A conceptual framework for predicting the toxicity of reactive chemicals: modeling soft electrophilicity

Although the literature is replete with QSAR models developed for many toxic effects caused by reversible chemical interactions, the development of QSARs for the toxic effects of reactive chemicals lacks a consistent approach. While limitations exit, an appropriate starting-point for modeling reactive toxicity is the applicability of the general rules of organic chemical reactions and the association of these reactions to cellular targets of importance in toxicology. The identification of plausible "molecular initiating events" based on covalent reactions with nucleophiles in proteins and DNA provides the unifying concept for a framework for reactive toxicity. This paper outlines the proposed framework for reactive toxicity. Empirical measures of the chemical reactivity of xenobiotics with a model nucleophile (thiol) are used to simulate the relative rates at which a reactive chemical is likely to bind irreversibly to cellular targets. These measures of intrinsic reactivity serve as correlates to a variety of toxic effects; what's more they appear to be more appropriate endpoints for QSAR modeling than the toxicity endpoints themselves.     

Excited state dynamics and fragmentation channels of the protonated dipeptide H2N-Leu-Trp-COOH

The excited state dynamics of the isolated and protonated peptide H(2)N-Leu-Trp-COOH are analyzed by fs pump-probe spectroscopy. The peptides are brought into the gas phase by electrospray ionization, and fs pump-probe excitation is detected by fragment ion formation. The pump laser addressed the excited pipi* state of the indole chromophore of the amino acid tryptophan. The subsequent excited state dynamics agreed with a biexponential decay with time constants of 500 fs and 10 ps. This is considerably shorter than the lifetime of neutral tryptophan in solution and in proteins, but similar to isolated, protonated tryptophan. Several models are discussed to explain the experimental results but the detailed quenching mechanism remains unresolved.     

PdnCO (n = 1,2): accurate Ab initio bond energies, geometries, and dipole moments and the applicability of density functional theory for fuel cell modeling

Electrode poisoning by CO is a major concern in fuel cells. As interest in applying computational methods to electrochemistry is increasing, it is important to understand the levels of theory required for reliable treatments of metal-CO interactions. In this paper we justify the use of relativistic effective core potentials for the treatment of PdCO and hence, by inference, for metal-CO interactions where the predominant bonding mechanism is charge transfer. We also sort out key issues involving basis sets and we recommend that bond energies of 17.2, 43.3, and 69.4 kcal/mol be used as the benchmark bond energy for dissociation of Pd2 into Pd atoms, PdCO into Pd and CO, and Pd2CO into Pd2 and CO, respectively. We calculated the dipole moments of PdCO and Pd2CO, and we recommend benchmark values of 2.49 and 2.81 D, respectively. Furthermore, we tested 27 density functionals for this system and found that only hybrid density functionals can qualitatively and quantitatively predict the nature of the sigma-donation/pi-back-donation mechanism that is associated with the Pd-CO and Pd2-CO bonds. The most accurate density functionals for the systems tested in this paper are O3LYP, OLYP, PW6B95, and PBEh.     

A Five Color Zero-Sum Generalization

Let g_zs(m, 2k) (g_zs(m, 2k+1)) be the minimal integer such that for any coloring Δ of the integers from 1, . . . , g_zs(m, 2k) by (the integers from 1 to g_zs(m, 2k+1) by ) there exist integers such that 1. there exists j_x such that Δ(x_i) ∈ for each i and ∑_i=1^m Δ(x_i) = 0 mod m (or Δ(x_i)=∞ for each i); 2. there exists j_y such that Δ(y_i) ∈ for each i and ∑_i=1^m Δ(y_i) = 0 mod m (or Δ(y_i)=∞ for each i); and 1. 2(x_m−x₁)≤y_m−x₁. In this note we show g_zs(m, 2)=5m−4 for m≥2, g_zs(m, 3)=7m+−6 for m≥4, g_zs(m, 4)=10m−9 for m≥3, and g_zs(m, 5)=13m−2 for m≥2. Supported by NSF grant DMS 0097317     

Theory of defect levels and the "band gap problem" in silicon

Quantitative predictions of defect properties in semiconductors using density functional theory have been crippled by two issues: the supercell approximation, which has incorrect boundary conditions for an isolated defect, and approximate functionals, that drastically underestimate the band gap. I describe modifications to the supercell method that incorporate boundary conditions appropriate to point defects, identify a common electron reservoir for net charge for all defects, deal with defect banding, and incorporate bulk polarization. The computed level spectrum for an extended set of silicon defects spans the experimental gap, i.e., exhibits no band gap problem, and agrees remarkably well with experiment.     

