Assessing Gas-Phase Ion Reactivity of 50 Elements with NO and the Direct Application for 239Pu in Complex Matrices Using ICP-MS/MS.

Understanding the reactivity of metal cations with various reaction gases in inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) is important to determine the best gas to use for a given analyte/interference pair. In this study, nitric oxide (NO) was investigated as the reaction gas following previous experimental designs. The reactions with 50 elements were investigated to examine periodic trends in reactivity, validate theoretical modeling of reaction enthalpies as a method to screen reactant gases, and provide a baseline data set for potential in-line gas separation methods. ICP-MS/MS studies involving actinides are typically limited to Th, U, and Pu, with analyses of Np and Am rarely reported in the literature. To date, only two previous methods have investigated the use of NO in ICP-MS/MS analyses. To showcase the utility of NO, a method was developed to measure 239Pu in the presence of environmental matrix constituent and other actinides, like what could be expected from postdetonation debris, with no chemical separation prior to analysis. 239Pu+ was reacted to form 239Pu16O+, eliminating interferences derived from the sample matrix by measuring the 239Pu+ intensity at m/z = 255 (239Pu16O+). To validate NO for 238U1H+ interference removal in environmental matrices, standard reference materials were diluted to 1 mg/g of solution and spiked to 0.05 pg/g of 239Pu and 1 µg/g 238U (Pu/U = 5 × 10-8). Measured 239Pu concentrations were within 6% of the spiked value. These results demonstrate that reliable 239Pu measurements can be made at levels relevant to nuclear forensics without the need for extensive chemical matrix separation prior to analysis.

Quantification of Hydrogen Isotopes Utilizing Raman Spectroscopy Paired with Chemometric Analysis for Application across Multiple Systems.

Online and real-time analysis of a chemical process is a major analytical challenge that can drastically change the way the chemical industry or chemical research operates. With in situ analyses, a new and powerful understanding of chemistry can be gained; however, building robust tools for long-term monitoring faces many challenges, including compensating for instrument drift, instrument replacement, and sensor or probe replacement. Accounting for these changes by recollecting calibration data and rebuilding quantification models can be costly and time-consuming. Here, methods to overcome these challenges are demonstrated with an application of Raman spectroscopy to monitoring hydrogen isotopes with varied speciation within dynamic gas streams. Specifically, chemical data science tools such as chemometric modeling are leveraged along with several examples of calibration transfer approaches. Furthermore, the optimization of instrument and sensor cell parameters for targeted gas-phase analyses is discussed. While the particular focus on hydrogen is highly beneficial within the nuclear energy sector, mechanisms built and demonstrated here are widely applicable to optical spectroscopy monitoring in numerous other chemical systems that can be leveraged in other processes.

f-Block reactions of metal cations with carbon dioxide studied by inductively coupled plasma tandem mass spectrometry.

f-Block chemistry offers an opportunity to test current knowledge of chemical reactivity. The energy dependence of lanthanide cation (Ln+ = Ce+, Pr+, Nd+-Eu+) and actinide cation (An+ = Th+, U+-Am+) oxidation reactions by CO2, was observed by inductively coupled plasma tandem mass spectrometry. This reaction is commonly spin-unallowed because the neutral reactant (CO2, 1Σ+g) and product (CO, 1Σ+) require the metal and metal oxide cations to have the same spin state. Correlation of the promotion energy (Ep) to the first state with two free d-electrons with the reaction efficiency indicates that spin conservation is not a primary factor in the reaction rate. The Ep likely influences the reaction rate by partially setting the crossing between the ground and reactive states. Comparison of Ln+ and An+ congener reactivity indicates that the 5f-orbitals play a small role in the An+ reactions.

Activation of CO2 by Actinide Cations (Th+, U+, Pu+, and Am+) as Studied by Guided Ion Beam and Triple Quadrupole Mass Spectrometry.

