Catalytic intermolecular olefin hydroamination is an enabling synthetic strategy that offers direct and atom-economical access to a variety of nitrogen-containing compounds from abundant feedstocks. However, despite numerous advances in catalyst design and reaction development, hydroamination of N-H azoles with unactivated olefins remains an unsolved problem in synthesis. We report a dual phosphine and photoredox catalytic protocol for the hydroamination of numerous structurally diverse and medicinally relevant N-H azoles with unactivated olefins. Hydroamination proceeds with high anti-Markovnikov regioselectivity and N-site selectivity. The mild conditions and high functional group tolerance of the reaction permit the rapid construction of molecular complexity and late-stage functionalization of bioactive compounds. N-H bond activation is proposed to proceed via polar addition of the N-H azole to a phosphine radical cation, followed by P-N α-scission from a phosphoranyl radical intermediate. Reactivity and N-site selectivity are classified by azole N-H BDFE and nitrogen-centered radical spin density, respectively, which can serve as a useful predictive aid in extending the reaction to unseen azoles.

There is growing interest in the potential of exercise interventions in therapy for individuals with Alzheimer’s disease (AD). This paper replicates and extends upon some of the analysis of a randomized controlled pilot study that investigates the effect of a 26-week aerobic exercise program on memory, executive function, functional ability, and depression in 68 participants who were likely to develop AD. The replication was focused specifically on the analysis performed on the Memory Composite outcome variable, reproducing an interaction model between two of the main variables, Treatment Arm (Stretching and Toning Exercise versus Aerobic Exercise) and Timepoint (Baseline, Week 13, Week 26). The replication yielded the same values as the original study with similarly insignificant p-values. Using RStudio, the present study tests three additional interaction models, the interaction between Sex and Treatment Arm, between Sex and Timepoint, and between Sex, Treatment Arm, and Timepoint. These tests yielded insignificant p-values, implying that, contrary to the previous literature on gender differences in AD and exercise interventions, gender may not be a differentiating factor in memory. The hypothesis was that the exercise type affects the interaction between time and memory loss in early AD patients.

The enzyme soybean lipoxygenase (SLO) provides a prototype for deep tunneling mechanisms in hydrogen transfer catalysis. This work combines room temperature X-ray studies with extended hydrogen-deuterium exchange experiments to define a catalytically-linked, radiating cone of aliphatic side chains that connects an active site iron center of SLO to the protein-solvent interface. Employing eight variants of SLO that have been appended with a fluorescent probe at the identified surface loop, nanosecond fluorescence Stokes shifts have been measured. We report a remarkable identity of the energies of activation (E_a) for the Stokes shifts decay rates and the millisecond C-H bond cleavage step that is restricted to side chain mutants within an identified thermal network. These findings implicate a direct coupling of distal protein motions surrounding the exposed fluorescent probe to active site motions controlling catalysis. While the role of dynamics in enzyme function has been predominantly attributed to a distributed protein conformational landscape, the presented data implicate a thermally initiated, cooperative protein reorganization that occurs on a timescale faster than nanosecond and represents the enthalpic barrier to the reaction of SLO.