Silicon Phthalocyanine Derivative Research Articles

Novel axially di-substituted natural, cationic and zwitter ionic silicon phthalocyanine derivatives: Synthesis, characterization, sono-photochemical properties

This study focuses on investigating the sono-photophysicochemical properties of recently synthesized and characterized di-axially substituted silicon phthalocyanine complexes, incorporating schiff-base groups and zwitter ions, imparting novel features and potential therapeutic applications. Specifically, our research focused on evaluating the suitability of these complexes for photodynamic therapy (PDT), sonodynamic therapy (SDT), and the emerging field of sono-photodynamic therapy (SPDT). The characterization process involved the application of various analytical techniques, including UV–Vis spectroscopy, infrared (FT-IR) spectroscopy, and proton nuclear magnetic resonance (1H NMR) spectroscopy. Experimental results displayed highly promising outcomes, revealing that the synthesized sensitizers exhibited exceptional efficiency in generating reactive oxygen species, a critical attribute necessary for effective therapeutic interventions. This finding significantly contributes to the development of novel therapeutic agents with enhanced photodynamic and sonodynamic properties. Harnessing the power of light and sound simultaneously through sonophotodynamic therapy offers a unique and synergistic approach, potentially amplifying the therapeutic efficacy of these complexes. The combination of sonochemical and photochemical applications produced better results, for the studied compounds, the quaternized complexes (cationic compounds) showed the higher result. Overall, the results suggest that SPDT is a promising combination therapy for cancer treatment.

A novel diaxially silicon phthalocyanine sensitizer for the generation of high efficiency singlet oxygen in photochemical and sono-photochemical studies

Cancer that is caused by unregulated proliferation and growth of cells in different organs and tissues throughout the body, is one of the most common, difficult to treat and deadly diseases of the century. While photodynamic therapy (PDT) method was primarily used in the treatment of cancer disease, sonodynamic therapy (SDT) method was then utilized as an alternative solution and finally sono-photodynamic therapy (SPDT) treatment was developed as the combination of these two therapeutic methods. Ultrasound waves have the ability to penetrate deep into tissues, allowing SDT and SPDT to reach and treat tumors located in deeper regions. The importance of these studies lies in their potential for non-invasive treatment, enhanced therapeutic efficacy, selective targeting, develop novel photosensitizers, deep tissue treatment, versatility in combination therapy, and their contribution to research and development in the field of therapeutic ultrasound and PDT. Today, the use of phthalocyanine complexes, known as sensitizers that can produce high amounts of reactive oxygen, is becoming increasingly important in these therapeutic methods. To achieve this objective, a novel silicon phthalocyanine derivative with bromo‑naphthoxy substitution was synthesized and subjected to characterization through various spectroscopic methods including elemental analysis, FT-IR, UV–Vis, MALDI-TOF MS, and 1HNMR. Photophysical, photochemical and sono-photochemical properties of the new complex were studied and analyzed. While the singlet oxygen efficiency in PDT method was found as ФΔ=0.78 in DMSO, ФΔ=0.69 in DMF, it was figured out in SPDT method as ФΔ=0.94 in DMSO and ФΔ=0.81 in DMF. This data shows that the new phthalocyanine compound is a good photosonosensitizer candidate that can be used in both PDT and SPDT methods.

Molecular Engineering of Silicon Phthalocyanine to Improve the Charge Transport and Ammonia Sensing Properties of Organic Heterojunction Gas Sensors

