A new theory for the study of the reactivity in Organic Chemistry, named Molecular Electron Density Theory (MEDT), is proposed herein. MEDT is based on the idea that while the electron density ...distribution at the ground state is responsible for physical and chemical molecular properties, as proposed by the Density Functional Theory (DFT), the capability for changes in electron density is responsible for molecular reactivity. Within MEDT, the reactivity in Organic Chemistry is studied through a rigorous quantum chemical analysis of the changes of the electron density as well as the energies associated with these changes along the reaction path in order to understand experimental outcomes. Studies performed using MEDT allow establishing a modern rationalisation and to gain insight into molecular mechanisms and reactivity in Organic Chemistry.
Theoretical reactivity indices based on the conceptual Density Functional Theory (DFT) have become a powerful tool for the semiquantitative study of organic reactivity. A large number of reactivity ...indices have been proposed in the literature. Herein, global quantities like the electronic chemical potential μ, the electrophilicity ω and the nucleophilicity N indices, and local condensed indices like the electrophilic P k + and nucleophilic P k - Parr functions, as the most relevant indices for the study of organic reactivity, are discussed.
The electrophilic/nucleophilic character of a series of captodative (CD) ethylenes involved in polar cycloaddition reactions has been studied using DFT methods at the B3LYP/6-31G(d) level of theory. ...The transition state structures for the electrophilic/nucleophilic interactions of two CD ethylenes toward a nucleophilically activated ethylene, 2-methylene-1,3-dioxolane, and an electrophilically activated ethylene, 1,1-dicyanoethyelene, have been studied, and their electronic structures have been characterized using both NBO and ELF methods. Analysis of the reactivity indexes of the CD ethylenes explains the reactivity of these species. While the electrophilicity of the molecules accounts for the reactivity toward nucleophiles, it is shown that a simple index chosen for the nucleophilicity, Ν, based on the HOMO energy is useful explaining the reactivity of these CD ethylenes toward electrophiles.
The Grignard reagent promoted 3+2 cycloaddition (32CA) reaction of mesitonitrile oxide (MNO) with Baylis-Hilman adduct (BHA) has been studied within the Molecular Electron Density Theory (MEDT) at ...the ωB97X-D/6-311G(d,p) computational level. Topological analysis of the Electron Localization Function (ELF) allows classifying MNO as a zwitterionic three-atom-component (TAC), participating in
zw-type
32CA reactions. In spite of the strong nucleophilic character of MNO, the low electrophilic character of BHA and the BHA:Mg(
ii
) complex make the corresponding 32CA reactions to have a very low polar character, respectively. The reaction presents total
ortho
regioselectivity to afford 2-isoxazolines, while the diastereoselectivity is reversed in the Mg(
ii
)-promoted 32CA reaction relative to that in the absence of the Mg(
ii
) cation, in complete agreement with the experiments. The preferred transition state structure (TS) associated with the Mg(
ii
)-promoted process shows complexation of the magnesium atom with the oxygens of MNO and BHA (hydroxyl oxygen), with the corresponding critical points (CPs) showing non-covalent interactions (NCIs) in the AIM-RDG isosurfaces. This MEDT study provides a complete comprehension of the role of the Grignard reagent in the
zw-type
32CA reactions of nitrile oxides with Baylis-Hilman adduct; although formation of the BHA:Mg(
ii
) complex slightly accelerates the 32CA reaction to decrease the activation Gibbs free energy by 3.1 kcal mol
−1
, the more remarkable role of the Mg(
ii
) cation is the change of the diastereoselectivity of these 32CA reactions involving a chiral ethylene.
The presence of Mg(
ii
) cation does not substantially accelerate this low polar
zw-type
3+2 cycloaddition reaction, but changes the facial diastereoselectivity. These low polar reactions are completely
ortho
regioselective.
The 3 + 2 cycloaddition (32CA) reaction of an α-santonin derivative, which has an exocyclic C⁻C double bond, with
-bromophenyl nitrile oxide yielding only one spiroisoxazoline, has been studied ...within the molecular electron density theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. Analysis of the conceptual density functional theory (CDFT) reactivity indices and the global electron density transfer (GEDT) account for the non-polar character of this
32CA reaction, which presents an activation enthalpy of 13.3 kcal·mol
. This 32CA reaction takes place with total
regioselectivity and
diastereofacial selectivity involving the exocyclic C⁻C double bond, which is in complete agreement with the experimental outcomes. While the C⁻C bond formation involving the β-conjugated carbon of α-santonin derivative is more favorable than the C⁻O one, which is responsible for the
regioselectivity, the favorable electronic interactions taking place between the oxygen of the nitrile oxide and two axial hydrogen atoms of the α-santonin derivative are responsible for the
diastereofacial selectivity.
