This study focuses on the synthesis, characterization, and investigation of the effects of new cobalt, copper, and manganese phthalocyanine complexes substituted at the peripheral positions with octa-4-[(6-bromonaphthalen-2-yl)oxy] groups on the oxidative balance in biological systems. The structures of these newly synthesized derivatives were confirmed using FT-IR, UV-Vis, and MALDI-TOF mass spectroscopy, and their spectral and aggregation properties in various solvents were extensively examined. The broad π-conjugated systems of phthalocyanines and the type of central metal atom directly influence their free radical scavenging and antioxidant capacities. In this context, the impact of the peripheral bromonaphthyl groups and metal center on the total antioxidant potential was quantitatively evaluated using total antioxidant status, total oxidant status, and oxidative stress index parameters. The findings indicate that the octa-4-[(6-bromonaphthalen-2-yl)oxy] substitution shapes the biological activities of the compounds by affecting their solubility and aggregation tendencies. This study provides significant data regarding the potential use of these specifically designed metallophthalocyanines as promising candidates for future studies on oxidative stress-related applications.

The aim of this work is to synthesize bis 4-[(6-bromonaphthalene-2)-oxy] substituted metal phthalocyanines at the peripheral positions and to investigate their biological properties. All synthesized compounds exhibited complete alpha-amylase inhibition activity 100% at a concentration of 100 mg/L. DNA interaction studies revealed that the compounds caused total degradation of DNA, as evidenced by gel electrophoresis analysis. Antimicrobial activity tests show that the complexes effectively inhibit the metabolic growth of the tested microorganisms. The minimum inhibitory concentration (MIC) values against Escherichia coli were determined as 32 mg/L for 4FFPcMn, 16 mg/L for 4FFPcCo, and 8 mg/L for 4FFPcCu. Additionally, 100% of E. coli cell viability was completely inhibited by all synthesized metallophthalocyanines, demonstrating their potent antimicrobial and photodynamic potential.

This study describes the fabrication of functional nanofibers via electrospinning by embedding tetra-substituted metallophthalocyanines (CoPc, CuPc, MnClPc) into a poly(acrylonitrile-co-vinyl acetate) (PAN) matrix. Comprehensive characterization with UV-Vis, FTIR, FE-SEM, EDX, and thermal analysis demonstrated the successful incorporation of phthalocyanines, resulting in smooth, homogenous nanofibers with consistent component distribution and improved thermal stability. Biological assessments demonstrated significant biomedical and biotechnological potential. In assessments associated with diabetes therapy, MnClPc/PAN had a dual-mode action on α-amylase, showing both activation (22.29 ± 1.43

In this study, a peripherally tetra-substituted zinc phthalocyanine with 2',3',5',6'-tetrafluoro-4'-carboxyethylthio-benzyloxy groups (2) was synthesized. FT-IR, NMR, MALDI-TOF MS, and UV-Vis spectroscopy techniques were used to characterize all the synthesized compounds. The photochemical and photophysical properties of compound 2 were also examined. The singlet oxygen quantum yield was calculated as 0.49 for compound 2 using only light irradiation in the photochemical method. Additionally, compound 2 showed moderate photostability under intense light irradiation. The biological properties of compound 2, including antioxidant, antidiabetic, antimicrobial, DNA cleavage, and anti-biofilm activities, were evaluated. The antioxidant activity was measured using the DPPH radical scavenging assay, where compound 2 demonstrated 18.12% activity. The antidiabetic potential was assessed through amylase inhibition tests, indicating that compound 2 has potential antidiabetic activity. The antimicrobial activity of compound 2 was tested with the microdilution method. It showed significant activity, especially against Gram-positive and Gram-negative bacteria. Furthermore, the antimicrobial effects of compound 2via photodynamic therapy showed enhanced activity. E. coli was used to evaluate the inhibitory effect of compound 2 on cell viability, demonstrating 100% inhibition. The compound's ability to inhibit biofilm formation of S. aureus and P. aeruginosa was also assessed, with compound 2 showing high biofilm inhibition. The anti-biofilm effect was generally more pronounced against S. aureus than P. aeruginosa. Importantly, the biocompatibility of compound 2 was confirmed in L929 fibroblast cells. While it exhibited concentration-dependent cytotoxicity in the dark, under light irradiation, cell viability remained close to or above the thresholds defined by ISO 10993-5 for non-cytotoxicity. As a result, compound 2 is a multifunctional phthalocyanine derivative that combines diverse biological activities with a safety profile, supporting its potential as a promising candidate for biomedical applications.

