Liposomal formulations of metallophthalocyanines-nanoparticle conjugates for hypoxic photodynamic therapy and photoelectrocatalysis
- Authors: Nwahara, Nnamdi Ugochinyere
- Date: 2023-10-13
- Subjects: Liposomes , Photochemotherapy , Phthalocyanines , Photoelectrochemistry , Cancer Treatment
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432159 , vital:72847 , DOI 10.21504/10962/432159
- Description: This thesis investigates new strategies to enhance the efficacy of photodynamic therapy (PDT) under hypoxic conditions using in-vitro cancer cell models. Phthalocyanines are chosen as viable photosensitizer complexes owing to the favourable absorption properties. To this end, this thesis reports on the synthesis and photophysicochemical properties of various zinc and silicon phthalocyanines (Pcs). To afford better photophysicochemical properties, the reported Pcs were conjugated to different nanoparticles (NPs) through chemisorption as well as amide bond formation to yield Pc-NP conjugates. All the studied Pcs showed relatively high triplet and singlet oxygen quantum yields corresponding to their low fluorescence quantum yields. The various mechanisms for hypoxic response include (i) Type I PDT, (ii) PDT coupled with oxygen-independent therapy and (iii) in-situ oxygen generation using catalase-mimicking nanoparticles which serve to supplement in-vitro oxygen concentrations using MPcs or MPc-NPs conjugates. The mechanisms were assessed using electrochemical, computational techniques and catalase mimicking experiments. The as-synthesised Pcs or Pc-NPs were subjected to liposomal loading before PDT studies which led to enhanced biocompatibility and aqueous dispersity. The in-vitro dark cytotoxicity tests and photodynamic therapy activities of the fabricated Pc-liposomes and Pc-NPs-liposomes on either Henrietta Lacks (HeLa) or Michigan Cancer Foundation-7 (MCF-7) breast cancer cells are presented herein. This work further showed that folic acid (FA) functionalization of liposomes could be exploited for active drug delivery and herein led to an almost 3-fold increase in drug uptake vs non-FA functionalised liposomes in accordance with folate receptor (FR) expression levels between HeLa and MCF-7 cells. The in-vitro dark cytotoxicity and photodynamic therapy of selected Pc complexes and conjugates were accessed using MCF-7 and HeLa cell lines. The various mechanisms; (i) Type I PDT, (ii) PDT coupled with oxygen -independent therapy and (iii) in-situ oxygen generation using catalase-mimicking nanoparticles were shown to adequately compensate for the otherwise attenuation of PDT activity under hypoxia. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
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The development of ionic zinc(II) phthalocyanines for sono-photodynamic combination therapy of cervical and breast cancer
- Authors: Nene, Lindokuhle Cindy
- Date: 2023-03-31
- Subjects: Phthalocyanines , Sonochemistry , Photochemotherapy , Cancer Treatment
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/422565 , vital:71958 , DOI 10.21504/10962/422565
- Description: This study focuses on the development of the sono-photodynamic combination therapy (SPDT) activity of phthalocyanines (Pcs) on the cervical and breast cancer cell lines in vitro. The SPDT technique utilizes ultrasound in combination with light to elicit cytotoxic effects for cancer eradication. In this work, a selection of tetra-peripherally substituted Zn(II) cationic and zwitterionic Pcs were prepared. The photophysical parameters of the Pcs were determined including their fluorescence behaviours and efficiency of the triplet excited state population. The effects of the ultrasonic parameters (frequencies (MHz) and power (W.cm-2)) on the stability of the Pcs were evaluated. Four parameters were evaluated: Par I (1 MHz: 1 W.cm-2), Par II (1 MHz: 2 W.cm-2), Par III (3 MHz: 1 W.cm-2) and Par IV (3 MHz: 2 W.cm-2). The stability of the Pcs reduced with the increase in the ultrasonic power (for Par II and Par IV). The Par I showed the least degradation compared to the other parameters and was therefore used for the SPDT treatments. The sonodynamic (SDT), photodynamic (PDT) therapy activities of the Pcs were studied and compared to their SPDT