A series of well-defined, air- and moisture-stable (NHC)Pd(allyl)Cl (NHC = N-heterocyclic carbene) complexes has been used in several catalytic reactions: Suzuki-Miyaura cross-coupling, catalytic dehalogenation of aryl halides, and aryl amination. The scope of the three processes using various substrates was examined. A general system involving the use of (IPr)Pd(allyl)Cl as catalyst and NaO(t)Bu as base has proven to be highly active for the Suzuki-Miyaura cross-coupling of activated and unactivated aryl chlorides and bromides, for the catalytic dehalogenation of aryl chlorides, and for the catalytic aryl amination of aryl triflates. All reactions proceed in short reaction times and at mild temperatures. The system has also proven to be compatible with the microwave-assisted Suzuki-Miyaura cross-coupling and catalytic dehalogenation processes, affording yields similar to those of the conventionally heated analogous reactions.

The hydrosilylation of various ketones is mediated by an imidazolium salt/Cu(I) salt system or by a well-defined (NHC)CuCl (NHC ) N-heterocyclic carbene) catalyst precursor system. Reactions are conducted at room temperature. The synthesis and characterization of well-defined (NHC)CuCl complexes are described.

The catalytic hydrosilylation of highly hindered and functionalized ketones is described. The combination of inexpensive catalyst precursors, CuCl and NHC.HX (NHC = N-heterocyclic carbene), leads to a highly efficient reduction mediator for the preparation of silyl ethers from unfunctionalized and functionalized alkyl, cyclic, bicyclic, aromatic, and heteroaromatic ketones. A series of catalyst precursors have been structurally characterized and a catalyst-structure activity relationship is discussed.

Summary Mycobacterium tuberculosis (Mtb) adaptation to hypoxia is considered crucial to its prolonged latent persistence in humans. Mtb lesions are known to contain physiologically heterogeneous microenvironments that bring about differential responses from bacteria. Here we exploit metabolic variability within biofilm cells to identify alternate respiratory polyketide quinones (PkQs) from both Mycobacterium smegmatis (Msmeg) and Mtb. PkQs are specifically expressed in biofilms and other oxygen-deficient niches to maintain cellular bioenergetics. Under such conditions, these metabolites function as mobile electron carriers in the respiratory electron transport chain. In the absence of PkQs, mycobacteria escape from the hypoxic core of biofilms and prefer oxygen-rich conditions. Unlike the ubiquitous isoprenoid pathway for the biosynthesis of respiratory quinones, PkQs are produced by type III polyketide synthases using fatty acyl-CoA precursors. The biosynthetic pathway is conserved in several other bacterial genomes, and our study reveals a redox-balancing chemicocellular process in microbial physiology.

A series of substituted 9-aminoacridines is evaluated for antiproliferative activity toward pancreatic cancer cells. The results indicate that the compounds inhibit cell proliferation by inducing a G1-S phase arrest. A model is also developed that explains the molecular basis to inhibition through a DNA "threading" mechanism. We conclude that the drug-DNA complex formed blocks topoisomerase II binding and activity leading to catalytic inhibition of the enzyme and the induction of apoptosis and programmed cell death.