Isoniazid@Fe2O3 Nanocontainers and Their Antibacterial Effect on Tuberculosis Mycobacteria

Isoniazid‐filled Fe₂O₃ hollow nanospheres (INH@Fe₂O₃, diameter <30 nm, 48 wt % INH‐load) are prepared for the first time and suggested for tuberculosis therapy. After dextran‐functionalization, the INH@Fe₂O₃@DEX nanocontainers show strong activity against Mycobacterium tuberculosis (M.tb.) and M.tb.‐infected macrophages. The nanocontainers can be considered as “Trojan horses” and show efficient, active uptake into both M.tb.‐infected macrophages and even into mycobacterial cells.     

Structure of the Sulfoxide Synthase EgtB from the Ergothioneine Biosynthetic Pathway

The non‐heme iron enzyme EgtB catalyzes O₂‐dependent C? S bond formation between γ‐glutamyl cysteine and N‐α‐trimethyl histidine as the central step in ergothioneine biosynthesis. Both, the catalytic activity and the architecture of EgtB are distinct from known sulfur transferases or thiol dioxygenases. The crystal structure of EgtB from Mycobacterium thermoresistibile in complex with γ‐glutamyl cysteine and N‐α‐trimethyl histidine reveals that the two substrates and three histidine residues serve as ligands in an octahedral iron binding site. This active site geometry is consistent with a catalytic mechanism in which C? S bond formation is initiated by an iron(III)‐complexed thiyl radical attacking the imidazole ring of N‐α‐trimethyl histidine.     

Protein-Templated Hit Identification through an Ugi Four-Component Reaction**

Kinetic target-guided synthesis represents an efficient hit-identification strategy, in which the protein assembles its own inhibitors from a pool of complementary building blocks via an irreversible reaction. Herein, we pioneered an in situ Ugi reaction for the identification of novel inhibitors of a model enzyme and binders for an important drug target, namely, the aspartic protease endothiapepsin and the bacterial β-sliding clamp DnaN, respectively. Highly sensitive mass-spectrometry methods enabled monitoring of the protein-templated reaction of four complementary reaction partners, which occurred in a background-free manner for endothiapepsin or with a clear amplification of two binders in the presence of DnaN. The Ugi products we identified show low micromolar activity on endothiapepsin or moderate affinity for the β-sliding clamp. We succeeded in expanding the portfolio of chemical reactions and biological targets and demonstrated the efficiency and sensitivity of this approach, which can find application on any drug target.     

The stereoselectivity of the alkylation of the dianion of ethyl 2-hydroxy-6-methylcyclohexanecarboxylates: Control of stereochemistry at three adjacent stereogenic centers

Yeast reduction of rac-ethyl 2-methyl-6-oxocylohexanecarboxylate (rac- 1 ) yielded selectively (+)-ethyl 2-hydroxy-6-methylcyclohexane carboxylate (+)- 2 (Scheme 1) which has been alkylated with 5-iodo-2-methylbut-2-ene by (the dianion method to furnish the 4-methylbut-3-enyl derivat 3 (Scheme 3)). NaBH₄ reduction of (+)- 1 led to three hydroxy-carboxylates (?)- 2 , (+)- 5 , and (?) -6 (Scheme 4). Allylation of the dianion of (+)- 5 afforded (+)- 7 .     

Complex clover cross-sectioned nanotubules exist in the structure of the first uranium borate phosphate

An actinide borate phosphate was prepared via a high temperature solid-state reaction. This phase exhibits unprecedented complex inorganic nanotubular fragments with an external diameter of ~2 × 2 nm. The nanotubular aggregates are based on borate tubes where the exterior of the tubes is decorated with UO(2)(PO(4))(3) moieties to form a complex shape with a cross-section similar to the clover cross.     

Tributyltin biomonitoring using prosobranchs as sentinel organisms

Tributyltin (TBT) compounds, some of the most toxic xenobiotics, produce a variety of pathological reactions in animals. A reliable biomonitoring method to assess the degree of environmental TBT pollution has been described based on investigations of virilization phenomena in prosobranch snails (Mollusca: Gastropoda). Examples are the imposex phenomenon in marine and freshwater species, the intersex reaction in littorinids and the reduction of female sexual glands and offspring numbers in further species resulting mainly in a sterilization of females. The degree of imposex or intersex in populations is determined by different biomonitoring indices which allow to assess the TBT pollution of the environment at low costs with high precision. The effectiveness of TBT legislations is analysed by extensive surveys in France and Ireland indicating that there is still a continuing threat to sensitive marine organisms. TBT disturbs the biosynthesis of steroid hormones on the level of estrogen biosynthesis. The observed virilization phenomena seem due to an inhibition of the cytochrome P-450 dependent aromatase by this organotin compound.