Synthesis and Analysis of Natural-Product-Like Macrocycles by Tandem Oxidation/Oxa-Conjugate Addition Reactions

As traditional small-molecule drug discovery programs focus on a relatively narrow range of chemical space, most human proteins are viewed as unreachable targets. Consequently, there is a strong interest in expanding the chemical space in drug discovery beyond traditional small molecules. Here, a strategy for the preparation of a broad natural-product-like macrocyclic library by using the tandem allylic oxidation/oxa-conjugate addition and macrocyclization reactions is reported. Cheminformatic analyses demonstrate that this tetrahydropyran-containing macrocyclic library shows a significant overlap with natural products in the chemical space. This approach can be used for designing libraries that may probe more deeply into natural-product-like space.     

Gallic acid-functionalized magnetic nanoparticles: a convenient and green approach for synthesis of α-aminonitriles under solvent-free conditions

Research on Chemical Intermediates - Gallic acid-coated magnetic nanoparticles were efficiently prepared, characterized by Fourier transform infrared spectroscopy, X-ray diffraction, vibrating...     

Structural characterization of the aquaporin inhibitor 2‐nicotinamido‐1,3,4‐thiadiazole

Nicotinamides are a class of compounds with a wide variety of applications, from use as antimicrobial agents to inhibitors of biological processes. These compounds are also cofactors, which are necessary components of metabolic processes. Structural modification gives rise to the activities observed. Similarly, 1,3,4‐thiadiazoles have been shown to possess antioxidant, antimicrobial, or anti‐inflammatory biological activity. To take advantage of each of the inherent characteristics of the two aforementioned functional groups, 2‐nicotinamido‐1,3,4‐thiadiazole, C₈H₆N₄OS, was synthesized. Since defining chemical connectivity is paramount in understanding biological activity, in this report, the structural characterization of 2‐nicotinamido‐1,3,4‐thiadiazole has been carried out using X‐ray crystallographic methods. The NMR‐derived assignments were made possible by utilizing one‐ (1D) and two‐dimensional (2D) NMR techniques. In addition, UV–Visible and IR spectroscopies, and elemental analysis were used to fully characterize the product synthesized by the one‐step reaction between nicotinoyl chloride hydrochloride and 2‐amino‐1,3,4‐thiadiazole. Computational parameters related to blood–brain barrier permeability are also presented.     

Singular cardinals and strong extenders

We investigate the circumstances under which there exist a singular cardinal µ and a short (κ,µ)-extender E witnessing “κ is µ-strong”, such that µ is singular in Ult(V, E).     

Paper-based microfluidic devices for analysis of clinically relevant analytes present in urine and saliva

We report the use of paper-based microfluidic devices fabricated from a novel polymer blend for the monitoring of urinary ketones, glucose, and salivary nitrite. Paper-based devices were fabricated via photolithography in less than 3 min and were immediately ready for use for these diagnostically relevant assays. Patterned channels on filter paper as small as 90 μm wide with barriers as narrow as 250 μm could be reliably patterned to permit and block fluid wicking, respectively. Colorimetric assays for ketones and nitrite were adapted from the dipstick format to this paper microfluidic chip for the quantification of acetoacetate in artificial urine, as well as nitrite in artificial saliva. Glucose assays were based on those previously demonstrated (Martinez et al., Angew Chem Int Ed 8:1318–1320, 1; Martinez et al., Anal Chem 10:3699–3707, 2; Martinez et al., Proc Nat Acad Sci USA 50:19606–19611, 3; Lu et al., Electrophoresis 9:1497–1500, 4; Abe et al., Anal Chem 18:6928–6934, 5). Reagents were spotted on the detection pad of the paper device and allowed to dry prior to spotting of samples. The ketone test was a two-step reaction requiring a derivitization step between the sample spotting pad and the detection pad, thus for the first time, confirming the ability of these paper devices to perform online multi-step chemical reactions. Following the spotting of the reagents and sample solution onto the paper device and subsequent drying, color images of the paper chips were recorded using a flatbed scanner, and images were converted to CMYK format in Adobe Photoshop CS4 where the intensity of the color change was quantified using the same software. The limit of detection (LOD) for acetoacetate in artificial urine was 0.5 mM, while the LOD for salivary nitrite was 5 μM, placing both of these analytes within the clinically relevant range for these assays. Calibration curves for urinary ketone (5 to 16 mM) and salivary nitrite (5 to 2,000 μM) were generated. The time of device fabrication to the time of test results was about 25 min.     

