Kinetic studies of preactivated derivatives of cyclophosphamide by /sup 31/P NMR spectroscopy

Thesis/Dissertation · Wed Jan 01 04:00:00 EST 1986

OSTI ID:7170929

Boyd, V L

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
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKYLATING AGENTS
ANIMAL CELLS
BIOCHEMICAL REACTION KINETICS
CARBON 13
CARBON ISOTOPES
CHEMICAL REACTIONS
DATA
DERIVATIZATION
DISEASES
DRUGS
ELEMENTS
ENDOXAN
EVEN-ODD NUCLEI
EXPERIMENTAL DATA
HYDROGEN
IMMUNOSUPPRESSIVE DRUGS
INFORMATION
ISOTOPES
KINETICS
LIGHT NUCLEI
LYMPHOMAS
MAGNETIC RESONANCE
METABOLITES
NEOPLASMS
NMR SPECTRA
NONMETALS
NUCLEAR MAGNETIC RESONANCE
NUCLEI
NUMERICAL DATA
ODD-EVEN NUCLEI
PHOSPHORUS 31
PHOSPHORUS ISOTOPES
REACTION KINETICS
RESONANCE
SPECTRA
STABLE ISOTOPES
SYNTHESIS