A diode laser study of the Cl + CH3CO reaction

Real-time kinetic measurements are reported for the Cl + CH₃CO → CH₂CO + HCl reaction. The experiments utilize infrared spectroscopy to determine the time dependence of the ketene formed via this reaction and of the CO produced from the subsequent rapid reaction between chlorine atoms and ketene. The reaction is investigated over a pressure range of 10–200 torr and a temperature range of 215–353 K. Within experimental error the rate constant under these conditions is k_5a = (1.8 ± 0.5) × 10⁻¹⁰ cm³ s⁻¹. We have also examined the Cl + CH₂CO reaction and found it to have a rate constant of k₆ = (2.5 ± 0.5) × 10⁻¹⁰ cm³ s⁻¹ independent of temperature. © John Wiley & Sons, Inc. Int J Chem Kinet 29: 421–429, 1997.     

Superposition of Spatially Interacting Aggregated Continuous Time Markov Chains

A system s{ X(t)} = {X ₁(t),X ₂(t),..., X _N(t)} of N interacting time reversible continuous time Markov chains is considered. The state space of each of the processes {X _i(t)} (i = 1, 2,...,N) is partitioned into two aggregates. Interaction between the processes {X _i(t)},{X ₂(t)},...,{X _N(t)} is introduced by allowing the transition rates of an individual process at time t to depend on the configuration of aggregates occupied by the other N - 1 processes at that time. The motivation for this work comes from ion channel modeling, where {(X}(t)} describes the gating mechanisms of N channels and the partitioning of the state space of {X _i(t)} correspond to whether the channel is conducting or not. Let S(t) denote the number of conducting channels at time t. For a time-reversible class of such processes, expressions are derived for the mean and probability density function of the sojourns of {S(t)} at its different levels when {X(t)} is in equilibrium. Particular attention is paid to the situation when the N channels are located on a circle with nearest neighbor interaction. Necessary and sufficient conditions for a general co-operative multiple channel system to be time reversible are derived.     

Single-Molecule Two-Color Coincidence Detection of Unlabeled alpha-Synuclein Aggregates

Protein misfolding and aggregation into oligomeric and fibrillar structures is a common feature of many neurogenerative disorders. Single-molecule techniques have enabled characterization of these lowly abundant, highly heterogeneous protein aggregates, previously inaccessible using ensemble averaging techniques. However, they usually rely on the use of recombinantly-expressed labeled protein, or on the addition of amyloid stains that are not protein-specific. To circumvent these challenges, we have made use of a high affinity antibody labeled with orthogonal fluorophores combined with fast-flow microfluidics and single-molecule confocal microscopy to specifically detect α-synuclein, the protein associated with Parkinson's disease. We used this approach to determine the number and size of α-synuclein aggregates down to picomolar concentrations in biologically relevant samples.     

Photochemically Mediated Ring Expansion of Indoles and Pyrroles with Chlorodiazirines: Synthetic Methodology and Thermal Hazard Assessment

We demonstrate that arylchlorodiazirines serve as photo-activated halocarbene precursors for the selective one-carbon ring expansion of N-substituted pyrroles and indoles to the corresponding pyridinium and quinolinium salts. Preliminary investigations indicate that the same strategy also enables the conversion of N-substituted pyrazoles to pyrimidinium salts. The N-substituent of the substrate plays an essential role in: (1) increasing substrate scope by preventing product degradation, (2) enhancing yields by suppressing co-product inhibition, and (3) activating the azinium products towards subsequent synthetic manipulations. This latter point is illustrated by subjecting the quinolinium salts to four complementary partial reductions, which provide concise access to ring-expanded products with different degrees of increased C(sp³) character. Thermal analysis of the diazirines by differential scanning calorimetry (DSC) provides detailed insight into their energetic properties, and highlights the safety benefits of photolyzing—rather than thermolyzing—these reagents.     

Skeletal Editing: Interconversion of Arenes and Heteroarenes

Skeletal editing involves making specific point-changes to the core of a molecule through the selective insertion, deletion or exchange of atoms. It thus represents a potentially powerful strategy for the step-economic modification of complex substrates and is a perfect complement to methods such as C−H functionalization that target the molecular periphery. Given their ubiquity in biologically active compounds, the ability to perform skeletal editing on – and therefore interconvert between – aromatic heterocycles is especially valuable. This review summarizes both recent and key historical examples of skeletal editing as applied to interconversion of aromatic rings; we anticipate that it will serve to highlight not only the innovative and enabling nature of current skeletal editing methods, but also the tremendous opportunities that still exist in the field.