AbstractNovel organic heterostructures fabricated with a bilayer consisting of an axially substituted silicon phthalocyanine (R2‐SiPc) derivative and lutetium bis‐phthalocyanine (LuPc2) are investigated for their ammonia sensing properties. Surface and microstructure characterization of the heterostructure films reveal either compact or highly porous surface topography in (345F)2‐SiPc and Cl2‐SiPc‐based heterostructures, while electrical characterization reveals a strong influence of the axial substituent in R2‐SiPc on NH3 sensing capabilities. Electrical characterization further demonstrates an apparent energy barrier for interfacial charge transport, which is higher in the (345F)2‐SiPc/LuPc2 heterojunction device. In‐depth charge transport studies by impedance spectroscopy further reveal a resistive interface in (345F)2‐SiPc/LuPc2 and faster bulk and interfacial charge transport in Cl2‐SiPc/LuPc2 heterojunction devices. Different interfacial charge transport capabilities and surface topographies affect NH3 sensing properties of the two heterojunction devices, in which (345F)2‐SiPc/LuPc2 reveals a fast and non‐linear response with a limit of detection (LOD) of 310 ppb, while Cl2‐SiPc/LuPc2 exhibits a slow, and linear response to NH3 with LOD of 100 ppb. Finally, different metrological parameters of the two sensors are correlated to the respective gas‐material interactions, in which adsorption and diffusion regimes are modulated by the surface topography and hydrophobicity of the sensing layer.

High Performance Solution Processed n‐Type OTFTs through Surface Engineered F–F Interactions Using Asymmetric Silicon Phthalocyanines

AbstractTwo novel asymmetric silicon phthalocyanine (SiPc) derivatives consisting of one axially substituted fluorine and one tri‐alkyl silane group are synthesized and characterized in n‐type solution processed bottom‐gate top‐contact organic thin‐film transistors (OTFTs). The effect of surface energy and fluorination are investigated at the dielectric/semiconductor interface by thin‐film X‐ray diffraction, atomic force microscopy, bright field real‐color microscopy, and grazing‐incidence wide‐angle X‐ray scattering to assess alterations in film conformation, microstructure, and morphology. Low surface energy dielectric modification and the presence of fluorine interactions produce films with large area crystalline domains that promote charge carrier transport resulting in high performing OTFTs, with a clear relationship determined between surface energy, fluorination, and OTFT operation. Through modifying deposition solvent and the exploitation of fluorine–fluorine interactions, the asymmetric SiPc derivative, (tri‐n‐hexylsilyl oxide) fluorosilicon phthalocyanine (F‐3HS‐SiPc), leads to high performing n‐type OTFTs with an average field‐effect mobility of 0.13 cm2 V−1 s−1 and a threshold voltage of 26.3 V. These results successfully demonstrate the use of asymmetric axial fluorination as a route to high performance n‐type OTFT devices through controlled self‐assembly by fluorine–fluorine interactions.

Chemo-photodynamic Activity of Silicon Phthalocyanines Bearing Cyclooxygenase Inhibitors on Colorectal Cancer Cell Lines.

Colorectal cancer ranks as the third most lethal cancer worldwide, resulting in over 1 million cases and 900 000 deaths per year. According to population-based studies, administration of long-term non-steroidal anti-inflammatory drugs (NSAIDs) was proven to reduce the risk of a subject developing colorectal cancer. In the present study, the anti-cancer activity of two different NSAIDs, sulindac- (Pc-1) or diclofenac-substituted (Pc-2) asymmetric silicon phthalocyanine derivatives, was evaluated in four different colorectal cancer cell lines bearing various carcinogenic mutations. In this context, the IC50 values of each compound after 24 and 48 h were determined on HCT116, SW480, LoVo, and HT29 cell lines, and the effects of the compounds on programmed cell death pathways apoptosis and autophagy, their impact on cell cycle progression, and the effect of NSAID moieties they bear on COX-1 and COX-2 proteins were analyzed. In addition, the photophysical and photochemical properties of a synthesized Pc derivative bearing axial diclofenac and triethylene glycol groups (Pc-2) have been investigated, and the compound has been characterized by using different analytical techniques. Our results indicated that both compounds inhibit COX protein expression levels, activate apoptosis in all cell lines, and lead to cell cycle arrest in the G2/M phase, depending on the COX expression profiles of the cell lines, indicating that NSAIDs can be coupled with Pc's to achieve increased anti-cancer activity, especially on cancer cells known to have high COX activity.

