Hybridization Properties of Modified Nucleotides with Potential Chemotherapeutic Use Studied by Spectroscopic Methods

Author: RNDr. Martin Kříž, Ph.D.
Supervisor: Prof. RNDr. Josef Štěpánek, CSc.
Consultants:
Type: Master

Abstract: The diploma thesis represents a continuation of the research of new modified nucleotides–potential "anti-sense" chemotherapeutics. It is devoted to mononucleotide's analogs having the riboso-phosphate part of the molecule replaced by the pyrrolidine-phosphonate one. Besides Raman spectroscopy also electron absorption and marginally fluorescence spectroscopies were used. The studied samples possessed unexpected spectroscopic properties: specific fluorescence background and peculiar Raman spectrum. Series of repeated cleaning attempts and spectroscopic measurements at various conditions have revealed that the effect is caused by an impurity in the samples, characteristic by a fluorescence band with maximum in the measured spectral region and by resonance Raman scattering. Not a repeated cleaning was able to remove the impurity completely. Its amount varied widely according to the series of the sample. The results of the thesis show that the impurity is produced from the sample itself by a photochemical effect of light at aerobic conditions. It is a mixture of at least two species. The impurity formation can be supported by increased temperature. On the other hand, it is possible to induce its photodegradation. By using methods of factor analysis, pH dependence of 3'-deoxythymidine analoges Raman spectra was found out. Two acido-basic transitions have been identified and interpreted as a conversion from a neutral molecule to a zwitterion and as a deprotonation of thymine moiety. Raman spectra of the three corresponding forms were isolated and interpreted.

Keywords: None