Porphyrinoid dyes for photodynamic anticancer and antimicrobial therapy treatments
- Authors: Soy, Rodah Cheruto
- Date: 2023-10-13
- Subjects: Porphyrins , Corrole , Chlorin , Photochemotherapy , Active oxygen , Photophysics , Photosensitizing compounds
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432252 , vital:72855 , DOI 10.21504/10962/432252
- Description: The search for alternative therapies and non-toxic photosensitizer drugs that can efficiently generate cytotoxic reactive oxygen species for biomedical applications, such as in alternative photodynamic therapy (PDT) for cancer treatment and photodynamic antimicrobial chemotherapy (PACT) for drug-resistant bacteria treatment is on the rise. Nevertheless, the lack of photosensitizer dyes that absorb light strongly within the therapeutic window (620−850 nm) that can locally target the tumor and bacterial cells and generate singlet oxygen efficiently are some of the main challenges in PDT and PACT treatment. This study sought to address the challenges that impede PDT and PACT from realizing their full potential by synthesizing a series of meso-aryltetrapyrrolic photosensitizer dyes that absorb light within the therapeutic window. These include meso-tetraarylporphyrin (Por), A3-type meso-triarylcorrole (Cor), meso-tetraarylchlorin (Chl), and N-confused meso-tetraarylporphyrin (NCP) dyes with 4-thiomethylphenyl (1), thien-3-yl (2), thien-2-yl (3), 5-bromo-thien-2-yl (4), 4-methoxyphenyl (5), 3-methoxyphenyl (6), 4-hydroxyphenyl (7) and 4-hydroxy-3-methoxyphenyl (8) meso-aryl rings. Por, Cor, Chl and NCP dyes and and their Ga(III), P(V), In(III) and/or Sn(IV) complexes with 1-8, 1-4, 5-8 and 5 meso-aryl rings were studied, along with two A2B-type Ga(III) meso-triarylcorroles with pentafluorophenyl rings at the A2 positions and 3,6-di-t-butyl-9H-carbazole (9) or N-butyl-4-carbazole (10) rings at the B position that were prepared in the laboratory of Prof. Xu Liang of Jiangsu University in the People’s Republic of China. The carbazole nitrogen of 10-GaCor was quaternized at Rhodes University with ethyl iodide to form a cationic species (10-GaCor-Q) for PDT and PACT activity studies. The structures of the synthesized dyes were confirmed using UV-visible absorption and 1H NMR spectroscopy, and MALDI-TOF-mass spectrometry. 1-4-InPor In(III) porphyrins, 1-4-PVCor, 1-4-GaCor A3 PV and GaIII corrole dyes were also conjugated to gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) via sulfur-gold and sulfur-silver affinities. The successful conjugation of the dyes onto the nanoparticles to form dye-AuNP or dye-AgNP nanoassemblies was confirmed using transmission electron microscopy (TEM), energy dispersive X-ray (EDX) spectroscopy, X-ray powered diffraction (XRD), and (X-ray photon spectroscopy) XPS. The photophysicochemical, photostability, and lipophilicity properties of the dyes and their PDT and PACT activities were investigated, and the structure-property relationships were analyzed. This was accomplished by analyzing the changes in the properties of the dyes due to the meso-aryl substituents, central ions, molecular symmetry, and heavy atom effects. Time-dependent-density functional theory (TD-DFT) calculations were also used to further probe the electronic and optical spectroscopic properties of the dyes. The analysis of the photophysicochemical, photostability, and lipophilicity data for the synthesized dyes demonstrated that there are inherent structure-property relationships for the dyes studied. The TD-DFT calculations also assisted in rationalizing the observed optical spectroscopic data for the dyes. The introduction of different meso-aryl substituents resulted in minor absorption spectral changes on the parent structures of the dyes due to their inductive and mesomeric effects, while the insertion of Ga(III), In(III), and Sn(IV) electropositive metal centers resulted in marked red shifts of the B bands due to favorable interactions with the porphyrin or porphyrinoid ligand core. The lower symmetries of the corrole, chlorin, and N-confused porphyrin dyes resulted in enhanced absorption properties within the therapeutic window relative to porphyrins. The heavy atom effect from the Ga(III), In(III), and Sn(IV) central ions, the meso-aryl groups, and the external heavy atom effect from the AuNPs and AgNPs significantly reduced the fluorescence quantum yield values of the dyes resulting in high singlet oxygen quantum yields. The dye complexes also exhibited properly balanced lipophilic properties and high photostabilities. The P(V) ion of the A3 PV corrole dyes reduced the aggregation effects, enhanced cellular uptake, and lowered the lipophilicity values relative to the A3 GaIII corrole dyes. The porphyrin and