Hybrid Sono-Photodynamic Combination Therapy Mediated by Water-Soluble Gallium Phthalocyanine Enhances the Cytotoxic Effect against Breast Cancer Cell Lines.

Breast cancer is a life-threatening disease that is gaining increasing importance due to its rising incidence, highlighting the need for novel treatment methods with the least disadvantages. Recently, scientists have focused on developing therapeutic treatment modalities for effective cancer treatment. In contrast to conventional cancer treatment methods such as immunotherapy, surgery, chemotherapy, or radiotherapy, photodynamic therapy (PDT) is gaining prominence. Besides, sonodynamic treatment (SDT) is a noninvasive therapeutic approach that uses ultrasound to induce high tissue penetration. In both methods, sensitizers are activated to generate cytotoxic reactive oxygen species such as •OH and 1O2. In particular, the combined use of hybrid and complementary treatment methods has become an important modality in cancer treatment in recent years. Sono-photodynamic therapy (SPDT), which is an important method applied in combination with PDT and SDT, has started to be preferred in terms of reducing potential side effects compared to monotherapy. One of the most important types of sensitizers used in PDT and SDT is known as phthalocyanines (Pcs). Motivated by these facts, this research presents the sono-photochemical, in vitro cytotoxicity, and theoretical evaluation of water-soluble gallium phthalocyanine (GaPc). The results indicate that the quantum yield of the generation of singlet oxygen increased in sono-photochemical studies (ΦΔ = 0.94), compared to photochemical studies (ΦΔ = 0.72). In vitro analyses revealed that GaPc did not exhibit significant cytotoxic effects at the specified varying concentration doses (1-20 µM). Furthermore, GaPc-mediated SPDT triggered cell death by inducing reactive oxygen species formation in the breast cancer cell line (MCF-7). The interaction mechanism of the GaPc with EGFR and VEGFR2 target proteins, which are critical regulators of metastasis, proliferation, and angiogenesis, was investigated by molecular docking simulation. GaPc has effective binding affinities against target proteins, and this affinity was found to be the highest against VEGFR2. Molecular docking results showed a good correlation with the obtained biological results. Eventually, this molecular building of the efficient water-soluble phthalocyanine-based sensitizer is a potential therapeutic for PDT, SDT, and SPDT applications.

Assessing cytotoxic activities, theoretical and in silico molecular docking calculations of phthalocyanines bearing cinnamyloxy-groups.

Cancer has been recognized as one of the deadliest diseases in the world in recent years. By chemically tailoring specific properties, anticancer agents can be prepared very effectively for the treatment of various cancer types. In this manner, as anticancer agents, a series of soluble metal-free and metallophthalocyanines carrying cinnamyloxy-groups at peripheral ß-positions have been prepared. All synthesized phthalocyanines were characterized by various spectroscopic approaches such as ultraviolet - visible (UV - Vis), Fourier transform infrared (FT-IR), and matrix-assisted laser deionization/ionization time-of-flight mass spectroscopy (MALDI-TOF MS) techniques. These compounds are highly soluble in dimethyl sulfoxide (DMSO) and soluble in common organic solvents. The spectroscopic properties, cytotoxicity, and theoretical calculations of these complexes have been investigated. In cytotoxicity tests, compounds 1, 4, and 7 are the most active against HT-29 cell lines with IC50 values of 36.9 µM, 32.5 µM, and 51.1 µM, respectively. Also, the most and the least cytotoxic compounds against healthy CCD cell line is compounds 5 and 6 with the IC50 value of 13.4 µM and >250 µM, respectively. The PDB ID:4BQG target protein representing the HT-29 cancer cell line and the anti-cancer activities of phthalonitrile and its phthalocyanines were supported by molecular docking studies. Density Functional Theory (DFT) study supported the experimental results, including the spectral data, and implied that the compounds 5-7 are comparable by their characteristics, such as electronic properties, optical properties, electrostatic potentials, reactivity parameters, with the earlier studied compounds 2-4, which were successfully proved to be good candidates for cancer treatment.Communicated by Ramaswamy H. Sarma.

Nanotechnology for Dentistry: Prospects and Applications.