Reactions of CO2 with Th+ have been studied using guided ion beam tandem mass spectrometry (GIBMS) and with An+ (An+ = Th+, U+, Pu+, and Am+) using triple quadrupole inductively coupled plasma mass spectrometry (QQQ-ICP-MS). Additionally, the reactions ThO+ + CO and ThO+ + CO2 were examined using GIBMS. Modeling the kinetic energy-dependent GIBMS data allowed the determination of bond dissociation energies (BDEs) for D0(Th+-O) and D0(OTh+-O) that are in reasonable agreement with previous GIBMS measurements. The QQQ-ICP-MS reactions were studied at higher pressures where multiple collisions between An+ and the neutral CO2 occur. As a consequence, both AnO+ and AnO2+ products were observed for all An+ except Am+, where only AmO+ was observed. The relative abundances of the observed monoxides compared to the dioxides are consistent with previous reports of the AnOn+ (n = 1, 2) BDEs. A comparison of the periodic trends of the group 4 transition metal, lanthanide (Ln), and actinide atomic cations in reactions with CO2 (a formally spin-forbidden reaction for most M+ ground states) and O2 (a spin-unrestricted reaction) indicates that spin conservation plays a minor role, if any, for the heavier Ln+ and An+ metals. Further correlation of Ln+ and An+ + CO2 reaction efficiencies with the promotion energy (Ep) to the first electronic state with two valence d-electrons (Ep(5d2) for Ln+ and Ep(6d2) for An+) indicates that the primary limitation in the activation of CO2 is the energetic cost to promote from the electronic ground state of the atomic metal ion to a reactive state.

On-Line Monitoring of Gas-Phase Molecular Iodine Using Raman and Fluorescence Spectroscopy Paired with Chemometric Analysis.

Molten salt reactors (MSRs) have the potential to safely support green energy goals while meeting baseload energy needs with diverse energy portfolios. While reactor designers have made tremendous strides with these systems, licensing and deployment of these reactors will be aided through the development of new technology such as on-line and remote monitoring tools. Of particular interest is quantifying reactor off-gas species, such as iodine, within off-gas streams to support the design and operational control of off-gas treatment systems. Here, the development of advanced Raman spectroscopy systems for the on-line analysis of gas composition is discussed, focusing on the key control species I2(g). Signal response was explored with two Raman instruments, utilizing 532 and 671 nm excitation sources, as a function of I2(g) pressure and temperature. Also explored is the integration of advanced data analysis methods to enable real-time and highly accurate analysis of complex optical data. Specifically, the application of chemometric modeling is discussed. Raman spectroscopy paired with chemometric analysis is demonstrated to provide a powerful route to analyzing I2(g) composition within the gas phase, which lays the foundation for applications within molten salt reactor off-gas analysis and other significant chemical processes producing iodine species.

Thermochemical studies of reactions of Re+ with SO2 using guided ion beam experiments and theory.

The kinetic energy dependent reactions of Re+ with SO2 were studied with guided ion beam tandem mass spectrometry. ReO+, ReO2+, and OReS+ species were observed as products, all in endothermic reactions. Modeling of the kinetic energy dependent cross sections yields 0 K bond dissociation energies (BDEs, in eV) of 4.78 ± 0.06 (Re+-O), 5.75 ± 0.02 (Re+-O2), and 4.35 ± 0.14 (Re+-SO). The latter two values can be combined with other information to derive the additional values 6.05 ± 0.05 (ORe+-O) and 4.89 ± 0.19 (ORe+-S). BDEs of ReO+ and ReO2+ agree with literature values whereas the values for OReS+ are the first measurements. The former result is obtained even though formation of ground state ReO+ is spin-forbidden. Quantum mechanical calculations at the B3LYP level of theory with a def2-TZVPPD basis set yield results that agree reasonably well with experimental values. Additional calculations at the BP86 and CCSD(T) levels of theory using def2-QZVPPD and aug-cc-pVxZ (x = T, Q, and 5) basis sets were performed to compare thermochemistry with experiment to determine that ReO2+ rather than the isobaric ReS+ is formed. Product ground states are 3Δ3(ReO+), 3B1(OReO+), 5Π-1(ReS+), and 3A''(OReS+) after including empirical spin-orbit corrections, which means that formation of ground state products is spin-forbidden for all three product channels. The potential energy surfaces for the ReSO2+ system were also explored at the B3LYP/def2-TZVPPD level and exhibited no barriers in excess of the endothermicities for all products. BDEs for rhenium oxide and sulfide diatomics and triatomics are compared and discussed. The present result for formation of ReO+ is compared to that for formation of ReO+ in the reactions of Re+ + O2 and CO, where the former system exhibited interesting dual cross section features. Results are consistent with the hypothesis that the distinction of in-plane and out-of-plane CS symmetry in the triatomic systems might be the explanation for the two endothermic features observed in the Re+ + O2 reaction.

