Synthesis of azaphthalocyanine quenchers of fluorescence for intrastrand binding to oligonucleotides

Charles University, Faculty of Pharmacy in Hradec Králové Department: Department of Pharmaceutical chemistry and Pharmaceutical analysis Candidate: Matěj Machan Supervisor: doc. PharmDr. Veronika Nováková, Ph.D. Title of thesis: Synthesis of novel azaphthalocyanines working as dark quenchers suitable for binding to the middle of an oligonucleotide chain Azaphthalocyanines (AzaPcs) are analogues of well-known phthalocyanines with benzene rings replaced for pyrazine ones. AzaPcs can be used in many applications due to their interesting spectral and photophysical properties, e.g. as photosensitisers in photodynamic therapy or as fluorescence sensors. The alkylamino substituted AzaPcs can be used as dark quenchers of fluorescence in mono-labeled DNA hybridization probes (FRET probes) or double-labeled probes as well. The AzaPcs for this application have typically three quarters identical (bearing alkylamino groups responsible for quenching of fluorescence) and the last quarter is modified with a functional group for attaching to oligonucleotide probe. The goal of this project was to synthesize unsymetrical AzaPc with a T-shape functional group carrying two hydroxy groups that can be used for attaching to oligonucleotide probe. The synthesis consisted of preparation of appropriately substituted..