In this study, the novel 4-(2-(pyrazin-2-yl) ethylthio) phthalonitrile (1) was synthesized as the starting material by reacting 4-nitrophthalonitrile with 2-(pyrazin-2-yl) ethanethiol. Using this intermediate, the peripherally tetra-pyrazine derivative-substituted phthalocyanine compounds (2,3) were synthesized for the first time. Subsequently, their water-soluble quaternized phthalocyanine derivatives (2a,3a) were prepared. All compounds used were characterized with various spectroscopic methods such as UV-Vis, FT-IR, 1H NMR, 13C NMR and MALDI-TOF MS. This study investigates the efficiency of photochemical and sono-photochemical approaches in boosting singlet oxygen generation, a key factor in photodynamic therapy applications. The synthesized phthalocyanines exhibited notable singlet oxygen quantum yields. Specifically, the phthalocyanines (2,3,2a,3a) achieved Phi Delta values of 0.64, 0.75, 0.18, and 0.21 under photochemical applications, and 0.77, 0.97, 0.27, and 0.39 under sono-photochemical applications, respectively. The antimicrobial activities of these compounds were evaluated by the broth microdilution method against a panel of Gram-positive and Gram-negative bacteria, including Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Enterococcus faecalis, and Klebsiella pneumoniae. The results revealed that quaternization significantly improved the antibacterial performance. While compounds (2) and (3) exhibited MIC values in the range of 16-32 mu g/mL, their quaternized analogues (2a) and (3a) demonstrated stronger inhibitory effects, with compound (3a) showing the highest potency (MIC: 4-8 mu g/ mL) across all tested strains. These findings highlight the potential of pyrazine-functionalized quaternized phthalocyanines as promising candidates for the development of novel antimicrobial agents. Gaussian software was used to calculate the ligand and metal complexes of phthalocyanine (Pc) derivatives (2,3,2a,3a) in 6-31 g and 6-31++g(d,p) basis sets at the B3LYP, HF, and M062X levels. The compounds' effects against different proteins were then contrasted, and their interactions were examined.

In recent years, photodynamic therapy (PDT) has emerged as a significant approach in cancer treatment, attributed to its selective cytotoxicity and minimal systemic toxicity. Nevertheless, its clinical application is constrained by limitations such as restricted light penetration, suboptimal therapeutic efficacy, and potential adverse effects on healthy tissues. To address these challenges, sonodynamic therapy (SDT) has been developed, offering advantages including greater penetration depth and reduced damage to surrounding tissues. Sonophotodynamic therapy (SPDT), which integrates the synergistic effects of both PDT and SDT, presents a more efficacious treatment strategy by enhancing the production of reactive oxygen species (ROS), particularly singlet oxygen (1O2), through the concurrent application of light and sound waves. In this context, phthalocyanine complexes are considered ideal candidates for SPDT applications, serving as both photosensitizers and sonosensitizers due to their structural modifiability, high photostability, and capacity for 1O2 production. This study involves the synthesis of Mg(II) (2), Zn(II) (3), and In(III) (4) phthalocyanine derivatives with naphthol groups carrying bromine atoms in non-peripheral positions, and a detailed investigation of the effects of substituent type and central metal on singlet oxygen yield using photochemical and sonophotochemical methods in DMSO. The single oxygen quantum yields obtained under photochemical excitation were determined to be 0.34 for 2, 0.77 for 3, and 0.85 for 4. Sono-photochemical excitation increased the singlet oxygen quantum yield by an average of 50% for 2, 3, and 4. This study has revealed the supportive effect of the excitation method on the production of singlet oxygen by synthesized compounds 2, 3, and 4, which play a significant role in the destruction of cancer cells. The findings contribute significantly to the development of new therapeutic agents with both light- and sound-sensitive properties, indicating that the synthesized complexes are promising candidates for future sonophotosensitizer studies.

