Mechanistic investigation leads to a synthetic improvement in the hydrolytic kinetic resolution of terminal epoxides

The mechanism of the hydrolytic kinetic resolution (HKR) of terminal epoxides was investigated by kinetic analysis using reaction calorimetry. The chiral (salen)Co-X complex (X = OAc, OTs, Cl) undergoes irreversible conversion to (salen)Co-OH during the course of the HKR and thus serves as both precatalyst and cocatalyst in a cooperative bimetallic catalytic mechanism. This insight led to the identification of more active catalysts for the HKR of synthetically useful terminal epoxides.     

Multifunctional gold nanoparticle-peptide complexes for nuclear targeting

The ability of peptide-modified gold nanoparticles to target the nucleus of HepG2 cells was explored. Five peptide/nanoparticle complexes were investigated, particles modified with (1) the nuclear localization signal (NLS) from the SV 40 virus; (2) the adenovirus NLS; (3) the adenovirus receptor-mediated endocytosis (RME) peptide; (4) one long peptide containing the adenovirus RME and NLS; and (5) the adenovirus RME and NLS peptides attached to the nanoparticle as separate pieces. Gold nanoparticles were used because they are easy to identify using video-enhanced color differential interference contrast microscopy, and they are excellent scaffolds from which to build multifunctional nuclear targeting vectors. For example, particles modified solely with NLS peptides were not able to target the nucleus of HepG2 cells from outside the plasma membrane, because they either could not enter the cell or were trapped in endosomes. The combination of NLS/RME particles (4) and (5) did reach the nucleus; however, nuclear targeting was more efficient when the two signals were attached to nanoparticles as separate short pieces versus one long peptide. These studies highlight the challenges associated with nuclear targeting and the potential advantages of designing multifunctional nanostructured materials as tools for intracellular diagnostics and therapeutic delivery.     

An Organization Device for Visualizing Mechanisms and Regiochemistry Rationales in Electrophilic Aromatic Substitution

Design and testing of a hand-held device, consisting of two sheets of card stock, presenting electrophilic aromatic substitution (EAS) data in an organized fashion, and designed to facilitate learning electrophilic aromatic substitution reactions is reported. The device includes a large amount of information with similar data grouped, and the groups are juxtaposed in order to facilitate pattern recognition and differentiation. This, in turn, facilitates visualization, retention, understanding, and use of the data presented. One sheet is placed over the other in order to visualize the mechanism between the substituted aromatic compound selected and the chosen reagent. It shows two aspects of EAS on separate pages and, then, demonstrates interactively how they interrelate. The two aspects are (1) the substitution itself, including the identity of the electrophile, the reagent(s) needed to generate it, and the substituent in the product and (2) the electronic effects of the groups in the aromatic compounds upon the intermediate(s) and the structure of the product. The effect of the use of the Electrophilic Aromatic Substitution Tool (also known as EAS-at-a-Glance) on the test performance of students enrolled in undergraduate organic chemistry was determined by a post-test-only control-group study. The subject samples were assigned to a control group and three device groups, differing with respect to use of the device. Results show that the EAS Tool enabled a better student performance (by 12.3% to 17.3%, depending upon the method of use), and that the best method of use is as an out-of-class supplement.