An Experimental Study of 2-Propanol Pyrolysis Chemistry.

In the present study, 2-propanol pyrolysis experiments were conducted in a rapid compression facility for a range of temperatures from 965 to 1193 K, pressures from 4.4 to 10.0 atm conditions, and times ranging from 2 to 47 ms after end-of-compression. Mixtures were composed of 2-propanol, nitrogen, and argon with the 2-propanol concentration held constant at 1.5% by mole fraction. The production of seven stable intermediate species (methane, acetylene, ethene, ethane, acetaldehyde, propene, and acetone) were measured using fast-gas sampling and gas chromatography. The high concentrations of propene observed experimentally indicated thermal decomposition of 2-propanol via dehydration was significant at all conditions studied. The observation of the simultaneous presence of methane and acetone indicated H atom abstraction from 2-propanol by H and CH3 radicals was also significant at all conditions. The relative concentrations of methane and acetone indicated an increase in the 2-propanol + CH3 channel at higher temperature. The experimental data showed negligible sensitivity to over a factor-of-two increase in pressure, indicating pressure-dependent reactions, like the thermal decomposition of 2-propanol via dehydration, were in the high-pressure limit. The experimental results were compared with model predictions made using a recently developed kinetic mechanism for C3-C4 alcohols, and the results showed generally good agreement. The most significant discrepancies were for 2-propanol consumption at the highest temperature condition (T = 1193 K), where 2-propanol consumption was predicted as much higher by the model (by more than an order of magnitude) compared with the experimental results, and at the lowest temperature (T = 965 K), ethane production was predicted as much lower (by more than an order of magnitude) compared with the experimental results.

Discovery of a series of potent and selective human H4 antagonists using ligand efficiency and libraries to explore structure-activity relationship (SAR).

We describe the identification of a potent, selective lead series that shows antagonism against the human histamine H4 receptor from thirteen actives identified in an HTS as part of a hit to lead program. By focusing on ligand efficiency and concurrently using a diversity based approach, compounds based around 2,4-diaminopyrimidine were identified with compound 25 being quickly shown to be a good lead. It also had the highest ligand efficiency in the series.

Scaling up of continuous-flow, microwave-assisted, organic reactions by varying the size of Pd-functionalized catalytic monoliths.

A product-scalable, catalytically mediated flow system has been developed to perform Suzuki-Miyaura reactions under a microwave heating regime, in which the volumetric throughput of a Pd-supported silica monolith can be used to increase the quantity of the product without changing the optimal operating conditions. Two silica monoliths (both 3 cm long), with comparable pore diameters and surface areas, were fabricated with diameters of 3.2 and 6.4 mm to give volumetric capacities of 0.205 and 0.790 mL, respectively. The two monoliths were functionalized with a loading of 4.5 wt % Pd and then sealed in heat-shrinkable Teflon(®) tubing to form a monolithic flow reactor. The Pd-supported silica monolith flow reactor was then placed into the microwave cavity and connected to an HPLC pump and a backpressure regulator to minimize the formation of gas bubbles. The flow rate and microwave power were varied to optimize the reactant contact time and temperature, respectively. Under optimal reaction conditions the quantity of product could be increased from 31 mg per hour to 340 mg per hour simply by changing the volumetric capacity of the monolith.

Multistep synthesis using modular flow reactors: Bestmann-Ohira reagent for the formation of alkynes and triazoles.

Multistep in flow: The Seyferth-Gilbert reagent 1 has been applied in a flow system to rapidly synthesize terminal alkynes. The system has been further applied to synthesize triazole 3 from alcohol 2 in a three-step oxidation/homologation/copper(I)-catalyzed azide-alkyne cycloaddition sequence without isolation of intermediates (see scheme).

Neuroprediction, Violence, and the Law: Setting the Stage.

In this paper, our goal is to (a) survey some of the legal contexts within which violence risk assessment already plays a prominent role, (b) explore whether developments in neuroscience could potentially be used to improve our ability to predict violence, and (c) discuss whether neuropredictive models of violence create any unique legal or moral problems above and beyond the well worn problems already associated with prediction more generally. In "Violence Risk Assessment and the Law", we briefly examine the role currently played by predictions of violence in three high stakes legal contexts: capital sentencing ("Violence Risk Assessment and Capital Sentencing"), civil commitment hearings ("Violence Risk Assessment and Civil Commitment"), and "sexual predator" statutes ("Violence Risk Assessment and Sexual Predator Statutes"). In "Clinical vs. Actuarial Violence Risk Assessment", we briefly examine the distinction between traditional clinical methods of predicting violence and more recently developed actuarial methods, exemplified by the Classification of Violence Risk (COVR) software created by John Monahan and colleagues as part of the MacArthur Study of Mental Disorder and Violence [1]. In "The Neural Correlates of Psychopathy", we explore what neuroscience currently tells us about the neural correlates of violence, using the recent neuroscientific research on psychopathy as our focus. We also discuss some recent advances in both data collection ("Cutting-Edge Data Collection: Genetically Informed Neuroimaging") and data analysis ("Cutting-Edge Data Analysis: Pattern Classification") that we believe will play an important role when it comes to future neuroscientific research on violence. In "The Potential Promise of Neuroprediction", we discuss whether neuroscience could potentially be used to improve our ability to predict future violence. Finally, in "The Potential Perils of Neuroprediction", we explore some potential evidentiary ("Evidentiary Issues"), constitutional ("Constitutional Issues"), and moral ("Moral Issues") issues that may arise in the context of the neuroprediction of violence.