Cyclobutenes by platinum-catalyzed cycloisomerization reactions of enynes

1,6-Enynes bearing (electron-rich) aryl substituents on their alkyne moiety rearrange to cyclobutene derivatives in the presence of catalytic amounts of PtCl2 in toluene. The reaction is significantly accelerated when performed under an atmosphere of CO (1 atm), most likely by increasing the electrophilicity of the metal template by temporary coordination to this pi-acidic ligand. This transformation allows the build up of considerable strain in the products as witnessed by the productive formation of tricyclic skeletons, such as 7 or 9. Moreover, these products provide evidence for the mechanistic scenario of platinum-catalyzed cycloisomerization reactions previously proposed, which are thought to proceed via organo-platinum species that mimic the reactivity of metal-complexed "nonclassical" carbocations.     

Quantification of primary fatty acid amides in commercial tallow and tallow fatty acid methyl esters by HPLC-APCI-MS

Primary fatty acid amides are a group of biologically highly active compounds which were already identified in nature. Here, these substances were determined in tallow and tallow fatty acid methyl esters for the first time. As tallow is growing in importance as an oleochemical feedstock for the soap manufacturing, the surfactant as well as the biodiesel industry, the amounts of primary fatty acid amides have to be considered. As these compounds are insoluble in tallow as well as in the corresponding product e.g. tallow fatty acid methyl esters, filter plugging can occur. For the quantification in these matrices a purification step and a LC-APCI-MS method were developed. Although quantification of these compounds can be performed by GC-MS, the presented approach omitted any derivatization and increased the sensitivity by two orders of magnitude. Internal standard calibration using heptadecanoic acid amide and validation of the method yielded a limit of detection of 18.5 fmol and recoveries for the tallow and fatty acid methyl ester matrices of 93% and 95%, respectively. A group of commercially available samples were investigated for their content of fatty acid amides resulting in an amount of up to 0.54%m/m (g per 100 g) in tallow and up to 0.16%m/m (g per 100 g) in fatty acid methyl esters.     

Stereoselective Cyclopolymerization of Polar 1,6‐Heptadiynes by Novel,Tailor‐Made Ruthenium‐Based Metathesis Catalysts

Summary: The cyclopolymerization of 4,4‐bis(hydroxymethyl)‐1,6‐heptadiyne ( M1 ), 4‐(carboxyethyl)‐1,6‐heptadiyne ( M2 ), 4‐(hydroxymethyl)‐1,6‐heptadiyne ( M3 ), and 4‐carboxy‐1,6‐heptadiyne ( M4 ) using five different well‐defined metathesis initiators was investigated. Control of molar mass was achieved with catalysts bearing trifluoroacetate ligands. ¹³C NMR experiments showed that poly‐ M2 , prepared by the action of any catalyst consisted solely of five‐membered ring structures, i.e., 1,2‐(cyclopent‐1‐enylene)vinylene units. Effective conjugation lengths of all polymers were calculated from the corresponding UV‐Vis absorption maxima, which varied reversibly with temperature.

     

Insertion reactions of GaCp*, InCp* and In[C(SiMe3)3] into the Ru-Cl bonds of [(p-cymene)RuIICl2]2 and [Cp*RuIICl]4

The first carbonyl free ruthenium/low valent Group 13 organyl complexes are presented, obtained by insertion of ER (ER = GaCp*, InCp*, In[C(SiMe(3))(3)]) into the Ru-Cl bonds of [(p-cymene)RuCl2]2, [Cp*RuCl]4 and [Cp*RuCl2]2. The compound [(p-cymene)RuCl2]2 reacts with GaCp*, giving a variety of isolated products depending on the reaction conditions. The Ru-Ru dimers [{(p-cymene)Ru}2(GaCp*)4(mu3-Cl)2] and the intermediate [{(p-cymene)Ru}2(mu-Cl)2] were isolated, as well as monomeric complexes [(p-cymene)Ru(GaCp*)3Cl2], [(p-cymene)Ru(GaCp*)2GaCl3] and [(p-cymene)Ru(GaCp*)2Cl2(DMSO)]. The reaction of [Cp*RuCl]4 with ER gives "piano-stool" complexes of the type [Cp*Ru(ER)3Cl](ER = InCp*, In[C(SiMe3)3], GaCp*. The chloride ligand in complex can be removed by NaBPh4, yielding [Cp*Ru(GaCp*)3]+[BPh4]-. The reaction of [Cp*RuCl2]2 with GaCp* however, does not lead to an insertion product, but to the ionic Ru(II) complex [Cp*Ru(GaCp*)3]+[Cp*GaCl3]-. The ER ligands in complexes 3, 5, 6, 7 and 8 are equivalent on the NMR timescale in solution due to a chloride exchange between the three Group 13 atoms even at low temperatures. The solid state structures, however, exhibit a different structural pattern. The chloride ligands exhibit two coordination modes: either terminal or bridging. The new compounds are fully characterized including single crystal X-ray diffraction. These results point out the different reactivities of the two precursors and the nature of the neutral p-cymene and the anionic Cp* ligand when bonding to a Ru(II) centre.     

