Solution-processed small molecule bulk-heterojunction solar cells represent a specific subset of organic photovoltaics (OPV). OPV devices rely on materials with appropriately aligned frontier molecular orbitals, bandgaps commensurate with the solar spectrum, and ultimately must self-assemble into a morphology conducive to high device performance. Optical electronic and physical properties in organic materials are highly sensitive to their chemical structure and the conformations of those structures in space. Materials can be engineered to exhibit specific traits; a process referred to as "molecular design." While the molecular design toolbox is ever-expanding, each of these properties requires unique considerations, and indeed vary greatly in the degree of control the synthetic chemist has in producing predictable properties. In order to elucidate the relationship between structure and properties, a class of small molecules was developed adhering to what can be described as a D'ADAD' architecture, where D, D' and A refer to an electron rich core, electron rich end-caps and electron deficient heterocyclic fragments, respectively. These fragments, as well as solubilizing side groups were systematically modified, yielding useful design rules for organic donor materials as well as record breaking small-molecule OPV devices. The top performing material in the group exhibited diminutive performance on the ubiquitous solution deposited substrate PEDOT:PSS due to interfacial chemistry. This led to the development of a new material, p-DTS(FBTTh2)2, which was not susceptible to the interfacial chemistry with PEDOT:PSS, and broke the previous performance record for solution-processed small molecule OPV devices. Four isostructural molecules, including p-DTS(FBTTh2)2 were investigated with single crystal x-ray diffraction. While all four molecules appear topologically equivalent, two types of crystal structure were observed with distinct crystal systems and each with a characteristic molecular geometry. A multi-scale theoretical investigation of simulated isolated molecules and experimentally determined crystal structures offers a clear explanation for the observed lattices, where useful experimental data is unavailable.

Chemotherapy is the practice of treating cancer with antineoplastic drugs. In general, these drugs are highly toxic, and in many patients the side effects from therapy become so severe that treatment is stopped before full tumor remission has occurred. Further, chemotherapeutics usually have poor water solubility and very short circulation lifetimes, which makes it difficult to get a significant fraction of the injected dose to the tumor site. The use of polymers as delivery vehicles for drugs is a strategy for improving the efficacy and reducing the side effects of toxic cancer drugs. The design of an ideal polymeric system for drug delivery is a very active area of research and PEGylated dendrimers are among the most promising. Here we report the design, synthesis and biological evaluation of a biodegradable and versatile PEGylated dendrimer. We also report the preliminary results of a project involving hyaluronic acid functionalized liposomes.

Chapter 1 is a brief overview of the background and history of polymers in drug delivery. The relevance of dendrimers is described in the context of other polymer delivery systems that have begun the transition into clinical development.

Chapter 2 describes the synthesis and characterization of a PEGylated dendrimer that is biodegradable, robust, and has a nine step synthesis to drug loaded material. The polymer was functionalized with the drug, doxorubicin, and evaluated in mice. The in vivo chemotherapy experiment in Balb/c mice inoculated with murine C26 colon carcinoma resulted in nine out of ten long fully cured mice.

Chapter 3 describes the application of PEGylated dendrimers with platinum therapeutics. In order to increase the number of drug attachment sites on the dendrimer, the dendrimer core is used as a macroinitiator to carry out a ring-opening radial growth polymerization of the N-carboxy anhydride of glutamic acid. The terminal amines are then PEGylated and platinum chelators are attached to the glutamic acid side chains. Preliminary biological evaluation revealed that the polymer released platinum too quickly and therefore did not significantly improve the efficacy of the drug. This information was what inspired the research in chapter 4.

Chapter 4 presents the synthesis and characterization of a small library of polymer bound platinum chelators. The chelators were loaded with diaminocyclohexane platinate (DACHPt). Differences in the ring size and ligand strength are examined in relation to drug release rate and cytotoxity. The most promising chelators were taken forward and evaluated in the C26 colon carcinoma model alongside the clinical drug, cisplatin, as a positive control.

Chapter 5 outlines an attempt to develop a new class of platinum (II) drugs that are specially tailored for polymeric drug delivery. A small library of heterocyclic diamine ligands functionalized with a ketone moiety was synthesized. The ligands were loaded with platinum (II) and the complexes were screened for their in vitro toxicity. The complexes with high potency were attached to polymers via a hydrazone bond and evaluated in vivo.

Chapter 6 outlines a new synthetic approach toward hyaluronic acid (HA) functionalized liposomes. HA, a naturally occurring polysaccharide is specific ligand for the CD44 receptor which is overexpressed on a number of cancer cell types. Using oxime chemistry, lipid molecules were attached to various lengths of HA oligomers at their reducing ends. The glycolipids were then incorporated into fluorescently labeled liposomes. The cells preferentially internalized the HA-targeted liposomes and did not internalize non-targeted control liposomes.

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Health-related quality of life is increasingly important in the management of patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). A few disease-specific questionnaires exist, but all with substantial flaws. We developed and validated a quality of life questionnaire suitable for use in all BCC and SCC patients. In an extensive four-phase trajectory, as recommended by the European Organisation for Research and Treatment of Cancer (EORTC), 33 items were selected and rephrased into a preliminary questionnaire. A population-based sample of 1173 patients from the Dutch Cancer Registry were invited to complete the questionnaire. The questionnaire was reduced using exploratory factor analysis and item response theory (IRT). Subsequently, individual item performance was assessed using 8 features of the classical test theory (CTT).

The 33-item preliminary questionnaire was completed by 721 patients, of whom 15% had SCC. The number of items in the questionnaire was reduced to 16, covering five subscales: “Worries”, “Appearance”, “Behaviour”, “Diagnosis & Treatment” and “Other People”. Confirmatory factor analysis showed a good fit. Cronbach’s α (range 0.67 – 0.82) were reasonable to high and demonstrated good internal consistency. Of the 8 CTT item performance features, only 1 item was suboptimal for 6 out of 16 items and only 2 for 2 items, suggesting a valid Basal and Squamous cell carcinoma Quality of Life (BaSQoL) questionnaire.