Computational study of the hydrodefluorination of fluoroarenes at [Ru(NHC)(PR₃)<sub style="vertical-align: sub;">2</sub>(CO)(H)<sub style="vertical-align: sub;">2</sub>]: predicted scope and regioselectivities

Density functional theory calculations have been employed to investigate the scope and selectivity of the hydrodefluorination (HDF) of fluoroarenes, C6F6-nHn (n = 0-5), at catalysts of the type [Ru(NHC)(PR3)(2)(CO)(H)(2)]. Based on our previous study (Angew. Chem., Int. Ed., 2011, 50, 2783) two mechanisms featuring the nucleophilic attack of a hydride ligand at a fluoroarene substrate were considered: (i) a concerted process with Ru-H/C-F exchange occurring in one step; and (ii) a stepwise pathway in which the rate-determining transition state involves formation of HF and a Ru-sigma-fluoroaryl complex. The nature of the metal coordination environment and, in particular, the NHC ligand was found to play an important role in both promoting the HDF reaction and determining the regioselectivity of this process. Thus for the reaction of C6F5H, the full experimental system (NHC = IMes, R = Ph) promotes HDF through (i) more facile initial PR3/fluoroarene substitution and (ii) the ability of the NHC N-aryl substituents to stabilise the key C-F bond breaking transition state through F center dot center dot center dot HC interactions. This latter effect is maximised along the lower energy stepwise pathway when an ortho-H substituent is present and this accounts for the ortho-selectivity seen in the reaction of C6F5H to give 1,2,3,4-C6F4H2. Computed C-F bond dissociation energies (BDEs) for C6F6-nHn substrates show a general increase with larger n and are most sensitive to the number of ortho-F substituents present. However, HDF is always computed to remain significantly exothermic when a silane such as Me3SiH is included as terminal reductant. Computed barriers to HDF also generally increase with greater n, and for the concerted pathway a good correlation between C-F BDE and barrier height is seen. The two mechanisms were found to have complementary regioselectivities. For the concerted pathway the reaction is directed to sites with two ortho-F substituents, as these have the weakest C-F bonds. In contrast, reaction along the stepwise pathway is directed to sites with only one ortho-F substituent, due to difficulties in accommodating ortho-F substituents in the C-F bond cleavage transition state. Calculations predict that 1,2,3,5-C6F4H2 and 1,2,3,4-C6F4H2 are viable candidates for HDF at [Ru(IMes)(PPh3)(2)(CO)(H)(2)] and that this would proceed selectively to give 1,2,4-C6F3H3 and 1,2,3-C6F3H3, respectively.</p

GAIA: An easy-to-use web-based application for interaction analysis of case-control data

BACKGROUND: The advent of cheap, large scale genotyping has led to widespread adoption of genetic association mapping as the tool of choice in the search for loci underlying susceptibility to common complex disease. Whilst simple single locus analysis is relatively trivial to conduct, this is not true of more complex analysis such as those involving interactions between loci. The importance of testing for interactions between loci in association analysis has been highlighted in a number of recent high profile publications. RESULTS: Genetic Association Interaction Analysis (GAIA) is a web-based application for testing for statistical interactions between loci. It is based upon the widely used case-control study design for genetic association analysis and is designed so that non-specialists may routinely apply tests for interaction. GAIA allows simple testing of both additive and additive plus dominance interaction models and includes permutation testing to appropriately correct for multiple testing. The application will find use both in candidate gene based studies and in genome-wide association studies. For large scale studies GAIA includes a screening approach which prioritizes loci (based on the significance of main effects at one or both loci) for further interaction analysis. CONCLUSION: GAIA is available a

Compression and shear wave sonic velocity measurements in hard rock

Compression wave sonic velocity (Vp) is routinely measured in rock testing laboratories. Shear wave sonic velocity (Vs) measurement for further application to geomechanical studies is not routinely conducted. This paper outlines the establishment of a laboratory testing technique including waveform analysis for the determination of shear wave velocity. The paper outlines the measurement of compressional and shear wave sonic velocities using ultrasonic pulse transmission technique, for several hard rock lithologies recovered during routine (NQ/HQ/PQ) exploration core drilling. Shear wave sonic velocities were measured using a pair of shear piezoelectric transducer elements. Measured shear wave sonic velocities are compared with fundamental and empirical formulas used to predict shear wave sonic velocity, in order to verify the method. This paper discusses the need for an Australian Standard that includes a provision for the measurement of shear wave sonic velocity. Measured results are used to calculate dynamic moduli of rock samples and are compared with static moduli. The application of dynamic moduli to geotechnical characterisation of the rock mass is explored

Analysis of pooled DNA samples on high density arrays without prior knowledge of differential hybridization rates

Array based DNA pooling techniques facilitate genome-wide scale genotyping of large samples. We describe a structured analysis method for pooled data using internal replication information in large scale genotyping sets. The method takes advantage of information from single nucleotide polymorphisms (SNPs) typed in parallel on a high density array to construct a test statistic with desirable statistical properties. We utilize a general linear model to appropriately account for the structured multiple measurements available with array data. The method does not require the use of additional arrays for the estimation of unequal hybridization rates and hence scales readily to accommodate arrays with several hundred thousand SNPs. Tests for differences between cases and controls can be conducted with very few arrays. We demonstrate the method on 384 endometriosis cases and controls, typed using Affymetrix Genechip© HindIII 50 K arrays. For a subset of this data there were accurate measures of hybridization rates available. Assuming equal hybridization rates is shown to have a negligible effect upon the results. With a total of only six arrays, the method extracted one-third of the information (in terms of equivalent sample size) available with individual genotyping (requiring 768 arrays). With 20 arrays (10 for cases, 10 for controls), over half of the information could be extracted from this sample