Creating and manipulating vortices in atomic wave functions with short electric field pulses

We demonstrate the creation of vortices in the electronic probability density of an atom subject to short electric field pulses, how these vortices evolve and can be manipulated by varying the applied pulses, and that they persist to macroscopic distances in the spectrum of ejected electrons. This opens the possibility to use practical femtosecond or shorter laser pulses to create and manipulate these vortex quasiparticles at the atomic scale and observe them in the laboratory. Within a hydrodynamic interpretation we also show, since the Schr?dinger equation is a particular instance of the Navier-Stokes equations, that for compressible fluids vortices can appear spontaneously and with a certain time delay, which is not expected to occur from the conventional point of view, illustrating applicability of the present study to vortex formation more broadly.     

Atomistic modeling of β-Sn surface energies and adatom diffusivity

Energies for low number Miller index surfaces of β-Sn (b.c.t. structure) were computed and the (1 0 0) plane was found to have the lowest un-relaxed energy of 0.0497 eV/Ų. We then used the Dimer method to find mechanisms and corresponding activation energies, E_A, for a Sn adatom moving on a β-Sn (1 0 0) surface. After extensive dimer searches and comparison to long molecular dynamics simulations, we conclude that two simple hopping mechanisms dominate transitions on this surface. For each, we determined hopping rates of the adatom using transition state theory and computed its tracer diffusivity. A hop of the adatom in the lattice c-direction gives D_300 K = 1.893 × 10⁻⁰⁶ cm²/s (E_A = 0.1493 eV), while in the lattice a-direction D_300 K = 3.994 × 10⁻⁰⁶ cm²/s (E_A = 0.1138 eV). When compared to studies on the existence of low energy multi-atom adatom diffusion on Cu and Al (1 0 0), we assert that β-Sn's successive (2 0 0) plane layering in the [1 0 0] direction provides for significantly lower activation energies and may contribute to the inability to locate any concerted atomic motion mechanisms.     

Dihydrogen complexes of iridium and rhodium

A series of iridium and rhodium pincer complexes have been synthesized and characterized: [(POCOP)Ir(H)(H(2))] [BAr(f)(4)] (1-H(3)), (POCOP)Rh(H(2)) (2-H(2)), [(PONOP)Ir(C(2)H(4))] [BAr(f)(4)] (3-C(2)H(4)), [(PONOP)Ir(H)(2))] [BAr(f)(4)] (3-H(2)), [(PONOP)Rh(C(2)H(4))] [BAr(f)(4)] (4-C(2)H(4)) and [(PONOP)Rh(H(2))] [BAr(f)(4)] (4-H(2)) (POCOP = κ(3)-C(6)H(3)-2,6-[OP(tBu)(2)](2); PONOP = 2,6-(tBu(2)PO)(2)C(5)H(3)N; BAr(f)(4) = tetrakis(3,5-trifluoromethylphenyl)borate). The nature of the dihydrogen-metal interaction was probed using NMR spectroscopic studies. Complexes 1-H(3), 2-H(2), and 4-H(2) retain the H-H bond and are classified as η(2)-dihydrogen adducts. In contrast, complex 3-H(2) is best described as a classical dihydride system. The presence of bound dihydrogen was determined using both T(1) and (1)J(HD) coupling values: T(1) = 14 ms, (1)J(HD) = 33 Hz for the dihydrogen ligand in 1-H(3), T(1)(min) = 23 ms, (1)J(HD) = 32 Hz for 2-H(2), T(1)(min) = 873 ms for 3-H(2), T(1)(min) = 33 ms, (1)J(HD) = 30.1 Hz for 4-H(2).     

Nb 1-y Fe 2+y thin film growth and characterization

We report on the growth of c-axis oriented thin films of NbFe(2) prepared by pulsed laser deposition. Variation of the deposition conditions results in variation of the composition of the Nb(1-y)Fe(2+y) films in the range from Nb rich to Fe rich films. Films near the stoichiometric composition (y?≈?0) are the most interesting. However, microstructural investigations of these films reveal two kinds of grain, which exhibit different shape, epitaxial relation and chemical composition. The different chemical compositions of opposing doping character result in two magnetic phases confirmed by means of magnetization and Hall measurements. This investigation demonstrates the possibility of NbFe(2) thin film growth and discusses the microstructural inhomogeneities occurring.     

New precision mass measurements of neutron-rich calcium and potassium isotopes and three-nucleon forces

We present precision Penning trap mass measurements of neutron-rich calcium and potassium isotopes in the vicinity of neutron number N=32. Using the TITAN system, the mass of ^{51}K was measured for the first time, and the precision of the ^{51,52}Ca mass values were improved significantly. The new mass values show a dramatic increase of the binding energy compared to those reported in the atomic mass evaluation. In particular, ^{52}Ca is more bound by 1.74?MeV, and the behavior with neutron number deviates substantially from the tabulated values. An increased binding was predicted recently based on calculations that include three-nucleon (3N) forces. We present a comparison to improved calculations, which agree remarkably with the evolution of masses with neutron number, making neutron-rich calcium isotopes an exciting region to probe 3N forces.