Porphyrins, chlorins, and their peptoid conjugates: multifunctional bio-inspired complexes

Abstract

Porphyrins are natural macrocyclic pigments having unique structural and photophysical properties. Nature utilizes porphyrins and porphyrin-protein complexes that perform multifunctional roles in biological processes. The porphyrins are precisely controlled by an adjacent protein matrix, enabling efficient redox catalysis, light-harvesting, energy transfer, and control level of reactive oxygen species (ROS). Continuous efforts have been made to understand the design principles of natural complexes and construct various types of bio-inspired complexes by introducing nature's strategies. At the molecular level, the utility and efficiency of porphyrins and porphyrin-protein complexes have been studied by directly modifying the structure of porphyrins or controlling the chiral environment of porphyrins with scaffolding materials. The applications of bio-inspired complexes have been reported, such as redox catalysts, artificial light-harvesting complexes (LHCs), photoresponsive sensors, and photodynamic therapy (PDT) agents. The present work suggests multifunctional bio-inspired complexes using porphyrins and peptoids. In chapter 1, porphyrins and peptoids were described from the structural characteristics, physicochemical properties, and examples of applications. Porphyrins have been studied as pigments and catalysts due to the advantages of the high extinction coefficients and formation of various metal complexes. Peptoids, N-substituted glycine polymers, are versatile molecular platforms constructed in a sequence-specific manner. The structural and functional advantages of peptoids are utilized in various applications such as materials, therapeutics, and scaffolds. In the same section, previous works on porphyrin-peptoid conjugates (PPCs) were introduced, studied as multifunctional biomimetic complexes. In chapter 2, we modified the core structure of porphyrins for building unusual metal complexes. Structural modifications of porphyrins provide a ligand with distinctive physicochemical properties compared to conventional porphyrins. A set of heteroatom-containing porphyrins and their metal complexes was synthesized, and their electrocatalytic activity was screened. The nickel complex of 21-oxatetraphenylporphyrin (Ni-N3O-TPP) showed promising catalytic activity in electrochemical CO2 reduction reaction and was characterized using single-crystal X-ray crystallography, NMR spectroscopy, and UV-vis absorption spectroscopy. It was confirmed that Ni-N3O-TPP has paramagnetic Ni(II) species, which are rarely found in typical Ni-N4-TPP. Furthermore, we demonstrated that the unusual Ni oxidation states were stabilized by the distorted D4h symmetry of heteroatom-containing porphyrins. In chapter 3, we constructed a novel artificial LHC by displaying flavone and porphyrin on a peptoid scaffold. For an efficient light-harvesting system, it is important to introduce different pigments to absorb a broad spectrum of light and control the orientations of each pigment to transfer the absorbed energy efficiently. The flavone-porphyrin-peptoid conjugate (FPPC) was synthesized through a C-C linkage between peptoid and pigment. Spectroscopic analyses indicated that the FPPC absorbs light from UV to the visible region (280–700 nm) and undergoes conformational switching from helix to loop depending on the solvent conditions. Furthermore, it was demonstrated that the intramolecular energy transfer from flavone to porphyrin was affected, resulting in greater efficiency in the helix than the loop conformation of FPPC. In chapters 4 and 5, we developed new PDT agents with photosensitizers and antimicrobial peptoids. Photoresponsive electron and energy transfer are accompanied by ROS generation, which could oxidize the biological components. Researchers have applied the features as a strategy to kill the target cells and pathogens with spatiotemporal advantages. In chapter 4, we prepared multitargeting antimicrobial PDT (aPDT) agents by combining photosensitizers, linkers, and peptoids. A library of photosensitizer-peptoid conjugates (PsPCs) was synthesized, and a structure-antimicrobial activity relationship was evaluated against E. coli. The selected PsPC, consisting of weakly helical peptoids, glycine linkers, and positively charged porphyrins, produced singlet oxygen upon the irradiation under blue light (420 nm), resulting in damage to the bacterial membrane and plasmid DNA. In chapter 5, we synthesized chlorin e6-peptoid conjugates (Ce6PCs) as dual antimicrobial and anticancer agents. The results of antimicrobial activity screening suggested the optimal combination of conjugate consisted of chlorin e6, PEG linker, and guanidine-containing helical peptoids. The red light (655 nm) irradiation of Ce6PC generated singlet oxygen, effectively killing various bacterial strains and cancer cells. A mechanism study with confocal laser scanning microscopy and flow cytometry indicated that the compounds entered the target cells, then generated singlet oxygen, which induced apoptotic cell death.