top tetrahydropyran ring involved Evans asymmetric alkylation as the key step. Initially, we relied on the diastereoselective alkylation of an α‐alkoxyacetimide derivative containing an α′ stereogenic center and investigated such an asymmetric alkylation reaction. Although alkylation proceeded in good yield, the lack of diastereoselectivity prompted us to explore alternative routes. Our subsequent successful synthetic strategies involved highly diastereoselective cycloaddition routes to both tetrahydropyran rings of lasonolide A. The top tetrahydropyran ring was constructed stereoselectively by an intramolecular 1,3‐dipolar cycloaddition reaction. The overall process constructed a bicyclic isoxazoline, which was later unravelled to a functionalized tetrahydropyran ring as well as a quaternary stereocenter present in the molecule. The lower tetrahydropyran ring was assembled by a Jacobsen catalytic asymmetric hetero‐Diels–Alder reaction as the key step. The synthesis also features a Lewis acid catalyzed epoxide opening to form a substituted ether stereoselectively.     

Total Synthesis of (−)‐Salinosporamide A via a Late Stage C−H Insertion

The synthesis of (?)‐salinosporamide A, a proteasome inhibitor, is described. The synthesis highlights the assembly of a densely decorated pyrrolidinone core via an aza‐Payne/hydroamination sequence. Central to the success of the synthesis is a late‐stage C?H insertion reaction to functionalize a sterically encumbered secondary carbon. The latter functionalization leads to an enabling transformation where most of the prototypical strategies failed.     

A Concise Enantioselective Total Synthesis of (−)‐Virosaine A

The total synthesis of (−)‐virosaine A ( 1 ) was achieved in ten steps starting from furan and 2‐bromoacrolein. A one‐pot Diels–Alder cycloaddition/organolithium addition initiated an efficient sequence to access a key oxime/epoxide intermediate. Heating this intermediate in acetic acid resulted in an intramolecular epoxide opening/nitrone [3+2] cycloaddition cascade to construct the caged core of 1 in a single step. Several methods of C−H functionalization were assessed on the cascade product, and ultimately, a directed lithiation/bromination effected selective C14 functionalization, enabling the synthesis of 1 .     

Enantioselective Total Synthesis of (+)‐Ophiobolin A

The enantioselective total synthesis of (+)‐ophiobolin A is described. This total synthesis features the construction of the spiro CD ring of (+)‐ophiobolin A through a stereoselective intramolecular Hosomi–Sakurai cyclization reaction, the joining of the A ring to the CD ring by using a reaction reported by Utimoto, and the construction of the ophiobolin eight‐membered carbocyclic ring through ring‐closing metathesis (RCM), which was performed for the first time in this study. This successful RCM reaction required the use of a substrate that contained either a benzyloxy or a methoxymethoxy group at the C5 position and either an isopropenyl group or its hydroxylated form at the C6 position.     

Iodine‐Catalyzed Highly Diastereoselective Synthesis of trans‐2,6‐Disubstituted‐3,4‐Dihydropyrans: Application to Concise Construction of C28–C37 Bicyclic Core of (+)‐Sorangicin A

A novel iodine‐catalyzed highly diastereoselective synthesis of trans‐2,6‐disubstituted‐3,4‐dihydropyrans have been achieved from δ‐hydroxy α,β‐unsaturated aldehydes by treating with allyltrimethyl silane in THF at room temperature with good to excellent yields. This methodology has been successfully implemented for a concise asymmetric synthesis of C28–C37 dioxabicyclo[3.2.1]octane ring system of (+)‐sorangicin A in 8 steps with 21 % overall yield.     

Enantioselective Total Synthesis of (+)‐Plumisclerin A

The first and enantioselective total synthesis of (+)‐plumisclerin A, a novel unique complex cytotoxic marine diterpenoid, has been accomplished. Around the central cyclopentane anchorage, a sequential ring‐formation protocol was adopted to generate the characteristic tricycle[4.3.1.0^1,5]decane and trans‐fused dihyrdopyran moiety. Scalable enantioselective La^III‐catalyzed Michael reaction, palladium(0)‐catalyzed carbonylation and SmI₂‐mediated radical conjugate addition were successfully applied in the synthesis, affording multiple grams of the complex and rigid B/C/D‐ring system having six continuous stereogenic centers and two all‐carbon quaternary centers. The trans‐fused dihyrdopyran moiety with an exo side‐chain was furnished in final stage through sequential redox transformations from a lactone precursor, which overcome the largish steric strain of the dense multiring system. The reported total synthesis also confirms the absolute chemistries of natural (+)‐plumisclerin A.