In the XXI century, application of nanostructures in oral medicine has become common. In oral medicine, using nanostructures for the treatment of dental caries constitutes a great challenge. There are extensive studies on the implementation of nanomaterials to dental composites in order to improve their properties, e.g., their adhesive strength. Moreover, nanostructures are helpful in dental implant applications as well as in maxillofacial surgery for accelerated healing, promoting osseointegration, and others. Dental personal care products are an important part of oral medicine where nanomaterials are increasingly used, e.g., toothpaste for hypersensitivity. Nowadays, nanoparticles such as macrocycles are used in different formulations for early cancer diagnosis in the oral area. Cancer of the oral cavity-human squamous carcinoma-is the sixth leading cause of death. Detection in the early stage offers the best chance at total cure. Along with diagnosis, macrocycles are used for photodynamic mechanism-based treatments, which possess many advantages, such as protecting healthy tissues and producing good cosmetic results. Application of nanostructures in medicine carries potential risks, like long-term influence of toxicity on body, which need to be studied further. The introduction and development of nanotechnologies and nanomaterials are no longer part of a hypothetical future, but an increasingly important element of today's medicine.

Correction: Evaluation of the effects of newly synthesized metallophthalocyanines on breast cancer cell lines with photodynamic therapy.

Correction for 'Evaluation of the effects of newly synthesized metallophthalocyanines on breast cancer cell lines with photodynamic therapy' by Hayrani Eren Bostanci et al., Dalton Trans., 2022, 51, 15996-16008, https://doi.org/10.1039/d2dt01912d.

Evaluation of the effects of newly synthesized metallophthalocyanines on breast cancer cell lines with photodynamic therapy.

In this study, the new phthalonitrile derivative 3-(4-(3-oxobutyl)phenoxy)phthalonitrile (1) and its non-peripheral metallophthalocyanine derivatives [zinc (2), copper (3), cobalt (4), manganese (5), gallium (6), and indium (7)] were synthesized. The newly synthesized phthalocyanines were characterized by standard spectroscopic methods, such as FT-IR, 1H NMR, UV-Vis, fluorescence spectroscopies, and MALDI-TOF spectrometry. Aggregation behaviors of the novel phthalocyanines were investigated by UV-Vis spectroscopy. The effect of pH change on the electronic and emission spectra of the newly synthesized phthalocyanine derivatives was studied in THF media. The electronic spectra of the new zinc (2), copper (3), and cobalt (4) phthalocyanines exhibited bathochromic shifts in acidic pH values due to the presence of monoprotonated forms. Surprisingly, the same effect was not observed for manganese (5) and indium (7) phthalocyanines. On the other hand, gallium (6) showed a slight red-shifted band with the addition of HCl to the medium. Also, it was determined that the synthesized zinc (2) and gallium (6) phthalocyanines had a selective phototoxic effect on the MCF-7 breast cancer cell line compared to the MCF-10A healthy breast cell line. The IC50 values of zinc (2) and gallium (6) phthalocyanines were determined for MCF-7 and MCF-10A cell lines. The IC50 values of MCF-7 for compounds 2 and 6 were found to be 1.721 ± 0.4 µg mL-1 and 7.406 ± 0.32 µg mL-1, respectively. The IC50 values of MCF-10A for phthalocyanines 2 and 6 were found to be 48.90 ± 0.69 µg mL-1 and 14.77 ± 1.09 µg mL-1, respectively. In the LDH (lactate dehydrogenase)-ELISA study, the LDH levels that formed on a cellular basis after the application were measured, and it was observed that the cells were directed towards apoptosis. In addition, it was observed that cancer cells underwent more apoptosis than healthy cells as a result of this application with cell-cycle and dead cell kits performed by flow cytometry. This research shows that non-peripheral substituted gallium and zinc phthalocyanine derivatives (2 and 6) can be suitable photosensitizers for the photodynamic treatment of breast cancers.

Zinc(II), Palladium(II), and Metal-Free Phthalocyanines Bearing Nipagin-Functionalized Substituents against Candida auris and Selected Multidrug-Resistant Microbes.

