Three emerging technologies were used in a large introductory chemistry class: a tablet PC, a lecture capture and replay software program, and an online homework program. At the end of the semester, student usage of the lecture replay and online homework systems was compared to course performance as measured by course grade and by a standardized final exam. Additionally, an attitudinal survey was used to assess the relative value students placed on each tool. While each tool received positive feedback, use of the tablet PC during lecture was rated the highest for enhancing learning and teaching effectiveness. Not surprisingly, students who completed most or all of the homework performed better than students who did not. Student usage of the lecture replay ranged from zero to over 30 h of viewing time. It was noted that international and ESL students were among the most voracious users of the lecture replay. Extensive use of the lecture replay did not correlate with course performance, as those who used this tool most heavily tended to place in the B–C grade brackets. The combination of the three tools appears to have a positive impact on retention compared with previous semesters, as 90% of students successfully completed this course.

The melanocortin receptors have been implicated as potential targets for a number of important therapeutic indications, including inflammation, sexual dysfunction, and obesity. We identified compound 1, an arylpiperazine attached to the dipeptide H-d-Tic-d-p-Cl-Phe-OH, as a novel melanocortin subtype-4 receptor (MC4R) agonist through iterative directed screening of nonpeptidyl G-protein-coupled receptor biased libraries. Structure-activity relationship (SAR) studies demonstrated that substitutions at the ortho position of the aryl ring improved binding and functional potency. For example, the o-isopropyl-substituted compound 29 (K(i) = 720 nM) possessed 9-fold better binding affinity compared to the unsubstituted aryl ring (K(i) = 6600 nM). Sulfonamide 39 (K(i) = 220 nM) fills this space with a polar substituent, resulting in a further 2-fold improvement in binding affinity. The most potent compounds such as the diethylamine 44 (K(i) = 60 nM) contain a basic group at this position. Basic heterocycles such as the imidazole 50 (K(i) = 110 nM) were similarly effective. We also demonstrated good oral bioavailability for sulfonamide 39.

This study focuses on the mechanism of action of N-alkylthio β-lactams, a new family of antibacterial compounds that show promising activity against Staphylococcus and Bacillus microbes. Previous investigations have determined that these compounds are highly selective towards which bacteria they target, and possess completely unprecedented structure-activity profiles for a β-lactam antibiotic. Unlike penicillin, which inhibits cell wall crosslinking proteins and affords a broad spectrum of bacteriocidal activity, these N-thiolated lactams are bacteriostatic in their behavior and act through a different mechanistic mode. Our current findings indicate that the compounds react rapidly within the bacterial cell with co-enzyme A (CoA) through in vivo transfer of the N-thio group to produce an alkyl-CoA mixed disulfide species, which then interferes with fatty acid biosynthesis. Our studies on coenzyme A disulfide reductase show that the CoA thiol redox buffer is not perturbed by these compounds; however, the lactams appear to act as prodrugs. The experimental evidence that these β-lactams inhibit fatty acid biosynthesis in bacteria, and the elucidation of coenzyme A as a primary cellular target, offers opportunities for the discovery of other small organic compounds that can be developed as therapeutics for MRSA and anthrax infections.

The synthetic correlation between two different antibiotic frameworks, the beta-lactams and 2-oxazolidinones, is described for the first time. In this approach, 2-oxazolidinones are prepared in stereomerically pure form from 3-hydroxy beta-lactams by a ring-opening-cyclization isomerization process. Application of this methodology to the total synthesis of the cytokine modulator, (-)-cytoxazone, and its three stereoisomers is demonstrated. [reaction: see text].