efficacies. The Pcs showed reactive oxygen species generation during the SDT, PDT and SPDT treatments. For the SDT and SPDT, singlet oxygen (1O2) and hydroxyl radicals (•OH) were detected. For PDT, only the 1O2 were detected. The cell cytotoxicity studies for the Pcs showed relatively higher therapeutic efficacies for the SDT treatments compared to the PDT treatments, where the SPDT showed higher therapeutic efficacies compared to both the SDT and PDT monotreatments on both the cell lines in vitro. Overall, the combination treatments were better compared to the monotreatments. The activities of the Pcs were compared by their differences in structures, including the type of R-group, type of quaternizing agent and type of nanoparticle conjugates. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
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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
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Singlet oxygen and optical limiting applications of BODIPYs and other molecular dyes
- Authors: May, Aviwe Khanya
- Date: 2022-04-08
- Subjects: Dyes and dyeing Chemistry , Phthalocyanines , Photochemotherapy , Active oxygen , Nonlinear optics , Time-dependent density functional theory , Photochemistry
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/294618 , vital:57238 , DOI 10.21504/10962/294620
- Description: A series of structurally diverse novel and previously synthesized BODIPY core dyes are synthesized and characterized in this thesis. These BODIPYs were synthesized using 2-methylpyrrole, 2-ethylpyrrole, 2,4-dimethylpyrrole and 3-ethyl-2,4-dimethylpyrrole as the starting pyrroles. The combination of different pyrroles with the same aldehyde results in BODIPY core dyes that are structural analogues. These core dyes were used as precursors to synthesise halogenated BODIPYs and novel styrylBODIPY dyes, which were successfully characterized using FT-IR and 1H NMR spectroscopy. The halogenated BODIPY core dyes and the styrylBODIPY dyes were also characterized using MALDI-TOF mass spectrometry. The introduction of heavy atoms on the BODIPY core leads to a red shift of the main spectral. In the presence of styryl groups, the main spectral band red shifts to the far red end of the visible region. As expected, the halogenated BODIPY core dyes also had moderate singlet oxygen quantum yields. These halogenated core dyes were found to be suitable as photosensitizers as all the dyes reduced bacterial viability to below 50% during photodynamic antimicrobial chemotherapy (PACT) studies against Staphylococcus aureus. The structure-property relationships studied demonstrate that the presence of protons rather than methyls at the 1,7-positions or iodines at the 2,6-positions results in more favorable PACT activity. This is likely to be related to the greater ability of the meso-aryl to rotate into the plane of the dipyrromethene ligand and suggests that there should be a stronger focus on dyes of this type in future studies in this field. During nonlinear optical (NLO) studies, all the styrylBODIPYs exhibited favorable reverse saturable absorption (RSA) responses. In the absence of methyl groups at the 1,7-positions, the meso-aryl ring lies closer to the π-system of the BODIPY core, enhancing donor (D)–π–acceptor (A) properties and resulting in slightly enhanced optical limiting (OL) parameters. Additionally, there is no evidence that the introduction of heavy atoms at the 2,6-positions significantly enhances OL properties. In a similar manner, alkyl substituents at these positions also do not significantly enhance OL properties; this was studied for the first time using 15 with ethyl groups at the 2,6-positions. The combination of z-scan data and transient spectroscopy for 16 demonstrated that the main mechanism responsible for the NLO properties of nonhalogenated BODIPY dyes is one-photon absorption from the ground state followed by ESA in the singlet manifold. From the NLO studies of 25, OL parameters of 1,3,5-tristyrylBODIPY dyes were found to be similar in magnitude to properties of distyrylBODIPY dyes, but to have less favorable optical properties for OL applications. The OL properties of scandium phthalocyanines were assessed for the first time, since the