Kinetic studies of preactivated derivatives of cyclophosphamide by /sup 31/P NMR spectroscopy
Selected derivatives of cyclophosphamide (CP) metabolites were synthesized and the solution chemistry of each was studied by /sup 31/P nuclear magnetic resonance (NMR) spectroscopy under a standard set of reaction conditions at physiological pH (7.4) and temperature (37/sup 0/C). Complementary /sup 2/H and /sup 13/C NMR spectral data was obtained using isotopically (/sup 2/G and /sup 13/C) enriched CP metabolites. The CP derivatives were synthesized by the ozonolysis of substituted 3-butenyl phosphorodiamidates, and were isolated as analogues of either cis and trans 4-hydroperoxy-CP or aldophosphamide (AP). The relative ratios of the tautomeric species, 4-hydroxy-CP and AP, and their half-lives (T/sub 1/2/) were measured by /sup 31/P NMR spectroscopy. The influence of CP metabolites on perfused U-937 cells, a CP-sensitive human lymphoma, was observed by high resolution /sup 31/P NMR spectroscopy. In this manner, it was possible to measure, for the first time, a rate constant for the intracellular disappearance of phosphoramide mustard, the ultimate alkylating metabolite of CP.
- Research Organization:
- Catholic Univ. of America, Washington, DC
- OSTI ID:
- 7170929
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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ENDOXAN
BIOCHEMICAL REACTION KINETICS
NMR SPECTRA
ANIMAL CELLS
CARBON 13
DERIVATIZATION
EXPERIMENTAL DATA
HYDROGEN
LYMPHOMAS
METABOLITES
NUCLEAR MAGNETIC RESONANCE
PHOSPHORUS 31
SYNTHESIS
ALKYLATING AGENTS
CARBON ISOTOPES
CHEMICAL REACTIONS
DATA
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EVEN-ODD NUCLEI
IMMUNOSUPPRESSIVE DRUGS
INFORMATION
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KINETICS
LIGHT NUCLEI
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NEOPLASMS
NONMETALS
NUCLEI
NUMERICAL DATA
ODD-EVEN NUCLEI
PHOSPHORUS ISOTOPES
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550201* - Biochemistry- Tracer Techniques