Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere

Pharmaceutical and agrochemical discovery programs are under considerable pressure to meet increasing global demand and thus require constant innovation. Classical hydrocarbon scaffolds have long assisted in bringing new molecules to the market place, but an obvious omission is that of the Platonic solid cubane. Eaton, however, suggested that this molecule has the potential to act as a benzene bioisostere. Herein, we report the validation of Eaton's hypothesis with cubane derivatives of five molecules that are used clinically or as agrochemicals. Two cubane analogues showed increased bioactivity compared to their benzene counterparts whereas two further analogues displayed equal bioactivity, and the fifth one demonstrated only partial efficacy. Ramifications from this study are best realized by reflecting on the number of bioactive molecules that contain a benzene ring. Substitution with the cubane scaffold where possible could revitalize these systems, and thus expedite much needed lead candidate identification.     

Syntheses and X-ray diffraction, photochemical, and optical characterization of Cu2SixSn1-xS3 (0.4 < or = x < or = 0.6) for photovoltaic applications

The study of the pseudobinary system Cu(2)SnS(3-)Cu(2)SiS(3) shows that a solid solution (Cu(2)Si(x)Sn(1-x)S(3)) exists in the range 0.4 < or = Si/(Sn+Si) < or = 0.6. Based on diffuse reflectance and photoelectrochemical measurements these compounds show potential as absorber materials for photovoltaic devices. The compounds were prepared at 850 degrees C from copper sulfide, silicon, tin, and sulfur and were analyzed with single-crystal (for x approximately 0.40) and powder diffraction techniques. Optical band gaps of 1.25, 1.35, and 1.45 eV were observed for the three compositions x = 0.39, 0.48, and 0.61; cathodic photocurrent occurring is significant.     

The Supramolecular Structural Chemistry of Pentafluorosulfanyl and Tetrafluorosulfanylene Compounds

The analysis of crystal structures of SF₅- or SF₄-containing molecules revealed that these groups are often surrounded by hydrogen or other fluorine atoms. Even though fluorine prefers F⋅⋅⋅H over F⋅⋅⋅F contacts, the latter appeared to be important in many compounds. In a significant number of datasets, the closest F⋅⋅⋅F contacts are below 95 % of the van der Waals distance of two F atoms. Moreover, a number of repeating structural motifs formed by contacts between SF₅ groups was identified, including different supramolecular dimers and infinite chains. Among SF₄-containing molecules, the study focused on SF₄Cl compounds, including the first solid-state structure analyses of these reactive species. Additionally, electrostatic potential surfaces of a series of Ph-SF₅ derivatives were calculated, pointing out the substituent influence on the ability of F⋅⋅⋅X contact formation (X=F or other electronegative atom). Interaction energies were calculated for different dimeric arrangements of Ph-SF₅, which were extracted from experimental crystal structure determinations.     

Spectroscopic ellipsometry of SU‐8 photoresist from 190 to 1680 nm (0.740–6.50 eV)

SU‐8 is an important, epoxy‐based, negative photoresist that can create high aspect ratio features. Spectroscopic ellipsometry (SE) is a nondestructive analytical technique that can be performed in the open air. In this study, reflection and transmission SE measurement data were combined to model the optical function of SU‐8 photoresist. The data were fit using three different models: (i) a B‐spline model, (ii) a four‐Gaussian oscillator model with an ultraviolet (UV) and an infrared (IR) pole, and (iii) a Cody–Lorentz model with three additional Gaussian oscillators. All three models successfully fit the data, where the B‐spline model showed the lowest mean squared error. In situ SE data were also collected and fitted to follow possible changes in the optical properties of the SU‐8 during its development. Time‐dependent density functional theory (TD‐DFT) modeling of a complete SU‐8 monomer is qualitatively and quantitatively consistent with the measured optical function.     