Recent advancements in sonophotodynamic therapy (SPDT) have highlighted the growing demand for the development of novel and effective sonosensitizers/sonophotosensitizers for cancer treatment. Among the various candidates, phthalocyanines have attracted significant attention due to their highly versatile molecular structures and tunable photophysical and physicochemical properties. In this study, 3-[4-(hexyl benzoate)] substituted metallophthalocyanines were synthesized with peripheral substitution and comprehensively characterized using standard spectroscopic techniques. The singlet oxygen generation efficiencies of the synthesized compounds were systematically evaluated under photochemical and sonophotochemical conditions. The results demonstrate that the newly designed phthalocyanines possess promising potential as efficient sensitizers for both PDT and SPDT applications, offering synergistic enhancement in singlet oxygen production.

This work reports the first-time synthesis of a novel starting compound, 4,5-bis(sodium 2-mercaptoethane sulfonate) phthalonitrile (1), and its transformation into a new series of water-soluble phthalocyanine derivatives bearing eight MESNA (sodium 2-mercaptoethanesulfonate) groups at the peripheral octa-positions. The resulting metallophthalocyanines-Cu(II) (2), MnCl(III) (3), GaCl(III) (4), and InCl(III) (5)-were successfully obtained and thoroughly characterized using a range of spectroscopic techniques, including UV–Vis, FT-IR, ¹H NMR, ¹³C NMR, and MALDI-TOF MS. The potential of photochemical and sono-photochemical techniques to enhance singlet oxygen (¹O₂) generation was evaluated. In this study, synthesized GaCl(III)Pc (4) and InCl(III)Pc (5) were investigated under both light-only and combined light + ultrasound conditions. The phthalocyanines demonstrated significant singlet oxygen quantum yields (ΦΔ), with gallium-based derivatives in particular showing enhanced 1O2 production, likely due to favorable triplet-state lifetimes and photophysical properties. These findings highlight the effectiveness of combining photochemical and sonochemical activation and underscore the promise of Ga(III) and In(III) phthalocyanines as potent photosensitizers in next-generation PDT and SPDT applications. The cytotoxic effects of the compounds on A549 lung cancer and C6 rat glioma cell lines were evaluated using the MTT test. Additionally, the inhibitory effects of the compounds on CA I and CA II enzymes were investigated. The results showed that these compounds inhibited CA I and CA II enzymes in a dose-dependent manner, and also had an effect that enhanced the destruction of cancer cells. In this study, the antioxidant activities of Ga(III)ClPc (4), Cu(II)Pc (2), In(III)ClPc (5), and Mn(III)ClPc (3) phthalocyanine derivatives were evaluated and compared with the standard antioxidant ascorbic acid by determining their IC50 values. Among the tested phthalocyanine complexes, In(III)ClPc (2367 ± 1.57 μg/mL) exhibited the highest antioxidant activity with the lowest IC50 value, whereas Mn(III)ClPc (3) (3093 ± 1.66 μg/mL) showed the weakest activity. The activity ranking of the phthalocyanine complexes was determined as In(III)ClPc (5) > Ga(III)ClPc (4) > Cu(II)Pc (2) > Mn(III)ClPc (3). newly synthesized metal phthalocyanine derivatives were evaluated for their in vitro antimicrobial activity against American Type Culture Collection (ATCC) reference strains using the broth microdilution method. The compounds exhibited selective antimicrobial activity, with MIC values ranging from 2.5 to 9.8 mg/mL. The lowest MIC value was observed against Bacillus cereus (2.5 mg/mL). Moderate antibacterial activity was detected against Escherichia coli (4.8–4.9 mg/mL) and Pseudomonas aeruginosa (4.7 mg/mL) for selected derivatives. Antifungal activity against Candida albicans was observed for gallium and manganese-containing compounds (4.8 mg/mL). In contrast, no effective inhibition was detected against Klebsiella pneumoniae or Staphylococcus aureus within the tested concentration range. These findings indicate that metal-dependent structural variations significantly influence the antimicrobial activity of phthalocyanine derivatives.

