The Anhydrous Racemate of the Carcinostatic Agent Cyclophosphamide and the Bicyclic Degradation Product 1-(2-Chloroethyl)tetrahydro-1H,5H-1,3,2-diazaphospholo[2,1-b][1,3,2]oxazaphosphorine 9-Oxide

DFT and MP2 Study of the Molecular Structure and Vibrational Spectra of the Anticancer Agent Cyclophosphamide

“…The comparison shall also be used to determine the limitations of the computed parameters for a description of the molecular structure of the system as found in the solid. Table 1 indicates that most of the bond lengths calculated with DFT and MP2 are not much different from each other and agree rather well with the experimental ones [6,21]. Only those for the PO and PN bonds are somewhat smaller in experiment, which might be due to hydrogen bonding interactions in the crystalline hydrate [6] or intermolecular interactions in the anhydrous form [21].…”

“…The results were compared to the X-ray structure data of the hydrate [6] and of the anhydrous form [21] and found to be in reasonable agreement. Reliable vibrational assignments of the normal modes of cyclophosphamide in its axial structure are provided on the basis of combined theoretical DFT and experimental infrared and Raman data.…”

“…The present study provides a thorough comparison between the X-ray structure of the monohydrate [6] and also of the anhydrous material [21] with the corresponding structure obtained at the DFT-B3LYP/6-311G** and MP2/6-311G** levels of computation. The equatorial conformer cannot be the ground state (as found in the calculations; see Table 2) because in the axial conformer the lone pairs of the oxygen and the nitrogen atoms in the ring can donate electrons into the antibonding orbitals of the phosphoryl PO group thus stabilizing the system in the axial conformer.…”

“…In the following we want to concentrate on the conformer that is also found in the two X-ray diffraction investigations [6,21]. The primary objective of the study is to compare the X-ray structure of the solid to the theoretical structure (which best represents an isolated molecule).…”

“…Note, that the set of internal coordinates is overcomplete in order to facilitate the Table 1. X-Ray (from the monohydrate [6] and the anhydrous form [21]) and calculated structural parameters of the non-hydrogen atoms of the axial conformer of cyclophosphamide. Table 2.…”