Redox-mediated reactions of vinylferrocene: Toward redox auxiliaries

Chemical redox reactions have been exploited to transform unreactive vinylferrocene into a powerful dienophile for the Diels–Alder reaction and reactive substrate for thiol addition reactions upon conversion to its ferrocenium state. We have further investigated the ability of these reactions to facilitate redox-auxiliary-like reactivity by further hydrogenolyisis of the Diels–Alder adduct to the corresponding cyclopentane derivative

Isomerisation of nido-[C₂B₁₀H₁₂]²⁻ dianions::Unprecedented rearrangements and new structural motifs in carborane cluster chemistry

We thank the EPSRC for support (DMcK funded by project EP/E02971X/1).Dianionic nido-[C2B10]2- species are key intermediates in the polyhedral expansion from 12- to 13-vertex carboranes and metallacarboranes, and the isomer adopted by these nido intermediates dictates the isomeric form of the 13-vertex product. Upon reduction and metallation of para-carborane up to five MC2B10 metallacarboranes can be produced (Angew. Chem., Int. Ed., 2007, 46, 6706), the structures of which imply the intermediacy of 1,7-, 3,7-, 4,7-, 7,9- and 7,10-isomers of the nido-[C2B10]2- species. In this paper we use density functional theory (DFT) calculations to characterise the reduction of closo-C2B10H12 carboranes and the subsequent isomerisations of the nido-[C2B10H12]2- dianions. Upon reduction para-carborane initially opens to [1,7-nido-C2B10H12]2- (abbreviated to 1,7) and [4,7-nido-C2B10H12]2- (4,7) and isomerisation pathways connecting 1,7 to 7,9, 4,7 to 7,10 and 1,7 to 3,7 have been characterised. For ortho- and meta-carborane the experimental reduction produces 7,9 in both cases and computed pathways for both processes are also defined; with ortho-carborane rearrangement occurs via 7,8, whereas with meta-carborane 7,9 is formed directly. The 7,9 isomer is the global minimum nido-structure. The characterisation of these isomerisation processes uncovers intermediates that adopt new structural motifs that we term basket and inverted nido. Basket intermediates feature a two-vertex basket handle bridging the remaining 10 vertices; inverted nido intermediates are related to known nido species, in that they have 5- and 6-membered belts, but where the latter, rather than the former, is capped, leaving a 5-membered open face. These new intermediates exhibit similar stability to the nido species, which is attributed to their relation to the 13-vertex docosahedron through the removal of 5-connected vertices. Isomerisation pathways starting from nido geometries are most often initiated by destabilisation of the cluster through a DSD process causing the 3-connected C7 vertex to move into a 4-connected site and a neighbouring B vertex to become 3-connected. The ensuing rearrangement of the cluster involves processes such as the pivoting of a 4-vertex diamond about its long diagonal, the pivoting of two 3-vertex triangles about a shared vertex and DSD processes. These processes are all ultimately driven by the preference for carbon to occupy low-connected vertices on the open 6-membered face of the resulting nido species.Publisher PDFPeer reviewe

The role of host identity in high latitude moss-associated nitrogen fixation

Mosses make up a significant portion of primary plant productivity in Arctic and boreal ecosystems and are important regulators of biogeochemical cycling. In addition to producing recalcitrant litter and insulating soils, mosses often host epiphytic microbes capable of fixing nitrogen (N) from the air at rates which make it the largest source of a limiting nutrient in these environments. Since the availability of N is linked to carbon (C) fixation and decomposition, the current and future rates of N2 fixation are important topics of research in an area which stores large amounts of C belowground. Past evidence indicates that host moss identity and environmental conditions can alter rates of moss-associated N2 fixation. However, past studies often focus on a limited number of species and use indirect methods to measure N2 fixation. This dissertation employs 15N2 incubations to measure rates of moss-associated fixation at sites ranging from 60° to 68° N in Alaska in both natural surveys and manipulative experiments in the field. We found that N2 fixation is almost ubiquitous among mosses and that moss identity is consistently an important predictor of associated N2 fixation rates. In subsequent analyses related to C stable isotopes and a reciprocal transplant, we also found a significant interaction between host identity and environment. The strength of the interaction term was typically host specific. As temperature and other abiotic conditions change along with climate and cause changes in moss biomass and diversity, it is critical to incorporate the interaction term into predictions of future N inputs

Accurate computed spin-state energetics for Co(iii) complexes:implications for modelling homogeneous catalysis

Co(III) complexes are increasingly prevalent in homogeneous catalysis. Catalytic cycles involve multiple intermediates, many of which will feature unsaturated metal centres. This raises the possibility of multistate character along reaction pathways and so requires an accurate approach to calculating spin-state energetics. Here we report an assessment of the performance of DLPNO-CCSD(T) (domain-based local pair natural orbital approximation to coupled cluster theory) against experimental Co-1 to Co-3 spin splitting energies for a series of pseudo-octahedral Co(III) complexes. The alternative NEVPT2 (strongly-contracted n-electron valence perturbation theory) and a range of density functionals are also assessed. DLPNO-CCSD(T) is identified as a highly promising method, with mean absolute deviations (MADs) as small as 1.3 kcal mol(-1) when Kohn-Sham reference orbitals are used. DLPNO-CCSD(T) out-performs NEVPT2 for which a MAD of 3.5 kcal mol(-)(1 )can be achieved when a (10,12) active space is employed. Of the nine DFT methods investigated TPSS is the leading functional, with a MAD of 1.9 kcal mol(-1). Our results show how DLPNO-CCSD(T) can provide accurate spin state energetics for Co(III) species in particular and first row transition metal systems in general. DLPNO-CCSD(T) is therefore a promising method for applications in the burgeoning field of homogeneous catalysis based on Co(III) species