Novel Functional Axially Substituted Silicon (IV) Phthalocyanine Derivative and its Photochemical Properties

Photodynamic therapy is a highly specific and clinically approved method in which a non-toxic photosensitizer drug is administered to the patient for cancer treatment. Phthalocyanines with their long wavelength absorption and fluorescence from 650 to 800 nm can be used as photosensitizers for photodynamic therapy and are used in clinical trials. In this study, functional novel axially substituted silicon (IV) phthalocyanine (PS-2) was synthesized. Unsubstituted dichlorosilicon (IV) phthalocyanine was synthesized from 1,3-diiminoisoindoline via cyclotetramerization. The axial substitution reaction was carried out using dichlorosilicon (IV) phthalocyanine and excess of N-Boc-ethanolamine. Structural characterization of this novel PS-2 by FT-IR, mass, 1H NMR and UV-Vis spectroscopy were performed. Photochemical properties (photo degradation quantum yields (d) and singlet oxygen quantum yield () of PS-2, which are the first steps for cancer treatment, were investigated.

Influence of photosensitizer concentration and polymer composition on photoinduced antimicrobial activity of PVA- and PVA-chitosan-based electrospun nanomaterials cross-linked with tailor-made silicon(IV) phthalocyanine

The ongoing effort to eradicate pathogenic bacteria and viruses is a major endeavor that requires development of new and innovative materials. Materials based on photodynamic action represent an emerging and attractive area of research, and therefore, a broad understanding of chemical design principles is required. In the present study, we investigated the antibacterial and antiviral activities of five different nanofibrous membranes composed of poly(vinyl alcohol) or poly(vinyl alcohol)-chitosan mixture cross-linked through silicon(IV)phthalocyanine derivative with the aim to identify the role of the carrier polymer and photosensitizers concentration on its efficacy. A straightforward cross-linking process was adopted to create a water-stable material with an almost uniform distribution of the fiber structure, as revealed by scanning electron microscopy. The results of the antimicrobial studies showed that the increase in the amount of chitosan in the polymer mixture, rather than the increase in the photosensitizer concentration, enhanced the activity of the material. Due to their visible light-triggered antimicrobial activity, the resulting materials provide valuable opportunities for both topical antimicrobial photodynamic therapy and the area of environmental remediation.Graphical abstract

Highlighting the processing versatility of a silicon phthalocyanine derivative for organic thin-film transistors

Silicon phthalocyanine (SiPc) derivatives have recently emerged as promising materials for n-type organic thin-film transistors (OTFTs) with the ability to be fabricated either by solid state or solution processes through axial functionalization.

Synthesis, Photophysical Properties and DNA-Photocleavage Activity of Silicon Phthalocyanine Derivatives

Synthesis, Photophysical Properties and DNA-Photocleavage Activity of Silicon Phthalocyanine Derivatives

Front Cover: EPR Characterisation of Phthalocyanine Radical Anions in Near‐Infrared Photocleavage of the Hydrophilic Axial Ligand of a Photoimmunotherapeutic Reagent, IR700 (ChemPhotoChem 1/2022)

The Front Cover depicts the formation mechanism of photo-induced cytotoxic aggregation through two-step cleavage reactions of the hydrophilic axial ligands of the silicon phthalocyanine derivative IR700 in photoimmunotherapy. More information can be found in the Article by Osamu Inanami, Wakako Hiraoka, Mikako Ogawa and co-workers.

EPR Characterisation of Phthalocyanine Radical Anions in Near‐Infrared Photocleavage of the Hydrophilic Axial Ligand of a Photoimmunotherapeutic Reagent, IR700

AbstractPhotoimmunotherapy (PIT) is a novel cancer therapy that utilises tumour‐specific monoclonal antibodies coupled with a silicon phthalocyanine derivative with biaxial ligands (IR700). Near‐infrared (NIR)‐induced cleavage of these axial ligands induces the aggregation of IR700 on the cell membrane, resulting in cell death. Using electron paramagnetic resonance (EPR) spectroscopy and computer spectral simulation, NIR irradiation of the IR700 aqueous solution under hypoxia revealed induced IR700 anion radicals in the presence of an electron donor. Two types of IR700 anion radicals with different anisotropies were identified as the precursors of the two‐step NIR‐induced cleavage reaction of the axial ligand of IR700. Under aerobic conditions, NIR irradiation of IR700 aqueous solution with and without the electron donor produced 1O2 and O2.−, respectively. These results suggest that NIR‐induced IR700 anion radicals are important for inducing the aggregation of IR700 and O2.−.

