Cyclophosphamide and isophosphamide - DFT conformational studies in the gas phase and solution

Justyna Wielińska , Justyna Bednarko , Henryk Myszka , Beata Liberek , Andrzej Nowacki

Abstract

Cyclophosphamide 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.
Author Justyna Wielińska (FCh / DOCh / LG)
Justyna Wielińska,,
- Laboratory of Glycochemistry
, Justyna Bednarko (FCh / DOCh / LG)
Justyna Bednarko,,
- Laboratory of Glycochemistry
, Henryk Myszka (FCh / DOCh / LG)
Henryk Myszka,,
- Laboratory of Glycochemistry
, Beata Liberek (FCh / DOCh / LG)
Beata Liberek,,
- Laboratory of Glycochemistry
, Andrzej Nowacki (FCh / DOCh / LG)
Andrzej Nowacki,,
- Laboratory of Glycochemistry
Journal seriesJournal of Molecular Graphics & Modelling, ISSN 1093-3263, (A 25 pkt)
Issue year2019
Vol90
Pages243-257
Publication size in sheets0.7
Keywords in EnglishCyclophosphamide, isophosphamide, DFT conformational studies, NBO analysis
ASJC Classification2505 Materials Chemistry; 1704 Computer Graphics and Computer-Aided Design; 1606 Physical and Theoretical Chemistry; 1607 Spectroscopy
DOIDOI:10.1016/j.jmgm.2019.05.009
URL https://doi.org/10.1016/j.jmgm.2019.05.009
Languageen angielski
Score (nominal)25
ScoreMinisterial score = 25.0, 24-07-2019, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2016 = 0.735; WoS Impact Factor: 2017 = 1.885 (2) - 2017=1.806 (5)
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