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Phenylisoserine in the gas-phase and water: Ab initio studies on neutral and zwitterion conformers.

Rode JE, Dobrowolski JC, Sadlej J - J Mol Model (2010)

Bottom Line: According to DFT calculations, the conformer equilibrium in the gas phase is dominated by one conformer, whereas the MP2 calculations suggest three PhIS structures to be significantly populated.Based on the AIM calculations, we found that for the neutral conformers in vacuum and in water, d(H...B) is linearly correlated with Laplacian at the H-bond critical point.One zwitterionic and one neutralconformer determine the equilibrium in water whereas in the gas phase the MP2 calculations suggest three PhIS structures to be significantly populated.

View Article: PubMed Central - PubMed

Affiliation: Industrial Chemistry Research Institute, 8 Rydygiera Street, 01-793 Warsaw, Poland.

ABSTRACT
The conformational landscape of phenylisoserine (PhIS) was studied. Trial structures were generated by allowing for all combinations of single-bond rotamers. Based on the B3LYP/aug-cc-pVDZ calculations 54 conformers were found to be stable in the gas phase. The six most stable conformers were further optimized at the B3LYP/aug-cc-pVTZ and MP2/aug-cc-pVDZ levels for which characteristic intramolecular hydrogen bond types were classified. To estimate the influence of water on PhIS conformation, the IEF-PCM/B3LYP/aug-cc-pVDZ calculations were carried out and showed 51 neutral and six zwitterionic conformers to be stable in water solution. According to DFT calculations, the conformer equilibrium in the gas phase is dominated by one conformer, whereas the MP2 calculations suggest three PhIS structures to be significantly populated. Comparison of DFT and MP2 energies of all 57 structures stable in water indicates that, in practice, one zwitterionic and one neutral conformer determine the equilibrium in water. Based on the AIM calculations, we found that for the neutral conformers in vacuum and in water, d(H...B) is linearly correlated with Laplacian at the H-bond critical point. Figure Phenylisoserine (PhIS) is an active side chain of cytotoxic Paclitaxel medicine. The conformational landscape of phenylisoserine was studied. One zwitterionic and one neutralconformer determine the equilibrium in water whereas in the gas phase the MP2 calculations suggest three PhIS structures to be significantly populated.

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The B3LYP/aug-cc-pVDZ optimized the most stable six structures of phenylisoserine in the gas phase. The relative total energies (ΔE, kcal mol−1) and free Gibbs energies (ΔG, kcal mol−1) referred to the most stable conformer are given in parentheses and square brackets, respectively
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Fig1: The B3LYP/aug-cc-pVDZ optimized the most stable six structures of phenylisoserine in the gas phase. The relative total energies (ΔE, kcal mol−1) and free Gibbs energies (ΔG, kcal mol−1) referred to the most stable conformer are given in parentheses and square brackets, respectively

Mentions: The phenylisoserine molecule has six single bonds around which free rotations may lead to as much as ca. 40 000 local minima. To generate the structures of it the relevant torsion angles were varied. Based on semiempirical AM1 search, 158 stable phenylisoserine conformers were appointed and reoptimized at the B3LYP/aug-cc-pVDZ level yielding 54 stable structures. Each of the phenylisoserine functional groups, carboxyl and alcoholic OH, C=O, and NH2, may operate as both a hydrogen bond donor or acceptor. Thus, because of internal hydrogen bonds some conformers are stabilized more than the other. Six low-energy structures of phenylisoserine (Fig. 1, Table 1) were further studied by using the B3LYP/aug-cc-pVTZ and MP2/aug-cc-pVDZ methods. They were found to be in the 3.5 kcal mol−1 energy range relative to the most stable form. Thermochemical properties at 298.15 K were computed for all the conformers and the relative abundances were estimated for six of them. Figures, energetic and selected dihedral angles of all 54 phenylisoserine conformers optimized at the B3LYP/aug-cc-pVDZ level are available in the electronic supplementary materials (Tables 1SI and 2SI, Fig. 1SI). In Table 3SI Cartesian coordinates are gathered for the six most stable structures calculated at the B3LYP/aug-cc-pVDZ level.Fig. 1


Phenylisoserine in the gas-phase and water: Ab initio studies on neutral and zwitterion conformers.