Bond energy of ThN+: A guided ion beam and quantum chemical investigation of the reactions of thorium cation with N2 and NO.

Kinetic-energy dependent reactions of Th+ with N2 and NO are studied using a guided ion beam tandem mass spectrometer. The formation of ThO+ in the reaction of Th+ with NO is observed to be exothermic and barrierless with a reaction efficiency at low energies of 0.91 ± 0.18. Formation of ThN+ in the reactions of Th+ with N2 and NO is endothermic in both cases. The kinetic-energy dependent cross sections for formation of this product ion were evaluated to determine a 0 K bond dissociation energy (BDE) of D0(Th+-N) = 6.51 ± 0.08 eV, the first direct measurement of this BDE. Additionally, the reactions were explored by quantum chemical calculations, including a full Feller-Peterson-Dixon composite approach with correlation contributions up to CCSDTQ for ThN and ThN+, as well as more approximate CCSD(T) calculations where a semiempirical model was used to estimate spin-orbit energy contributions. The ThN+ BDE is found to be larger than those of the transition metal congeners, TiN+ along with estimated values for ZrN+ and HfN+, believed to be a result of the actinide contraction.

An orally available, brain-penetrant CAMKK2 inhibitor reduces food intake in rodent model.

Hypothalamic CAMKK2 represents a potential mechanism for chemically affecting satiety and promoting weight loss in clinically obese patients. Single-digit nanomolar inhibitors of CAMKK2 were identified in three related ATP-competitive series. Limited optimization of kinase selectivity, solubility, and pharmacokinetic properties were undertaken on all three series, as SAR was often transferrable. Ultimately, a 2,4-diaryl 7-azaindole was optimized to afford a tool molecule that potently inhibits AMPK phosphorylation in a hypothalamus-derived cell line, is orally bioavailable, and crosses the blood-brain barrier. When dosed orally in rodents, compound 4 t limited ghrelin-induced food intake.

Lanthanides as Catalysts: Guided Ion Beam and Theoretical Studies of Sm+ + COS.

Reactions of samarium cations with carbonyl sulfide are examined using a guided ion beam tandem mass spectrometer and a variable temperature selected ion flow tube apparatus. Formation of SmS+ + CO is observed in both instruments with a kinetic energy and temperature dependence demonstrating a barrierless reaction occurring with an efficiency of 26 ± 9%. Formation of SmO+ + CS is also observed at high kinetic energies and exhibits a threshold determined as 2.81 ± 0.32 eV, substantially higher than expected from known thermochemistry. The potential energy surfaces for these reactions along sextet and octet spin surfaces are also examined theoretically at the MP2 and CCSD(T) levels. The observed barrier for oxidation is shown to likely correspond to the energy of the crossing between surfaces corresponding to the ground state electronic configuration of Sm+ (8F,4f66s1) and an excited surface having two electrons in the valence space (excluding 4f), which are needed to form the strong SmO+ bond. In contrast, the S-CO bond is activated much more readily because this crossing occurs at much lower energies. This result is attributed to the much weaker S-CO bond energy as well as the ability of sulfur to bind effectively at different angles. Although both reactions are spin-forbidden, evidence for a more efficient spin-allowed process is also observed in the SmS+ + CO cross section.

Potential energy surface for the reaction Sm+ + CO2 → SmO+ + CO: guided ion beam and theoretical studies.

