Conjugated porphyrin dimers as probes of microviscosity

Abstract

The cell membrane is a recent target for the imaging and quantification of viscosity in light of evidence which suggests that abnormal membrane behaviour is related to various disease states. We propose the use of a novel technique involving a class of compounds termed ‘molecular rotors’, which can image cellular viscosity with high spatial and temporal resolution. This Thesis concerns one type of molecular rotors, conjugated porphyrin dimers, which have dual functionality: as viscosity sensors and as photosensitizers for photoinduced cell death during Photodynamic Therapy of cancer (PDT). First, we consider the photophysics of several conjugated dimers bearing various substituents and assess the effect of various parameters on dimer’s intermolecular rotation. We find that the photophysical properties of most dimers are primarily sensitive to the viscosity of their environment and are minimally sensitive to temperature and solution polarity. Secondly, using polymer solutions and melts, we establish the physical origin of the porphyrin dimer’s viscosity sensitivity as detection of solvent ‘free volume’, which is related to both macromolecular crowding and solvent hydrodynamic pressure. Thirdly, we establish conditions for the inclusion of a porphyrin dimer into model lipid membranes; demonstrating the detection of lipid phase as a function of temperature, sensitivity to free-volume occupancy of lipid tails according to saturation, and finally reporting viscosity values in close agreement with those from literature obtained using alternative methods. Finally we find that under conditions of imaging using fluorescence microscopy, the porphyrin dimer has compromised fluorescence signal due to limitations of solubility during sample preparation. However, by combining the detection from a poprhyrin dimer and a well-known molecular rotor BODIPY-C10 we were able to detect a viscosity increase in unsaturated lipid membranes upon increased exposure to light, replicating conditions of singlet oxygen production during PDT.