Rode JE, Dobrowolski JC, Sadlej J - J Mol Model (2010)

The B3LYP/aug-cc-pVDZ optimized the most stable six structures of phenylisoserine in the gas phase. The relative total energies (ΔE, kcal mol−1) and free Gibbs energies (ΔG, kcal mol−1) referred to the most stable conformer are given in parentheses and square brackets, respectively
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3094660&req=5

Fig1: The B3LYP/aug-cc-pVDZ optimized the most stable six structures of phenylisoserine in the gas phase. The relative total energies (ΔE, kcal mol−1) and free Gibbs energies (ΔG, kcal mol−1) referred to the most stable conformer are given in parentheses and square brackets, respectively
Mentions: The phenylisoserine molecule has six single bonds around which free rotations may lead to as much as ca. 40 000 local minima. To generate the structures of it the relevant torsion angles were varied. Based on semiempirical AM1 search, 158 stable phenylisoserine conformers were appointed and reoptimized at the B3LYP/aug-cc-pVDZ level yielding 54 stable structures. Each of the phenylisoserine functional groups, carboxyl and alcoholic OH, C=O, and NH2, may operate as both a hydrogen bond donor or acceptor. Thus, because of internal hydrogen bonds some conformers are stabilized more than the other. Six low-energy structures of phenylisoserine (Fig. 1, Table 1) were further studied by using the B3LYP/aug-cc-pVTZ and MP2/aug-cc-pVDZ methods. They were found to be in the 3.5 kcal mol−1 energy range relative to the most stable form. Thermochemical properties at 298.15 K were computed for all the conformers and the relative abundances were estimated for six of them. Figures, energetic and selected dihedral angles of all 54 phenylisoserine conformers optimized at the B3LYP/aug-cc-pVDZ level are available in the electronic supplementary materials (Tables 1SI and 2SI, Fig. 1SI). In Table 3SI Cartesian coordinates are gathered for the six most stable structures calculated at the B3LYP/aug-cc-pVDZ level.Fig. 1

Bottom Line: According to DFT calculations, the conformer equilibrium in the gas phase is dominated by one conformer, whereas the MP2 calculations suggest three PhIS structures to be significantly populated.Based on the AIM calculations, we found that for the neutral conformers in vacuum and in water, d(H...B) is linearly correlated with Laplacian at the H-bond critical point.One zwitterionic and one neutralconformer determine the equilibrium in water whereas in the gas phase the MP2 calculations suggest three PhIS structures to be significantly populated.

View Article: PubMed Central - PubMed

Affiliation: Industrial Chemistry Research Institute, 8 Rydygiera Street, 01-793 Warsaw, Poland.

ABSTRACT
The conformational landscape of phenylisoserine (PhIS) was studied. Trial structures were generated by allowing for all combinations of single-bond rotamers. Based on the B3LYP/aug-cc-pVDZ calculations 54 conformers were found to be stable in the gas phase. The six most stable conformers were further optimized at the B3LYP/aug-cc-pVTZ and MP2/aug-cc-pVDZ levels for which characteristic intramolecular hydrogen bond types were classified. To estimate the influence of water on PhIS conformation, the IEF-PCM/B3LYP/aug-cc-pVDZ calculations were carried out and showed 51 neutral and six zwitterionic conformers to be stable in water solution. According to DFT calculations, the conformer equilibrium in the gas phase is dominated by one conformer, whereas the MP2 calculations suggest three PhIS structures to be significantly populated. Comparison of DFT and MP2 energies of all 57 structures stable in water indicates that, in practice, one zwitterionic and one neutral conformer determine the equilibrium in water. Based on the AIM calculations, we found that for the neutral conformers in vacuum and in water, d(H...B) is linearly correlated with Laplacian at the H-bond critical point. Figure Phenylisoserine (PhIS) is an active side chain of cytotoxic Paclitaxel medicine. The conformational landscape of phenylisoserine was studied. One zwitterionic and one neutralconformer determine the equilibrium in water whereas in the gas phase the MP2 calculations suggest three PhIS structures to be significantly populated.

Show MeSH