The potential energy surface (PES) for the oxidation of samarium cations by carbon dioxide is explored both experimentally and theoretically. Using guided ion beam tandem mass spectrometry, several reactions are examined as a function of kinetic energy. These include the title reaction as well as its reverse along with the collision-induced dissociation of Sm+(CO2) and OSm+(CO) with Xe. Analysis of the kinetic energy dependent cross sections yields barriers for the forward and reverse oxidation reaction of 1.77 ± 0.11 and 2.04 ± 0.13 eV, respectively, and Sm+-OCO and OSm+-CO bond dissociation energies (BDEs) of 0.42 ± 0.03 and 0.97 ± 0.07 eV, respectively. BDEs for Sm+(CO2)x for x = 2 and 3 are also determined as 0.40 ± 0.13 and 0.48 ± 0.12 eV, respectively. The PESs for the title reaction along the sextet and octet spin surfaces are also examined theoretically at the MP2 and CCSD(T) levels using both effective core potential and all-electron basis sets. Reasonable agreement between theory and experiment is obtained for the experimentally characterized intermediates, although all-electron basis sets and spin-orbit effects are needed for quantitative agreement. The observed barrier for oxidation is shown to likely correspond to the energy of the crossing between surfaces corresponding to the ground state electronic configuration of Sm+ (8F,4f66s1) and an excited surface having two electrons in the valence space (excluding 4f), which are needed to form the strong SmO+ bond.

Guided ion beam and theoretical studies of the reactions of Re+, Os+, and Ir+ with CO.

The kinetic-energy dependences of the reactions M+ + CO where M+ = Re+, Os+, and Ir+ are studied using guided ion-beam tandem mass spectrometry. Formation of both MO+ and MC+ was observed in endothermic processes for all three metals. Modeling of the data provides thresholds that yield 0 K bond dissociation energies (BDEs, in eV) of 4.67 ± 0.09 (Re+-O), 4.82 ± 0.14 (Os+-O), 4.25 ± 0.11 (Ir+-O), 5.13 ± 0.12 (Re+-C), 6.14 ± 0.14 (Os+-C), and 6.58 ± 0.12 (Ir+-C). These BDEs agree well with literature values within experimental uncertainties demonstrating that ground state products are formed for all cases even though some of the reactions are formally spin forbidden. Quantum mechanical calculations at several levels of theory and using several basis sets were performed for MC+ and MO+ (with comparable results taken from the literature in some cases). B3LYP and CCSD(T) calculated ground state BDEs agree reasonably well with experimental values. The ground states in B3LYP and CCSD(T)/CBS calculations are Σ-3 (ReC+), Δ2 (OsC+), and Σ+1 or Δ3 (IrC+) after including spin-orbit considerations. Relaxed potential energy surfaces (PESs) for the M+ + CO reactions show crossings between surfaces of different spin states such that products can be formed with no barriers in excess of the substantial endothermicities. Unlike results for these metal cations reacting with O2, the kinetic energy dependent cross sections for the formation of MO+ in the M+ + CO reactions exhibit only one feature. Reasons for this differential behavior are discussed in detail.

Bond energies of ThO(+) and ThC(+): A guided ion beam and quantum chemical investigation of the reactions of thorium cation with O2 and CO.

Kinetic energy dependent reactions of Th(+) with O2 and CO are studied using a guided ion beam tandem mass spectrometer. The formation of ThO(+) in the reaction of Th(+) with O2 is observed to be exothermic and barrierless with a reaction efficiency at low energies of k/kLGS = 1.21 ± 0.24 similar to the efficiency observed in ion cyclotron resonance experiments. Formation of ThO(+) and ThC(+) in the reaction of Th(+) with CO is endothermic in both cases. The kinetic energy dependent cross sections for formation of these product ions were evaluated to determine 0 K bond dissociation energies (BDEs) of D0(Th(+)-O) = 8.57 ± 0.14 eV and D0(Th(+)-C) = 4.82 ± 0.29 eV. The present value of D0 (Th(+)-O) is within experimental uncertainty of previously reported experimental values, whereas this is the first report of D0 (Th(+)-C). Both BDEs are observed to be larger than those of their transition metal congeners, TiL(+), ZrL(+), and HfL(+) (L = O and C), believed to be a result of lanthanide contraction. Additionally, the reactions were explored by quantum chemical calculations, including a full Feller-Peterson-Dixon composite approach with correlation contributions up to coupled-cluster singles and doubles with iterative triples and quadruples (CCSDTQ) for ThC, ThC(+), ThO, and ThO(+), as well as more approximate CCSD with perturbative (triples) [CCSD(T)] calculations where a semi-empirical model was used to estimate spin-orbit energy contributions. Finally, the ThO(+) BDE is compared to other actinide (An) oxide cation BDEs and a simple model utilizing An(+) promotion energies to the reactive state is used to estimate AnO(+) and AnC(+) BDEs. For AnO(+), this model yields predictions that are typically within experimental uncertainty and performs better than density functional theory calculations presented previously.