Hurdles for the wide implementation of photoimmunotherapy.

Near infrared photoimmunotherapy (NIR-PIT) is a molecularly targeted treatment for cancers achieved by injecting a conjugate of IRDye700DX® (IR700), a water-soluble silicon phthalocyanine derivative in the near infrared, and a monoclonal antibody that targets cancer cell antigens. NIR-PIT is a highly specific treatment with few side effects thatresults in rapid immunogenic cell death. Despite it being a very effective and innovative therapy, there are a few challenges preventingfull implementation in clinical practice. These include the limits of near infrared light penetration, selection of targets, concerns about tumor lysis syndromeand drug costs. However, NIR-PIT has been approved by the regulatory authorities in Japan, allowing for exploration of how to mitigate challenges while maximizing the benefits of this treatment modality.

Sequential intraparticle Förster resonance energy transfer for multi-wavelength bioimaging

Core/shell nanoparticles composed of a silica core over which a propargyl methacrylate (PMA) shell was polymerized around were synthesized. To employ the shell coating, the surface of the silica nanoparticles (SiNPs) was modified with an alkene-terminated organometallic silane linker that allowed for the covalent attachment of a poly(propargyl methacrylate) (pPMA) shell. The alkyne groups resulting from the pPMA shell were utilized in copper(I)-catalyzed azide/alkyne cycloaddition (CuAAC) reactions to attach azide-modified Förster resonance energy transfer (FRET) pairs of naphthalimide (azNap), rhodamine B (azRhod), and silicon phthalocyanine (azSiPc) derivatives to the shell surface. The luminescence of the system was manipulated by the covalent attachment of one, two, or three of the fluorophores resulting in no energy transfer, one energy transfer, or two energy transfers, respectively. When all three fluorophores were attached to the core/shell particles, an excitation of azNap with a wavelength of 400 nm resulted in the sequential energy transfer between two FRET pairs and the sole emission of azSiPc at 670 nm. These particles may have applications as bioimaging probes as their luminescence is easily detected using fluorescence microscopy.

Discotic liquid crystals of silicon phthalocyanine-based singledeckers and doubledeckers: Influence of the axial substituent groups on their mesomorphism

Three kinds of silicon phthalocyanine derivatives axially substituted by different groups were prepared and Singledecker-C[Formula: see text]PcSiCl2 (1a), Singledecker-C[Formula: see text]PcSi2(OH)4 (3a, b) and Doubledecker-(C[Formula: see text]PcSi)2Cl2 (4a, b) were obtained in order to investigate their mesomorphism for [Formula: see text] = 8 (a) and 12 (b). The mesomorphism was established by using polarizing microscopic observations, differential scanning calorimetric measurements, temperature-dependent electronic absorption spectra and temperature-dependent X-ray diffraction analysis. From the results, each of the derivatives, 1a, 3a, 3b, 4a and 4b showed columnar mesophases; 1a: Col[Formula: see text](P21/a), pseudo Col[Formula: see text] and Col[Formula: see text]; 3a, b: Col[Formula: see text](P21/a) and Col[Formula: see text]; 4a, b: two kinds of Col[Formula: see text]. Interestingly, each of the virgin samples of singledeckers, C8PcSiCl2 (1a), C8PcSi2(OH)4 (3a) and C8PcSi2(OH)4 (3a), were green in color but changed into blue over ca.180–190 [Formula: see text]C by polymerization. On the other hand, each of the double-deckers, (C[Formula: see text]PcSi)2Cl2derivatives (4a and 4b), decomposed over ca. 180–240[Formula: see text]C. Thus, the influence of the axial groups is so large on their mesomorphism that they exhibit unusual mesomorphic behaviors accompanied by color change.

Synthesis and photodynamic activities of novel silicon(iv) phthalocyanines axially substituted with water soluble groups against HeLa cancer cell line.

