Classical Elements in the Works of Thomas Gray

[No abstract provided.

Insights into the structures adopted by titanocalix[6 and 8]arenes and their use in the ring opening polymerization of cyclic esters

Interaction of p-tert-butylcalix[6]areneH6, L1H6, with [TiCl4] afforded the complex [Ti2Cl3(MeCN)2(OH2)(L1H)][Ti2Cl3(MeCN)3(L1H)]∙4.5MeCN (1∙4.5MeCN), in which two pseudo octahedral titanium centres are bound to one calix[6]arene. A similar reaction but employing THF resulted in the THF ring-opened product [Ti4Cl2(μ3-O)2(NCMe)2(L)2(O(CH2)4Cl)2]∙4MeCN (2∙4MeCN), where LH4 = p-tert-butylcalix[4]areneH4. Interaction of L1H6 with TiF4 (3 equiv.) led, after work-up, to the complex [(TiF)2(μ -F)L1H]2∙6.5MeCN (3∙6.5MeCN). Treatment of p-tert-butylcalix[8]areneH8, L2H8, with [TiCl4] led to the isolation of the complex [(TiCl)2(TiClNCMe)2(μ3-O)2(L2)]∙1.5MeCN (4∙1.5MeCN). From a similar reaction, a co-crystallized complex [Ti4O2Cl4(MeCN)2(L2)][Ti3Cl6(MeCN)5(OH2)(L2H2)]·H2O∙11MeCN (5·H2O 11MeCN) was isolated. Extension of the L2H8 chemistry to [TiBr4] afforded, depending on the stoichiometry, the complexes [(TiBr)2(TiBrNCMe)2(μ3-O)2(L2)]∙6MeCN (6∙6MeCN) or [Ti(NCMe)2Br]2[Ti(O)Br2(NCMe)](L2)]∙7.5MeCN (7∙7.5MeCN), whilst use of [TiF4] afforded complexes containing Ca2+ and Na+, thought to originate from drying agents, namely [Ti8CaF20(OH2)Na2(MeCN)4(L2)2]∙14MeCN (8∙14MeCN), [Na(MeCN)2][Ti8CaF20NaO16(L2)2]∙7MeCN (9∙7MeCN) or [Na]6[Ti8F20Na(MeCN)2(L2)][Ti8F20Na(MeCN)0.5(L2)]∙15.5(C2H3N) (10∙15.5MeCN). In the case of TiI4, the ladder [(TiI)2(TiINCMe)2(μ3-O)2(L2)]∙7.25CH2Cl2 (11∙7.25CH2Cl2) was isolated. These complexes have been screened for their potential to act as catalysts in the ring opening polymerization (ROP) of ε-caprolactone (ε-CL), δ-valerolactone (δ-VL) and rac-lactide (r-LA), both in air and N2. For ε-CL and δ-VL, moderate activity at 130 oC over 24 h was observed for 1, 9 and 11; for r-LA, only 1 exhibited reasonable activity. In the case of the co-polymerization of ε-CL with δ-VL, the complexes 1 and 11 afforded reasonable conversions and low molecular weight polymers, whilst 4, 6, and 9 were less effective. None of the complexes proved to be active in the co-polymerization of ε-CL and r-LA under the conditions employed herein

Synthesis and vectorial functionalisation of pyrazolo[3,4- c ]pyridines

Heterocycles are a cornerstone of fragment-based drug discovery (FBDD) due to their prevalence in biologically active compounds. However, novel heterocyclic fragments are only valuable if they can be suitably elaborated to compliment a chosen target protein. Here we describe the synthesis of 5-halo-1H-pyrazolo[3,4-c]pyridine scaffolds and demonstrate how these compounds can be selectively elaborated along multiple growth-vectors. Specifically, N-1 and N-2 are accessed through protection-group and N-alkylation reactions; C-3 through tandem borylation and Suzuki–Miyaura cross-coupling reactions; C-5 through Pd-catalysed Buchwald–Hartwig amination; and C-7 through selective metalation with TMPMgCl.LiCl followed by reaction with electrophiles or transmetalation to ZnCl2 and Negishi cross-coupling. Linking multiple functionalisation strategies emulates a hit-to-lead pathway and demonstrates the utility of pyrazolo[3,4-c]pyridines to FBDD

