Cyclophosphamide and isophosphamide - DFT conformational studies in the gas phase and solution
Justyna Wielińska , Justyna Bednarko , Henryk Myszka , Beata Liberek , Andrzej Nowacki
AbstractCyclophosphamide and isophosphamide have been subjected to comprehensive conformational studies in the vacuum and solution using the SMD solvation model. Vacuum calculations were conducted using the B3LYP, M05-2X, M06-2X and uB97XD functionals. Natural bond orbital (NBO) analysis has been performed for selected geometries. A preference for a chair conformation with the axial P¼O bond is shown (1C4). The 5S0 conformation is 1.25e2.31 kcal/mol and 1.72e2.92 kcal/mol higher in energy than the global minimum conformations of cyclophosphamide and isophosphamide, respectively. In the gas phase, the chair conformation with the equatorial P¼O bond (4C1) is of comparable stability or less stable than the skew form, depending on the method used, while it is slightly more favored than the 5S0 conformation in solution. The stereoelectronic effects do not differentiate the ring conformer stability. The steric strains between N(EtCl)1e2 and the C4 and C6 carbon atoms mainly influence the stability of cyclophosphamide and isophosphamide conformers.
|Journal series||Journal of Molecular Graphics & Modelling, ISSN 1093-3263, (N/A 70 pkt)|
|Publication size in sheets||0.7|
|Keywords in English||Cyclophosphamide, isophosphamide, DFT conformational studies, NBO analysis|
|ASJC Classification||; ; ;|
|Score||= 70.0, 10-01-2020, ArticleFromJournal|
|Publication indicators||= 0; = 0; : 2018 = 0.605; : 2018 = 1.863 (2) - 2018=1.793 (5)|
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