Two structurally related furan-based chalcone derivatives FAZO bearing an azo linkage and FEST containing an ester moiety have been presented. The incorporation of azo and ester groups aimed to improve electronic delocalization, target binding affinity, and biological efficacy. The chemical structures of the synthesized chalcone/azo and chalcone/ester derivatives were confirmed by classical spectroscopic methods such as proton nuclear magnetic resonance spectroscopy (1H NMR), carbon-13 attached proton test nuclear magnetic resonance spectroscopy (13C(APT)-NMR), Fourier-Transform Infrared Spectroscopy (FT-IR), and High Resolution-Mass Spectrometry (HR-MS). FAZO and FEST demonstrated moderate antioxidant activity, exhibiting 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging efficiencies of 37.02% and 34.01%, respectively. Both compounds effectively inhibited amylase, particularly at 100 mg/L, suggesting their potential as antidiabetic agents. FAZO and FEST induced complete Deoxyribonucleic acid (DNA) cleavage at concentrations of 50, 100, and 200 mg/L. Both compounds showed the highest antimicrobial activity against Enterococcus faecalis (E. faecalis) and Candida albicans (C. albicans) among the tested microorganisms. At 200 mg/L, FAZO inhibited Staphylococcus aureus (S. Aureus) biofilm formation as 64.11%, whereas FEST showed 63.59% inhibition. At the same concentration, FAZO and FEST inhibited Pseudomonas aeruginosa (P. Aeruginosa) biofilm by 71.65% and 78.52%, respectively. FAZO and FEST demonstrated superior microbial cell viability inhibition capabilities as 98.12% and 100% against Escherichia coli (E. coli) under dark conditions at 200 mg/L, respectively, and they displayed photodynamic antimicrobial abilities (PDaT) against E. coli as 94.66% and 100% inhibition at 100 mg/L and also 100% and 100% inhibition, respectively. Based on the results of molecular docking study, −8.33 and −6.84 kcal/mol were found for the strength of interactions for FAZO and FEST ligands towards the α-amylase target and −12.43 and −9.87 kcal/mol were found for their strengths towards the DNA target revealing them as potential inhibitors. These values highlight the various potential applications of FAZO and FEST in biomedical industries.

In the current study, the synthesis of a novel unsymmetrical zinc phthalocyanine, ZnPc (5), carrying tert-butyl and isothiocyanatophenoxy groups was achieved by the statistical condensation of two different phthalonitriles. Compound 5 was obtained in three steps, starting from tert-butylphthalonitrile and 4-(4-nitrophenoxy)phtha-lonitrile. The isothiocyanate unit was selected to ensure selective bioconjugation under mild reaction conditions and to reduce side product formation, while tert-butyl groups were incorporated to increase solubility and tailor photophysical and photochemical properties relevant to cellular imaging and diagnostic applications. The fluorescence properties and singlet oxygen formation ability of this compound were examined using UV-Vis absorption and fluorescence emission spectroscopy Compound 5 showed a higher singlet oxygen yield than the standard zinc phthalocyanine (0.82 for 5 and 0.67 for the standard). In addition to the photochemical properties, photodynamic therapy (PDT) activity and cellular uptake of compound 5 were investigated. Fluorescence imaging demonstrated efficient cytoplasmic localization of compound 5, while cytotoxicity assays confirmed that no significant dark toxicity or PDT-induced cytotoxicity was observed. These findings indicate that ZnPc (5) is more suitable for cellular imaging and diagnostic applications rather than for PDT treatment.