porphyrinoid complexes studied exhibited relatively low in vitro dark cytotoxicity toward MCF-7 cancer cells, which is enhanced for AuNP nanoconjugates of 1-InPor, 1-3-PVCor, and 1-3-GaCor. The dyes also have low in vitro dark cytotoxicity toward planktonic and biofilm cells of S. aureus and E. coli. The complexes also exhibited favorable PDT and PACT activities toward MCF-7 cancer cells, and planktonic and biofilm S. aureus and E. coli bacteria due to their high singlet oxygen quantum yields. AuNP and AgNP nanoconjugates of 1-4-InPor, 1-4-PVCor, and 1-4-GaCor exhibited enhanced PDT and PACT activities due to the favorable synergistic effects of nanoparticles. The PDT and PACT activities of A3 PV corrole dyes and the nanoconjugates of 1-4-PVCor are slightly higher than those of A3-type GaIII corroles and their nanoconjugates due to decreased aggregation effects and enhanced PS drug uptake. The cationic 10-GaCor-Q species also exhibit favorable PDT and PACT activities in contrast to the neutral 9-10-GaCor dyes due to enhanced PS drug penetration into the tumor or bacteria cells. The complexes also exhibited high Log10 reduction values for planktonic S. aureus suggesting that the dyes are highly efficient PS dyes. The activities of the complexes toward planktonic E. coli bacteria are moderate except for 10-GaCor-Q, 2-4-PVCor-AgNPs, and 5-8-SnChl chlorins exhibiting relatively favorable activity with > 3 Log10 CFU.mL−1 values. The dyes also exhibit moderate activities toward the S. aureus and E. coli biofilm cells, which are lower than for the planktonic cells, as shown by their lower Log10 reduction values. The data demonstrate that the low symmetry corrole, chlorin, and N-confused porphyrin complexes that absorb light strongly within the therapeutic window have significantly enhanced PDT and PACT activities relative to their porphyrin analogs. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Soy, Rodah Cheruto
- Date: 2023-10-13
- Subjects: Porphyrins , Corrole , Chlorin , Photochemotherapy , Active oxygen , Photophysics , Photosensitizing compounds
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432252 , vital:72855 , DOI 10.21504/10962/432252
- Description: The search for alternative therapies and non-toxic photosensitizer drugs that can efficiently generate cytotoxic reactive oxygen species for biomedical applications, such as in alternative photodynamic therapy (PDT) for cancer treatment and photodynamic antimicrobial chemotherapy (PACT) for drug-resistant bacteria treatment is on the rise. Nevertheless, the lack of photosensitizer dyes that absorb light strongly within the therapeutic window (620−850 nm) that can locally target the tumor and bacterial cells and generate singlet oxygen efficiently are some of the main challenges in PDT and PACT treatment. This study sought to address the challenges that impede PDT and PACT from realizing their full potential by synthesizing a series of meso-aryltetrapyrrolic photosensitizer dyes that absorb light within the therapeutic window. These include meso-tetraarylporphyrin (Por), A3-type meso-triarylcorrole (Cor), meso-tetraarylchlorin (Chl), and N-confused meso-tetraarylporphyrin (NCP) dyes with 4-thiomethylphenyl (1), thien-3-yl (2), thien-2-yl (3), 5-bromo-thien-2-yl (4), 4-methoxyphenyl (5), 3-methoxyphenyl (6), 4-hydroxyphenyl (7) and 4-hydroxy-3-methoxyphenyl (8) meso-aryl rings. Por, Cor, Chl and NCP dyes and and their Ga(III), P(V), In(III) and/or Sn(IV) complexes with 1-8, 1-4, 5-8 and 5 meso-aryl rings were studied, along with two A2B-type Ga(III) meso-triarylcorroles with pentafluorophenyl rings at the A2 positions and 3,6-di-t-butyl-9H-carbazole (9) or N-butyl-4-carbazole (10) rings at the B position that were prepared in the laboratory of Prof. Xu Liang of Jiangsu University in the People’s Republic of China. The carbazole nitrogen of 10-GaCor was quaternized at Rhodes University with ethyl iodide to form a cationic species (10-GaCor-Q) for PDT and PACT activity studies. The structures of the synthesized dyes were confirmed using UV-visible absorption and 1H NMR spectroscopy, and MALDI-TOF-mass spectrometry. 