Sc(III) ion, unusually for a first row transition metal ion, is known to readily form sandwich complexes. The presence of a Sc(III) ion does not significantly enhance the OL properties of phthalocyanines relative to those of rare earth metal ions that also form complexes of this type. Because BODIPYs and phthalocyanines typically absorb significantly in the visible region, transparent PBC polymer thin films of disilane-bridged compounds with minimal absorption in this region were studied and exhibited an excellent RSA response. These compounds may be useful in the design of OL materials that can protect the human eye. The optimized geometries and spectroscopic properties of selected BODIPYs were studied. As expected, the presence of bromine, iodine, ethyl and styryl groups at different positions of the BODIPY core leads to a narrowing of the HOMO–LUMO band gap, which results in a red-shift of the main spectral band. Partial atomic charges have also been calculated for some of the styrylBODIPY dyes studied for application in OL, and electrostatic potential energy maps were also visualized to better assess how the dipole moment of BODIPY dyes can be modulated since this can affect the OL properties. For all the BODIPYs studied, the electronegativity of the atoms present influences charge distribution on the BODIPY structure. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
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The construction of phthalocyanine- carbon nanoparticle conjugates for applications in photodynamic therapy and non-linear optics
- Authors: Matshitse, Refilwe Manyama Stephina
- Date: 2021-10-29
- Subjects: Phthalocyanines , Nanodiamonds , Photochemotherapy , Nonlinear optics , Quantum dots
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/188397 , vital:44750 , 10.21504/10962/188397
- Description: The syntheses and characterization of symmetric and asymmetric Pcs functionalized at the peripheral position and sometimes positively charged are reported. The Pcs had either H2, zinc or silicon as central metals and have pyridyloxy, benzothiozole phenoxy, and respective cationic analogues as ring substituents. The Pcs were linked to carbon based nanoparticles such as graphene quantum dots, carbon dots, and detonation nanodiamonds (DNDs) via an ester, amide bond and/or π - π stacking. The physicochemical characteristics of the Pcs were assessed when alone and when in a conjugated system. Both symmetrically and asymmetrically substituted benzothiozole Pcs when quaternised displayed higher triplet and singlet oxygen quantum yields than their unquaternised counterparts. Linkage to carbon nanoparticles (especially to detonation nanodiamonds) had an increasing effect on triplet and singlet oxygen quantum yield. However, a general decrease in singlet oxygen quantum yield on linkage to doped detonation nanodiamonds was associated with the screening effect of DNDs. Heteroatom doped DNDs-Pc nanohybrids have less singlet oxygen than Pcs alone due to molecular structural stability associated with strain that is relatively reduced upon linking Pcs. The In vitro dark cytotoxicity and photodynamic therapy of selected Pc complexes and conjugates against MCF-7 cells was tested. All studied Pc complexes and conjugates showed minimum dark toxicity making them applicable for PDT. When Pc complexes are alone, there is less phototoxicity with >22% cell viability at concentrations ≤ 50 μg/mL relative to conjugates with <22% cell viability at concentrations ≤ 50 μg/mL. There was no direct relationship between PDT and singlet oxygen quantum yields. Nonlinear optical characteristics of complexes was improved upon conjugation of DNDs. Absorbance, input energy, percentage loading, central metal, substituent of Pc and nature of interaction (covalent, noncovalent) are amongst some of the factors that influence nonlinear absorption properties of materials used in this study. All materials followed reverse saturable absorption through two photon absorption mechanism at the excitation wavelength of 532 nm. Aggregates reduce excited state lifetime and Beff under high concentrations/absorbance. A direct relationship between absorbance and Beff of DNDs nanoconjugated systems at low concentrations result in increased optical limiting characteristics of materials. The findings from this work show the importance of linking (nonlinear optics and photodynamic therapy) and doping (photodynamic therapy) photosensitisers such as phthalocyanines and sometimes boron dipyrromethenes onto carbon based nanoparticles for the enhanced characteristics in variable applications. , Thesis (PhD) -- Faculty of Science, Chemistry, 2021