Grouped Functional Time Series Forecasting: An Application to Age-Specific Mortality Rates

Age-specific mortality rates are often disaggregated by different attributes, such as sex, state, and ethnicity. Forecasting age-specific mortality rates at the national and sub-national levels plays an important role in developing social policy. However, independent forecasts at the sub-national levels may not add up to the forecasts at the national level. To address this issue, we consider reconciling forecasts of age-specific mortality rates, extending the methods of Hyndman et al. in 2011 Hyndman, R. J., Ahmed, R. A., Athanasopoulos, G., and Shang, H. L. (2011), “Optimal Combination Forecasts for Hierarchical Time Series,” Computational Statistics and Data Analysis, 55, 2579–2589.[Crossref], [Web of Science ®] , [Google Scholar] to functional time series, where age is considered as a continuum. The grouped functional time series methods are used to produce point forecasts of mortality rates that are aggregated appropriately across different disaggregation factors. For evaluating forecast uncertainty, we propose a bootstrap method for reconciling interval forecasts. Using the regional age-specific mortality rates in Japan, obtained from the Japanese Mortality Database, we investigate the one- to ten-step-ahead point and interval forecast accuracies between the independent and grouped functional time series forecasting methods. The proposed methods are shown to be useful for reconciling forecasts of age-specific mortality rates at the national and sub-national levels. They also enjoy improved forecast accuracy averaged over different disaggregation factors. Supplementary materials for the article are available online.     

A Convolution Method for Numerical Solution of Backward Stochastic Differential Equations

We propose a new method for the numerical solution of backward stochastic differential equations (BSDEs) which finds its roots in Fourier analysis. The method consists of an Euler time discretization of the BSDE with certain conditional expectations expressed in terms of Fourier transforms and computed using the fast Fourier transform (FFT). The problem of error control is addressed and a local error analysis is provided. We consider the extension of the method to forward-backward stochastic differential equations (FBSDEs) and reflected FBSDEs. Numerical examples are considered from finance demonstrating the performance of the method.     

Gaussian factor models futures and forward prices

Email: hyndman{at}mathstat.concordia.ca Received on 31 July 2006. Accepted on 19 March 2007. We completely characterize the futures price and forward priceof a risky asset (commodity) paying a stochastic dividend yield(convenience yield). The asset (commodity) price is modelledas an exponential affine function of a Gaussian factors process,while the interest rate and dividend yield are affine functionsof the factors process. The characterization we provide is basedon the method of stochastic flows. We believe this method leadsto simpler and more clear-cut derivations of the futures priceand forward price formulae than alternative methods. Hedginga long-term forward contract with shorter term futures contractsand bonds is also examined.     

Anhydrous TEMPO-H: reactions of a good hydrogen atom donor with low-valent carbon centres

In this paper, we report a novel synthesis of anhydrous 1-hydroxy-2,2,6,6-tetramethyl-piperidine (TEMPO-H). An X-ray crystal structure and full characterization of the compound are included. Compared to hydrated TEMPO-H, its anhydrous form exhibits improved stability and a differing chemical reactivity. The reactions of anhydrous TEMPO-H with a variety of low-valent carbon centres are described. For example, anhydrous TEMPO-H was reacted with 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes), an unsaturated NHC. Crystals of [CHNC(6)H(2)(CH(3))(3)](2)C···HO(NC(5)H(6)(CH(3))(4)), IMes···TEMPO-H, were isolated and a crystal structure determined. The experimental structure is compared to the results of theoretical calculations on the hydrogen-bonded dimer. Anhydrous TEMPO-H was also reacted with the saturated NHC, 1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene (SIPr), giving the product [CH(2)Ni-Pr(2)C(6)H(3)](2)CH···O(NC(5)H(6)(CH(3))(4)). In contrast, the reaction of hydrated TEMPO-H with 1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene gave small amounts of the hydrolysis product, N-(2,6-diisopropylphenyl)-N-[2-(2,6-diisopropylphenylamino)ethyl]formamide. Finally, anhydrous TEMPO-H was reacted with (triphenylphosphoranylidene)ketene to generate Ph(3)PC(H)C(=O)O(NC(5)H(6)(CH(3))(4)). A full characterization of the product, including an X-ray crystal structure, is described.