1-4-InPor In(III) porphyrins, 1-4-PVCor, 1-4-GaCor A3 PV and GaIII corrole dyes were also conjugated to gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) via sulfur-gold and sulfur-silver affinities. The successful conjugation of the dyes onto the nanoparticles to form dye-AuNP or dye-AgNP nanoassemblies was confirmed using transmission electron microscopy (TEM), energy dispersive X-ray (EDX) spectroscopy, X-ray powered diffraction (XRD), and (X-ray photon spectroscopy) XPS. The photophysicochemical, photostability, and lipophilicity properties of the dyes and their PDT and PACT activities were investigated, and the structure-property relationships were analyzed. This was accomplished by analyzing the changes in the properties of the dyes due to the meso-aryl substituents, central ions, molecular symmetry, and heavy atom effects. Time-dependent-density functional theory (TD-DFT) calculations were also used to further probe the electronic and optical spectroscopic properties of the dyes. The analysis of the photophysicochemical, photostability, and lipophilicity data for the synthesized dyes demonstrated that there are inherent structure-property relationships for the dyes studied. The TD-DFT calculations also assisted in rationalizing the observed optical spectroscopic data for the dyes. The introduction of different meso-aryl substituents resulted in minor absorption spectral changes on the parent structures of the dyes due to their inductive and mesomeric effects, while the insertion of Ga(III), In(III), and Sn(IV) electropositive metal centers resulted in marked red shifts of the B bands due to favorable interactions with the porphyrin or porphyrinoid ligand core. The lower symmetries of the corrole, chlorin, and N-confused porphyrin dyes resulted in enhanced absorption properties within the therapeutic window relative to porphyrins. The heavy atom effect from the Ga(III), In(III), and Sn(IV) central ions, the meso-aryl groups, and the external heavy atom effect from the AuNPs and AgNPs significantly reduced the fluorescence quantum yield values of the dyes resulting in high singlet oxygen quantum yields. The dye complexes also exhibited properly balanced lipophilic properties and high photostabilities. The P(V) ion of the A3 PV corrole dyes reduced the aggregation effects, enhanced cellular uptake, and lowered the lipophilicity values relative to the A3 GaIII corrole dyes. The porphyrin and porphyrinoid complexes studied exhibited relatively low in vitro dark cytotoxicity toward MCF-7 cancer cells, which is enhanced for AuNP nanoconjugates of 1-InPor, 1-3-PVCor, and 1-3-GaCor. The dyes also have low in vitro dark cytotoxicity toward planktonic and biofilm cells of S. aureus and E. coli. The complexes also exhibited favorable PDT and PACT activities toward MCF-7 cancer cells, and planktonic and biofilm S. aureus and E. coli bacteria due to their high singlet oxygen quantum yields. AuNP and AgNP nanoconjugates of 1-4-InPor, 1-4-PVCor, and 1-4-GaCor exhibited enhanced PDT and PACT activities due to the favorable synergistic effects of nanoparticles. The PDT and PACT activities of A3 PV corrole dyes and the nanoconjugates of 1-4-PVCor are slightly higher than those of A3-type GaIII corroles and their nanoconjugates due to decreased aggregation effects and enhanced PS drug uptake. The cationic 10-GaCor-Q species also exhibit favorable PDT and PACT activities in contrast to the neutral 9-10-GaCor dyes due to enhanced PS drug penetration into the tumor or bacteria cells. The complexes also exhibited high Log10 reduction values for planktonic S. aureus suggesting that the dyes are highly efficient PS dyes. The activities of the complexes toward planktonic E. coli bacteria are moderate except for 10-GaCor-Q, 2-4-PVCor-AgNPs, and 5-8-SnChl chlorins exhibiting relatively favorable activity with > 3 Log10 CFU.mL−1 values. The dyes also exhibit moderate activities toward the S. aureus and E. coli biofilm cells, which are lower than for the planktonic cells, as shown by their lower Log10 reduction values. The data demonstrate that the low symmetry corrole, chlorin, and N-confused porphyrin complexes that absorb light strongly within the therapeutic window have significantly enhanced PDT and PACT activities relative to their porphyrin analogs. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
The photodynamic therapeutic activities and optical limiting properties of metalated asymmetric porphyrins and corroles
- Authors: Burgess, Kristen Paige
- Date: 2023-10-13
- Subjects: Porphyrins , Corrole , Photochemotherapy , Anti-infective agents , Nonlinear optics , Z-scan technique , Active oxygen , Time-dependent density functional theory , Chemical synthesis
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424490 , vital:72158
