An electron spin resonance study of drug binding to nucleic acids

Abstract

The thesis presents a study of the interaction of paramagnetic derivatives of drugs with the nucleic acids, carried out using the electron spin resonance (ESR) technique. The general principles of ESR (particularly those concerned with the free radicals) are outlined and spin labelling techniques as applied to biological specimens are described. The interaction of nucleic acids with small molecules is also reviewed.
Most of the work was performed using the radical cation of the tranquilizer chlorpromazine (CPZ+). Measurements were taken at X and Q-band frequencies and were coupled with extensive theoretical simulations of the ESR spectra. The hyperfine tensor elements arising
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from the N atom of the chlorpromazine ion were determined by computer fitting, from the spectrum obtained from a DNA-CPZ gel. The analysis of the spectra obtained from oriented DNA-CPZ fibre specimens led to the formulation of a fibre model according to which the DNA molecules described a Gaussian distribution of orientations about the fibre axis (with a half width in the range from 27 to 40°). The results were compared with data obtained by other techniques (particularly optical linear dichroism).
The measurements were extended to the investigation of other nucleic acid species and drugs and the results were discussed in relation to their biophysical significance.