Patrick H. Willoughby|Matthew J. Jansma|Thomas R. Hoye
A guide to small-molecule structure assignment through computation of (1H and 13C) NMR chemical shifts
University of Minnesota|University of Minnesota|University of Minnesota
protocol intended provide chemists discover make new organic compounds valuable tool validating structural assignments new chemical entities experimental 1h andor 13c nmr spectral data proper interpretation compound interest required starting point approach involves following steps using molecular mechanics calculations eg macromodel generate library conformers ii using density functional theory dft calculations eg gaussian 09 determine optimal geometry free energies chemical shifts conformer iii determining boltzmannweighted proton carbon chemical shifts iv comparing computed chemical shifts two candidate structures experimental data determine best fit typical structure assignment small organic molecule eg fewer 10 nonh atoms 180 amu 20 conformers protocol completed 2 h active effort 2d period complex molecules eg fewer 30 nonh atoms 500 amu 50 conformers protocol requires 36 h active effort 2week period demonstrate method chosen analysis cis versus transdiastereoisomers 3methylcyclohexanol 1 cis versus 1 trans protocol written manner makes computation chemical shifts tractable chemists may otherwise rudimentary computational experience