- Description: Cancer is a devastating disease that is a leading cause of death worldwide. Despite the available cancer treatments, there is a significant need to improve the therapeutic approach towards this disease. Photodynamic therapy (PDT) is an alternative approach for treating cancer, which requires a photosensitiser, molecular oxygen and light. Although some porphyrin-based derivatives have been approved by the United States Food and Drug Administration (FDA) and other similar agencies elsewhere for photodynamic therapy, their relatively poor photophysicochemical properties mean that there is an ongoing need for new photosensitiser dyes. Singlet oxygen photosensitiser dyes can also be used to treat bacteria that develop antimicrobial resistance in the context of photodynamic antimicrobial chemotherapy (PACT). The main aim of this study was to synthesise and characterise a series of porphyrin dyes with 4-quinolinyl, thien-2-yl and 4-bromo-thien-2-yl meso-aryl groups and their Sn(IV) and In(III) complexes, as well as their corrole analogues. Corroles are contracted macrocycles that have interesting optical properties. The corroles selected for study were found to be difficult to synthesise and purify and had unfavourable photophysicochemical properties and were thus omitted from the PDT and PACT biological applications within this thesis. High- and low-symmetry A4 and ABAB type meso-tetraarylporphyrins porphyrins were synthesised to improve the photophysicochemical properties of the photosensitisers; the utility of these dyes as photosensitisers was studied against the MCF-7 breast cancer cell line for PDT and against Staphylococcus aureus and Escherichia coli for PACT. The thienyl-2-yl rings were introduced to red shift the lowest energy Q band towards the phototherapeutic window, while quaternisation of the nitrogen and sulfur atoms of the 4-quinolinyl and thien-2-yl rings to introduce a cationic nature was explored to improve the bioavailability of the drugs and uptake into the target cell walls for improved efficacy. Heavy Sn(IV) and In(III) central metal ions were introduced to enhance the singlet oxygen quantum yields and limit aggregation through axial ligation. The bromine atoms of the 4-bromo-thien-2-yl meso-aryl rings were also introduced to enhance the singlet oxygen quantum yields of the dyes. Furthermore, the utility of the porphyrin and corrole molecules for optical limiting properties to limit laser radiation to protect optical devices, including eyes, was explored by the z-scan technique. One of the dyes studied, Sn(IV) tetrathien-2-ylporphyrin, that exhibited the most favourable reverse saturable absorbance (RSA) response was embedded into a poly(bisphenol carbonate A) polymer thin film to further explore its suitability for practical applications. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Burgess, Kristen Paige
- Date: 2023-10-13
- Subjects: Porphyrins , Corrole , Photochemotherapy , Anti-infective agents , Nonlinear optics , Z-scan technique , Active oxygen , Time-dependent density functional theory , Chemical synthesis
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424490 , vital:72158
- Description: Cancer is a devastating disease that is a leading cause of death worldwide. Despite the available cancer treatments, there is a significant need to improve the therapeutic approach towards this disease. Photodynamic therapy (PDT) is an alternative approach for treating cancer, which requires a photosensitiser, molecular oxygen and light. Although some porphyrin-based derivatives have been approved by the United States Food and Drug Administration (FDA) and other similar agencies elsewhere for photodynamic therapy, their relatively poor photophysicochemical properties mean that there is an ongoing need for new photosensitiser dyes. Singlet oxygen photosensitiser dyes can also be used to treat bacteria that develop antimicrobial resistance in the context of photodynamic antimicrobial chemotherapy (PACT). The main aim of this study was to synthesise and characterise a series of porphyrin dyes with 4-quinolinyl, thien-2-yl and 4-bromo-thien-2-yl meso-aryl groups and their Sn(IV) and In(III) complexes, as well as their corrole analogues. Corroles are contracted macrocycles that have interesting optical properties. The corroles selected for study were found to be difficult to synthesise and purify and had unfavourable photophysicochemical properties and were thus omitted from the PDT and PACT biological applications within this thesis. High- and low-symmetry A4 and ABAB type meso-tetraarylporphyrins porphyrins were synthesised to improve the photophysicochemical properties of the photosensitisers; the utility of these dyes as photosensitisers was studied against the MCF-7 breast cancer cell line for PDT and against Staphylococcus aureus and Escherichia coli for PACT. The thienyl-2-yl rings were introduced to red shift the lowest energy Q band towards the phototherapeutic window, while quaternisation of the nitrogen and sulfur atoms of the 4-quinolinyl and thien-2-yl rings to introduce a cationic nature was explored to improve the bioavailability of the drugs and uptake into the target cell walls for improved efficacy. Heavy Sn(IV) and In(III) central metal ions were introduced to enhance the singlet oxygen quantum yields and limit aggregation through axial ligation. The bromine atoms of the 4-bromo-thien-2-yl meso-aryl rings were also introduced to enhance the singlet oxygen quantum yields of the dyes. Furthermore, the utility of the porphyrin and corrole molecules for optical limiting properties to limit laser radiation to protect optical devices, including eyes, was explored by the z-scan technique. One of the dyes studied, Sn(IV) tetrathien-2-ylporphyrin, that exhibited the most favourable reverse saturable absorbance (RSA) response was embedded into a poly(bisphenol carbonate A) polymer thin film to further explore its suitability for practical applications. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
Dual and targeted photodynamic therapy ablation of bacterial and cancer cells using phthalocyanines and porphyrins in the presence of carbon-based nanomaterials
- Authors: Openda, Yolande Ikala
- Date: 2022-10-14
- Subjects: Phthalocyanines , Porphyrins , Active oxygen , Biofilms , Breast Cancer Treatment , Nanostructured materials , Combination therapy , Photochemotherapy
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365945 , vital:65804 , DOI https://doi.org/10.21504/10962//365946
- Description: Phthalocyanines (Pcs) and porphyrins bearing substituents that possess antibacterial/anticancer properties are used as photosensitizers (PS) for the first time in the work. For targeting specificity and improved photoactivity, the PSs were afterward functionalized with carbon nanomaterials such as graphene quantum dots (GQDs) and detonation nanodiamonds (DNDs) via covalent conjugation (amide or ester bonds) or by non-covalent conjugation (π-π stacking and electrostatic interactions). Furthermore, the PSs-DNDs nanoconjugates were conjugated to either chitosan-capped silver nanoparticles (CSAg) via amide bonds or to the bare silver nanoparticles (Ag NPs) using the silver- nitrogen affinity. The as-synthesized nanoconjugates were also fully characterized by spectroscopic and microscopic methods together with thermal analysis. The potential photocytotoxicity of the complexes alone and their nanoconjugates against S. aureus and/or E. coli planktonic and biofilm cultures has been evaluated in vitro. Compared to the non- quaternized PSs, the cationic analogs exhibited a higher photodynamic inactivation against the planktonic cells with log10 reduction values above 9 in the viable count using a concentration of ca. 1.25 μM following 30 min exposure to light (Light dose: 943 J/cm2 for Pcs and 250 mW/cm2 for porphyrins). Whereas, at a concentration of ca. 100 μM the cationic PSs showed complete eradication of biofilms upon 30 min exposure to light. As a result of conjugation to carbon-based nanomaterials and silver nanoparticles, the compounds proved to be more effective as they exhibited stronger antibacterial and anti-biofilm activities on the multi-drug resistant bacteria strains due to synergetic effect, compared to PSs alone. This suggests that the newly prepared nanohybrids (PS concentration ca. 100 μM) could be used as potential antimicrobial agents in the treatment of biofilm-related infections. The target nanoconjugates showed all the advantages of two different groups existing on a single entity. In light of the potential advantages of combined chemotherapy and photodynamic antimicrobial chemotherapy (PACT), this work reports for the first time the use of PACT-ciprofloxacin (CIP) dual therapy using selected indium quaternized PSs which showed higher photoactivity with complete eradication of both Gram-positive and Gram-negative bacteria biofilms at concentrations of 8 μM of PS versus 2 μg/mL of the antibiotic following 15 min irradiation time (light dose: 471 J/cm2 for Pcs and fluence: 250 mW/cm2 for porphyrins) on S. aureus. Whereas the total killing of E. coli was obtained when combining 8 or 16 μM of PS combined with 4 μg/mL of CIP. The combined treatment resulted in the complete eradication of the matured biofilms with the highest log10 reduction values of 7.05 and 7.20 on S. aureus and E. coli, respectively. Used as a model, positively charged dimethylamino-chalcone Pcs also exhibited interesting photodynamic therapy (PDT) activity against MCF-7 cancer cells giving IC50 values of 17.9 and 7.4 μM, respectively following 15 min irradiation. Additionally, the TD-B3LYP/LanL2DZ calculations were run on the dimethylaminophenyl- porphyrins to compare the singlet excitation energies of quaternized and non-quaternized porphyrins in vacuo. the study shows excellent agreement between time-dependent density- functional theory (TD-DFT) exciting energies and the experimental S1>S0 excitation energies. The small deviation observed between the calculated and experimental spectra arises from the solvent effect. The excitation energies observed in these UV-Vis spectra mostly originated from electron promotion between the highest occupied molecular orbital (HOMO) for the less intense band and the HOMO-1 for the most intense band of the ground states to the lower unoccupied molecular orbital (LUMO) of the excited states. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