The critical role of global electron density transfer (GEDT) in increasing the reaction rate of polar organic reactions has been studied within the framework of Molecular Electron Density Theory ...(MEDT). To this end, the series of the polar Diels-Alder (P-DA) reactions of cyclopentadiene with cyanoethylene derivatives, for which experimental kinetic data are available, have been chosen. A complete linear correlation between the computed activation Gibbs free energies and the GEDT taking place at the polar transition state structures (TSs) is found; the higher the GEDT at the TS, the lower the activation Gibbs free energy. An interacting quantum atoms energy partitioning analysis allows for establishing a complete linear correlation between the electronic stabilization of the electrophilic ethylene frameworks and the GEDT taking place at the polar TSs. This finding supports Parr's proposal for the definition of the electrophilicity ω index. The present MEDT study establishes the critical role of the GEDT in the acceleration of polar reactions, since the electronic stabilization of the electrophilic framework with the electron density gain is greater than the destabilization of the nucleophilic one, making a net favorable electronic contribution to the decrease in the activation energy.
A good correlation between the activation energy and the polar character of Diels-Alder reactions measured as the charge transfer at the transition state structure has been found. This electronic ...parameter controls the reaction rate to an even greater extent than other recognized structural features. The proposed polar mechanism, which is characterized by the electrophilic/nucleophilic interactions at the transition state structure, can be easily predicted by analyzing the electrophilicity/nucleophilicity indices defined within the conceptual density functional theory. Due to the significance of the polarity of the reaction, Diels-Alder reactions should be classified as non-polar (N), polar (P), and ionic (I).
The effects of metal-based Lewis acid (LA) catalysts on the reaction rate and regioselectivity in polar Diels-Alder (P-DA) reactions has been analyzed within the molecular electron density theory ...(MEDT). A clear linear correlation between the reduction of the activation energies and the increase of the polar character of the reactions measured by analysis of the global electron density transfer at the corresponding transition state structures (TS) is found, a behavior easily predictable by analysis of the electrophilicity ω and nucleophilicity
indices of the reagents. The presence of a strong electron-releasing group in the diene changes the mechanism of these P-DA reactions from a
to a two-step one via formation of a zwitterionic intermediate. However, this change in the reaction mechanism does not have any chemical relevance. This MEDT study makes it possible to establish that the more favorable nucleophilic/electrophilic interactions taking place at the TSs of LA catalyzed P-DA reactions are responsible for the high acceleration and complete regioselectivity experimentally observed.
Undergraduate diversity is fostered across many contexts
Ethnic minorities comprise rapidly growing portions of the populations of most developed countries (
1
) but are underrepresented in fields of ...science, technology, engineering, and mathematics (STEM) (
2
,
3
). Efforts to increase diversity in the STEM workforce, important for developing more effective approaches to group problem-solving (
4
–
6
), have been under way in the United States for decades, but widespread impact remains relatively low (
3
). The Meyerhoff Scholars Program (MYS) at the University of Maryland, Baltimore County (UMBC), provides a promising model for increasing retention and academic performance of underrepresented minority (URM) undergraduates in STEM and for preparing those undergraduates to pursue and succeed in graduate and professional programs (
7
,
8
). Although MYS is nearly 30 years old and outcomes for African-American STEM majors have been extensively documented see (
7
,
8
) and references therein, no other majority university not meeting the definition of being a minority-serving institution (MSI) (
9
) has achieved similar outcomes (
10
). We describe here some promising early indicators that an interinstitutional partnership approach can help enable MYS-like outcomes at majority universities with different URM compositions, geographies, and institutional sizes and cultures: The University of North Carolina at Chapel Hill (UNC) and Pennsylvania State University at University Park (PSU).
Deep brain stimulation is an established therapy for multiple brain disorders, with rapidly expanding potential indications. Neuroimaging has advanced the field of deep brain stimulation through ...improvements in delineation of anatomy, and, more recently, application of brain connectomics. Older lesion-derived, localizationist theories of these conditions have evolved to newer, network-based "circuitopathies," aided by the ability to directly assess these brain circuits in vivo through the use of advanced neuroimaging techniques, such as diffusion tractography and fMRI. In this review, we use a combination of ultra-high-field MR imaging and diffusion tractography to highlight relevant anatomy for the currently approved indications for deep brain stimulation in the United States: essential tremor, Parkinson disease, drug-resistant epilepsy, dystonia, and obsessive-compulsive disorder. We also review the literature regarding the use of fMRI and diffusion tractography in understanding the role of deep brain stimulation in these disorders, as well as their potential use in both surgical targeting and device programming.
PDF