Due to the rapidly increasing problem of antibiotic resistance in recent years, the use of phthalocyanines as photosensitizers with their superior properties in photodynamic antimicrobial therapy (PACT) applications has become important. In this study, magnesium(II) 1,4,8,11,15,18,22,25-octakis(4-[4-butoxycarbonylphenoxy]butyloxy)phthalocyanine was used in the demetalation reaction in trifluoroacetic acid, and subsequently subjected to metalation reaction in dimethylformamide with zinc(II) acetate and bis(benzonitrile)palladium(II) chloride towards zinc(II) and palladium(II) derivatives. Three phthalocyanines, including a demetalated one as well as two metalated, in the core with zinc(II) and palladium(II) were characterized using 1D and 2D NMR spectroscopy and mass spectrometry. In addition, all macrocycles were subjected to absorption and emission studies as well as photostability tests. In a photochemical study, zinc(II) and palladium(II) phthalocyanine complexes appeared to be efficient singlet oxygen generators. There were noted quantum yields of singlet oxygen generation for zinc(II) phthalocyanine derivative in DMF and DMSO at 0.55 and 0.72, whereas for palladium(II) complex at 0.73 and 0.77, respectively. Liposomal formulations of phthalocyanine derivatives were prepared, and their activity was evaluated against a broad spectrum of antibiotic-resistant microorganisms, such as methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli (ESBL+), Candida albicans resistant to fluconazole, C. auris, and against dermatophytes. Phthalocyanine palladium(II) complex showed the highest bactericidal activity against all antibiotic-resistant microorganisms, including reducing C. auris growth at 3.54 log.

Excited State and Reactive Oxygen Species against Cancer and Pathogens: A Review on Sonodynamic and Sono-Photodynamic Therapy.

Photodynamic and sonodynamic therapy are therapies having great potential in the treatment of bacterial infections and cancer. Their background is associated with photo- and sonosensitizers - substances that can be excited when exposed to light or ultrasound. These sensitizers belong to a various groups of compound, including porphyrins, porphyrazines, and phthalocyanines. Releasing the energy when returning to the ground state can occur in the manner of transferring it to oxygen molecules, leading to reactive oxygen species able to disrupt membranes of bacterial and cancer cells, leaving the organism's cells unaffected. In recent years, the number of reports on numerous sensitizers being effective has been constantly growing. Therefore, the development of this field may prove beneficial for dealing with cancer and microbes. This review describes the development of photodynamic and sonodynamic therapy, as well as their combination, with emphasis on sonodynamic therapy and its potential in the treatment of cancer and bacterial infections.

Ultrasound versus Light: Exploring Photophysicochemical and Sonochemical Properties of Phthalocyanine-Based Therapeutics, Theoretical Study, and In Vitro Evaluations.

Photodynamic therapy (PDT) applications carried out with the assistance of ultrasound have attracted significant attention in recent years. The use of phthalocyanines, which are an important component as photosensitizers in PDT, is becoming more important day by day. In therapeutic applications, phthalocyanines can promote the production of reactive oxygen species. Motivated by this fact, the syntheses of metal-free (2), gallium (3), and indium (4) phthalocyanines have been achieved by substituting 4-(cinnamyloxy)phthalonitrile for the first time to evaluate their therapeutic applications. Additionally, photophysicochemical, sonophotochemical, and in vitro evaluations of phthalocyanines have been reported. To the best of our knowledge, this is the first study of the use of phthalocyanines with different metal ions as potential photosensitizers for sonophotodynamic therapy (SPDT) applications in gastric cancer cell lines. The results show that the quantum yield of the generation of singlet oxygen increased in sonophotochemical studies (ΦΔ = 0.55 (2), 0.85 (3), 0.96 (4)), compared to photochemical studies (ΦΔ = 0.22 (2), 0.61 (3), 0.78 (4)). The density functional theory (DFT) results are in good agreement with the experimental results and suggest increased reactivity of phthalocyanines 3 and 4 in various redox processes, thus implying their applicability and usefulness as potential therapeutic agents. These phthalocyanines are effective sensitizers for PDT, sonodynamic therapy (SDT), and SPDT against MKN-28 gastric cancer cell line in vitro. All three treatments decreased cell viability and induced apoptosis in the gastric cancer cell line. However, indium phthalocyanine (4)-mediated SPDT was a more effective treatment modality compared to indium phthalocyanine (4)-mediated PDT and SDT. Also, indium phthalocyanine (4) was found to be a more effective sensitizer to activate apoptosis compared to the other phthalocyanines. To sum up, phthalocyanine-mediated SPDT enhances the cytotoxic effect on gastric cancer cells more than the effect of SDT or PDT alone.

