Jason DeChancie | PubMed Health

PubMed2004

Density functional theory determination of an axial gateway to explain the rate and endo selectivity enhancement of Diels-Alder reactions by bis(oxazoline)-Cu(II).

A novel conceptual model and unique understanding of rate and endo selectivity enhancements delivered by bis(oxazoline)-Cu(II) Lewis acid catalysts in the Diels-Alder reaction of cyclopentadiene and acrylate imide is presented. Despite previously reported kinetic and spectroscopic studies, the physical reasons for endo selectivity and rate enhancements remain poorly understood. Large-scale density functional calculations using Becke three-parameter density functional theory with the nonlocal correlation of Lee, Yang, and Parr and the 6-31G(d) basis set have been carried out for the first time to understand the geometric and energetic consequences of C(2)-substituent variation. The unique positioning of the tert-butyl C(2)-substituent with respect to the diene, referred to as the "axial gateway", maintains the electrophilicity of the catalyst by shielding the reactive metal center from nucleophilic attack. The interplay between steric and electronic factors is crucial to understanding the observed enhanced rates and endo selectivity.

Journal Article↗

PubMed2004

Enhanced sampling by multiple molecular dynamics trajectories: carbonmonoxy myoglobin 10 micros A0-->A(1-3) transition from ten 400 picosecond simulations.

The utility of multiple trajectories to extend the time scale of molecular dynamics simulations is reported for the spectroscopic A-states of carbonmonoxy myoglobin (MbCO). Experimentally, the A0-->A(1-3) transition has been observed to be 10 micros at 300 K, which is beyond the time scale of standard molecular dynamics simulations. To simulate this transition, 10 short (400 ps) and two longer time (1.2 ns) molecular dynamics trajectories, starting from five different crystallographic and solution phase structures with random initial velocities centered in a 37 A radius sphere of water, have been used to sample the native-fold of MbCO. Analysis of the ensemble of structures gathered over the cumulative 5.6 ns reveals two biomolecular motions involving the side chains of His64 and Arg45 to explain the spectroscopic states of MbCO. The 10 micros A0-->A(1-3) transition involves the motion of His64, where distance between His64 and CO is found to vary up to 8.8 +/- 1.0 A during the transition of His64 from the ligand (A(1-3)) to bulk solvent (A0). The His64 motion occurs within a single trajectory only once, however the multiple trajectories populate the spectroscopic A-states fully. Consequently, multiple independent molecular dynamics simulations have been found to extend biomolecular motion from 5 ns of total simulation to experimental phenomena on the microsecond time scale.

Animals↗