The objectives of this project are twofold: (1) the synthesis and characterization of a number of spin-labeled derivatives of daunomycin and adriamycin expected to have application in cancer treatment, and (2) experimental studies, using multi-frequency (Q-band, X-band, S-band and L-band) electron spin resonance (ESR) spectroscopy, on magnetic spin-spin interactions between the spin-labeled drugs and a near-by copper (II) atoms. In regard to the ESR measurement, the lineshapes will be calculated using matrix diagonalization techniques. The values of the copper...nitroxyl spin-spin coupling constants, J0, will be determined from the temperature dependence of the area of the ESR signals. The dipolar distance between the copper atom and the nitroxyl radical in the triplet state will be estimated using both lineshape simulation and a general relationship for zero-field splitting. The interspin distance will also be calculated from the relative intensity of the half-field line compared to the full-field line using Eatons' formula. The 'magnetic geometry' of the Cu (II)...spin-labeled drug complex and the metal binding site will then be determined.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15CA043599-01
Application #
3437304
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1986-09-30
Project End
1987-08-31
Budget Start
1986-09-30
Budget End
1987-08-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Ball State University
Department
Type
Schools of Arts and Sciences
DUNS #
065540726
City
Muncie
State
IN
Country
United States
Zip Code
47306