Geometric Model Describing the Banded Morphology of Particle Films Formed by Convective Assembly

Nanoparticle films coated on smooth substrates by convective assembly from dilute suspensions in dip‐coating configuration are known to have discrete film morphologies. Specifically, the film morphology is characterized by alternating bands of densely packed particles and bands of bare substrate. Convective assembly is a frontal film‐growth process that occurs at the three‐phase contact line formed by the substrate, the suspension in which it is submersed, and the surrounding air. The bands are parallel to this contact line and can be either monolayered or multilayered. Monolayered bands result whenever the substrate is withdrawn from the suspension at a rate too high for particles to assemble into a continuous film. We report a new insight to the mechanism behind this banding phenomenon, namely, that inter‐band spacing is strongly influenced by the constituent particle size. We therefore propose a geometric model relating the inter‐band spacing to the particle size. By making banded films with systematically varied particle sizes (silica/zeolite, 20 to 500 nm), we are able to quantitatively validate our model. Furthermore, the model correctly predicts that multilayered banded films have higher inter‐band spacings than monolayered banded films comprising the same particles.     

Transferring specialized content knowledge to elementary classrooms: preservice teachers’ learning to teach the associative property

This study explores how preservice teachers (PSTs) transfer the intended specialized content knowledge (SCK) to elementary classrooms. Focusing on the case of the associative property of multiplication, we compared three PSTs’ SCK during enacted lessons in fourth grade classrooms with their own learning in professional development (PD) settings. Findings revealed the PSTs’ successes and challenges in unpacking an example task, especially in areas of making connections between concrete and abstract representations and asking deep questions that target quantitative interactions. Factors that may have supported or hindered PSTs’ SCK transfer include the complex nature of teacher knowledge, the PD effort and the outside factors such as the support from textbooks and cooperating teachers. Implications for teacher education and directions for future research are discussed.     

An L-like model containing very large cardinals

We force and construct a model in which level by level equivalence between strong compactness and supercompactness holds, along with a strong form of diamond and a version of square consistent with supercompactness. This generalises a result due to the first author. There are no restrictions in our model on the structure of the class of supercompact cardinals. A. W. Apter’s research was partially supported by PSC-CUNY Grants and CUNY Collaborative Incentive Grants. J. Cummings’s research was partially supported by NSF Grant DMS-0400982.     

Some Independence Results on Reflection

It is proved that there is a certain degree of independencebetween stationary reflection phenomena at different cofinalities.     

Kinetic study of competing first-order processes: simultaneous quantification of hemoglobin and methemoglobin in whole blood

The development and evaluation of a kinetic method for the simultaneous quantification of methemoglobin and hemoglobin is described. A unique feature of the reaction/monitoring system is that the two species produce signals that change in opposite directions. Attempts to optimize the reaction conditions, procedures for preparing reliable standards, a new multiwavelength method used for comparison purposes and results for synthetic standards and blood samples to which known amounts of methemoglobin are added are described. Combined effects of competing directions of signal change, large concentration differences and conditions required for pseudo-first-order behavior results in a relativity narrowly defined set of conditions that permit simultaneous determinations. Even so, results for methemoglobin were in reasonable agreement between the kinetic and spectrophotometric methods (slope 1.05, intercept 0.17 mmol l^?1); difficulties in achieving pseudo-first-order behavior yielded less reliable results for hemoglobin with a least-squares slope of 1.16 for a comparison of results by kinetic and spectrophotometric methods. This latter problem had an adverse effect on comparison of percentages of methemoglobin in samples even though concentration values were in good agreement.