Use of titanocalix[4]arenes in the ring opening polymerization of cyclic esters

The known dichloride complexes [TiCl2L(O)2(OR)2] (type I: R = Me (1), n-Pr (2) and n-pentyl (3); L(OH)2(OR)2 = 1,3-dialkyloxy-p-tert-butylcalix[4]arene), together with the new complexes {[TiL(O)3(OR)]2(μ-Cl)2}·6MeCN (R = n-decyl (4·6MeCN)), and [Ti(NCMe)Cl(L(O)3(OR))]·MeCN (type II: R = Me, 5·MeCN) are reported. Attempts to prepare type II for R = n-Pr and n-pentyl using [TiCl4] resulted in the complexes {[TiL(O)3(On-propyl)]2(μ-Cl)(μ-OH)} 6·7MeCN and {[TiL(O)3(On-pentyl)]2(μ-Cl)(μ-OH)}·7.5MeCN (7·7.5MeCN), respectively; use of [TiCl4(THF)2] resulted in a co-crystallized THF ring-opened product [Ti(NCMe)(μ3-O)L(O)4TiCl(O(CH2)4Cl)]2-2[TiCl(NCMe)(L(O)3(On-Pr))]·11MeCN (8·11MeCN). The molecular structures of 2·2MeCN, 4·6MeCN, and 5·MeCN together with the hydrolysis products {[TiL(O)3(OR)]2(μ-Cl)(μ-OH)} (R = n-Pr 6·7MeCN; n-pentyl, 7·7.5MeCN, 9·9MeCN); R = n-decyl 10·8.5MeCN) and that of the ring opened product 8·11MeCN and the co-crystallized species [Ti2(OH)Cl(L(O)3(OR))][L(OH)2(OR)2]·2.85(C2H3N)·0.43(H2O) (R = n-pentyl, 11·2.85(C2H3N)·0.43(H2O)) are reported. Type I and II complexes have been screened for their ability to act as catalysts in the ring opening polymerization (ROP) of ϵ-caprolactone (ϵ-CL), δ-valerolactone (δ-VL), ω-pentadecalactone (ω-PDL) and rac-lactide (r-LA), both with and without benzyl alcohol present and either under N2 or in air. The copolymerization of ϵ-CL with δ-VL and with r-LA has also been investigated. For the ROP of ϵ-CL, all performed efficiently (>99% conversion) at 130 °C over 24 h both under N2 and in air, whilst over 1 h, for the type I complexes the trend was 3 > 2 > 1 but all were poor (≤12% conversion). By contrast, 5 over 1 h at 130 °C was highly active (85% conversion). At 80 °C, the activity trend followed the order 5 ≈ 4 > 3 > 2 > 1. For δ-VL, at 80 °C the activity trend 5 ≈ 4 > 1 > 2 > 3 was observed. ROP of the larger ω-PDL was only possible using 5 at 130 °C over 24 h with moderate activity (48% conversion). For r-LA, only low molecular weight products were obtained, whilst for the co-polymerization of ϵ-CL with δ-VL using 5, high activity was observed at 80 °C affording a polymer of molecular weight >23,000 Da and with equal incorporation of each monomer. In the case of ϵ-CL/r-LA co-polymerization using 5 either under N2 or air, the polymerization was more sluggish and only 65% conversion of CL was observed and the resultant co-polymer had 65:35 incorporation. Complex 5 could also be supported on silica, however this system was not as active as its homogeneous counterpart. Finally, the activity of these complexes is compared with that of three benchmark species: a di-phenolate Ti compound {TiCl2(2,2′-CH3CH[4,6-(t-Bu)2C6H2O]2)} (12) and a previously reported NO2-containing titanocalix[4]arene catalyst, namely cone-5,17-bis-tert-butyl-11,23-dinitro-25,27-dipropyloxy-26,28-dioxo-calix[4]arene titanium dichloride (13), as well as [Ti(Oi-Pr)4]; the parent calixarenes were also screened

A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies

A multilaboratory comparison of calibration accuracy and the performance of external references in analytical ultracentrifugation.