Potential thiosemicarbazone-based enzyme inhibitors: Assessment of antiproliferative activity, metabolic enzyme inhibition properties, and molecular docking calculations.

A new series of thiosemicarbazone derivatives (1-11) were prepared from various aldehydes and isocyanates with high yields and practical methods. The structures of these compounds were elucidated by Fourier transform infrared, 1 H-nuclear magnetic resonance (NMR), 13 C-NMR spectroscopic methods and elemental analysis. Cytotoxic effects of target compounds were determined by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay and compound 1 showed significant cytotoxic activity against both MCF-7 and MDA-MB-231 cells, with half-maximal inhibitory concentration values of 2.97 µM and 6.57 µM, respectively. Moreover, in this study, the anticholinergic and antidiabetic potentials of these compounds were investigated. To this aim, the effect of the newly synthesized thiosemicarbazone derivatives on the activities of acetylcholinesterase (AChE) and αglycosidase (α-Gly) was evaluated spectrophotometrically. The title compounds demonstrated high inhibitory activities compared to standard inhibitors with Ki values in the range of 122.15-333.61 nM for α-Gly (Ki value for standard inhibitor = 75.48 nM), 1.93-12.36 nM for AChE (Ki value for standard inhibitor = 17.45 nM). Antiproliferative activity and enzyme inhibition at the molecular level were performed molecular docking studies for thiosemicarbazone derivatives. 1M17, 5FI2, and 4EY6, 4J5T target proteins with protein data bank identification with (1-11) compounds were docked for anticancer and enzyme inhibition, respectively.

Phthalocyanine complexes with (4-isopropylbenzyl)oxy substituents: preparation and evaluation of anti-carbonic anhydrase, anticholinesterase enzymes and molecular docking studies.

In this study, the preparation, aggregation behavior and investigation of carbonic anhydrase and cholinesterase enzyme inhibition features of non-peripherally (4-isopropylbenzyl)oxy-substituted phthalocyanines (4-6) are reported for the first time. The chemical structures of these new phthalocyanines were elucidated by UV-Vis (ultraviolet-visible), FT-IR (Fourier transform infrared spectrometry), NMR (nuclear magnetic resonance) and MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry. The substitution of 4-isopropylbenzyl)oxy groups benefits a remarkable solubility and redshift of the phthalocyanines Q-band. Also, these complexes were tested against some enzymes such as butyrylcholinesterase enzyme, human carbonic anhydrase I and II isoforms and acetylcholinesterase enzyme. The phthalocyanine complexes showed Ki values of in the range of 478.13 ± 57.25-887.25 ± 101.20 µM against hCA I, 525.16 ± 45.87-921.14 ± 81.25 µM against hCA II, 68.33 ± 9.13-201.15 ± 35.86 µM against AChE and 86.25 ± 13.65-237.54 ± 24.7 µM against BChE. Molecular docking studies were performed to investigate the binding modes and interaction energies of the (2-6) complexes with the hCA I (PDB ID:1BMZ), hCA II (PDB ID:2ABE), AChE (PDB ID:4EY6) and BChE (PDB ID:2PM8).

1,2,3-Triazole substituted phthalocyanine metal complexes as potential inhibitors for anticholinesterase and antidiabetic enzymes with molecular docking studies.

