2. Activatable Photosensitizer Design Considerations 2842 2.1. Activation Strategy 2842 2.2. Photosensitizer Selection 2844 2.3. Photosensitizer Conjugation 2845 3. Examples of Activatable Photosensitizers 2845 3.1. Environment-Activated Photosensitizers 2845 3.2. Enzyme-Activated Photosensitizers 2846 3.3. Nucleic Acid-Activated Photosensitizers 2852 3.4. Other Activation Mechanisms 2853 4. Conclusion and Outlook 2855 5. Abbreviations 2855 6. Acknowledgments 2855 7. References 2855

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Activatable photosensitizers for imaging and therapy

Singlet molecular oxygen, 02(’Ag) , has been intensively investigated over the last few decades, primarily in relation to photosensitization reactions. In combination with the increasing awareness and interest in singlet oxygen has been the development of various methodologies for the detection and quantification of singlet oxygen production. A large body of literature now exists concerning the singlet oxygengenerating abilities of a large variety of endogenous and exogenous compounds that can be photoactivated in the UV and visible regions of the electromagnetic spectrum. The purpose of this review was to compile data from many different sources to provide a convenient resource for biological scientists with interest in this area. This compilation is essentially an updated subset of the excellent comprehensive review on singlet oxygen yields by Wilkinson et af. (l), which, unlike this compilation, was not limited to biological molecules. The data are current up to the early months of 1999. The following tables include various related parameters in addition to the central parameter of the quantum yield of singlet oxygen generation (QA) for a given photosensitizer. The methodology or technique used to measure the QA value for each entry is given and ranges from direct detection of the luminescence produced on relaxation of singlet oxygen (time-resolved [TRILIT or steady-state [SSIL]), calorimetric

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1751-1097.1999.tb08240.x

A Compilation of Singlet Oxygen Yields from Biologically Relevant Molecules

Covalent organic-frameworks (COFs) are an emerging class of porous and ordered materials formed by condensation reactions of organic molecules. Recently, the Schiff-base chemistry or dynamic imine-chemistry has been widely explored for the synthesis of COFs. The main reason for this new tendency is based on their high chemical stability, porosity and crystallinity in comparison to previously reported COFs. This critical review article summarizes the current state-of-the-art on the design principles and synthetic strategies toward COFs based on Schiff-base chemistry, collects and rationalizes their physicochemical properties, as well as aims to provide perspectives of potential applications which are at the forefront of research in materials science.

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Covalent organic frameworks based on Schiff-base chemistry: synthesis, properties and potential applications

Metal Complexes as Photo- and Radiosensitizers

A highly efficient drug vector for photodynamic therapy (PDT) drug delivery was developed by synthesizing PEGylated gold nanoparticle conjugates, which act as a water-soluble and biocompatible "cage" that allows delivery of a hydrophobic drug to its site of PDT action. The dynamics of drug release in vitro in a two-phase solution system and in vivo in cancer-bearing mice indicates that the process of drug delivery is highly efficient, and passive targeting prefers the tumor site. With the Au NP-Pc 4 conjugates, the drug delivery time required for PDT has been greatly reduced to less than 2 h, compared to 2 days for the free drug.

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Highly efficient drug delivery with gold nanoparticle vectors for in vivo photodynamic therapy of cancer.

The singlet oxygen luminescence method and the photochemical methods using 1,3-diphenylisobenzofuran (DPBF) or bilirubin ditaurate (BDT) as chemical quenchers were employed to determine the single oxygen quantum yields (ΦΔ) of different phthalocyanines and tris(2,2″-bipyridyl)ruthenium(II) dichloride in dimethylformamide (DMF) or aqueous micellar solution of 0.1 M CTAC (cetyltrimethylammonium chloride). Additionally, a perylenetetracarboxylic acid diimide derivative was examined in DMF. In a series of tetrasulfonated phthalocyanines (PTS) the following order was found: ZnPTS > GaPTS > AlPTS ≈ H2PTS > CoPTS. In general, the singlet oxygen quantum yields are higher in DMF than in 0.1 M CTAC/H2O. The results obtained with the photochemical systems are comparable with those obtained by the photophysical method. The photochemical DPBF method results in absolute values of ΦΔ. However, in micellar solution, chain reactions occur when DPBF is used as chemical quencher in the photo-oxidative process. This problem ...

Singlet Oxygen Quantum Yields of Different Photosensitizers in Polar Solvents and Micellar Solutions

Unsymmetrical zinc(II) complexes of benzonaphthoporphyrazines 5a-12a bearing between one and eight pyridyloxy substituents are synthesized by statistical tetramerization of 6-(1,1-dimethylethyl)-2,3-naphthalenedicarbonitrile (1) with 4-(3-pyridyloxy)- or 4,5-bis-(3-pyridyloxy)-1,2-benzenedicarbonitrile (2, 3). Methylation of 5a-12a leads to the catianic pyridyloxybenzonaphthoporphyrazines 5b-12b having between one to eight positive charges. The Q-band transition in the visible spectra exhibits a bathochromic shift from 680 to 760 nm dependent upon the number of annelated naphthalene rings. The singlet oxygen quantum yields of the benzonaphthoporphyrazines determined by the dye-sensitized photooxidation of 1,3-diphenylisobenzofurane is surprisingly high (in the range of zinc phthalocyanine). The photooxidative stabilities of the photosensitizers described quantitatively by first-order kinetics decrease with the number of annelated naphtho groups. A linear correlation between the logarithm of the decomposition rate constant and the position of the highest occupied molecular orbital (HOMO)-level of the photosensitizers is found. Destabilization of the HOMO leads to a decrease of the photostability. Due to their adjustable long wavelength absorption, their intramolecular polarity axis and their different hydrophilic/hydrophobic character, these novel compounds may be suitable photosensitizers for the photodynamic therapy of cancer.

