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The cyanobacterium Prochloron didemni, an obligate symbiont of different species of colonial ascidians, occurring in the Pacific and Indian Oceans, produces a variety of cyclic peptides. These patellamide‐type macrocycles lead to relatively stable dicopper(II) complexes that are extremely efficient carbonic anhydrase mimics, the most active model systems known so far. Importantly, it recently was shown that copper(II) is coordinated to patellamide derivatives in Prochloron cells. An interesting question therefore is, whether the biological function of patellamide‐type macrocycles is related to the catalytic activity in CO2 hydration or its reverse. Here, we present a computational study to evaluate the energetics of the catalytic cycle in search of a possible answer to these questions and compare the computed energy barriers with the experimental kinetic data. It emerges that release of the bridging carbonate is a critical step and that the catalysis product inhibits catalysis at pH values above approx. 7. Therefore, carbonate transport rather than CO2 hydrolysis is proposed as the biological function of copper(II)‐patellamide complexes in the Prochloron‐Ascidian symbiosis. [ABSTRACT FROM AUTHOR]

Discussed are two picolinate appended bispidine ligands (3,7‐diazabicyclo[3.3.1]nonane derivatives) in comparison with an earlier described bis‐pyridine derivative, which are all known to strongly bind CuII. The radiopharmacological characterization of the two isomeric bispidine complexes includes quantitative labeling with 64CuII at ambient conditions with high radiochemical purities and yields (molar activities >200 MBq/nmol). Challenge experiments in presence of EDTA, cyclam, human serum and SOD demonstrate high stability and inertness of the 64Cu‐bispidine complexes. Biodistribution studies performed in Wistar rats indicate a rapid renal elimination for both 64Cu‐labeled chelates. The bispidine ligand with the picolinate group in N7 position was selected for further biological experiments, and its backbone was therefore substituted with a benzyl‐NCS group at C9. Two tumor target modules (TMs), targeting prostate stem cell antigen (PSCA), overexpressed in prostate cancer, and the fibroblast activation protein (FAP) in fibrosarcoma, were selected for thiourea coupling with the NCS‐functionalized ligand and lysine residues of TMs. Small animal PET experiments on tumor‐bearing mice showed specific accumulation of the 64Cu‐labeled TMs in PSCA‐ and FAP‐overexpressing tumors (standardized uptake value (SUV) for PC3: 2.7±0.6 and HT1080: 7.2±1.25) with almost no uptake in wild type tumors. [ABSTRACT FROM AUTHOR]

An organocatalytic route has been developed for the isomerization of exo‐vinylene carbonates (exo‐VCs) to endo‐vinylene carbonates (endo‐VCs). The exo‐VC starting material can easily be obtained from propargylic alcohols via cyclization with carbon dioxide. In this study, these exo‐VCs are shown to isomerize to the thermodynamically more stable endo‐VCs in the presence of an N‐heterocyclic base and phenol. Density functional theory (DFT) studies were conducted to elucidate the mechanism, tackling difficulties of the description of charge separation steps. This isomerization process delivers an ample diversity of endo‐VCs in good to excellent yields and chemoselectivities under mild reaction conditions. [ABSTRACT FROM AUTHOR]

Owing to their high reactivity and selectivity, variations in the spin ground state and a range of possible pathways, high‐valent FeIV=O species are popular models with potential bioinspired applications. An interesting example of a structure–reactivity pattern is the detailed study with five nonheme amine‐pyridine pentadentate ligand FeIV=O species, including N4py: [(L1)FeIV=O]2+ (1), bntpen: [(L2)FeIV=O]2+ (2), py2tacn: [(L3)FeIV=O]2+ (3), and two isomeric bispidine derivatives: [(L4)FeIV=O]2+ (4) and [(L5)FeIV=O]2+ (5). In this set, the order of increasing reactivity in the hydroxylation of cyclohexane differs from that with cyclohexadiene as substrate. A comprehensive DFT, ab initio CASSCF/NEVPT2 and DLPNO‐CCSD(T) study is presented to untangle the observed patterns. These are well reproduced when both activation barriers for the C−H abstraction and the OH rebound are taken into account. An MO, NBO and deformation energy analysis reveals the importance of π(pyr) → π*xz(FeIII‐OH) electron donation for weakening the FeIII‐OH bond and thus reducing the rebound barrier. This requires that pyridine rings are oriented perpendicularly to the FeIII‐OH bond and this is a subtle but crucial point in ligand design for non‐heme iron alkane hydroxylation. [ABSTRACT FROM AUTHOR]

The reactivity of FeIII‐alkylperoxido complexes has remained a riddle to inorganic chemists owing to their thermal instability and impotency towards organic substrates. These iron‐oxygen adducts have been known as sluggish oxidants towards oxidative electrophilic and nucleophilic reactions. Herein, we report the synthesis and spectroscopic characterization of a relatively stable mononuclear high‐spin FeIII‐alkylperoxido complex supported by an engineered bispidine framework. Against the notion, this FeIII‐alkylperoxido complex serves as a rare example of versatile reactivity in both electrophilic and nucleophilic reactions. Detailed mechanistic studies and computational calculations reveal a novel reaction mechanism, where a putative superoxido intermediate orchestrates the amphoteric property of the oxidant. The design of the backbone is pivotal to convey stability and reactivity to alkylperoxido and superoxido intermediates. Contrary to the well‐known O−O bond cleavage that generates an FeIV‐oxido species, the FeIII‐alkylperoxido complex reported here undergoes O−C bond scission to generate a superoxido moiety that is responsible for the amphiphilic reactivity. [ABSTRACT FROM AUTHOR]