Application of Computational Chemical Shift Prediction Techniques to the Cereoanhydride Structure Problem-Carboxylate Complications.

Despite the vast array of techniques available to modern-day chemists, structural misassignments still occur. These misassignments are often only realized upon attempted synthesis, when the spectra of synthesized products do not match previously reported spectra. This was the case with marine natural product cereoanhydride. The originally proposed 7-membered ring anhydride (1) was shown to be incorrect, although a likely precursor to the correct structure (2) in both its laboratory synthesis and biosynthesis. Herein, in addition to showing how NMR computations could have been used to arrive at the correct structure, we show that the conversion of 1 to 2 is indeed energetically viable, and we highlight complications in predicting NMR chemical shifts for molecules with acidic protons

Cryptic post-transition state bifurcations that reduce the efficiency of lactone-forming Rh-carbenoid C-H insertions.

Byproducts of chemical reactions are generally thought to result from the competition between two reaction pathways, each with its own rate-determining transition state structure. We show here, however, that pathways with a single transition state structure followed by a post-transition state bifurcation may also be a source of undesired products, especially those whose appearance is unexpected. The viability of this scenario for intramolecular C-H insertion reactions affording β-lactones via Rh-carbenoid intermediates is assessed through quantum chemical calculations on potential energy surfaces and quasi-classical molecular dynamics simulations. It appears that, in these cases, the rhodium catalyst is to blame for the accessibility of a second, unintended, pathway following the transition state structure for β-lactone formation that leads to fragmentation to a ketene and carbonyl compound. If an unexpected product is formed via a post-transition state bifurcation, conventional strategies for suppressing its formation are unlikely to succeed. Guidelines for recognizing the presence of a post-transition state bifurcation are described here, along with hints at means for controlling product distributions

Mechanistically informed predictions of binding modes for carbocation intermediates of a sesquiterpene synthase reaction.

Sesquiterpenoids comprise a class of terpenoid natural products with thousands of compounds that are highly diverse in structure, generally containing a polycyclic carbon backbone that is constructed by a sesquiterpene synthase. Decades of experimental and computational studies have demonstrated that these enzymes generate a carbocation in the active site, which undergoes a series of structural rearrangements until a product is formed via deprotonation or nucleophile attack. However, for the vast majority of these enzymes the productive binding orientation of the intermediate carbocations has remained unclear. In this work, a method that combines quantum mechanics and computational docking is used to generate an all-atom model of every putative intermediate formed in the context of the enzyme active site for tobacco epi-aristolochene synthase (TEAS). This method identifies a single pathway that links the first intermediate to the last, enabling us to propose the first high-resolution model for the reaction intermediates in the active site of TEAS, and providing testable predictions

Bush\u27s Legacy

While former President George W. Bush\u27s historical legacy is still being hotly debated, a clear bright spot is often overlooked. The President\u27s Emergency Plan for AIDS Relief (PEPFAR) paid for antiretroviral medications for 1.4 million patients in Africa and the Caribbean compared to only 50,000 before the program. The program is far from perfect. An important criticism of PEPFAR is that the program is too restrictive. For example, one third of the money for prevention must go to abstinence only sexual education. The harm that is done to women and children by suggesting that they have the autonomy to insist on abstinence is clearly demonstrated by the high rates of HIV in these populations. True prevention will only be possible when the situation of women is improved and they are empowered to make decisions in their reproductive lives. Sadly, politics and religion are preventing Bush\u27s legacy” from having the impact that it otherwise could have had

Modulation of inherent dynamical tendencies of the bisabolyl cation via preorganization in epi-isozizaene synthase.

The relative importance of preorganization, selective transition state stabilization and inherent reactivity are assessed through quantum chemical and docking calculations for a sesquiterpene synthase (epi-isozizaene synthase, EIZS). Inherent reactivity of the bisabolyl cation, both static and dynamic, appears to determine the pathway to product, although preorganization and selective binding of the final transition state structure in the multi-step carbocation cascade that forms epi-isozizaene appear to play important roles

Carbocations and the Complex Flavor and Bouquet of Wine: Mechanistic Aspects of Terpene Biosynthesis in Wine Grapes.

Computational chemistry approaches for studying the formation of terpenes/terpenoids in wines are presented, using five particular terpenes/terpenoids (1,8-cineole, α-ylangene, botrydial, rotundone, and the wine lactone), volatile compounds (or their precursors) found in wine and/or wine grapes, as representative examples. Through these examples, we show how modern computational quantum chemistry can be employed as an effective tool for assessing the validity of proposed mechanisms for terpene/terpenoid formation

Tipping the balance: theoretical interrogation of divergent extended heterolytic fragmentations.

Herein we interrogate a type of heterolytic fragmentation reaction called a 'divergent fragmentation' using density functional theory (DFT), natural bond orbital (NBO) analysis, ab initio molecular dynamics (AIMD), and external electric field (EEF) calculations. We demonstrate that substituents, electrostatic environment and non-statistical dynamic effects all influence product selectivity in reactions that involve divergent fragmentation pathways. Direct dynamics simulations reveal an unexpected post-transition state bifurcation (PTSB), and EEF calculations suggest that some transition states for divergent pathways can, in principle, be selectively stabilized if an electric field of the correct magnitude is oriented appropriately

Infant Mortality

Despite an overall downward trend in neonatal and post neonatal deaths in recent years, the United States continues to rank poorly among developed nations for infant mortality. According to the Central Intelligence Agency\u27s World Factbook, the United States ranked 180 out of 221 countries in 2007 (with the lowest infant mortality rate belonging to the country ranked 221). This paper seeks to explore continuing racial and socioeconomic disparities among U.S. women and their contribution to this disheartening truth

The Relationship Between Time of Day, Mood, and Electroencephalography (EEG) Asymmetry

Previous researchers have had success in finding a correlation between exercise and an increase in positive mood. Researchers have also found a correlation between time of day and mood. The current study will explore the relationship between time of day, mood, and electroencephalography (EEG) asymmetry. The study utilized a convenient sample of ten undergraduate students at Bowling Green State University. Participants had baseline EEG recordings taken, and then participated in moderate exercise, followed by another EEG recording. Participants’ mood was assessed through a self-reported mood questionnaire before the condition as well as immediately after. Due to multiple statistical tests, the alpha level for rejection of the null hypothesis was set at .016. While no statistically significant differences were found, the difference between baseline EEG asymmetry and post-task EEG asymmetry approached significance. Specifically, there was greater left hemispheric activity post-task which is indicative of a more positive mood