First-principle studies of intermolecular and intramolecular catalysis of protonated cocaine

We have performed a series of first-principles electronic structure calculations to examine the reaction pathways and the corresponding free energy barriers for the ester hydrolysis of protonated cocaine in its chair and boat conformations. The calculated free energy barriers for the benzoyl ester hydrolysis of protonated chair cocaine are close to the corresponding barriers calculated for the benzoyl ester hydrolysis of neutral cocaine. However, the free energy barrier calculated for the methyl ester hydrolysis of protonated cocaine in its chair conformation is significantly lower than for the methyl ester hydrolysis of neutral cocaine and for the dominant pathway of the benzoyl ester hydrolysis of protonated cocaine. The significant decrease of the free energy barrier, ∼4 kcal/mol, is attributed to the intramolecular acid catalysis of the methyl ester hydrolysis of protonated cocaine, because the transition state structure is stabilized by the strong hydrogen bond between the carbonyl oxygen of the methyl ester moiety and the protonated tropane N. The relative magnitudes of the free energy barriers calculated for different pathways of the ester hydrolysis of protonated chair cocaine are consistent with the experimental kinetic data for cocaine hydrolysis under physiologic conditions. Similar intramolecular acid catalysis also occurs for the benzoyl ester hydrolysis of (protonated) boat cocaine in the physiologic condition, although the contribution of the intramolecular hydrogen bonding to transition state stabilization is negligible. Nonetheless, the predictability of the intramolecular hydrogen bonding could be useful in generating antibody-based catalysts that recruit cocaine to the boat conformation and an analog that elicited antibodies to approximate the protonated tropane N and the benzoyl O more closely than the natural boat conformer might increase the contribution from hydrogen bonding. Such a stable analog of the transition state for intramolecular catalysis of cocaine benzoyl-ester hydrolysis was synthesized and used to successfully elicit a number of anticocaine catalytic antibodies.

Accounting for Fetal Death: Vital Statistics and the Medicalization of Pregnancy in the United States

Recent reports by the Centers for Disease Control and Prevention have decried the high rate of fetal mortality in the contemporary United States. Much of the data about fetal and infant deaths, as well as other poor pregnancy outcomes, are tabulated and tracked through vital statistics. In this article, I demonstrate how notions of fetal death became increasingly tied to the surveillance of maternal bodies through the tabulating and tracking of vital statistics in the middle part of the twentieth century. Using a historical analysis of the revisions to the United States Standard Certificate of Live Birth, and the United States Standard Report of Fetal Death, I examine how the categories of analysis utilized in these documents becomes integrally linked to contemporary ideas about fetal and perinatal death, gestational age, and prematurity. While it is evident that there are relationships between maternal behavior and birth outcomes, in this article I interrogate the ways in which the surveillance of maternal bodies through vital statistics has naturalized these relationships. Copyright 2013 Elsevier Ltd. All rights reserved.

From Unsuitable Ally to Vital Parter: The Case of US-Korean Relations and The Vietnam War, 1954-1966

This is the history of the decade prior to the entrance of Korean troops into the Vietnam War, roughly covering the years 1953-1965.