Activation of CH4 by Th(+) as studied by guided ion beam mass spectrometry and quantum chemistry.

The reaction of atomic thorium cations with CH4 (CD4) and the collision-induced dissociation (CID) of ThCH4(+) with Xe are studied using guided ion beam tandem mass spectrometry. In the methane reactions at low energies, ThCH2(+) (ThCD2(+)) is the only product; however, the energy dependence of the cross-section is inconsistent with a barrierless exothermic reaction as previously assumed on the basis of ion cyclotron resonance mass spectrometry results. The dominant product at higher energies is ThH(+) (ThD(+)), with ThCH3(+) (ThCD3(+)) having a similar threshold energy. The latter product subsequently decomposes at still higher energies to ThCH(+) (ThCD(+)). CID of ThCH4(+) yields atomic Th(+) as the exclusive product. The cross-sections of all product ions are modeled to provide 0 K bond dissociation energies (in eV) of D0(Th(+)-H) ≥ 2.25 ± 0.18, D0(Th(+)-CH) = 6.19 ± 0.16, D0(Th(+)-CH2) ≥ 4.54 ± 0.09, D0(Th(+)-CH3) = 2.60 ± 0.30, and D0(Th(+)-CH4) = 0.47 ± 0.05. Quantum chemical calculations at several levels of theory are used to explore the potential energy surfaces for activation of methane by Th(+), and the effects of spin-orbit coupling are carefully considered. When spin-orbit coupling is explicitly considered, a barrier for C-H bond activation that is consistent with the threshold measured for ThCH2(+) formation (0.17 ± 0.02 eV) is found at all levels of theory, whereas this barrier is observed only at the BHLYP and CCSD(T) levels otherwise. The observation that the CID of the ThCH4(+) complex produces Th(+) as the only product with a threshold of 0.47 eV indicates that this species has a Th(+)(CH4) structure, which is also consistent with a barrier for C-H bond activation. This barrier is thought to exist as a result of the mixed ((4)F,(2)D) electronic character of the Th(+) J = (3)/2 ground level combined with extensive spin-orbit effects.

Evaluation of the exothermicity of the chemi-ionization reaction Sm + O → SmO(+) + e(.).

The exothermicity of the chemi-ionization reaction Sm + O → SmO(+) + e(-) has been re-evaluated through the combination of several experimental methods. The thermal reactivity (300-650 K) of Sm(+) and SmO(+) with a range of species measured using a selected ion flow tube-mass spectrometer apparatus is reported and provides limits for the bond strength of SmO(+), 5.661 eV ≤ D0(Sm(+)-O) ≤ 6.500 eV. A more precise value is measured to be 5.725 ± 0.07 eV, bracketed by the observed reactivity of Sm(+) and SmO(+) with several species using a guided ion beam tandem mass spectrometer (GIBMS). Combined with the established Sm ionization energy (IE), this value indicates an exothermicity of the title reaction of 0.08 ± 0.07 eV, ∼0.2 eV smaller than previous determinations. In addition, the ionization energy of SmO has been measured by resonantly enhanced two-photon ionization and pulsed-field ionization zero kinetic energy photoelectron spectroscopy to be 5.7427 ± 0.0006 eV, significantly higher than the literature value. Combined with literature bond energies of SmO, this value indicates an exothermicity of the title reaction of 0.14 ± 0.17 eV, independent from and in agreement with the GIBMS result presented here. The evaluated thermochemistry also suggests that D0(SmO) = 5.83 ± 0.07 eV, consistent with but more precise than the literature values. Implications of these results for interpretation of chemical release experiments in the thermosphere are discussed.