Unsymmetrically substituted benzonaphthoporphyrazines: a new class of cationic photosensitizers for the photodynamic therapy of cancer.

The photo-oxidative stability of various annelated and substituted tetraazaporphyrin derivatives were investigated in N,N-dimethylformamide by irradiation in the presence of air. First-order rate constants were calculated. In addition, the positions of the HOMO and LUMO energy levels of the compounds were calculated using a commercially available program. A linear correlation between the experimental values of the rate constants and the theoretical values of the HOMO position exists. The method described allows one to predict the photo-oxidative stability by calculating their HOMO levels, which is very important for the use of macrocyclic metal complexes in photo-oxidation reactions in solution. From the calculated triplet energies it is considered that the macrocyclic metal complexes can convert by photoinduced energy transfer triplet oxygen to singlet oxygen. Experimentally, tetraazaporphyrin derivatives show high quantum yields of singlet oxygen formation under irradiation. No correlations of the quant...

Photo-oxidative Stability and its Correlation with Semi-empirical MO Calculations of Various Tetraazaporphyrin Derivatives in Solution

Monofunctional phthalocyanines 7a,b, one bearing a sulfo and the other one a carboxyl group, were synthesized by lithium alkoxyde-catalyzed statistical tetramerization of 4-(4-tert-butylphenoxy)-1,2-benzenedicarbonitrile (3c) with 1,2-dicyanobenzenes 3a,b carrying a carboxyl or sulfo group. Tribenzonaphthoporphyrazines 9a,b with one carboxyl or amino group were prepared under similar reaction conditions by tetramerization of 3,6-dihexyloxy-1,2-benzenedicar-bonitrile with 6-amino- or 6-carboxy-2,3-naphthalenedicar-bonitrile 6b,6a. The zinc(II)-containing macrocycles 7a, b, 9a, b obtained in yields of 11–20% were purified by column chromatography and characterized by UV/Vis, mass, and 1H-NMR spectroscopy.

Synthesis of phthalocyanines with one sulfonic acid, carboxylic acid, or amino group

The aim of this study is to report the synthesis and photochemical and phototherapeutic activities of tetraamido-substituted 2,3-naphthalocyanine zinc(II) complexes (ZnNcs 5-8). Four naphthalocyanine complexes, tetrabenzamido- (ZnNc 5), tetramethoxybenzamido- (ZnNc 6), tetrahexylamido- (ZnNc 7) and tetradodecylamido- (ZnNc 8) naphthalocyanine zinc complexes absorbing at around 770 nm were synthesized. The dye-sensitized photo-oxidation of 1,3-diphenylisobenzofuran via 1O2 was studied in more detail in order to compare the quantum yields of these different sensitizers. Pharmacokinetic and photodynamic therapy studies of Lewis lung carcinoma in mice were carried out after administration of liposome incorporated ZnNcs 5-8. The phototherapeutic efficiency was evaluated by changes in the mean tumour diameter with time, regrowth delay (days), average survival time (days) and electron microscopy observations. According to all assessment criteria used, the most promising photosensitizer seems to be tetrabenzamido-substituted ZnNc 5. We suggest that mainly structural properties are the reason for the better results observed. The morphological analysis confirms the mechanism of photonecrosis, which was observed in our previous work with unsubstituted and substituted ZnNcs 1-4. Direct photodamage to the membrane, mitochondria and rough endoplasmic reticulum in the neoplastic cells and delayed photodestruction of the endothelial cells surrounding the tumour tissue were detected. Also, changes in lysosomes were observed. The data presented through different parameters are compared with such obtained for other photodynamic therapy sensitizers.

Tetraamido-substituted 2,3-naphthalocyanine zinc(II) complexes as phototherapeutic agents: synthesis, comparative photochemical and photobiological studies

H. Kliesch

Papers

Singlet Oxygen Quantum Yields of Different Photosensitizers in Polar Solvents and Micellar Solutions

Unsymmetrically substituted benzonaphthoporphyrazines: a new class of cationic photosensitizers for the photodynamic therapy of cancer.

Photo-oxidative Stability and its Correlation with Semi-empirical MO Calculations of Various Tetraazaporphyrin Derivatives in Solution

Synthesis of phthalocyanines with one sulfonic acid, carboxylic acid, or amino group

Tetraamido-substituted 2,3-naphthalocyanine zinc(II) complexes as phototherapeutic agents: synthesis, comparative photochemical and photobiological studies