Synthesis of Elusive Chloropnictenium Ions

This work describes the synthesis and full characterization of elusive chloropnictenium ion salts of the type [^RAr*N(SiMe)ECl][A] (^RAr*=2,6‐(CHPh₂)‐4‐R‐C₆H₂, R=Me, tBu; E=Sb, Bi; A^?=GaCl₄, Al(OCH(CF₃)₂)₄). In these species the cation is significantly stabilized by weak arene interactions to flanking phenyl groups of the ^RAr* moiety. In this context the bonding situation has been studied by computational means and the reactivity towards the Lewis base 4‐dimethylaminopyridine (dmap) was investigated.     

Selective Benzylic CH-Borylations by Tandem Cobalt Catalysis

Metal-catalyzed C?H activations are environmentally and economically attractive synthetic strategies for the construction of functional molecules as they obviate the need for pre-functionalized substrates and minimize waste generation. Great challenges reside in the control of selectivities, the utilization of unbiased hydrocarbons, and the operation of atom-economical dehydrocoupling mechanisms. An especially mild borylation of benzylic CH bonds was developed with the ligand-free pre-catalyst Co[N(SiMe₃)₂]₂ and the bench-stable and inexpensive borylation reagent B₂pin₂ that produces H₂ as the only by-product. A full set of kinetic, spectroscopic, and preparative mechanistic studies are indicative of a tandem catalysis mechanism of CH-borylation and dehydrocoupling via molecular Co^I catalysts.     

A cationic cysteine-hydrazide as an enrichment tool for the mass spectrometric characterization of bacterial free oligosaccharides

In Campylobacterales and related ε-proteobacteria with N-linked glycosylation (NLG) pathways, free oligosaccharides (fOS) are released into the periplasmic space from lipid-linked precursors by the bacterial oligosaccharyltransferase (PglB). This hydrolysis results in the same molecular structure as the oligosaccharide that is transferred to a protein to be glycosylated. This allowed for the general elucidation of the fOS-branched structures and monosaccharides from a number of species using standard enrichment and mass spectrometry methods. To aid characterization of fOS, hydrazide chemistry has often been used for chemical modification of the reducing part of oligosaccharides resulting in better selectivity and sensitivity in mass spectrometry; however, the removal of the unreacted reagents used for the modification often causes the loss of the sample. Here, we develop a more robust method for fOS purification and characterize glycostructures using complementary tandem mass spectrometry (MS/MS) analysis. A cationic cysteine hydrazide derivative was synthesized to selectively isolate fOS from periplasmic fractions of bacteria. The cysteine hydrazide nicotinamide (Cyhn) probe possesses both thiol and cationic moieties. The former enables reversible conjugation to a thiol-activated solid support, while the latter improves the ionization signal during MS analysis. This enrichment was validated on the well-studied Campylobacter jejuni by identifying fOS from the periplasmic extracts. Using complementary MS/MS analysis, we approximated data of a known structure of the fOS from Campylobacter concisus. This versatile enrichment technique allows for the exploration of a diversity of protein glycosylation pathways.     

Synthetic Matching of Complex Monoterpene Indole Alkaloid Chemical Space

Monoterpene indole alkaloids (MIAs) are endowed with high structural and spatial complexity and characterized by diverse biological activities. Given this complexity-activity combination in MIAs, rapid and efficient access to chemical matter related to and with complexity similar to these alkaloids would be highly desirable, since such compound classes might display novel bioactivity. We describe the design and synthesis of a pseudo-natural product (pseudo-NP) collection obtained by the unprecedented combination of MIA fragments through complexity-generating transformations, resulting in arrangements not currently accessible by biosynthetic pathways. Cheminformatic analyses revealed that both the pseudo-NPs and the MIAs reside in a unique and common area of chemical space with high spatial complexity-density that is only sparsely populated by other natural products and drugs. Investigation of bioactivity guided by morphological profiling identified pseudo-NPs that inhibit DNA synthesis and modulate tubulin. These results demonstrate that the pseudo-NP collection occupies similar biologically relevant chemical space that Nature has endowed MIAs with.     

Planar Iron Hydride Nanoclusters: Combined Spectroscopic and Theoretical Insights into Structures and Building Principles

The controlled assembly of well-defined planar nanoclusters from molecular precursors is synthetically challenging and often plagued by the predominant formation of 3D-structures and nanoparticles. Herein, we report planar iron hydride nanoclusters from reactions of main group element hydrides with iron(II) bis(hexamethyldisilazide). The structures and properties of isolated Fe₄, Fe₆, and Fe₇ nanoplatelets and calculated intermediates enable an unprecedented insight into the underlying building principle and growth mechanism of iron clusters, metal monolayers, and nanoparticles.