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Effect of the nature of nanoparticles on the photophysicochemical properties and photodynamic antimicrobial chemotherapy of phthalocyanines
- Authors: Magadla, Aviwe
- Date: 2020
- Subjects: Nanoparticles , Phthalocyanines , Anti-infective agents -- Therapeutic use , Photochemotherapy , Photochemistry
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/123107 , vital:35406
- Description: In this work, the syntheses and characterisation of Zn monocaffeic acid tri–tert–butyl phthalocyanine (1), Zn monocarboxyphenoxy tri– tert–butylphenoxyl phthalocyanine (2), tetrakis phenoxy N,N-dimethyl-4-(methylimino) phthalocyanine indium (III) chloride (3) and tetrakis N,N-dimethyl-4-(methylimino) phthalocyanine indium (III) chloride (5) are presented. Complexes 3 and 5 were further quartenised with 1,3- propanesultone to form corresponding complexes (4) and (6), respectively. Complexes 1 and 2 were covalently linked to amino functionalised nanoparticles (NPs). Complexes 3, 4, 5 and 6 where linked to oleic acid/oleylamine capped (OLA/OLM) silver-iron dimers (Ag-Fe3O4 OLA/OLM) and silver-iron core shell (Ag@Fe3O4 OLA/OLM) NPs via interaction between the nanoparticles and the imino group on the phthalocyanines. The phthalocyanine-NP conjugates afforded an increase in triplet quantum yields with a corresponding decrease in fluorescence quantum yield as compared to the phthalocyanine complexes alone. Complexes 3, 4 and their conjugates were then used for photodynamic antimicrobial chemotherapy on E. coli. The zwitterionic photosensitiser 4 and its conjugates showed better efficiency for photodynamic antimicrobial chemotherapy compared to their neutral counterparts.
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Metallophthalocyanines linked to metal nanoparticles and folic acid for use in photodynamic therapy of cancer and photoinactivation of bacterial microorganisms.
- Authors: Matlou, Gauta Gold
- Date: 2020
- Subjects: Cancer -- Photochemotherapy , Nanoparticles , Phthalocyanines , Anti-infective agents -- Therapeutic use , Photochemotherapy , Photochemistry
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/166540 , vital:41377
- Description: This thesis presents on the synthesis and characterization of novel asymmetric and symmetrical metallophthalocyanines (MPcs) substituted with carboxylic acid functional groups and centrally metallated with zinc and indium. The MPcs are further covalently linked to cysteine capped silver nanoparticles (cys-AgNPs), amino functionalized magnetic nanoparticles (AMNPs) and folic acid (FA) through an amide bond between the carboxylic group of MPcs and the amino group of FA, cys-AgNPs or AMNPs. The covalent linkage of MPcs to FA improved the water solubility of MPcs and allowed for singlet oxygen quantum yield determination in water. Asymmetric MPcs and their conjugates were found to have improved photochemical and photophysical properties compared to symmetrical MPcs and their conjugates. The heavy atom effect of AMNPs and AgNPs improved the triplet and singlet oxygen quantum yields of MPcs. MPcs and their conjugates (MPc-FA, MPc-AMNPs, MPc-AgNPs) were found to have lower in vitro dark cytotoxicity and higher photodynamic therapy (PDT) activity on MCF-7 breast cancer cells. The water soluble MPc-FA had better PDT activity when compared to MPc-AMNPs due to the active targeting of folic acid-folate binding on cancer cell surface. MPcs and MPc-AgNPs conjugates also showed excellent in vitro cytotoxicity on S. aureus under light irradiation compared to dark cytotoxicity. The photosensitizing properties of MPcs and their conjugates are demonstrated for the first time in this thesis, both on breast cancer cells (MCF-7) through photodynamic therapy and on microorganisms (S. aureus) through photodynamic antimicrobial chemotherapy.