The importance of ion kinetic energy for interference removal in ICP-MS/MS.

The effect of ion kinetic energy on gas phase ion reactivity with ICP-MS/MS was investigated in order to explore tuning strategies for interference removal. The collision/reaction gases CO2, N2O and O2 were used to observe the ion product distribution for 48 elements using an Agilent tandem ICP-MS (ICP-MS/MS) as a function of reaction gas flow rate (pressure) and ion kinetic energy. The kinetic energy of the incident ion was varied by adjusting the octopole bias (Voct). The three gases all form oxides (MO+) as the primary product with differing reaction enthalpies that result in distinct differences in the ion energies required for reaction with product ion distributions that vary with Voct. Consequently, by varying the ion kinetic energy (i.e., Voct), differences in interference reactivity can be used to achieve maximum separation. Three practical application examples were reported to demonstrate how the ion kinetic energy can be varied to achieve the ideal ion product distribution for interference resolution: CO2 for the removal of 238U in Pu analyses, CO2 for the removal of 40Ar16O vs. 56Fe, and O2 for the removal of Sm in Eu analyses, analogous to Pu/Am. The results demonstrate how the starting ion energy defined by Voct is an important factor to fully leverage the utility of any given reaction gas to remove interferences in the mass spectrum using ICP-MS/MS.

QSAR workbench: automating QSAR modeling to drive compound design.

We describe the QSAR Workbench, a system for the building and analysis of QSAR models. The system is built around the Pipeline Pilot workflow tool and provides access to a variety of model building algorithms for both continuous and categorical data. Traditionally models are built on a one by one basis and fully exploring the model space of algorithms and descriptor subsets is a time consuming basis. The QSAR Workbench provides a framework to allow for multiple models to be built over a number of modeling algorithms, descriptor combinations and data splits (training and test sets). Methods to analyze and compare models are provided, enabling the user to select the most appropriate model. The Workbench provides a consistent set of routines for data preparation and chemistry normalization that are also applied for predictions. The Workbench provides a large degree of automation with the ability to publish preconfigured model building workflows for a variety of problem domains, whilst providing experienced users full access to the underlying parameterization if required. Methods are provided to allow for publication of selected models as web services, thus providing integration with the chemistry desktop. We describe the design and implementation of the QSAR Workbench and demonstrate its utility through application to two public domain datasets.

Functional antagonism of IL-1alpha induced gene expression profiles define the cAMP/PKA pathway as a unique regulator of IL-1alpha signaling networks.

Interleukin-1 (IL-1alpha) induced inflammatory and pro-fibrotic responses in human lung fibroblasts are mediated by activation of MAPK and NFkappaB pathways. The purpose of the present study was to broadly profile the activity of a variety of compounds which function as inhibitors of these key signaling pathways that may affect IL-1alpha mediated gene changes. A reference set of genes was derived from microarray analysis of IL-1alpha stimulated cells. The genes were chosen to provide a range of expression profiles which serve to represent the actions of the underlying signaling network. We show that G(s)-coupled receptor agonists have a unique pattern of activity as represented by their impact on IL-1alpha dependent gene changes. These effects were not mimicked by direct inhibitors of p38, JNK, MEK or IKK but were mimicked by forskolin and cAMP analogs. These findings indicate that cAMP/PKA serves as a point of convergence for regulation of IL-1alpha responses by multiple G(s)-coupled receptors and regulates IL-1alpha responses by a distinct mechanism that does not solely involve direct inhibition of p38, JNK, MEK or IKK. The data also point to a potentially useful paradigm wherein monitoring of a small subset of genes is sufficient to identify pathway activity of novel compounds.

Activation of Water by Thorium Cation: A Guided Ion Beam and Quantum Chemical Study.

