Scientific assessment of the use of sugars as cigarette tobacco ingredients: A review of published and other publicly available studies

Sugars, such as sucrose or invert sugar, have been used as tobacco ingredients in American-blend cigarettes to replenish the sugars lost during curing of the Burley component of the blended tobacco in order to maintain a balanced flavor. Chemical-analytical studies of the mainstream smoke of research cigarettes with various sugar application levels revealed that most of the smoke constituents determined did not show any sugar-related changes in yields (per mg nicotine), while ten constituents were found to either increase (formaldehyde, acrolein, 2-butanone, isoprene, benzene, toluene, benzo[k]fluoranthene) or decrease (4-aminobiphenyl, N-nitrosodimethylamine, N-nitrosonornicotine) in a statistically significant manner with increasing sugar application levels. Such constituent yields were modeled into constituent uptake distributions using simulations of nicotine uptake distributions generated on the basis of published nicotine biomonitoring data, which were multiplied by the constituent/nicotine ratios determined in the current analysis. These simulations revealed extensive overlaps for the constituent uptake distributions with and without sugar application. Moreover, the differences in smoke composition did not lead to relevant changes in the activity in in vitro or in vivo assays. The potential impact of using sugars as tobacco ingredients was further assessed in an indirect manner by comparing published data from markets with predominantly American-blend or Virginia-type (no added sugars) cigarettes. No relevant difference was found between these markets for smoking prevalence, intensity, some markers of dependence, nicotine uptake, or mortality from smoking-related lung cancer and chronic obstructive pulmonary disease. In conclusion, thorough examination of the data available suggests that the use of sugars as ingredients in cigarette tobacco does not increase the inherent risk and harm of cigarette smoking

Woodward–Hoffmann’s <i>Stereochemistry of Electrocyclic Reactions</i>: From Day 1 to the <i>JACS</i> Receipt Date (May 5, 1964 to November 30, 1964)

The publication in January 1965 of the first Woodward–Hoffmann paper, <i>The Stereochemistry of Electrocyclic Reactions</i>, ushered into organic chemistry both an explanation of the stereochemistry and “allowedness” or “forbiddenness” of concerted reactions and an impetus for untold numbers of research projects. In the current paper, details of the collaboration between R. B. Woodward and R. Hoffmann, from when they first met to discuss the solution to the “no-mechanism problem” to the date their first paper was received in the offices of the <i>Journal of the American Chemical Society</i>, will be discussed and analyzed. The primary focus will be on the historically relevant extant documents from the early 1960s. These include Hoffmann’s laboratory notebooks describing his research, including his extended Hückel calculations used to explain and predict the stereochemistry of electrocyclic reactions. Drafts of the <i>Stereochemistry of Electrocyclic Reactions</i> paper and letters and notes by Woodward, Jerome Berson, and others will further illuminate the development of this first Woodward–Hoffmann paper

Understanding chemistry: from “heuristic (soft) explanations and reasoning by analogy” to “quantum chemistry”

"Soft theories," i.e., "heuristic models based on reasoning by analogy" largely drove chemistry understanding for 150 years or more. But soft theories have their limitations and with the expansion of chemistry in the mid-20th century, more and more inexplicable (by soft theory) experimental results were being obtained. In the past 50 years, quantum chemistry, most often in the guise of applied theoretical chemistry including computational chemistry, has provided (a) the underlying "hard evidence" for many soft theories and (b) the explanations for chemical phenomena that were unavailable by soft theories. In this publication, we define "hard theories" as "theories derived from quantum chemistry." Both soft and hard theories can be qualitative and quantitative, and the "Houk quadrant" is proposed as a helpful categorization tool. Furthermore, the language of soft theories is often used appropriately to describe quantum chemical results. A valid and useful way of doing science is the appropriate use and application of both soft and hard theories along with the best nomenclature available for successful communication of results and ideas

Rolf Huisgen’s Classic Studies of Cyclic Triene Diels-Alder Reactions Elaborated by Modern Computational Analysis.

Rolf Huisgen explored the Diels–Alder reactions of 1,3,5-cycloheptatriene (CHT) and cyclooctatetraene (COT) with the dienophiles maleic anhydride and 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) to determine the kinetics and mechanisms of various electrocyclizations and Diels–Alder reactions. These reactions have been examined with density functional theory. Modern computational chemistry has provided information not previously available by experiment. Transition states for all the reactions have been identified, and their Gibbs energies are used to explain the experimental reactivities. Zwitterionic intermediates were not found in the [4+2] cycloadditions of both CHT or COT with PTAD and are thus not involved in these reactions. [2+2+2] cycloadditions, as an alternative path to the Diels–Alder products, are highly disfavored. Rapid double nitrogen inversion was found for the cycloaddition products with PTAD