Sono-photodynamic therapy (SPDT), an innovative approach that uses light and ultrasound stimulants together, has been accepted as a more effective treatment method than photodynamic therapy (PDT) owing to its markedly enhanced treatment efficacy. Building on this, in the present article, zinc- and indium-metallated phthalocyanine (Pc) derivatives carrying 2-hydroxyquinoline segment at their peripheral positions have been synthesized. The molecular structures of the synthesized complexes have been clarified using 1H NMR, FT-IR and mass spectroscopic techniques. Photophysical, photochemical and sono-photochemical measurements were performed in order to reveal the singlet oxygen generation capacities of the Pcs for both photodynamic therapy (PDT) and sono-photodynamic therapy (SPDT) applications. The singlet oxygen quantum yield (Phi Delta) of the molecules was obtained as 0.49 for 2 and 0.86 for 3 upon photochemical measurements (utilizing only light irradiation), whereas these values increased to 0.75 for 2 and 1.29 for 3 upon sono-photochemical (utilizing light and ultrasound together) studies. The results demonstrate that the singlet oxygen production of a sensitizer is profoundly governed by stimulation modality, emphasizing the power of the synergistic effect of light and ultrasound in SPDT over PDT.

Schiff base-decorated non-ionic phthalocyanine compounds with different metals and a metal-free derivative were synthesized and characterized using different spectroscopic techniques. The influence of the central metal on the photophysicochemical properties was systematically investigated in DMSO. The obtained results reveal that the singlet oxygen quantum yield followed the order In3b > Zn3b > 3bH2Pc in DMSO. The synthesized non-ionic phthalocyanine compounds, except metal-free phthalocyanine (0.12 for 3bH2Pc), have good ΦΔ values (0.71 for Zn3b and 0.85 for In3b) compared with the unsubstituted ZnPc in DMSO (ΦΔ = 0.67). In addition to the photophysicochemical studies, in vitro PDT studies were also performed on PC3 prostate cancer cells to evaluate the biological activity of Pcs. All compounds exhibited low dark cytotoxicity at the selected concentration. Upon light irradiation, phthalocyanine-mediated PDT significantly reduced cell viability and induced apoptotic cell death. These effects were accompanied by a pronounced increase in intracellular ROS generation, particularly in the cells treated with metallophthalocyanine-mediated PDT. In particular, In3b- and Zn3b-mediated PDT exhibited markedly enhanced cytotoxic and apoptotic effects compared with metal-free 3bH2Pc. These findings demonstrate a strong correlation between improved photophysical properties, increased ROS generation, and enhanced in vitro PDT efficacy.

This study reports the synthesis of a novel ligand, sodium 6-(2,3-dicyanophenoxy)naphthalene-2-sulfonate (1), and the corresponding non-peripherally substituted metallophthalocyanines (MPcs) [M = Zn(II) (2), Ga(III) (3); X = Cl, In(III) (4); X = Cl]. These compounds were functionalized with 6-naphthoxy-2-sulfonic acid sodium salt groups. Given the limitations of conventional photodynamic therapy (PDT), we investigated the potential of sonophotodynamic therapy (SPDT), a dual-modality approach combining light and ultrasound, to enhance singlet oxygen (¹O2) production. Among the synthesized metallophthalocyanines, the zinc(II) complex (2) shows the highest ¹O2 production in both organic and aqueous media under both photochemical and sonophotochemical conditions, showing promise for SPDT applications. Furthermore, the inhibitory effects of these complexes on acetylcholinesterase (AChE) and human carbonic anhydrase isoenzymes (hCA I and II), important targets for Alzheimer’s disease, glaucoma, and epilepsy, were evaluated. The compounds showed strong inhibition with Ki values ranging from 130.31 ± 6.18 to 157.47 ± 9.37 µM for hCA I (compared to AZA: 177.41 ± 11.40 µM), 99.18 ± 8.13 to 106.72 ± 8.50 µM for hCA II (compared to AZA: 143.51 ± 9.94 µM) and 0.31 ± 0.03 to 1.21 ± 0.01 µM for AChE (compared to TAC: 1.24 ± 0.21 µM). Molecular docking revealed strong binding affinities: In(III)-Pc (4) showed the highest affinity for AChE (BE: -26.96 kcal/mol), while Ga(III)-Pc (3) preferentially bound to hCA I and II (BE: -13.90 and − 15.39 kcal/mol, respectively). These findings position the synthesized MPcs as multifunctional agents for SPDT and enzyme-targeted therapies.

