Stable,Reactive, and Orthogonal Tetrazines: Dispersion Forces Promote the Cycloaddition with Isonitriles

The isocyano group is a structurally compact bioorthogonal functional group that reacts with tetrazines under physiological conditions. Now it is shown that bulky tetrazine substituents accelerate this cycloaddition. Computational studies suggest that dispersion forces between the isocyano group and the tetrazine substituents in the transition state contribute to the atypical structure–activity relationship. Stable asymmetric tetrazines that react with isonitriles at rate constants as high as 57 L mol^?1 s^?1 were accessible by combining bulky and electron‐withdrawing substituents. Sterically encumbered tetrazines react selectively with isonitriles in the presence of strained alkenes/alkynes, which allows for the orthogonal labeling of three proteins. The established principles will open new opportunities for developing tetrazine reactants with improved characteristics for diverse labeling and release applications with isonitriles.     

autoDIAS: a python tool for an automated distortion/interaction activation strain analysis

The distortion/interaction activation strain (DIAS) analysis is a powerful tool for the investigation of energy barriers. However, setup and data analysis of such a calculation can be cumbersome and requires lengthy intervention of the user. We present autoDIAS, a python tool for the automated setup, performance, and data extraction of the DIAS analysis, including automated detection of fragments and relevant geometric parameters. © 2019 Wiley Periodicals, Inc.     

Exceptional sets related to Hayman's alternative

Let E be a subset of the complex plane C consisting of a countable set of points tending to ∞ and let k?1 be an integer. We derive a spacing condition (dependent on k) on the points of E which ensures that, if f is a function meromorphic in C with sufficiently large Nevanlinna deficiency at the poles, then either f takes every complex value infinitely often, or the kth derivative f(k) takes every non-zero complex value infinitely often, in C−E. This improves a previous result of Langley.     

A Convergent Strategy for the Asymmetric Synthesis of Enantiomerically Pure Bicyclic Compounds by Using a Silicon-Directed Cycloaddition Reaction: The Synthesis of Enantiomerically Pure Bicyclo[3.2.0]hept-2-en-6-one

An asymmetric allylmetalation followed by a silicon-stereodirected cycloaddition gives enantiomerically pure bicyclic compounds. The synthesis of enantiopure 1 (see scheme) in a yield of 65–74 %, 93 % ee, and >98 % de provides an illustration of the efficacy of the method. The preferential formation of 1 rather than its diastereoisomer (32:1), during the cycloaddition step, matches the result predicted by RHF and density functional theory studies.     

Conjugated block copolymers via functionalized initiators and click chemistry

Conjugated block copolymers are potentially useful for organic electronic applications and the study of interfacial charge and energy transfer processes; yet few synthetic methods are available to prepare polymers with well‐defined conjugated blocks. Here, we report the synthesis and thin film morphology of a series of conjugated poly(3‐hexylthiophene)‐block‐poly(9,9‐dioctylfluorene) (P3HT‐b‐PF) and poly(3‐dodecylthiophene)‐block‐poly(9,9‐dioctylfluorene) (P3DDT‐b‐PF) block copolymers prepared by functional external initiators and click chemistry. Functional group control is quantified by proton nuclear magnetic resonance spectroscopy, size‐exclusion chromatography, and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. The thin film morphology of the resulting all‐conjugated block copolymers is analyzed by a combination of grazing‐incidence X‐ray scattering, atomic force microscopy, and transmission electron microscopy. Crystallization of the P3HT or P3DDT blocks is present in thin films for all materials studied, and P3DDT‐b‐PF films exhibit significant PF/P3DDT co‐crystallization. Processing conditions are found to impact thin film crystallinity and orientation of the π–π stacking direction of polymer crystallites. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 154–163     

Quantification of dynamic contrast-enhanced MR imaging of the knee in children with juvenile rheumatoid arthritis based on pharmacokinetic modeling