- Authors: Openda, Yolande Ikala
- Date: 2022-10-14
- Subjects: Phthalocyanines , Porphyrins , Active oxygen , Biofilms , Breast Cancer Treatment , Nanostructured materials , Combination therapy , Photochemotherapy
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365945 , vital:65804 , DOI https://doi.org/10.21504/10962//365946
- Description: Phthalocyanines (Pcs) and porphyrins bearing substituents that possess antibacterial/anticancer properties are used as photosensitizers (PS) for the first time in the work. For targeting specificity and improved photoactivity, the PSs were afterward functionalized with carbon nanomaterials such as graphene quantum dots (GQDs) and detonation nanodiamonds (DNDs) via covalent conjugation (amide or ester bonds) or by non-covalent conjugation (π-π stacking and electrostatic interactions). Furthermore, the PSs-DNDs nanoconjugates were conjugated to either chitosan-capped silver nanoparticles (CSAg) via amide bonds or to the bare silver nanoparticles (Ag NPs) using the silver- nitrogen affinity. The as-synthesized nanoconjugates were also fully characterized by spectroscopic and microscopic methods together with thermal analysis. The potential photocytotoxicity of the complexes alone and their nanoconjugates against S. aureus and/or E. coli planktonic and biofilm cultures has been evaluated in vitro. Compared to the non- quaternized PSs, the cationic analogs exhibited a higher photodynamic inactivation against the planktonic cells with log10 reduction values above 9 in the viable count using a concentration of ca. 1.25 μM following 30 min exposure to light (Light dose: 943 J/cm2 for Pcs and 250 mW/cm2 for porphyrins). Whereas, at a concentration of ca. 100 μM the cationic PSs showed complete eradication of biofilms upon 30 min exposure to light. As a result of conjugation to carbon-based nanomaterials and silver nanoparticles, the compounds proved to be more effective as they exhibited stronger antibacterial and anti-biofilm activities on the multi-drug resistant bacteria strains due to synergetic effect, compared to PSs alone. This suggests that the newly prepared nanohybrids (PS concentration ca. 100 μM) could be used as potential antimicrobial agents in the treatment of biofilm-related infections. The target nanoconjugates showed all the advantages of two different groups existing on a single entity. In light of the potential advantages of combined chemotherapy and photodynamic antimicrobial chemotherapy (PACT), this work reports for the first time the use of PACT-ciprofloxacin (CIP) dual therapy using selected indium quaternized PSs which showed higher photoactivity with complete eradication of both Gram-positive and Gram-negative bacteria biofilms at concentrations of 8 μM of PS versus 2 μg/mL of the antibiotic following 15 min irradiation time (light dose: 471 J/cm2 for Pcs and fluence: 250 mW/cm2 for porphyrins) on S. aureus. Whereas the total killing of E. coli was obtained when combining 8 or 16 μM of PS combined with 4 μg/mL of CIP. The combined treatment resulted in the complete eradication of the matured biofilms with the highest log10 reduction values of 7.05 and 7.20 on S. aureus and E. coli, respectively. Used as a model, positively charged dimethylamino-chalcone Pcs also exhibited interesting photodynamic therapy (PDT) activity against MCF-7 cancer cells giving IC50 values of 17.9 and 7.4 μM, respectively following 15 min irradiation. Additionally, the TD-B3LYP/LanL2DZ calculations were run on the dimethylaminophenyl- porphyrins to compare the singlet excitation energies of quaternized and non-quaternized porphyrins in vacuo. the study shows excellent agreement between time-dependent density- functional theory (TD-DFT) exciting energies and the experimental S1>S0 excitation energies. The small deviation observed between the calculated and experimental spectra arises from the solvent effect. The excitation energies observed in these UV-Vis spectra mostly originated from electron promotion between the highest occupied molecular orbital (HOMO) for the less intense band and the HOMO-1 for the most intense band of the ground states to the lower unoccupied molecular orbital (LUMO) of the excited states. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
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