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Synthesis, photophysicochemical properties and photodynamic therapy activities of indium and zinc phthalocyanines when incorporated into Pluronic polymer micelles
- Authors: Motloung, Banele Mike
- Date: 2020
- Subjects: Indium , Zinc , Phthalocyanines , Polymers , Photochemotherapy , Micelles
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/167529 , vital:41489
- Description: This thesis reports on the syntheses, photophysicochemical properties and photodynamic therapy activities of symmetrical metallophthalocyanines (MPcs) when alone or when incorporated into Pluronic polymer micelles. The Pcs contain either zinc or indium as central metals and have phenyldiazenylphenoxy, pyridine-2-yloxy and benzo[d]thiazol-2-ylthio as ring substituents. Spectroscopic and microscopic techniques were used to confirm the formation MPcs with micelles. The photophysics and photochemistry of the Pcs were assessed when alone and with micelles. All the studied Pcs showed good photophysicochemical behavior with relatively high triplet and singlet oxygen quantum yields corresponding to their low fluorescence quantum yields. The Pcs with indium in their central cavity exhibited higher triplet and singlet oxygen quantum yields in comparison to their zinc counterparts due to the heavy atom effect obtained from the former. The in vitro dark cytotoxicity and photodynamic therapy of the Pc complexes and conjugates against MCF7 cells was tested. All studied Pc complexes alone and with micelles showed minimum dark toxicity making them applicable for PDT. All complexes displayed good phototoxicity < 50% cell viability (except for complex 2 > 50% cell viability) at concentrations ≤100 μg/mL, however the conjugates showed < 45% cell viability at concentrations ≤ 100 μg/mL, probably due to the small micellar size and EPR effect. The findings from this work show the importance of incorporating photosensitizers such as phthalocyanines into Pluronic polymers micelles and making them water soluble and ultimately improving their photodynamic effect.
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Synthesis of indium phthalocyanines for photodynamic antimicrobial chemotherapy and photo-oxidation of pollutants
- Authors: Sindelo, Azole
- Date: 2019
- Subjects: Phthalocyanines , Azo dyes , Indium compounds , Photochemotherapy , Nanoparticles , Photodegradation , Pollutants , Water -- Purification
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/67581 , vital:29116
- Description: Indium (III) octacarboxyl phthalocyanine (ClInOCPc) alone and when conjugated to magnetic nanoparticles (MNP-ClInOCPc), 2(3),9(10),16(17),23(24)-octapyridylsulfanyl phthalocyaninato chloroindium (III) (ClInOPyPc) and its quaternized derivative 2(3),9(10),16(17),23(24)-octamethylpyridylsulfanyl phthalocyaninato chloroindium (III) (ClInOMePyPc) were synthesized. All Pcs were tested for both photodynamic antimicrobial chemotherapy (PACT) of an unknown water sample and photo-degradation of methyl red (MR). The singlet quantum yield (ΦΔ) for the ClInOCPc and MNP-ClInOCPc in PAN polymer fibers were 0.36 and 0.20 respectively using ADMA as a quencher in water. The photo-inactivation of bacteria in a water sample with unknown microbes was tested, with the MNP-ClInOCPc inactivating 90.6 % of the microbes and the ClInOCPc with 84.8 %. When embedded to the polymer, there was 48% bacterial clearance for ClInOCPc and 64% clearance for the MNP-ClInOCPc. The rate of degradation of MR increased with decrease of the MR concentration, with the MNP-ClInOCPc having the fastest rate. For ClInOPyPc and ClInOMePyPc, the singlet quantum yields were 0.46 and 0.33 in dimethylformamide (DMF), respectively. The PACT activity of ClInOMePyPc (containing 8 positive charges) was compared to those of 9(10),16(17),23(24)-tri-N-methyl-4-pyridylsulfanyl-2(3)-(4-aminophenoxy) phthalocyaninato chloro indium (III) triiodide (1) (containing 3 positive charges) and 2-[4-(N-methylpyridyloxy) phthalocyaninato] chloroindium (III) iodide (2) (containing 4 positive charges). When comparing ClInOMePyPc, 1 and 2, the largest log reduction for E. coli were obtained for complex 2 containing four positive charges hence showing it is not always the charge that determines the PACT activity, but the bridging atom in the phthalocyanine plays a role.
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