Guest-accelerated molecular rotor.

A molecular rotor was designed in which the rate of rotation is accelerated by guest complexation. The binding of an acetate guest to the urea groups lowers the barrier of the adjacent C(aryl)-N(imide) bond by 2 to 4 kcal/mol. This behavior is in contrast to most molecular rotors in which guest complexation slows rotation.

Differential reactivity of thiophene-2-carboxylic and thiophene-3-carboxylic acids: Results from DFT and Hartree-Fock theory.

In the course of investigating the propensity of aromatic acids to react with selected nucleophiles, we came across an interesting difference in yields for two structurally similar thiophene carboxylic acids. Given that these yields were consistent across more than 40 repetitions for each structure, we felt that the difference was real, and worth exploration. To extract the potential steric and electronic origins of such differences, we employed both DFT B3LYP/6-31G* and HF/6-311+G** levels of theory to evaluate structures and energetics. Two somewhat different pictures emerge of the origin of the differences between the carboxylic acids and their individual conformations. In particular, Hartree-Fock calculations with the larger 6-311+G** basis set, which includes multiple diffuse functions, show a profound difference in the delocalization of the LUMO, relative to the DFT method which, expectedly, provides a more localized picture of the contributions to the LUMO. For each of the conformers, the molecular electrostatic potential and the ionization potential (ESP and IP, respectively), together with charge distributions, dipole moments and orbital energies have been explored. A potential explanation for the somewhat more reactive character of the thiophene-2-carboxylic acid appears to arise from the presence of a conformer which has an internal hydrogen bond to the thiophene sulfur, which, in turn, polarizes the acid function significantly relative to other conformers, and optimizes the angle of attack of the nucleophile.

Origins of selectivity for the [2+2] cycloaddition of alpha,beta-unsaturated ketones within a porous self-assembled organic framework.

This article studies the origins of selectivity for the [2+2] cycloadditions of alpha,beta-unsaturated ketones within a porous crystalline host. The host, formed by the self-assembly of a bis-urea macrocycle, contains accessible channels of approximately 6 A diameter and forms stable inclusion complexes with a variety of cyclic and acyclic alpha,beta-unsaturated ketone derivatives. Host 1 crystals provide a robust confined reaction environment for the highly selective [2+2] cycloaddition of 3-methyl-2-cyclopentenone, 2-cyclohexenone, and 2-methyl-2-cyclopentenone, forming their respective exo head-to-tail dimers in high conversion. The products are readily extracted from the self-assembled host and the crystalline host can be efficiently recovered and reused. Molecular modeling studies indicate that the origin of the observed selectivity is due to the excellent match between the size and shape of these guests to dimensions of the host channel and to the preorganization of neighboring enones into favorable reaction geometries. Small substrates, such as acrylic acid and methylvinylketone, were bound by the host and were protected from photoreactions. Larger substrates, such as 4,4-dimethyl-2-cyclohexenone and mesityl oxide, do not undergo selective [2+2] cycloaddition reactions. In an effort to understand these differences in reactivity, we examined these host-guest complexes by thermogravimetric analysis (TGA), NMR, powder X-ray diffraction (PXRD) and molecular modeling.

Discovery of imidazole glycerol phosphate dehydratase inhibitors through 3-D database searching.

Imidazole glycerol phosphate dehydratase (IGPD) has become an attractive target for herbicide discovery since it is present in plants and not in mammals. Currently no knowledge is available on the 3-D structure of the IGPD active site. Therefore, we used a pharmacophore model based on known inhibitors and 3-D database searches to identify new active compounds. In vitro testing of compounds from the database searches led to the identification of a class of pyrrole aldehydes as novel inhibitors of IGPD.