Hangman salen platforms containing two xanthene scaffolds

A synthetic strategy for the construction of chiral salen ligands bearing two rigid xanthene spacers functionalized with carboxylic acid and ester groups is presented. Suzuki cross-coupling methodology is used to furnish the appropriately functionalized xanthene spacers to a salicylaldehyde, which is subsequently condensed with (1R,2R)-(-)-1,2-diaminocyclohexane to produce salen ligands featuring an expandable molecular cleft capable of multiple hydrogen-bonding interactions in addition to metallosalen oxidation chemistry. The ability of these "Hangman" platforms to support multielectron chemistry mediated by proton-coupled electron transfer (PCET) is established by their proclivity to promote the catalytic disproportionation of hydrogen peroxide to oxygen and water via a high-valent metal oxo. Within this functionalized Hangman framework, the stereochemistry of the cyclohexyl backbone of the salen platform is revealed in the epoxidation of 1,2-dihydronaphthalene by the metal oxo.     

Self-aggregated perfluoroalkylated hexa-peri-hexabenzocoronene fibers observed by cryo-SEM and fluorescence spectroscopy

The self-assembled architectures in solution of a new HBC derivative bearing perfluoroalkylated side chains were investigated by optical excitation and emission spectroscopy and correlated to cryo-SEM, a new technique in organic chemistry.     

Antibody interference with N-acyl homoserine lactone-mediated bacterial quorum sensing

Many bacterial pathogens coordinate their virulence factor expression in a cell density-dependent manner. This population-dependent coordination of gene expression in bacteria has been termed "quorum sensing" (QS). N-Acyl homoserine lactones (AHLs) are used by over 70 Gram-negative bacterial species as autoinducers. Inhibition of QS signaling might represent a new target for antimicrobial therapy. Here we report the hapten design, synthesis, generation of monoclonal antibodies (mAbs) against AHLs, and the evaluation of these mAbs for their ability to blunt QS signaling and inhibit virulence factor expression in P. aeruginosa. The mAbs can be envisioned as a tool for future investigations into AHL-based QS, which may aid in gaining new insights into the pathogenesis of P. aeruginosa and may ultimately lead to the development of new strategies to combat bacterial diseases.     

Calciomics: prediction and analysis of EF-hand calcium binding proteins by protein engineering

Ca²⁺ plays a pivotal role in the physiology and biochemistry of prokaryotic and mammalian organisms. Viruses also utilize the universal Ca²⁺ signal to create a specific cellular environment to achieve coexistence with the host, and to propagate. In this paper we first describe our development of a grafting approach to understand site-specific Ca²⁺ binding properties of EF-hand proteins with a helix-loop-helix Ca²⁺ binding motif, then summarize our prediction and identification of EF-hand Ca²⁺ binding sites on a genome-wide scale in bacteria and virus, and next report the application of the grafting approach to probe the metal binding capability of predicted EF-hand motifs within the streptococcal hemoprotein receptor (Shr) of Streptococcus pyrogenes and the nonstructural protein 1 (nsP1) of Sindbis virus. When methods such as the grafting approach are developed in conjunction with prediction algorithms we are better able to probe continuous Ca²⁺-binding sites that have been previously underrepresented due to the limitation of conventional methodology.     

Variations of the P2 group in HIV-1 protease inhibitors containing a tertiary alcohol in the transition-state mimicking scaffold

A short synthetic protocol leading to HIV-1 protease inhibitors with a tertiary alcohol based transition-state mimicking unit and different P2 side chains has been developed.     

Preparation and biological evaluation of key fragments and open analogs of scleritodermin A

The synthesis of key fragments of scleritodermin A, their assembly, and their biological evaluation as cytotoxic and anthelmintic were performed. Highlights of the synthetic route include formation of the α-ketoamide linkage and use of stereocontrolled reactions. Open analogs of this natural product were obtained using a convergent strategy.     

X-Ray crystal analysis of the substrates of aconitase: XI. Manganous citrate decahydrate

The crystal structure of hydrated manganese citrate, [Mn(H₂O)₆] [Mn C₆H₅O₇(H₂O)]₂2H₂O has been determined. The crystals are monoclinic, space group P2₁/n cell dimensions a = 20.575 ± 0.005, b = 6.755 ± 0.002, c = 9.230 ± 0.002 Å, β = 96.74 ± 0.01°. The structure is isomorphous with that of the magnesium salt for which the structure has been determined⁴. There are two [Mn(H₂O)₆]²⁺ ions, four [Mn C₆H₅O₇(H₂O)] ions and four water molecules per unit cell. Each citrate ion forms a tridentate chelate to one manganese ion. A correlation of Mn²⁺ ? H distances for manganese citrate, found in this crystallographic study, was made with those determined by NMR studies in solutions in the absence and presence of the enzyme aconitase, and indicated that the assumption that citrate chelates to enzyme-bound manganese ion fits all the available data.