The aim of this work is to synthesize bis 4-[(6-bromonaphthalene-2)-oxy] substituted metal phthalocyanines at the peripheral positions and to investigate their biological properties. All synthesized compounds exhibited complete α-amylase inhibition activity 100% at a concentration of 100 mg/L. DNA interaction studies revealed that the compounds caused total degradation of DNA, as evidenced by gel electrophoresis analysis. Antimicrobial activity tests show that the complexes effectively inhibit the metabolic growth of the tested microorganisms. The minimum inhibitory concentration (MIC) values against Escherichia coli were determined as 32 mg/L for 4FFPcMn, 16 mg/L for 4FFPcCo, and 8 mg/L for 4FFPcCu. Additionally, 100% of E. coli cell viability was completely inhibited by all synthesized metallophthalocyanines, demonstrating their potent antimicrobial and photodynamic potential.

In this study, the novel "3-(2-(pyrazin-2-yl) ethylthio) phthalonitrile (1)" as starting material was synthesized and its non-peripherally tetra- "pyrazine derivative" -substituted phthalocynine compound (2) was synthesized for the first time. Then, its water soluble-quaternized phthalocyanine compound (2a) was prepared. All compounds used were characterized with various spectroscopic methods such as UV-Vis, FT-IR, 1H NMR, 13C NMR, SEM and MALDI-TOF MS. The potential of photochemical and sono-photochemical techniques to enhance singlet oxygen production-an essential component in photodynamic therapy-was evaluated. The newly synthesized phthalocynines displayed significant singlet oxygen quantum efficiencies. Among them, the phthalocynine (2) and (2a) yielded ΦΔ values of 0.53 and 0.14 for the photochemical method, while the corresponding values under sono-photochemical conditions were 0.67 and 0.26. Additionally, the antimicrobial efficacy of the newly synthesized phthalocyanine (Pc) derivatives (2) and (2a) was evaluated using the broth microdilution method against a broader panel of Gram-positive and Gram-negative bacterial strains, including Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Both compounds exhibited measurable antibacterial activity, with minimum inhibitory concentrations (MICs) ranging from 4 to 32 μg/mL. Notably, compound (2a) demonstrated the strongest effect against E. faecalis (MIC = 4 μg/mL) and S. aureus (MIC = 8 μg/mL), while also showing enhanced inhibition of K. pneumoniae (MIC = 8 μg/mL) compared to compound (2) (MIC = 32 μg/mL). For E. coli and P. aeruginosa, both derivatives displayed similar MIC values of 16 μg/mL. These results indicate that quaternization significantly improves the antibacterial potency of the phthalocyanine derivative, particularly against E. faecalis and K. pneumoniae. Calculations of the ligand (1) and its phthalocyanine (Pc) derivatives (2) and (2a) were carried out with Gaussian software program at B3LYP, HF, and M062X level in 6-31 g, 6-31++g, and 6-31++g(d,p) basis sets. Afterwards, the activities of the molecules against various proteins were compared and their interactions were investigated.

Singlet oxygen in biological systems is primarily produced via photosensitization, where an excited sensitizer transfers energy to molecular oxygen. In photodynamic therapy (PDT), this reactive oxygen species is employed to induce cancer cell death. Sono-photodynamic therapy (SPDT), integrating ultrasound and light activation, offers enhanced singlet oxygen quantum yields. In this study, peripheral octa-4-[(6-bromonaphthalen-2-yl)oxy] substituted metallophthalocyanines were synthesized and characterized in terms of their spectral, aggregation, and sono-photochemical properties. Their efficacy as photosensitizers was evaluated under both photochemical and sono-photochemical conditions. The singlet oxygen quantum yields (Phi Delta) obtained in photochemical studies were 0.68 for ZnPc, 0.76 for InPc, and 0.54 for MgPc. In sono-photochemical studies, these values increased to 0.87, 0.94, and 0.68, respectively, indicating a clear enhancement of singlet oxygen generation through the synergistic effect of ultrasound and light. Overall, the results demonstrate that the designed metallophthalocyanines possess favorable photochemical and sono-photochemical characteristics, suggesting their strong potential as dual-function photosensitizer candidates for both PDT and SPDT applications.

