Search

This thesis reports a theoretical study of polymers in the presence of particles. An analytical theory is used to describe the potential of mean force between spheres for the case where the polymer molecular weight dispersity is described by the Schulz-Flory distribution. Exact results are derived for systems where the particle radius (RS) is small in comparison to the radius of gyration (Rg) of the polymer molecules. Numerical results are obtained in the case of particles immersed in a solution of polymers. It is shown that when q = Rg/RS ≥ 10 a spherical approximation can be used to describe the potential of mean force. This result has significant consequences on the many-body interactions mediated by polymers between particles in the particle/polymer mixtures. The theory is then applied to study the phase behaviour of particle/polymer mixtures in electrolyte solutions wherein the particles are charged. Thus the particles have a combination of depletion attraction and screened electrostatic repulsion. We show that a generalized potential of mean force is an accurate and computationally efficient means by which to treat this system. In addition to the two studies above, we also consider the case of an equilibrium polymer consisting of associating co-monomers. We generalize the density functional theory of polymers to describe this scenario and study the case where the polymer is in the vicinity of an attractive surface. Interestingly, A surface phase transition is observed in ideal polymers, which is suppressed when monomers exclude each other. We use this theory to model the formation of linear peptide aggregates on the surfaces of particles. In particular, we consider a specific model for an amyloidal peptide responsible for Alzheimer disease. The thesis concludes with a discussion on possible theoretical developments in the future.

The binding of the aza-anthracenedione anti-neoplastic drug pixantrone (6,9-bis[92- aminoethyl)amino]benzo[g]isoquinoline-5,10-dione fumarate) to the tridecanucleotide d(CCGAGAATTCCGG)2 that contains a single bulged adenine on each strand and the oligonucleotide duplex d(TACGATGAGTA) : d(TACCATCGTA), that contains a single bulge and a single 5’-CpG site, have been studied by low temperature NMR spectroscopy and molecular modelling. Large upfield shifts of the pixantrone aromatic protons have been observed, consistent with pixantrone binding d(CCGAGAATTCCGG)2 by intercalation. Strong NOEs between the pixantrone H7/H8 and H4 with the tridecanucleotide A4H1’ and G3H1’ protons, respectively, were observed suggesting that pixantrone binds d(CCGAGAATTCCGG)2 from minor groove at the bulge 5’-G3pA4 site and from major groove at the C2pG3 site. The oligonucleotide d(TACGATGAGTA) : d(TACCATCGTA) was chosen to determine the pixantrone binding preference between isolated 5’-CpG and bulge sites. The selective reduction in the sequential NOE between the G7-A8 and A8-G9 nucleotides suggested that pixantrone binds at the bulge site by intercalation. Additionally, only NOEs from the pixantrone H7/H8 to A8H1’ were observed, indicating pixantrone preferentially binds from minor groove at the bulge site. Furthermore, strong NOEs from pixantrone Ha to G9H1’ were found while only weak NOEs were observed between Ha and G7H1’, consistent with the energy minimized models that showed the A8pG9 is the more favoured site than the G7pA8 site. Large upfield shifts for the G9 imino resonance, compared to the G7 resonance, upon pixantrone binding were also observed, consistent with pixantrone binding at the A8-G9 bulge site. The results of this study highlight a new favourable binding site for pixantrone, and suggest that pixantrone may be a particularly effective anti-cancer agent for cell lines that have a significant number of unrepaired bulge sites, i.e. those with a deficient mismatch repair pathway.