The reaction of atomic thorium cations with deuterated water as a function of kinetic energy from thermal to 10 eV was studied using guided ion beam tandem mass spectrometry. At thermal energies, both ThO+ + D2 and DThO+ + D are formed in barrierless exothermic processes and reproduce results in the literature obtained using ion cyclotron resonance mass spectrometry. As the energy is increased, the branching ratio between these two channels changes such that the dominant product changes from ThO+ to DThO+ and back to ThO+, until ThD+ + OD is energetically available and is the dominant product channel. To help understand these experimental results, a variety of theoretical approaches were tried and used to establish a potential energy surface, which compares well with previous theoretical studies. Utilizing the theoretical results, the kinetic energy dependent branching ratio between the ThO+ + D2 and DThO+ + D channels was calculated using both RRKM and phase space theory (PST). The results indicate that consideration of angular momentum conservation (as in PST) and spin-orbit corrected energies are needed to reproduce experimental results quantitatively. The PST modeling also provides relative energies for the two competing transition states that lead to the primary products, for which theory provides reasonable agreement. Graphical Abstract Note: This data is.

Survival and central photopenia detected by fluorine-18 fluoro-deoxy-glucose positron emission tomography (FDG-PET) in patients with locoregional non-small cell lung cancer treated with radiotherapy.

BACKGROUND: Primary non-small cell lung cancer cavitation and central photopenia, detected by radiology and FDG-PET scanning respectively, are thought to be the result of tumor necrosis. Such regions may contain hypoxic but viable carcinoma cells which may be relatively radioresistant compared with fully oxygenated regions. We hypothesized that photopenic tumors treated with radiotherapy with or without chemotherapy would be associated with worse survival compared with tumors not showing central photopenia. PATIENTS AND METHODS: The data were from a prospective trial (TROG 99-05) investigating the prognostic significance of primary tumor volume in patients receiving radical radiotherapy for locoregional non-small cell lung cancer (NSCLC). A subset of patients who had a pre-treatment FDG-PET scan formed the study population. The scans were evaluated by two observers for central photopenia in the primary tumor using a visual scoring system. The relationship of photopenia with survival was determined after adjusting for other prognostic factors. RESULTS: There were 172 eligible patients. The two observers agreed on the presence of photopenia in 90% of cases (Kappa=0.822, p<0.001). Seventy-three patients were scored as having photopenia. Photopenia was not associated with worse survival, either on univariate analysis, or after adjusting for sex, performance status and nodal status (HR=1.20, 95% CI 0.78-1.87, p=0.4) Photopenia was however significantly associated with larger tumor volume and weight loss. CONCLUSIONS: This study failed to demonstrate a significantly worse survival associated with central photopenia in patients treated with radiotherapy for NSCLC.

Reactions of Th(+) + H2, D2, and HD Studied by Guided Ion Beam Tandem Mass Spectrometry and Quantum Chemical Calculations.

Kinetic energy dependent reactions of Th(+) with H2, D2, and HD were studied using a guided ion beam tandem mass spectrometer. Formation of ThH(+) and ThD(+) is endothermic in all cases with similar thresholds. Branching ratio results for the reaction with HD indicate that Th(+) reacts via a statistical mechanism, similar to Hf(+). The kinetic energy dependent cross sections for formation of ThH(+) and ThD(+) were evaluated to determine a 0 K bond dissociation energy (BDE) of D0(Th(+)-H) = 2.45 ± 0.07 eV. This value is in good agreement with a previous result obtained from analysis of the Th(+) + CH4 reaction. D0(Th(+)-H) is observed to be larger than its transition metal congeners, TiH(+), ZrH(+), and HfH(+), believed to be a result of lanthanide contraction. The reactions with H2 were also explored using quantum chemical calculations that include a semiempirical estimation and explicit calculation of spin-orbit contributions. These calculations agree nicely and indicate that ThH(+) most likely has a (3)Δ1 ground level with a low-lying (1)Σ(+) excited state. Theory also provides the reaction potential energy surfaces and BDEs that are in reasonable agreement with experiment.