The crystal structure of a bis(2,6-pyridinedicarboxylato)chromate(III) anion with an elaborate network of hydrogen bonding and π stacking

The synthesis, X-ray crystallography, spectroscopic, and electrochemical properties of the title compound, [Hdpa][Cr(dipic)₂]·3H₂O, 1, are reported. Compound 1 crystallized in the triclinic space group P-1 with a = 7.1057(11) ?, b = 12.965(2) ?, c = 14.269(2) ?, α = 80.306(3)°, β = 82.101(2)°, γ = 83.799(2)°, and V = 1278.6(4) ?³ with Z = 2. The distorted octahedral chromium anions are part of an elaborate network of hydrogen bonding formed by the waters of solvation, the anion, and cation as well as π-stacking interactions.     

Nonlinear dynamics of a two-dimensional lattice

The dynamics of the nonlinear excitations in a two-dimensional (2D) φ⁴-diatomic lattice, with nonlinear on-site electron-phonon coupling at the polarizable ion site has been presented, without considering the self consistent phonon approximation. One of the major results obtained from our calculations is in the understanding of continuous structural phase transition, where we have obtained the minimum in soft mode frequency at a soft mode temperatureT _s (>T _c), not at critical temperatureT _c. This occurs due to the anisotropy of such 2D systems.     

Ontology aided modeling of organic reaction mechanisms with flexible and fragment based XML markup procedures

The mechanism models for primary organic reactions encoding the structural fragments undergoing substitution, addition, elimination, and rearrangements are developed. In the proposed models, each and every structural component of mechanistic pathways is represented with flexible and fragment based markup technique in XML syntax. A significant feature of the system is the encoding of the electron movements along with the other components like charges, partial charges, half bonded species, lone pair electrons, free radicals, reaction arrows, etc. needed for a complete representation of reaction mechanism. The rendering of reaction schemes described with the proposed methodology is achieved with a concise XML extension language interoperating with the structure markup. The reaction scheme is visualized as 2D graphics in a browser by converting them into SVG documents enabling the desired layouts normally perceived by the chemists conventionally. An automatic representation of the complex patterns of the reaction mechanism is achieved by reusing the knowledge in chemical ontologies and developing artificial intelligence components in terms of axioms.     

Mechanism-of-action determination of GMP synthase inhibitors and target validation in Candida albicans and Aspergillus fumigatus

Mechanism-of-action (MOA) studies of bioactive compounds are fundamental to drug discovery. However, in vitro studies alone may not recapitulate a compound's MOA in whole cells. Here, we apply a chemogenomics approach in Candida albicans to evaluate compounds affecting purine metabolism. They include the IMP dehydrogenase inhibitors mycophenolic acid and mizoribine and the previously reported GMP synthase inhibitors acivicin and 6-diazo-5-oxo-L-norleucine (DON). We report important aspects of their whole-cell activity, including their primary target, off-target activity, and drug metabolism. Further, we describe ECC1385, an inhibitor of GMP synthase, and provide biochemical and genetic evidence supporting its MOA to be distinct from acivicin or DON. Importantly, GMP synthase activity is conditionally essential in C. albicans and Aspergillus fumigatus and is required for virulence of both pathogens, thus constituting an unexpected antifungal target.     

Chemical genetic screening identifies critical pathways in anthrax lethal toxin-induced pathogenesis

Anthrax lethal toxin (LT)-induced cell death via mitogen-activated protein kinase kinase (MAPKK) cleavage remains questionable. Here, a chemical genetics approach was used to investigate what pathways mediate LT-induced cell death. Several small molecules were found to protect macrophages from anthrax LT cytotoxicity and MAPKK from cleavage by lethal factor (LF), without inhibiting LF enzymatic activity or cellular proteasome activity. Interestingly, the compounds activated MAPK-signaling molecules, induced proinflammatory cytokine production, and inhibited LT-induced macrophage apoptosis in a concentration-dependent manner. We propose that induction of antiapoptotic responses by MAPK-dependent or -independent pathways and activation of host innate responses may protect macrophages from anthrax LT-induced cell death. Altering host responses through a chemical genetics approach can help identify critical cellular pathways involved in the pathogenesis of anthrax and can be exploited to further explore host-pathogen interactions.