In recent years, acetylcholinesterase (AChE) and α-glycosidase (α-gly) inhibition have emerged as a promising and important approach for pharmacological intervention in many diseases such as glaucoma, epilepsy, obesity, cancer, and Alzheimer's. In this manner, the preparation and enzyme inhibition activities of peripherally 1,2,3-triazole group substituted metallophthalocyanine derivatives with strong absorption in the visible region were presented. These novel metallophthalocyanine derivatives (2-6) effectively inhibited AChE, with Ki values in the range of 40.11 ± 5.61 to 78.27 ± 15.42 µM. For α-glycosidase, the most effective Ki values of compounds 1 and 2 were with Ki values of 16.11 ± 3.13 and 18.31 ± 2.42 µM, respectively. Also, theoretical calculations were investigated to compare the chemical and biological activities of the ligand (1) and its metal complexes (2-6). Biological activities of 1 and its complexes against acetylcholinesterase for ID 4M0E (AChE) and α-glycosidase for ID 1R47 (α-gly) are calculated. Theoretical calculations were compatible with the experimental results and these 1,2,3-triazole substituted phthalocyanine metal complexes were found to be efficient inhibitors for anticholinesterase and antidiabetic enzymes.Communicated by Ramaswamy H. Sarma.

Assessment of in vitro Cytotoxic, iNOS, Antioxidant and Photodynamic Antimicrobial Activities of Water-soluble Sulfonated Phthalocyanines.

In recent years, much effort has been devoted to the development of effective anticancer agents. In this manner, the utilization of water-soluble sulfonated phthalocyanines is crucial for many cancer cell lines. In this study, phthalonitrile and metallophthalocyanine compounds linked by benzenesulfonic acid groups have been prepared. Antimicrobial behaviors of those compounds were investigated by performing disk diffusion and photodynamic assays on gram-positive and negative bacteria. Indium phthalocyanine (InClPc) (3) showed inhibition activity against B. cereus, B. subtilis and S. aureus with disk diffusion assay. Also, gallium and indium phthalocyanines (2 and 3) exhibited inhibitory activity on both gram-positive and -negative microorganisms after light activation. Increasing the inhibitor concentration and light exposure time increased the inhibition activity for both molecules. GaClPc (2) demonstrated the maximum reducing power capacity among studied compounds, and CoPc (4) showed even better DPPH radical scavenging ability than the standard molecule Trolox at 2000 µg mL-1 concentration. The dose-dependent effect of compounds on cytotoxicity was studied against cancer cells PANC-1, MDA-MB-231, HepG2, A549, HeLa, CaCo-2 and non-tumorigenic cells HEK-293. All compounds showed no significant cytotoxic effect on any cell line up to the highest treated concentration at 50 µg mL-1 . However, all phthalocyanines had significant nitric oxide inhibition activity, and only in copper phthalocyanine (CuPc) (5), the MTT IC50 value was reached on LPS-activated RAW 264.7 macrophage cells. The lowest inducible nitric oxide synthase (iNOS) IC50 values were defined as 6 ± 1 µg mL-1 and 7 ± 0.5 µg mL-1 for CuPc (5) and InClPc (3), respectively.

Exploring of antioxidant and antibacterial properties of novel 1,3,4-thiadiazole derivatives: Facile synthesis, structural elucidation and DFT approach to antioxidant characteristics.

In recent years, compounds containing thiophene and 1,3,4-thiadiazole skeletons have become important cyclic compounds, especially in medicinal chemistry. In this manner, we synthesized and isolated seven 1,3,4-thiadiazole derivatives with thiophene groups and fully characterized by elemental analysis and general spectroscopic methods such as 1H NMR, 13C NMR, and FT-IR. Antibacterial activities of the title compounds were investigated by using TLC-Dot blot, macro dilution, well diffusion, and growth curve analysis methods. Compounds 1 and 6 showed inhibitory activities against all tested gram-negative and gram-positive bacteria. TLC-DPPH and DPPH assays, on the other hand, were performed to detect the antioxidant activities of the 1,3,4-thiadiazole derivatives and compound 1 exhibited the highest antioxidant activity at all tested concentrations. QTAIM and NCI calculations were performed as well as structural, electronic, and spectral analyzes using density functional theory (DFT). Calculations were carried out at the B3lyp/6-311 + +g(2d,2p) level of theory, and the data were used to examine the antioxidant activity of the compounds.

Biologically active phthalocyanine metal complexes: Preparation, evaluation of α-glycosidase and anticholinesterase enzyme inhibition activities, and molecular docking studies.