Heavy Chains: Synthesis,Reactivity and Decomposition of Interpnictogen Chains with Terminal Diaryl Bismuth Fragments

In this work, we report the preparation of multiple interpnictogen chain compounds with three consecutive pnictogen atoms and terminal Ar₂Bi fragments (Ar=Ph, Mes). Symmetrical compounds of the form Ar₂Bi−E(tBu)−Bi₂Ar ( 1 : Ar=Ph, E=P; 2 : Ar=Ph, Mes, E=As) as well as ternary interpnictogen compounds of the form Ar₂Bi−E¹(tBu)−E²tBu₂ (Ar=Ph, Mes; 4 : E¹=P, E²=As; 5 : E¹=P, E²=Sb; 6 : E¹=As, E²=P) were prepared. The decomposition in solution at room temperature and under the influence of light was studied for compounds 1 – 6 . The reactivity of 1_Ph and 2_Ph with the small N-heterocyclic carbene 1,3,4,5-tetramethylimidazol-2-ylidene (Me₂IMe) was also studied. In the case of 1_Ph , the formation and consecutive decomposition of Me₂IMe=PtBu ( 8 ) was observed in solution. Hence, it was shown that 1_Ph can react as a “masked phosphinidene”. In the case of 2_Ph , no reaction with Me₂IMe was observed. All isolated compounds were analysed by NMR and IR spectroscopy, mass spectrometry, elemental analysis and single-crystal X-ray diffraction.     

Clickable report tags for identification of modified peptides by mass spectrometry

The identification and quantification of modified peptides are critical for the functional characterization of post-translational protein modifications (PTMs) to elucidate their biological function. Nowadays, quantitative mass spectrometry coupled with various bioinformatic pipelines has been successfully used for the determination of a wide range of PTMs. However, direct characterization of low abundant protein PTMs in bottom-up proteomic workflow remains challenging. Here, we present the synthesis and evaluation of tandem mass spectrometry tags (TMT) which are introduced via click-chemistry into peptides bearing alkyne handles. The fragmentation properties of the two mass tags were validated and used for screening in a model system and analysis of AMPylated proteins. The presented tags provide a valuable tool for diagnostic peak generation to increase confidence in the identification of modified peptides and potentially for direct peptide-PTM quantification from various experimental conditions.     

Light-Sensitive Phenacyl Crosslinked Dextran Hydrogels for Controlled Delivery**

Stimuli-responsive soft materials enable controlled release of loaded drug molecules and biomolecules. Controlled release of potent chemotherapeutic or immunotherapeutic agents is crucial to reduce unwanted side effects. In an effort to develop controlled release strategies that can be triggered by using Cerenkov luminescence, we have developed polymer hydrogels that can release bovine serum albumin and immunoglobulin G by using light (254 nm–375 nm) as a trigger. We describe the synthesis and photochemical characterization of two light sensitive phenacyl bis-azide crosslinkers that are used to prepare transparent self-supporting hydrogel patches. One crosslinker was designed to optimize the overlap with the Cerenkov luminescence emission window, bearing an π-extended phenacyl core, resulting in a high quantum yield (14 %) of photocleavage when irradiated with 375 nm light. We used the extended phenacyl crosslinker for the preparation of protein-loaded dextran hydrogel patches, which showed efficient and selective dosed release of bovine serum albumin or immunoglobulin G after irradiation with 375 nm light. Cerenkov-triggered release is as yet inconclusive due to unexpected side-reactivity. Based on the high quantum yield, efficient release and large overlap with the Cerenkov window, we envision application of these photosensitive soft materials in radiation targeted drug release.     

Borane Adducts of Aromatic Phosphorus Heterocycles: Synthesis,Crystallographic Characterization and Reactivity of a Phosphinine-B(C6F5)3 Lewis Pair

A phosphinine-borane adduct of a Me₃Si-functionalized phosphinine and the Lewis acid B(C₆F₅)₃ has been synthesized and characterized crystallographically for the first time. The reaction strongly depends on the nature of the substituents in the α-position of the phosphorus heterocycle. In contrast, the reaction of B₂H₆ with various substituted phosphinines leads to an equilibrium between the starting materials and the phosphinine–borane adducts that is determined by the Lewis basicity of the phosphinine. The novel phosphinine borane adduct ( 6 -B(C₆F₅)₃) shows rapid and facile insertion and [4+2] cycloaddition reactivity towards phenylacetylene. A hitherto unknown dihydro-1-phosphabarrelene is formed with styrene. The reaction with an ester provides a new, facile and selective route to 1-R-phosphininium salts. These salts then undergo a [4+2] cycloaddition in the presence of Me₃Si−C≡CH and styrene to cleanly form unprecedented derivatives of 1-R-phosphabarrelenium salts.     

[2+3] Amide Cages by Oxidation of [2+3] Imine Cages – Revisiting Molecular Hosts for Highly Efficient Nitrate Binding

The pollution of groundwater with nitrate is a serious issue because nitrate can cause several diseases such as methemoglobinemia or cancer. Therefore, selective removal of nitrate by efficient binding to supramolecular hosts is highly desired. Here we describe how to make [2+3] amide cages in very high to quantitative yields by applying an optimized Pinnick oxidation protocol for the conversion of corresponding imine cages. By NMR titration experiments of the eight different [2+3] amide cages with nitrate, chloride and hydrogen sulfate we identified one cage with an unprecedented high selectivity towards nitrate binding vs. chloride (S=705) or hydrogensulfate (S>13500) in CD₂Cl₂/CD₃CN (1 : 3). NMR experiments as well as single-crystal structure comparison of host-guest complexes give insight into structure-property-relationships.     

Synthesis and Characterization of GaIII,YIII, and LuIII Complexes with Etifenin and Analogues

Complexes of etifenin ( 1a ), disofenin ( 1b ), and mebrofenin ( 1c ) with Ga^III, Y^III, and Lu^III were synthesized and characterized by NMR spectroscopy and UV/Vis spectroscopy. Stability and protonation constants of the complexes of 1a were determined by potentiometry and distribution diagrams were calculated. It was shown that the Y^III and Lu^III species are most stable as bis chelates at higher pH, whereas the Ga^III complex degrades at pH < 4.5.