engleski

The overlapping spheres method for finding low-energy conformations: conformational analysis of two epimers of 1-[N-(tert-butoxycarbonyl)amino]-2-hidroxymethylcyclopropan-1-carboxylic acid

The model of overlapping spheres (OS) for finding the low-energy conformations (N. Raos, J. Comput. Chem. 21 (2000) 1353) – which is based on the minimization of the van der Waals excluded volume inside the sphere with radius Rv, centered at the geometrical center of a molecular segment – was applied on two epimers, (1S,2R) and (1S,2S), of 1-[N-(tert-butoxycarbonyl)amino]-2-hidroxymethylcyclopropancarboxylic acid. By using the molecular mechanics method and systematic search of conformation space by varying torsion angles, 100 and 164 conformers of (1S,2R)- and {(1S,2S)-1-[N-(tert-butoxycarbonyl)amino]-2-hidroxymethylcyclopropan-1-carboxylato}copper(II) was found, respectively. For the “seed” conformation one conformer of each stereoisomeric complex, (N-S,1S,2S), (N-R,1S,2S), (N-S,1S,2R), and (N-R,1S,2R) was chosen. The molecular segment was defined as the longest chain in the molecule, i. e. H3C-C-O-CO-NH-CH-CH2-OH. Two strategies were applied: (1) systematic increase of Rv value (0.3, 0.4, 0.5 and 0.6 nm) in each minimization run, keeping the segmentation constant, and (2) systematic increase of Rv value and repeating the cycle with other two segmentations. (There are three segmentations, differing in terminal methyl group.) The configuration of atom 2 was occasionally changed in all runs, except the runs for the conformer having the configuration (RSS). By using the strategy (1) we obtained 5-7, 2-5, 2-8, and 4-7 conformers of isomer (SSS), (SSR), (RSR), and (RSS), respectively, and strategy (2) yielded 11, 9 and 9 conformers of isomer (SSR), (RSR) and (RSS), respectively. These conformers had usually lower energy than the initial conformation. The first conformer obtained from a “seed” conformation had substantially lower energy than energy of “seed” conformation in all 15 cases. Also, we found four conformations which were not obtained by convenient search of conformational space.

conformational analysis; molecular mechanics; coordination compounds

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