25 research outputs found
Addiction medicine for health care professionals /
No full textIncludes bibliographical references and index.Online resource; title from PDF title page (ScienceDirect, viewed July 8, 2019).Elsevie
Enantioselective Multi-Component Reactions: Conjunctive Coupling and Related Processes
No full textThesis advisor: James P. MorkenThis dissertation details the discovery, development, and mechanistic exploration of several enantioselective processes involving organoboronic esters. The first chapter will discuss electrophile-induced metallate rearrangement reactions, the fundamental reactivity that underlies much of the subsequently discussed work. The second chapter details the discovery and mechanistic study of the metal-induced metallate rearrangement reaction and the multi-component conjunctive coupling reaction manifold and related reactions it enables. The factors that govern the competition between metal-induced metallate rearrangement versus transmetallation will be explored. The third chapter will discuss efforts to understand and overcome the initial limitations of the conjunctive coupling reaction including halide inhibition of palladium catalysis and the inability to engage other organometallic reagents such as organomagnesium nucleophiles, and how this allowed the development of a more general reaction. The fourth chapter discusses the development of an enantioselective triamine–nickel-catalyzed conjunctive coupling reaction of alkyl electrophiles as well as a related nickel-promoted radical-polar crossover reaction and the mechanistic features leading to one reaction manifold or the other. A related enantioselective diamine–nickel-catalyzed tandem radical addition cross coupling reaction of alkyl iodides, alkenylboron reagents, and alkyl- or arylzinc reagents will also be discussed. The fifth chapter will cover the discovery of a diamine–nickel-catalyzed enantioselective carbozincation reaction of alkenylboron compounds which produces enantioenriched α-boryl alkylzinc reagents. The mechanistic investigations undertaken and application of these species in a variety of stereospecific transformation will be discussed along with the preliminary discovery and optimization of a diphosphine-Pd-catalyzed stereoconvergent Negishi cross-coupling reaction of racemic α-boryl alkylzinc reagents.Thesis (PhD) — Boston College, 2019.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Chemistry
Ni-Catalyzed Enantioselective Conjunctive Coupling with C(sp<sup>3</sup>) Electrophiles: A Radical-Ionic Mechanistic Dichotomy
No full textEnantioselective Arbuzov Reaction Enabled by Catalytic Ion-Pair Reorganization
No full textThe stereocontrolled synthesis of stereogenic-at-phosphorus compounds is a long-standing challenge in organic chemistry that has received heightened research attention in recent years. None of the catalytic approaches taken to date have leveraged the rich manifold of transformations proceeding through nucleophilic dealkylation of phosphonium ion intermediates (e.g. Michaelis–Arbuzov, Pudovik, and Appel reactions). Here, we report enantioselective hydrogen-bond-donor-catalyzed Michaelis–Arbuzov reactions of dialkylphosphonites with hydrogen chloride to afford H-phosphinates, which are versatile P-chiral building blocks. Mechanistic and computational investigations reveal that the catalyst diminishes the reactivity of the chloride nucleophile, yet accelerates the rate-determining dealkylation step by preorganizing the phosphonium chloride resting state into a geometry that is primed to enter the SN2 transition state
Pd-Catalyzed Conjunctive Cross-Coupling between Grignard-Derived Boron “Ate” Complexes and C(sp<sup>2</sup>) Halides or Triflates: NaOTf as a Grignard Activator and Halide Scavenger
No full textA statistical framework for analysis of trial-level temporal dynamics in fiber photometry experiments
No full textFiber photometry has become a popular technique to measure neural activity in vivo, but common analysis strategies can reduce the detection of effects because they condense within-trial signals into summary measures, and discard trial-level information by averaging across-trials. We propose a novel photometry statistical framework based on functional linear mixed modeling, which enables hypothesis testing of variable effects at every trial time-point, and uses trial-level signals without averaging. This makes it possible to compare the timing and magnitude of signals across conditions while accounting for between-animal differences. Our framework produces a series of plots that illustrate covariate effect estimates and statistical significance at each trial time-point. By exploiting signal autocorrelation, our methodology yields joint 95% confidence intervals that account for inspecting effects across the entire trial and improve the detection of event-related signal changes over common multiple comparisons correction strategies. We reanalyze data from a recent study proposing a theory for the role of mesolimbic dopamine in reward learning, and show the capability of our framework to reveal significant effects obscured by standard analysis approaches. For example, our method identifies two dopamine components with distinct temporal dynamics in response to reward delivery. In simulation experiments, our methodology yields improved statistical power over common analysis approaches. Finally, we provide an open-source package and analysis guide for applying our framework
Enantioselective Radical Addition/Cross‐Coupling of Organozinc Reagents, Alkyl Iodides, and Alkenyl Boron Reagents
No full textEnantioselective Radical Addition/Cross‐Coupling of Organozinc Reagents, Alkyl Iodides, and Alkenyl Boron Reagents
No full textMechanisms of amygdala facilitated cortico-striatal plasticity:
No full textThe amygdala is known to mediate the enhancing effects of emotional arousal on learning and memory. The increased firing rate of neurons in the basolateral complex of the amygdala (BLA) is believed to facilitate memory storage in various target structures, such as the striatum. Changes in the efficacy of cortical inputs to the striatum are thought to underlie motor learning and habit formation, making this pathway a perfect model to test the effects of BLA activity on synaptic plasticity and learning. My thesis provides evidence that BLA synapses have an N-methyl-D-aspartate receptor – to α-amino-5-hydroxy-3-methyl-4-isoxazole propionic acid receptor ratio higher than that of cortical synapses onto the same striatal neurons (Chapter 3). This property allows BLA inputs to facilitate the induction of heterosynaptic long term potentiation in vitro (Chapters 4 and 5). I also show that temporal coupling of BLA and striatal neurons in vivo occurs during coherent bursts of gamma activity observed in the local field potentials. Changes in the coherence of BLA-striatal gamma paralleled learning of a striatal-dependent task (Chapter 6). Together, these findings point towards a new mechanism of amygdala-facilitated learning.Ph.D.Includes bibliographical references (p. 111-123)by Andrei Tiberiu Popesc
