Light-Activated Antimicrobial Materials Based on Perylene Imides and Phthalocyanines

Abstract

In the era of globalization, the spread of infectious diseases is a serious concern. The emergence of drug resistant bacteria and healthcare associated infections in particular, poses a great danger to human health. Self-disinfecting surfaces may play a significant role in controlling the spread of pathogenic diseases. Photodynamic antimicrobial chemotherapy (PACT) can be a very efficient way of inactivation of drug resistant bacteria and biofilms. However, making a self-disinfecting surface based on PACT principles requires novel photosensitizers, which can efficiently generate reactive oxygen species, and are stable and accessible. In this thesis, attempts are undertaken to synthesize novel photosensitizers based on peryleneimides and phthalocyanines. We propose a novel efficient method for the direct and regioselective amination of peryleneimides. The substitution occurs with high yields exclusively at 1,6- and 7,12-positions of the bay region of perylenediimide and perylenemonoimide diester. We also report the synthesis of novel cationic peryleneimides, which can be potentially used as photosensitizers in PACT. Phthalocyanines are known to be efficient photosensitizers. In this thesis we present the synthesis of novel pyridinyl-substituted phthalocyanine and its tetracationic derivatives. As a unique synthetic approach, pyridinyl groups are connected to α-phthalo positions of the macrocycle via direct C-C bonds. Prototype self-disinfecting materials are prepared by impregnating filter paper with the synthesized dyes. Binding of the dyes occurs via electrostatic interactions and does not require any special chemical modification. A fast and simple setup for the evaluation of antimicrobial efficacies of dyed papers is proposed. The setup employs bioluminescent bacteria and allows for a fast screening of a large number of dyes. According to the screening results, tetracationic phthalocyanines are the most efficient antimicrobial photosensitizers. The antimicrobial efficacies of phthalocyanine derivatives are evaluated quantitatively with the help of colony forming unit (CFU) counting method. The papers impregnated with as little as 80 mg/m2 of cationic zinc phthalocyanine exhibit 2.7 and 3.4 log reduction in CFU against Escherichia coli (E. coli) and Acinetobacter baylyi (A. baylyi), respectively after illumination with the light intensity 18 mW/cm2 in a solar simulator. Similar antimicrobial efficacies are achieved under illumination with consumer light emitting diode (LED) lights. Phthalocyanine-impregnated papers show very good stability. Incubation of the dye-impregnated papers in phosphatebuffered saline demonstrates superior binding ability of phthalocyanine, with basically no detectable leaching of the dye. Photostability of the dyed paper is also high. Continuous illumination with 42 mW/cm2 LED light for 64 h decreases the absorptance of dyed papers only by 10%.