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A series of Pd/NHC species undergoes R–NHC coupling reaction forming catalytically active NHC-free complexes and/or colloidal Pd nanoparticles.

It has recently been shown that palladium-catalyzed reactions with N-heterocyclic carbene (NHC) ligands involve R− NHC coupling accompanied by transformation of the molecular catalytic system into the nanoscale catalytic system. An important question appeared in this regard is whether such a change in the catalytic system is irreversible. More specifically, is the reverse nanoto-molecular transformation possible? In view of the paramount significance of this question to the area of catalyst design, we studied the capability of 2-substituted azolium salts to undergo the breakage of C−C bond and exchange substituents on the carbene carbon with corresponding aryl halides in the presence of Pd nanoparticles. The study provides important experimental evidence of possibility of the reversible R−NHC coupling. The observed behavior indicates that the nanosized metal species are capable of reverse transition to molecular species. Such an option, known for phosphine ligands, was previously unexplored for NHC ligands. The present study for the first time demonstrates bidirectional dynamic transitions between the molecular and nanostructured states in Pd/NHC systems. As a unique feature, surprisingly small activation barriers (<18 kcal/mol) and noticeable thermodynamic driving force (−5 to −7 kcal/mol) were calculated for C−C bond oxidative addition to Pd(0) centers in the studied system. The first example of NHCmediated Pd leaching from metal nanoparticles to solution was observed and formation of Pd/NHC complex in solution was detected by ESI-MS.

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Background Difficult to express peptides are usually produced by co-expression with fusion partners. In this case, a significant mass part of the recombinant product falls on the subsequently removed fusion partner. On the other hand, multimerization of peptides is known to improve its proteolytic stability in E. coli due to the inclusion of body formation, which is sequence specific. Thereby, the peptide itself may serve as a fusion partner and one may produce more than one mole of the desired product per mole of fusion protein. This paper proposes a method for multimeric production of a human alpha-fetoprotein fragment with optimized multimer design and processing. This fragment may further find its application in the cytotoxic drug delivery field or as an inhibitor of endogenous alpha-fetoprotein. Results Multimerization of the extended alpha-fetoprotein receptor-binding peptide improved its stability in E. coli, and pentamer was found to be the largest stable with the highest expression level. As high as 10 aspartate-proline bonds used to separate peptide repeats were easily hydrolyzed in optimized formic acid-based conditions with 100% multimer conversion. The major product was represented by unaltered functional alpha-fetoprotein fragment while most side-products were its formyl-Pro, formyl-Tyr, and formyl-Lys derivatives. Single-step semi-preparative RP-HPLC was enough to separate unaltered peptide from the hydrolysis mixture. Conclusions A recombinant peptide derived from human alpha-fetoprotein can be produced via multimerization with subsequent formic acid hydrolysis and RP-HPLC purification. The reported procedure is characterized by the lower reagent cost in comparison with enzymatic hydrolysis of peptide fusions and solid-phase synthesis. This method may be adopted for different peptide expression, especially with low amino and hydroxy side chain content.

Pyrrolo[2,3-e]indazole is a promising scaffold for the development of novel neuraminidase inhibitors that are active against influenza A virus and S. pneumoniae.