In this work, experimental results of the effect of Mn ions incorporation on the structural, optical and luminescence properties of spray deposited ZnO thin films by varying the Mn molar ratio x in the precursor solution. For x = 0.00, XRD peaks revealed that the deposited film correspond to the hexagonal wurtzite structure of ZnO. For x = 0.02 and x = 0.04, the variation of crystalline parameters indicated the presence of compressive stress caused by the incorporation of Mn ions in ZnO. The stress relaxation, for x = 0.06, was accompanied by the appearance of other phases such as MnO2 and ZnMnO3 indicating the decomposition of ZnO phase. The crystallite size decreased from 72 to 35 nm as a function of Mn molar ratio confirming the loss of ZnO crystallinity. The disappearance of Zn-O-Zn bond related peaks in the ATR-FTIR spectrum, for x = 0.06, confirmed XRD results. As a function of Mn molar ratio x, the mean transmittance in the visible light region decreased from 80 to 60

This study reports the synthesis and characterization of an asymmetric zinc(II) phthalocyanine (5) containing three tetraethyleneglycol monomethyl ether groups and one isothiocyanatophenoxy group at its periphery. The isothiocyanate unit was selected to ensure selective bioconjugation under mild reaction conditions and to reduce side product formation, while tetraethyleneglycol monomethyl ether groups were incorporated to increase solubility and tailor photophysical and photochemical properties relevant to photodynamic therapy applications. The compound showed a singlet oxygen quantum yield (ΦΔ) of 0.38, confirming efficient photosensitizer performance. Photodynamic activity was evaluated across multiple cancer cell lines in both 2D monolayer and 3D spheroid cultures. In 2D models, compound 5 produced pronounced light-dependent cytotoxicity accompanied by increased intracellular ROS. Cell-death profiles varied among cancer types, with FaDu cells showing the highest sensitivity under the tested conditions, consistent with differences in cellular susceptibility to compound 5-mediated PDT. In 3D spheroids, efficacy was reduced, in line with known limitations of PDT in compact tumor-like structures, including restricted light propagation, oxygen gradients, and limited compound penetration. Minimal phototoxicity in non-malignant fibroblasts under the same conditions suggests preferential photodynamic activity in the tested cancer models. Overall, these results support the PDT potential of compound 5 and highlight the influence of cellular context and 3D architecture on treatment responses.

Remarkable results have been achieved by using the synergistic effect of light and ultrasound in sono-photodynamic therapy (SPDT). This application, which has been defined as a combination treatment method in recent years, aims to increase the amount of singlet oxygen produced by sono-photosensitizers. This research aims to assess the singlet oxygen generation potential of BODIPY compounds through the utilization of the SPDT method. Motivated by this fact, we synthesized and characterized a new water-soluble BODIPY compound doped with a heavy-atom and a distyryl moiety. The singlet oxygen production capacities of the compounds were investigated both photochemically and sono-photochemically. To assess their biological performance, in vitro studies were conducted using the MDA-MB-231 breast cancer cell line. Cytotoxicity and apoptosis were determined by MTT and Annexin V-FITC/PI assays, while ROS generation was detected using DHE staining under confocal microscopy. MnSOD and GPX1 expression levels were analyzed to evaluate mitochondrial antioxidant responses. The results demonstrated that both BODIPY compounds significantly enhanced reactive oxygen species (ROS) generation and apoptosis under SPDT, accompanied by increased MnSOD and GPX1 expression. In addition, molecular docking studies were conducted to evaluate the binding interactions of the newly synthesized compounds with the EGFR target protein, providing insight into their potential as multifunctional agents with both photodynamic and molecular-targeting capabilities. Molecular docking results demonstrated that the newly synthesized compounds possess markedly higher EGFR binding affinity than cisplatin, supported by lower binding energy values and stronger active-site interactions. These findings suggest that the synthesized BODIPY derivatives act as efficient sono-photosensitizers capable of inducing ROS-mediated apoptosis, highlighting their potential as promising agents for cancer therapy. Although BODIPY derivatives are well known as photosensitizers in PDT, their potential as sono-photosensitizers in SPDT has been rarely explored. This study therefore addresses an important gap by assessing the SPDT efficacy of newly synthesized water-soluble BODIPY derivatives in MDA-MB-231 cells.