Hydrogen Bonding Parameters by Rapid Colorimetric Assessment: Evaluation of Structural Components Found in Biological Ligands and Organocatalysts.

Hydrogen bonding is a key molecular interaction in biological processes, drug delivery, and catalysis. This report describes a high throughput UV-Vis spectroscopic method to measure hydrogen bonding capacity using a pyrazinone sensor. This colormetric sensor reversibly binds to a hydrogen bond donor, resulting in a blue shift as additional equivalents of donor are added. Titration with excess equivalents of donor is used to determine the binding coefficient, ln(Keq ). Over 100 titrations were performed for a variety of biologically relevant compounds. This data enabled development a multiple linear regression model that is capable of predicting 95 % of ln(Keq ) values within 1 unit, allowing for the estimation of hydrogen bonding affinity from a single measurement. To show the effectiveness of the single point measurements, hydrogen bond strengths were obtained for a set of carboxylic acid bioisosteres. The values from the single point measurements were validated with full titrations.

Oxidative Coupling in Complexity Building Transforms.

Since many synthetic targets in organic chemistry are larger, more functionalized, and more oxidized than the starting inputs used, methods that unite fragments with an increase in oxidation state possess inherent efficiencies. Thus, the potential for complexity building transforms by union of activated or unactivated C-H, N-H, or O-H centers is considerable, and the challenge lies in how to obtain selective reactions from any two of these centers.

Support of academic synthetic chemistry using separation technologies from the pharmaceutical industry.

The use of state-of-the-art separation tools from the pharmaceutical industry for addressing intractable separation problems from academic synthetic chemistry is evaluated, showing fast and useful results for the resolution of complex mixtures, separation of closely related components, visualization of difficult to detect compounds and purification of synthetic intermediates. Some recommendations for potential near term deployment of separation tools within academia and the evolution of next generation separation technologies are discussed.

Mild aromatic palladium-catalyzed protodecarboxylation: kinetic assessment of the decarboxylative palladation and the protodepalladation steps.

Mechanism studies of a mild palladium-catalyzed decarboxylation of aromatic carboxylic acids are described. In particular, reaction orders and activation parameters for the two stages of the transformation were determined. These studies guided development of a catalytic system capable of turnover. Further evidence reinforces that the second stage, protonation of the arylpalladium intermediate, is the rate-determining step of the reaction. The first step, decarboxylative palladation, is proposed to occur through an intramolecular electrophilic palladation pathway, which is supported by computational and mechanism studies. In contrast to the reverse reaction (C-H insertion), the data support an electrophilic aromatic substitution mechanism involving a stepwise intramolecular protonation sequence for the protodepalladation portion of the reaction.