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

Abstract

The possible conformations in the most stable structure of cyclophosphamide were investigated at the DFT-B3LYP and MP2/6-311G** levels of calculation. The axial structure is calculated to be lower in energy than the equatorial form of cyclophosphamide by 5 (MP2) to 6 (DFT) kcal mol −1 because of a very weak anomeric effect and weak conjugation. Further it is the same structure as the one found in the X-ray investigations both of the hydrate and of the anhydrous form. The computed DFT vibrational frequencies of the axial structure were used to analyze the infrared and Raman spectra using normal-coordinate calculations to provide reliable assignments to the normal modes of the molecule.

Analysis of the Fragmentation Pathways for the Collision-Induced Dissociation of Protonated Cyclophosphamide: A Mass Spectrometry and Quantum Mechanical Study

“…11,13 A more recent computational study reported the axial structure to be lower in energy than the equatorial form by about 5 kcal/mol. 14 Structures, energetics, and several important chemical parameters of some alkylating drug molecules reported at the DFT B3LYP level of theory showed that for most of the drug molecules studied, including cyclophosphamide, the guanine moiety in DNA is their primary target, validating earlier experimental findings. 15 In this paper, we present a detailed examination of the collision-induced product ions of protonated cyclophosphamide and employ quantum mechanical calculations to elucidate the structures of these products and their precursors, suggest plausible fragmentation pathways, as well as provide an accurate description of the corresponding energetics.…”

“…AM1 calculations showed a preference of the phosphoryl oxygen to be in an axial position while PM3 calculations did not . X-ray diffraction studies showed the heterocyclic ring of cyclophosphamide to take a chair conformation with an axial phosphoryl oxygen and an equatorial nitrogen mustard group. , A more recent computational study reported the axial structure to be lower in energy than the equatorial form by about 5 kcal/mol . Structures, energetics, and several important chemical parameters of some alkylating drug molecules reported at the DFT B3LYP level of theory showed that for most of the drug molecules studied, including cyclophosphamide, the guanine moiety in DNA is their primary target, validating earlier experimental findings …”

Vibrational spectroscopy for discrimination and quantification of clinical chemotherapeutic preparations

“…The chemical structure of ifosfamide (Figure 1) is comprised of chloroethyl groups attached to an endocyclic nitrogen (32,52). The main spectral characteristics of HOLOXAN ® (Figure 2A, spectrum c) are thus observed at 668 cm -1 (ring bending), 791 cm -1 (C-Cl stretching), 1052 cm -1 (C-C aliphatic chain stretching), 1295 cm -1 (ring stretching), 1452 cm -1 (N-H bending), 1484 cm -1 (CH2 scissoring) and 1649 (CH2 deformation) (53,54).…”

Ultrasensitive SERS Substrate for Label-Free Therapeutic-Drug Monitoring of Paclitaxel and Cyclophosphamide in Blood Serum

“…These significant increases in the SERS intensities at the respective peaks were observed when 1 × 10 –6 M CYC in blood serum was incorporated on the l -cysteine SAuNPs@GO hybrid compared with when 1 × 10 –5 M CYC in blood serum was incorporated on the l -cysteine SAuNPs and bare GO (see Figure a,b). The CYC Raman peak at 1465 cm –1 does not overlap with the SERS spectra of blood serum, which can be clearly distinguished, as indicated in Figure c . To further investigate the detection limit, different concentrations of CYC in blood serum were incorporated on the l -cysteine SAuNPs@GO hybrid, and SERS measurements were carried out.…”

“…The CYC Raman peak at 1465 cm −1 does not overlap with the SERS spectra of blood serum, which can be clearly distinguished, as indicated in Figure 6c. 47 To further investigate the detection limit, different concentrations of CYC in blood serum were incorporated on the L-cysteine SAuNPs@GO hybrid, and SERS measurements were carried out. The detection limit of CYC in the bloodserum mixture was found to be 5 × 10 −9 M, which is equivalent to 2.64 × 10 −17 moles or 8.33 × 10 5 molecules in the laser-spot area (see Figure 6d and Table S5).…”