In this study, preparation, as well as investigation of α-glycosidase and cholinesterase (ChE) enzyme inhibition activities of furan-2-ylmethoxy-substituted compounds 1-7, are reported. Peripherally, tetra-substituted copper and manganese phthalocyanines (5 and 6) were synthesized for the first time. The substitution of furan-2-ylmethoxy groups provides remarkable solubility to the complex and redshift of the phthalocyanines Q-band. Besides, the inhibitory effects of these compounds on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glycosidase (α-Gly) enzymes have been investigated. The AChE was inhibited by these compounds (1-7) in low micromolar levels, and K i values were recorded between 11.17 ± 1.03 and 83.28 ± 11.08 µM. Against the BChE, the compounds demonstrated K i values from 7.55 ± 0.98 to 81.35 ± 12.80 µM. Also, these compounds (1-7) effectively inhibited α-glycosidase, with K i values in the range of 744.87 ± 67.33 to 1094.38 ± 88.91 µM. For α-glycosidase, the most effective K i values of phthalocyanines 3 and 6 were with K i values of 744.87 ± 67.33 and 880.36 ± 56.77 µM, respectively. Moreover, the studied metal complexes were docked with target proteins PDB ID: 4PQE, 1P0I, and 3WY1. Pharmacokinetic parameters and secondary chemical interactions that play an active role in interaction were predicted with docking simulation results. Overall, furan-2-ylmethoxy-substituted phthalocyanines can be considered as potential agents for the treatment of Alzheimer's diseases and diabetes mellitus.

Insight into the effects of the anchoring groups on the photovoltaic performance of unsymmetrical phthalocyanine based dye-sensitized solar cells.

Push-pull zinc phthalocyanine dyes bearing hexylsulfanyl moieties as electron donors and carboxyethynyl as mono- or di-anchoring groups have been designed, synthesized and tested as sensitizers in dye-sensitized solar cells (DSSCs). The effects of the anchoring groups on the optical, electrochemical and photovoltaic properties were investigated. The incorporation of a carboxyethynyl group in GT23 has a considerable effect on preventing dye aggregation due to its relatively non-planar structure. The mono-anchoring dye bearing a phenyl carboxyethynyl group, GT5, has a higher molar extinction coefficient and sufficient charge injection into the TiO2 conduction band. Therefore, GT5 achieved at least 90% higher power conversion efficiency than the di-anchoring dyes (GT31 and GT32). Time-dependent density functional theory (PBE0/6-31G(d,p)) was also used to calculate the electronic absorption spectra, which predicted very well the measured UV-Vis with an error of up to 0.11 eV for the Q bands and 0.3 eV for the B bands. The longest charge transfer bands are obtained in the visible light region and they correspond to a transfer phthalocyanine core → substituent with a carboxyethynyl group where the absorptions of GT32 (465 nm) and GT31 (461 nm) are red-shifted compared to GT23 (429 nm) and GT5 (441 nm). The interaction energy between the phthalocyanine and a cluster of anatase-TiO2 (H4Ti40O82) was calculated using density functional theory. For all phthalocyanines, the interaction favored is monodentate and corresponds to -O(OH)Ti(TiO2), where the stronger interaction occurs for GT32 (-2.11 eV) and GT31 (-2.25 eV). This study presents the molecular combination of the anchoring groups in zinc phthalocyanine sensitizers, which is one of the effective strategies for improving the performance of DSSCs.

Evaluation of carbonic anhydrase and paraoxonase inhibition activities and molecular docking studies of highly water-soluble sulfonated phthalocyanines.