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies

Using genetic tools to investigate distribution and connectivity of two Sierra Nevada amphibians, Rana sierrae and Rana boylii

Genetic tools that identify species could supplement traditional survey methods and be utilized to clarify distribution. The capture of environmental DNA (eDNA), or genetic material shed into water, could help assess occupancy of species that are difficult to find. The first part of our study determined an effective eDNA sampling protocols for stream and lake systems for two rare and phenotypically similar species: the Sierra Nevada yellow-legged frog (Rana sierrae) and the foothill yellow-legged frog (R. boylii). We sampled in streams and lakes and filtered two different volumes of water, four times over the summer of 2016. We analyzed samples using species-specific quantitative PCR (qPCR) assays we developed and validated, then analyzed detection results using generalized linear mixed effect models. Filtering 2 L increased the odds of detection in streams 5.42X (95% CI: 3.2-9.19X). Lake sample volumes were limited by filter clogging and we found no effect of volume or filter type. Sampling later in the season increased the odds of detection in streams by 1.96X for every 30 days (95% CI: 1.3 - 2.97X) but we did not find an effect for lakes. Spatial autocorrelation of the amount of yellow-legged frog eDNA captured in streams was found to be unrelated at 100 m indicating that sampling at close intervals is important for detection. There is uncertainty to the validity of lower elevational records (below 1371 m) of R. sierrae maintained by the Forest Service and the second part of this study assessed the distribution of R. sierrae by utilizing both eDNA and genetic sampling of individuals in Plumas National Forest. We sampled 16 lower elevation historic sites with records of R. sierrae and swabbed 144 individuals for genetic identification. We created climatic suitability models using both current (1980-2000) and future (2060-2080) climate models to assess climatic factors and overlap of suitability between R. sierrae and R. boylii. We detected R. sierrae at one historic site at 1201 m and all swabbed individuals were identified as R. boylii. We found evidence that ranges of both species are impacted by winter temperatures and future suitability is expected to dramatically decrease

Comparison Of Three Computer-Administered Cognitive Tasks As Putative Endophenotypes Of Schizophrenia

It has been repeatedly demonstrated that individuals with schizotypal personality features (SPF) exhibit similar endophenotypic traits as persons with schizophrenia. Less research has compared the relative sensitivity of different endophenotypes in the same sample of individuals with SPF. Fourteen university students with SPF (mean age 20.5 ± 1.6; 43% male) and 26 controls (mean age 20.3 ± 1.1; 31% male) were defined by the Abbreviated Schizotypal Personality Questionnaire (SPQ-B). All participants reported no known biological relative with schizophrenia. Participants completed three computer-administered cognitive tasks: a 6-min degraded-stimuli A-X Continuous Performance Test (CPT), the Wisconsin Card Sort Test (WCST), and a Span of Apprehension (SOA) task (6- and 12-letter arrays). On the CPT, only omission errors resulted in a statistically significant group difference, U = 115.5, p = .05, Cohen\u27s d = 0.54 (medium effect size), with the SPF group (mean errors: 3.43 ± 3.28) making more omission errors than controls (mean errors: 1.88 ± 2.66). Notably, 46% of the controls had no omission errors, compared to 14% of the SPF group. The only SPQ-B factor score to show a statistically significant linear relationship with CPT omission errors was the Cognitive-Perceptual factor (rs = .33, p = .04). Group differences on performance indices from the SOA and WCST did not approach statistical significance. Based on performance from the community-identified schizotypes, results suggest that performance on the CPT may represent a more robust endophenotype of schizophrenia, compared to the SOA and WCST. © 2006 Elsevier B.V. All rights reserved

Game-Based Learning: The Impact of Flow State and Videogame Self-Efficacy

The science of serious games is growing at a substantial pace, providing new insights into the nature of game-based learning. Recently, research has begun to focus on the elements that comprise serious games and how these elements relate to learning (Wilson et al., 2009; Pavlas et al., 2009). As part of an effort to understand how these attributes impact learning outcomes, a study manipulating a number of game attributes in an immune system game was conducted. From this effort, two psychological constructs initially considered as mere covariates – video game self-efficacy and flow state – emerged as significant and highly explanatory predictors of learning. This article provides an overview of these constructs, describes the research that led to this finding, presents the results of this research, and offers implications and suggestions for future work