Improved management of arthritis requires a reliable, quantifiable, noninvasive method to monitor the degree of inflammation and therapeutic response during the early phase of the disease. For this purpose, the uptake of Gd-DTPA in the distal femoral physis and synovium in children with juvenile rheumatoid arthritis (JRA) was evaluated with a two-compartment pharmacokinetic model and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Employing a two-compartment pharmacokinetic model, the theoretical signal enhancement from Gd-DTPA enhanced dynamic 3D gradient-recalled echo (GRE) images was shown to have a simple linear relationship with tissue concentration independent of flip angle. The signal-enhancement patterns for each individual knee were found to be characterized by three pharmacokinetic parameters: k(ep) (min(-1)), the rate constant; k(el) (min(-1)), the elimination rate constant; and E(R) (min(-1)), the initial enhancement rate, which is proportional to the transfer constant K(trans) (min(-1)). Characteristic patterns were observed in the image signal intensity-time course. The initial enhancement rate, E(R), in regions of interest (ROIs) was found to have a wide range of variation: 5 to 38 min(-1) over the distal femoral physis and 1 to 10 min(-1) in the synovium. The E(R) of the synovium was correlated with the E(R) of the distal femoral physis (P<.05). In addition, the E(R) of the synovium was correlated to the clinical outcome measures of knee swelling. Further investigation is needed to determine whether wide variations in the pharmacokinetic parameters reflect the degree of disease activity, and whether there are changes in response to therapy. This method can also be applied in adults with rheumatoid arthritis (RA) and other disorders where T(1)-weighted contrast is used (breast cancer, brain tumors).     

Paired pulse voltammetry for differentiating complex analytes

Although fast-scan cyclic voltammetry (FSCV) has contributed to important advances in neuroscience research, the technique is encumbered by significant analytical challenges. Confounding factors such as pH change and transient effects at the microelectrode surface make it difficult to discern the analytes represented by complex voltammograms. Here we introduce paired-pulse voltammetry (PPV), that mitigates the confounding factors and simplifies the analytical task. PPV consists of a selected binary waveform with a specific time gap between each of its two comprising pulses, such that each binary wave is repeated, while holding the electrode at a negative potential between the waves. This allows two simultaneous yet very different voltammograms (primary and secondary) to be obtained, each corresponding to the two pulses in the binary waveform. PPV was evaluated in the flow cell to characterize three different analytes, (dopamine, adenosine, and pH changes). The peak oxidation current decreased by approximately 50%, 80%, and 4% for dopamine, adenosine, and pH, in the secondary voltammogram compared with the primary voltammogram, respectively. Thus, the influence of pH changes could be virtually eliminated using the difference between the primary and secondary voltammograms in the PPV technique, which discriminates analytes on the basis of their adsorption characteristics to the carbon fiber electrode. These results demonstrate that PPV can be effectively used for differentiating complex analytes.     

Near-thermal reactions of Au(+)(1S,3D) with CH3X (X = F,Cl)

Reactions of Au(+)((1)S) and Au(+)((3)D) with CH(3)F and CH(3)Cl have been carried out in a drift cell in He at a pressure of 3.5 Torr at both room temperature and reduced temperatures in order to explore the influence of the electronic state of the metal on reaction outcomes. State-specific product channels and overall two-body rate constants were identified using electronic state chromatography. These results indicate that Au(+)((1)S) reacts to yield an association product in addition to AuCH(2)(+) in parallel steps with both neutrals. Product distributions for association vs HX elimination were determined to be 79% association/21% HX elimination for X = F and 50% association/50% HX elimination when X = Cl. Reaction of Au(+)((3)D) with CH(3)F also results in HF elimination, which in this case is thought to produce (3)AuCH(2)(+). With CH(3)Cl, Au(+)((3)D) reacts to form AuCH(3)(+) and CH(3)Cl(+) in parallel steps. An additional product channel initiated by Au(+)((3)D) is also observed with both methyl halides, which yields CH(2)X(+) as a higher-order product. Kinetic measurements indicate that the reaction efficiency for both Au(+) states is significantly greater with CH(3)Cl than with CH(3)F. The observed two-body rate constant for depletion of Au(+)((1)S) by CH(3)F represents less than 5% of the limiting rate constant predicted by the average dipole orientation model (ADO) at room temperature and 226 K, whereas CH(3)Cl reacts with Au(+)((1)S) at the ADO limit at both room temperature and 218 K. Rate constants for depletion of Au(+)((3)D) by CH(3)F and CH(3)Cl were measured at 226 and 218 K respectively, and indicate that Au(+)((3)D) is consumed at approximately 2% of the ADO limit by CH(3)F and 69% of the ADO limit by CH(3)Cl. Product formation and overall efficiency for all four reactions are consistent with previous experimental results and available theoretical models.