Synthesis of Poly(oxanorbornene) Derivatives Containing Phthalocyanine and Investigation of Their Antimicrobial Photodynamic Properties
Thesis Type: Doctorate
Institution Of The Thesis: Yildiz Technical University, Faculty of Arts & Science, Department of Chemistry, Turkey
Approval Date: 2022
Thesis Language: English
Student: Erem Ahmetali
Supervisor: Muhammet Kasım Şener
Open Archive Collection: AVESIS Open Access Collection
Abstract:Bacterial infection is a serious problem in today's world. Excessive using of traditional drugs such as antibiotics have given rise to the developing of resistance mechanisms of bacteria to these drugs. Thus, the search for potential agents that can inactivate bacteria is increasing day by day. Antibacterial polymers have taken attention because they successfully mimic antibacterial peptides and can be synthesized quickly and on purpose in the laboratory environment. Their mechanism of action originates the electrostatic interaction between the negatively charged cell membrane of the bacteria and the cationic polymer, and the hydrophobic interaction between the tail groups of the phospholipids in the cell wall and the hydrophobic groups on the polymer. PONs are polymeric structures which are synthesized by the ROMP method with the help of various metal complexes. They have significant place among the stars of the antibacterial polymers thanks to being easily changed their substituents and controlled of their parameters such as molecular weight and charge density. On the other hand, aPDT is an important method based on ROS formation on inactivation of bacteria. When the molecules called PS interacts with light of the appropriate wavelength, it can achieve intersystem crossing and produce ROS. Thus, they lead to protein dysfunction, DNA damage, cell membrane disruption and provide photoinactivation of bacteria. Pcs are among the most used PSs with the convenient absorption wavelength, long triplet lifetime, and high ROS generation. In addition, Pcs can carry hydrophobic, hydrophilic or cationic groups in their many positions that can contribute to the struggle against bacteria. Within the scope of this thesis, two antimicrobial agents (cationic poly(oxanorbornene) and photosensitizer zinc phthalocyanine), each with a different antimicrobial mechanism, have combined in a single molecule and the antibacterial properties of sytnhesized polymers containing these components in different ratios were examined comparatively. In the first part of the thesis, the synthesis of PONs containing tert-butyl substituted ZnPc in their side chains was aimed. For this purpose, firstly, the "Polymer Bound Precursor" method was used. Oxanorbornene substituted phthalonitrile compound was synthesized (M1), this compound was polymerized by ROMP method (P1) and P1 was reacted with excess amount of tert-butyl substituted phthalonitrile compound for the synthesis of phthalocyanine-containing polymer (P2). However, although the monomer and the starting polymer were successfully synthesized and characterized (M1 and P1), the characteristic polymer peak could not be seen in the 1H NMR of the final product and it was understood that the polymer backbone could not be protected during phthalocyanine formation reaction (P2). Therefore, it was decided to change the synthesis strategy and use the "Phthalocyanine-Containing Monomer" method. For this purpose, oxanorbornene monomer (M2) containing tert-butyl substituted ZnPc was synthesized for the first time, and other oxanorbornene monomers (M3, M4) containing phosphonium groups were synthesized in accordance with the literature. Then, the synthesis and characterization of homopolymer (P3) containing only M2 monomer and copolymers (P4-P7) containing M2, M3 and M4 monomers in different ratios were carried out. Photophysical and photochemical parameters of all polymers (P3-P7) (first series) were measured, and aPDT activities against gram-negative E. coli and gram-positive S. aureus bacteria were investigated. In addition, the bacterial polymer interaction has been demonstrated by scanning electron microscopy. In the second part of the thesis, in order to increase biocompatibility, oxanorbornene monomer (M5) containing TEGMM substituted ZnPc in its side chains instead of tert-butyl groups was synthesized, and then the synthesis and characterization of its homopolymer (P8) and copolymers (P9-P11) containing M3 and M5 monomers in different ratios were carried out. Photophysical and photochemical parameters of all polymers (P8-P11) (second series) were investigated. Unlike the first series, aPDT activities were investigated against B. subtilis as gram-positive bacteria and E. coli as gram-negative bacteria, and the bacterial-polymer interaction was proved with the help of fluorescence microscopy. Keywords: poly(oxanorbornene), ring-opening metathesis polymerization, phthalocyanine, antimicrobial photodynamic therapy, macromolecular photosensitizer, singlet oxygen generation