In this study, compounds 1 and 2, and their silicon(iv) phthalocyanine (SiPc) derivatives 3 and 4, which bear these ligands as substituents on the axial positions were synthesized. These SiPcs (3 and 4) were also converted to their water soluble derivatives (3a and 4a). All these novel compounds were fully characterized by a combination of spectroscopic data such as FT-IR, 1H-NMR, 13C-NMR and UV-vis as well as mass spectroscopy. The photophysicochemical properties (fluorescence quantum yields and lifetimes, singlet oxygen, and photodegradation quantum yields) were investigated in DMSO for all the studied SiPcs (3 and 4) and in both DMSO and aqueous solutions for the water soluble SiPcs (3a and 4a). Effects of quaternization of these phthalocyanines on photophysicochemical properties were also determined. The photodynamic therapy activities of the water soluble SiPcs (3a and 4a) were tested against to the HeLa cancer cell lines and these phthalocyanines exhibited cytotoxicity against these cell lines.

Chitosan‐Silicon Phthalocyanine Conjugate as Effective Photo‐Functional Hydrogel for Tracking and Killing of Bacteria

Hydrogels are attractive materials for many biomedical applications, including drug delivery and wound healing. A light‐triggered antibacterial activity can be conferred to the material with the introduction of appropriate photosensitizers (PS). In this study, we have synthesized water‐soluble silicon(IV)phthalocyanine derivative (SiPc) that contains four carboxylic groups on the periphery of the macrocycle. Obtained PS serves not only as an active chromophore but also as a cross‐linking gelator, enabling simple and easy synthesis of chitosan conjugate (SiPcCh). Although UV/Vis and fluorescence spectroscopic methods showed that both free and conjugated PS are non‐aggregated in water media, only SiPcCh possess remarkable antibacterial effect against Gram‐positive B. subtilis and Gram‐negative E. coli.

Surface Modification of Liposomes Using IR700 Enables Efficient Controlled Contents Release Triggered by Near-IR Light.

Stimuli-responsive liposomes are promising drug carriers for cancer treatment because they enable controlled drug release and the maintenance of desired drug concentrations in tumor tissue. In particular, near-IR (NIR) light is a useful stimulus for triggering drug release from liposomes based on its advantages such as deep tissue penetration and safety. Previously, we found that a silicon phthalocyanine derivative, IR700, conjugated to antibodies, can induce the rupture of the cell membrane following irradiation by NIR light. Based on this finding, we constructed IR700-modified liposomes (IR700 liposomes) and evaluated their drug release properties triggered by NIR light. IR700 liposomes released substantial amounts of encapsulated calcein following irradiation by NIR light. Drug release was substantially suppressed by the addition of sodium azide, suggesting that liposomal membrane permeabilization was mediated by singlet oxygen generated from IR700. Moreover, calcein release from IR700 liposomes triggered by NIR light was promoted under conditions of deoxygenation and the presence of electron donors. Thus, membrane disruption should be induced by the physical change of IR700 from highly hydrophilic to hydrophobic as we previously described, although singlet oxygen can cause a certain level of membrane disruption under normoxia. We also observed that doxorubicin-encapsulated IR700 liposomes exhibited significant cytotoxic effects against CT-26 murine colon carcinoma cells following NIR light exposure. These results indicate that IR700 liposomes can efficiently release anti-cancer drugs following NIR light irradiation even under hypoxic conditions and, therefore, they would be useful for cancer treatment.

Near-Infrared Photoimmunotherapy of Cancer.

