29 research outputs found
Chromosome damage in underground coal miners: detection by conventional cytogenetic techniques and by submitting lymphocytes of unexposed individuals to plasma from at-risk groups
Fragmentation Reaction via an Ipso-Attack in the Multistep Synthesis of Regioselectively Functionalized Calix[8]arene
Studies on the Himbert Intramolecular Arene/Allene Diels–Alder Cycloaddition. Mechanistic Studies and Expansion of Scope to All-Carbon Tethers
Computation and Experiment Reveal That the Ring-Rearrangement Metathesis of Himbert Cycloadducts Can Be Subject to Kinetic or Thermodynamic Control
Unusual observations in the ring-rearrangement metathesis (RRM) of Himbert arene/allene cycloadducts to form fused polycylic lactams led to a more in-depth experimental study that yielded conflicting results. Differences in reactivity within related systems and unexpected changes in diastereoselectivity among other similar substrates were not readily explained on the basis of the experimental results. Computational investigations demonstrated substrate-dependent changes in reaction pathways (ring-opening metathesis/ring-closing metathesis [ROM/RCM] cascade vs. ring-closing metathesis/ring-opening metathesis [RCM/ROM] cascade). Furthermore, some reactions were judged to be under thermodynamic control, and others under kinetic control. The greater understanding of the most likely reaction pathways and their energetics provided a reasonable explanation for the previously irreconcilable results
Theoretical Investigation of the Origins of Catalysis of a Retro-Diels-Alder Reaction by Antibody 10F11
EMBM − A New Enzyme Mechanism-Based Method for Rational Design of Chemical Sites of Covalent Inhibitors
Conformational and enantioselectivity in host-guest chemistry: the selective binding of cis amides examined by free energy calculations
Relative binding free energies of amino acid derivatives to the host macrobicycle 12 in chloroform are calculated to determine the effect of stereochemistry and amide bond conformation. Simulations are performed for three different amino acid derivatives using Monte Carlo simulations, free energy perturbations, and the generalized Born/surface area solvation model. The free energy results support previous experimental findings that the L enantiomers of N-acetyl phenylalanine carboxylate and N-acetyl alanine carboxylate bind preferentially over the D enantiomers and that the amide bond is in the cis conformation for the bound L enantiomers. The enantioselectivity arises because of better shape complementarity, and the cis stabilization is achieved by a selective hydrogen bond to the cavity rim of the host and a remote steric stabilization of the side-chain chi(1) dihedral angle. This computational approach was also applied to N-acetyl glycine carboxylate and indicated that, for this amino acid derivative, both the trans and the cis forms of the acetyl amide can be accommodated within the macrobicycle cavity. Experimental evidence to support this finding was obtained by detailed NMR experiments on a 1:1 complex of M12 and N-acetyl glycine. The study demonstrates two important points regarding binding and conformation: First, the destabilization of the chi(1) dihedral angle of N-acetyl phenylalanine away from the most stable conformation appears to stabilize the cis conformation of the preceding amide bond, suggesting that amino acids other than proline might be able to increase the likelihood of cis amide bonds. More generally, internal conformational coupling is an important factor to consider in molecular recognition. Second, the comprehensive sampling protocol undertaken for this relatively small system that allows the host to adjust properly to each guest is shown to be crucial in obtaining converged free energies and different binding modes. Subtle changes in host geometry have profound effects on binding. Conversely, different binding modes arising from small changes in guest conformation, chirality, or side chain serve as a reminder that binding modes are not always transferable between apparently similar molecules