Optoelectronically active sensitisers for the selective detection of nucleic acid biomarkers

This thesis presents biophysical studies of new optoelecronically active DNA-binders. Chapter one gives a brief overview of the importance of DNA in medicine, of DNA structure and of the mode of interactions of small molecules with double-stranded DNA, including electrostatic, intercalation and groove interactions. Various examples of small-molecule binding to DNA are discussed. Additionally, this chapter briefly describes the biophysical techniques which can be exploited to quantify the interaction between small-molecules and duplex DNA. Chapter two describes the results of studies of the interactions of a group of 1,8-naphthalimide derivatives with double-stranded DNA using a variety of techniques viz. spectroscopy, calorimetry, viscosity and molecular docking studies. Additionally, this chapter also presents sequence selectivity studies of this group of compounds for specific sequences (dAdT)12●(dAdT)12 and (dGdC)12●(dGdC)12 through UV-visible spectroscopy. The 1,8-napthtalimide unit is shown to be a useful element for inducing DNA-binding. Chapter three describes studies of the interactions of a family of dendrimeric compounds with double-stranded DNA, again using spectroscopy, calorimetry, viscosity and molecular docking studies. Furthermore, this chapter includes sequence selectivity studies of this group of compounds for (dAdT)12●(dAdT)12 and (dGdC)12●(dGdC)12 via UV-visible spectroscopy. The charge and the length of the dendritic structures is shown to strongly affect nucleic acid affinities of this series of molecules. Chapter four describes the results of studies of the interactions of miscellaneous compounds with double-stranded DNA using variety of techniques viz. spectroscopy, calorimetry, viscosity and molecular docking studies. In addition, this chapter displays sequence selectivity studies of this group of compounds for specific sequences (dAdT)12●(dAdT)12 and (dGdC)12●(dGdC)12 via UV-visible spectroscopy. Chapter five gives an overview and general conclusions about the DNA binding studies presented in Chapters 2, 3 & 4 and finishes with suggestions for future work