ConspectusThis Account is the first comprehensive review article on the newly developed, photochemistry-based cancer therapy near-infrared (NIR) photoimmunotherapy (PIT). NIR-PIT is a molecularly targeted phototherapy for cancer that is based on injecting a conjugate of a near-infrared, water-soluble, silicon-phthalocyanine derivative, IRdye700DX (IR700), and a monoclonal antibody (mAb) that targets an expressed antigen on the cancer cell surface. Subsequent local exposure to NIR light turns on this photochemical “death” switch, resulting in the rapid and highly selective immunogenic cell death (ICD) of targeted cancer cells. ICD occurs as early as 1 min after exposure to NIR light and results in irreversible morphologic changes only in target-expressing cells based on the newly discovered photoinduced ligand release reaction that induces physical changes on conjugated antibody/antigen complex resulting in functional damage on cell membrane. Meanwhile, immediately adjacent receptor-negative cells are totally unharmed. Because of its highly targeted nature, NIR-PIT carries few side effects and healing is rapid. Evaluation of the tumor microenvironment reveals that ICD induced by NIR-PIT results in rapid maturation of immature dendritic cells adjacent to dying cancer cells initiating a host anticancer immune response, resulting in repriming of polyclonal CD8+T cells against various released cancer antigens, which amplifies the therapeutic effect of NIR-PIT. NIR-PIT can target and treat virtually any cell surface antigens including cancer stem cell markers, that is, CD44 and CD133. A first-in-human phase 1/2 clinical trial of NIR-PIT using cetuximab-IR700 (RM1929) targeting EGFR in inoperable recurrent head and neck cancer patients successfully concluded in 2017 and led to “fast tracking” by the FDA and a phase 3 trial (https://clinicaltrials.gov/ct2/show/NCT03769506) that is currently underway in 3 countries in Asia, US/Canada, and 4 countries in EU. The next step for NIR-PIT is to further exploit the immune response. Preclinical research in animals with intact immune systems has shown that NIT-PIT targeting of immunosuppressor cells within the tumor, such as regulatory T-cells, can further enhance tumor-cell-selective systemic host-immunity leading to significant responses in distant metastatic tumors, which are not treated with light. By combining cancer-targeting NIR-PIT and immune-activating NIR-PIT or other cancer immunotherapies, NIR-PIT of a local tumor, could lead to responses in distant metastases and may also inhibit recurrences due to activation of systemic anticancer immunity and long-term immune memory without the systemic autoimmune adverse effects often associated with immune checkpoint inhibitors. Furthermore, NIR-PIT also enhances nanodrug delivery into tumors up to 24-fold superior to untreated tumors with conventional EPR effects by intensively damaging cancer cells behind tumor vessels. We conclude by describing future advances in this novel photochemical cancer therapy that are likely to further enhance the efficacy of NIR-PIT.

Determining and unravelling origins of reduced photoinactivation efficacy of bacteria in milk

Bovine mastitis is an endemic disease of dairy cattle that is considered to be one of the most frequent and costly diseases in veterinary medicine. An increase in the incidence of disease results in the increased use of antibiotics, which in turn increases the potential of bacterial resistance. This study aimed to investigate the effectiveness of antimicrobial photodynamic therapy (aPDT) in the treatment of bovine mastitis, as an alternative to systemic antibiotics. To identify the key factors affecting photoinactivation efficacy, realistic experiments in view of the end-use were conducted in milk samples using two different photosensitizers: methylene blue (MB) and silicon (IV) phthalocyanine derivative (SiPc). We explored the effects of divalent ions and fat content on the aPDT outcome and determined influence of different proteins on aPDT efficacy. Levels of bacterial sensitivity to PSs varied depending on the type of bacteria (Gram-positive vs. Gram-negative) and light exposure time. Critical interrelated factors affecting aPDT in milk were identified and an efficient combination of treatment conditions that can lead to a full photodynamic inactivation of bacteria was determined.

Photoinduced Ligand Release from a Silicon Phthalocyanine Dye Conjugated with Monoclonal Antibodies: A Mechanism of Cancer Cell Cytotoxicity after Near-Infrared Photoimmunotherapy

Photochemical reactions can dramatically alter physical characteristics of reacted molecules. In this study, we demonstrate that near-infrared (NIR) light induces an axial ligand-releasing reaction, which dramatically alters hydrophilicity of a silicon phthalocyanine derivative (IR700) dye leading to a change in the shape of the conjugate and its propensity to aggregate in aqueous solution. This photochemical reaction is proposed as a major mechanism of cell death induced by NIR photoimmunotherapy (NIR-PIT), which was recently developed as a molecularly targeted cancer therapy. Once the antibody-IR700 conjugate is bound to its target, activation by NIR light causes physical changes in the shape of antibody antigen complexes that are thought to induce physical stress within the cellular membrane leading to increases in transmembrane water flow that eventually lead to cell bursting and necrotic cell death.