The investigation of carbonic anhydrase and paraoxonase enzyme inhibition properties of water-soluble zinc and gallium phthalocyanine complexes ( 1 and 2 ) are reported for the first time. The binding of p-sulfonylphenoxy moieties to the phthalocyanine structure favors excellent solubilities in water, as well as providing an inhibition effect on carbonic anhydrase (CA) I and II isoenzymes and paraoxonase (PON1) enzyme. According to biological activity results, both complexes inhibited hCA I, hCA II, and PON1. Whereas 1 and 2 showed moderate hCA I and hCA II (off-target cytosolic isoforms) inhibitory activity (Ki values of 26.09 µM and 43.11 µM for hCA I and 30.95 µM and 33.19 µM for hCA II, respectively), they exhibited strong PON1 (associated with high-density lipoprotein [HDL]) inhibitory activity (Ki values of 0.37 µM and 0.27 µM, respectively). The inhibition kinetics were analyzed by Lineweaver-Burk double reciprocal plots. It revealed that 1 and 2 were noncompetitive inhibitors against PON1, hCA I, and hCA II. These complexes can be more advantageous than other synthetic CA and PON inhibitors due to their water solubility. Docking studies were carried out to examine the interactions between hCA I, hCA II, and PON1 inhibitors and metal complexes at a molecular level and to predict binding energies.

Aminopyrazole-substituted metallophthalocyanines: Preparation, aggregation behavior, and investigation of metabolic enzymes inhibition properties.

The synthesis, characterization, aggregation behavior, theoretical studies, and investigation of antimicrobial, antidiabetic, and anticholinergic properties of 4-(2-(5-amino-4-(4-bromophenyl)-3-methyl-1H-pyrazol-1-yl)ethoxy)phthalonitrile (2) and its soluble aminopyrazole-substituted peripheral metallo (Mn, Co, and Ni)-phthalocyanine complexes (3-5) are reported for the first time. The synthesized compounds and phthalocyanine complexes were characterized spectroscopically. The new phthalonitrile derivative (2) and its peripheral metallophthalocyanine complexes (3-5) were found to be effective inhibitors of α-glycosidase, acetylcholinesterase (AChE), human carbonic anhydrase I and II isoforms (hCA I and II), and butyrylcholinesterase (BChE) with Ki values in the range of 1.55 ± 0.47 to 10.85 ± 3.43 nM for α-glycosidase, 8.44 ± 0.32 to 21.31 ± 7.91 nM for hCA I, 11.73 ± 2.82 to 31.03 ± 4.81 nM for hCA II, 101.62 ± 26.58 to 326.54 ± 89.67 nM for AChE, and 68.68 ± 11.15 to 109.53 ± 19.55 nM for BChE. This is the first study of peripherally substituted phthalocyanines containing an aminopyrazole group as potential carbonic anhydrase enzyme inhibitor. Also, the antimicrobial activities of the synthesized compounds were evaluated against six microorganisms (four bacteria and two Candida species) using the broth microdilution method. The gram-positive bacteria were detected to be more sensitive than gram-negative bacteria and yeasts in the synthesized compounds.

Dual-purpose zinc and silicon complexes of 1,2,3-triazole group substituted phthalocyanine photosensitizers: synthesis and evaluation of photophysical, singlet oxygen generation, electrochemical and photovoltaic properties.

The synthesis, photophysical, singlet oxygen generation, electrochemical and photovoltaic properties of peripheral and axial 1,2,3-triazole group substituted zinc and silicon phthalocyanine complexes with strong absorption in the visible region were described. All novel complexes have been characterized by spectroscopic and electrochemical techniques. All the new compounds are highly soluble in most common organic solvents. The electronic absorption and fluorescence spectral properties of complexes 4 and 5 are investigated. The effects of the triazole group, different metal centers and position of the substituent on the photophysical, electrochemical and photovoltaic properties of the new phthalocyanines were also investigated for the first time in this work. According to the fluorescence measurements, the axially substituted silicon complex (5) showed higher fluorescence quantum yield (Φ F = 0.28) than the peripherally substituted zinc complex (4). In addition, quantum yields for singlet oxygen generation (Φ Δ = 0.32 for silicon complex (4) and Φ Δ = 0.76 for zinc complex (5) in DMSO) were obtained. Electrochemical studies show that complex 5 is present in non-aggregated form as a result of steric hindrance of the axial groups; the LUMO level of this complex is slightly more negative than the conduction band of TiO2 and electron injection might be less effective. Therefore, the power conversion efficiency of 1.30% for a complex 4 based dye-sensitized solar cell (DSSC) is higher than complex 5 (0.90%). Consequently, these zinc and silicon complexes are promising candidates not only for photodynamic therapy but also solar power conversion.