Photochemistry of Coumarin Functionalized Silica Nanoparticles and Photochemically Induced Drug Delivery Utilizing o-Nitrobenzyl Compounds

Within this work two different approaches to synthesize new composite materials for photochemical drug delivery and their potential application in IOLs were investigated. In the first part of this thesis the photochemical properties of coumarin functionalized silica nanoparticles were examined. Employing two different synthetic methods particles of 45 nm and 16 nm were produced. The larger ones synthesized utilizing the Stöber synthesis, bear a Coumarin double layer on the surface and form stable dispersions in ACN. The smaller particles were synthesized by modifying the recently developed protocol of Yokoi et al.,[108] resulting in particles functionalized with a coumarin monolayer, which form stable dispersions in water. The following photochemical investigations revealed that, analog to the photochemistry in solution, the coumarin groups on the particle surface undergo [2π+2π]-cycloaddition as well as [2π+2π]-cycloreversion. The quantum yield for the cycloreversion at 280 nm was determined to be Φ = 0.27 for both particles, confirming the hypothesis that the photochemistry of the coumarin groups on the surface is independent from particle size. Investigations on the reversibility of the reaction revealed an astonishing wavelength dependency. On the nanoparticle surface the covalently anchored coumarin moieties are in close proximity and a simultaneous dimerization and photo cleavage is observed. This coincides with a wavelength-dependent equilibrium state. The forward and the backward reaction rate become of the same order of magnitude, resulting in a change in the reaction order. The closer proximity of the coumarin moieties increased the photo dimerization rate about 2000-fold. This fast reaction on the nanoparticle surface was found to be the reason for the fact that hetero dimerization of the coumarin groups with the model drug 5FU in solution was ineffective and only negligible drug loads were obtained. To achieve a suitable amount of drug load a different approach had to be investigated, utilizing an already drug loaded functionalization agent. Taking those considerations into account, in the second part of this thesis a four step synthesis, which was improved in yield and reaction time compared to the literature, was utilized to create an ortho-nitrobenzyl compound (o-NBnC) for photochemical drug delivery. Photochemical investigations in solution revealed a single photon quantum yield of Φ = 0.27 and a two-photon cross section of σ = 2.41 GM. Those values exceeded the results reported in literature for similar compounds and are competitive to other photochemical drug delivery systems. Furthermore it was proven that two-photon induced drug delivery is possible in presence of an UV-absorbing agent. For the investigated molar ratio, only a decrease in drug delivery of 6% was observed, concluding that the UV-absorbing agent is not completely two-photon inactive, but its two-photon cross section is at least one order of magnitude lower than for the o-NBnC. Within the experimental framework no structural changes due to two-photon absorption of the UV-absorbing agent were noticed, being indispensable for a drug delivery approach. Functionalization of the o-NBnC with a methacrylic moiety enabled investigations on the drug delivery behavior from a polymeric matrix, by copolymerization with a polymer common for the potential application in IOLs, as well as the actual fabrication of model IOLs, from which the two-photon absorption induced drug delivery in presence of an UV-absorbing agent has been successfully proven. In conclusion the photochemistry of silica nanoparticles was investigated in detail, revealing interesting new properties of the [2π+2π]-cycloreversion reaction of coumarin moieties bound to a surface which could not be observed in solution, polymer matrix or SAM before. Utilizing the synthesized o-NBnC it was proven that those photoactive compounds are a suitable platform for drug delivery with potential application in IOLs. The photochemical properties are comparable to those of prior studies utilizing coumarin or tetralone hetero dimers for drug delivery, while the synthetic effort could be simplified and reduced. The problem of the o-NBnC being incompatible with free radical polymerization could be easily overcome in future investigations by transferring these promising results onto a silicon based monomer, which could be easily copolymerized without any undesired side reactions by polycondensation. Finally both approaches were successfully combined by functionalization of silica nanoparticles with o-NBnC, overcoming the limitation resulting from photochemical drug load. Further the resulting particles may be dispersed within a silicon based polymer for IOLs increasing their lower refractive index, one of the disadvantages of silicon based IOLs over methacrylic IOLs, while still preserving their drug release properties. Owing to this reason those particles are the most promising composite material, aiming at photo active IOLs for drug delivery and are well worth future research