Reduction Potential Predictions for Thirty-Seven 1,4-di-N-Oxide Quinoxaline-2-Carboxamide Derivatives with Anti-Tuberculosis Activity

The ability for density functional theory with the B3LYP functional with the lanl2dz basis set to predict the 1st (Wave 1) and 2nd (Wave 2) reductions of the diazine ring in a series of thirty-seven (37) 1,4-di-N-oxide quinoxaline-2-carboxamide derivatives in dimethylformamide was examined. The B3LYP/lanl2dz method had a strong correlation and low correlation to the experimental potentials for Wave 1 and Wave 2, respectively. There are nine identifiable analogs based on similarities of structure. The predicted reduction potentials for the derivatives of each analog generally fit the modified Hammett equation. The B3LYP/lanl2dz method is shown to be useful in accurately predicting the Wave 1 potentials for quinoxaline-di-N-oxide derivatives. For derivatives with assessable anti-tuberculosis activity, the predicted Wave 1 potentials have a similar correlation with the bioactivity when compared to the experimental wave 1 potentials.</jats:p

Perceived burdensomeness and suicide ideation in older adults.

Older adults have the highest risk of death by suicide in the United States. Improving our understanding of the factors that lead to increased risk of suicide in older adults will greatly inform our ability to prevent suicide in this high-risk group. Two studies were conducted to test the effect of perceived burdensomeness, a component of the interpersonal-psychological theory of suicide (Joiner, 2005), on suicide ideation in older adults. Further, gender was examined as a moderator of this association to determine if perceived burdensomeness exerted a greater influence on suicide ideation in males. The results of these studies suggest that perceived burdensomeness accounts for significant variance in suicide ideation, even after predictors such as depressive symptoms, hopelessness, and functional impairment are controlled. Gender did not moderate the association. The implications of these findings for treatment of older adults with suicide ideation and elevated suicide risk are discussed

Reduction Potential Predictions for Some 3-Aryl-Quinoxaline-2-Carbonitrile 1,4-Di-N-Oxide Derivatives with Known Anti-Tumor Properties

The ability for DFT: B3LYP calculations using the 6-31g and lanl2dz basis sets to predict the electrochemical properties of twenty (20) 3-aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives with varying degrees of cytotoxic activity in dimethylformamide (DMF) was investigated. There was a strong correlation for the first reduction and moderate-to-low correlation of the second reduction of the diazine ring between the computational and the experimental data, with the exception of the derivative containing the nitro functionality. The four (4) nitro group derivatives are clear outliers in the overall data sets and the derivative E4 is ill-behaved. The remaining three (3) derivatives containing the nitro groups had a strong correlation between the computational and experimental data; however, the computational data falls substantially outside of the expected range

MoD-QM/MM Structural Refinement Method: Characterization of Hydrogen Bonding in the <i>Oxytricha nova</i> G‑Quadruplex

A generalization of the Moving-Domain Quantum Mechanics/Molecular Mechanics (MoD-QM/MM) hybrid method [Gascon, J. A.; Leung, S. S. F.; Batista, E. R.; Batista, V. S. <i>J. Chem. Theory Comput.</i> <b>2006</b>, <i>2</i>, 175–186] is introduced to provide a self-consistent computational protocol for structural refinement of extended systems. The method partitions the system into molecular domains that are iteratively optimized as quantum mechanical (QM) layers embedded in their surrounding molecular environment to obtain an ab initio quality description of the geometry and the molecular electrostatic potential of the extended system composed of those constituent fragments. The resulting methodology is benchmarked as applied to model systems that allow for full QM optimization as well as through refinement of the hydrogen bonding geometry in <i>Oxytricha nova</i> guanine quadruplex for which several studies have been reported, including the X-ray structure and NMR data. Calculations of ¹H NMR chemical shifts based on the gauge independent atomic orbital (GIAO) method and direct comparisons with experiments show that solvated MoD-QM/MM structures, sampled from explicit solvent molecular dynamics simulations, allow for NMR simulations in much improved agreement with experimental data than models based on the X-ray structure or those optimized using classical molecular mechanics force fields