Direct,Late-Stage Mono-N-arylation of Pentamidine: Method Development,Mechanistic Insight,and Expedient Access to Novel Antiparastitics against Diamidine-Resistant Parasites

A selective mono-N-arylation strategy of amidines under Chan-Lam conditions is described. During the reaction optimization phase, the isolation of a mononuclear Cu(II) complex provided unique mechanistic insight into the operation of Chan-Lam mono-N-arylation. The scope of the process is demonstrated, and then applied to access the first mono-N-arylated analogues of pentamidine. Sub-micromolar activity against kinetoplastid parasites was observed for several analogues with no cross-resistance in pentamidine and diminazene-resistant trypanosome strains and against Leishmania mexicana. A fluorescent mono-N-arylated pentamidine analogue revealed rapid cellular uptake, accumulating in parasite nuclei and the kinetoplasts. The DNA binding capability of the mono-N-arylated pentamidine series was confirmed by UV-melt measurements using AT-rich DNA. This work highlights the potential to use Chan-Lam mono-N-arylation to develop therapeutic leads against diamidine-resistant trypanosomiasis and leishmaniasis.     

Reprint of “Driving avoidance by older adults: Is it always self-regulation?”

Self-regulation shows promise as a means by which older adults can continue to drive at some level without having to stop altogether. Self-regulation is generally described as the process of modifying or adjusting one's driving patterns by driving less or intentionally avoiding driving situations considered to be challenging, typically in response to an awareness that driving skills have declined. However, most studies asking older adults whether they avoid certain driving situations or have reduced the amount of driving they do under certain circumstances have not delved deeper into the motivations for such avoidance or driving reduction. There are many reasons for modifying driving that have nothing to do with self-regulation, such as no longer needing to take trips at certain times of day because of changes in preferences or lifestyles. The purpose of this study was to examine self-regulatory practices among older adults at multiple levels of driver performance and decision making, taking into account the specific motivations for avoiding particular driving situations or engaging in other driving practices. Study participants completed a computer-based questionnaire on driving self-regulation. Results suggest that self-regulation is a complex process that cannot be defined simply by the reported driving modifications made by drivers. Understanding the motivations for these behaviors is necessary and the study showed that they are varied and differ considerably across driving situations. Reasons for driving avoidance or other practices were often more closely related to lifestyle or preferences than to self-regulation. Based on these findings, three distinct groups were identified with regard to whether and for what reasons participants modified their driving.     

Perfectionism, negative social feedback, and interpersonal rumination in depression and social anxiety.

The current study investigated the associations among trait perfectionism, perfectionistic self-presentation, negative social feedback, interpersonal rumination, depressive symptoms, and social anxiety. New measures of negative social feedback and interpersonal rumination were used to evaluate their relevance to the social aspects of perfectionism and their roles in distress. A sample of 155 undergraduate students completed the Multidimensional Perfectionism Scale, the Perfectionistic Self-Presentation Scale, the Social Feedback Questionnaire, Rumination About an Interpersonal Offense, and measures of depressive symptoms and social anxiety. The results confirmed that socially prescribed perfectionism and perfectionistic self-presentation were associated significantly with negative social feedback and rumination following interpersonal events (i.e., being hurt, humiliated, mistreated). Also, depressive symptoms and social anxiety were associated significantly with negative social feedback, interpersonal rumination, trait perfectionism, and perfectionistic self-presentation. Additional analyses indicated that negative social feedback and interpersonal rumination mediated the links between components of the perfectionism construct and distress. Overall, our findings suggest that self-reported receipt of frequent negative feedback from others and engaging in rumination about an interpersonal event play important roles in the distress experienced by certain individuals with high levels of perfectionism. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Carbon as a catalyst in oxidation reactions and hydrogen halide elimination reactions

Carbon catalyses many reactions, mainly oxidation reactions with oxygen and with halogens, e.g. $\text{SO}{}_2\text{+}\text{1}\text{20}{}_2\text{→ SO}{}_3$, or CO + Cl₂→ COCl₂. It is known, however, that different carbons behave quite differently in the reduction of oxygen on fuel cell cathodes. Therefore the catalytic activity of carbons has been studied in other reactions. A convenient test reaction is the oxidation of dilute aqueous sulphurous acid. It became apparent that all catalytically active carbons contain small quantities of nitrogen, and inactive carbons such as wood charcoal or carbon blacks can be rendered highly active by treatment with N H₃ or HCN at elevated temperatures. Photoelectron spectra indicate that the catalytic activity increases parallel to the incorporation of a nitrogen species which is pyridine-like, i.e. incorporated in the aromatic layers. Treatment with NH₃ at 900 °C leads also to massive gasification of the carbons, increasing their surface area. Other reactions studied included the oxidation of aqueous oxalic acid and of methanol to formaldehyde. A quite different type of reaction is the elimination of hydrogen chloride from 1-chloroalkanes, e.g. 1 -chlorobutane. Again, activity changes in parallel to nitrogen content. Reaction products are olefins, dimers of the alkyl groups, and a polymer on the catalyst surface. The formation of alkyl dimers, e.g. n-octane in the case of n-butylchloride, suggests that radicals are involved in the reaction.