Sulfanyl Porphyrazines with Morpholinylethyl Periphery—Synthesis,Electrochemistry, and Photocatalytic Studies after Deposition on Titanium(IV) Oxide P25 Nanoparticles

The syntheses, spectral UV–Vis, NMR, and electrochemical as well as photocatalytic properties of novel magnesium(II) and zinc(II) symmetrical sulfanyl porphyrazines with 2-(morpholin-4-yl)ethylsulfanyl peripheral substituents are presented. Both porphyrazine derivatives were synthesized in cyclotetramerization reactions and subsequently embedded on the surface of commercially available P25 titanium(IV) oxide nanoparticles. The obtained macrocyclic compounds were broadly characterized by ESI MS spectrometry, 1D and 2D NMR techniques, UV–Vis spectroscopy, and subjected to electrochemical studies. Both hybrid materials, consisting of porphyrazine derivatives embedded on the titanium(IV) oxide nanoparticles’ surface, were characterized in terms of particle size and distribution. Next, they were subjected to photocatalytic studies with 1,3-diphenylisobenzofuran, a known singlet oxygen quencher. The applicability of the obtained hybrid material consisting of titanium(IV) oxide P25 nanoparticles and magnesium(II) porphyrazine derivative was assessed in photocatalytic studies with selected active pharmaceutical ingredients, such as diclofenac sodium salt and ibuprofen.     

Photochemical and spectral characterization of peripherally modified porphyrazines

The photochemical properties of a new family of porphyrazines with annulated strongly electron-withdrawing 1,2,5-selenadiazole rings were studied. The experiments were performed on three compounds, two metallated at the core with Mg(II) or Zn(II) ions, and a third one that was demetallated.The photostability of these porphyrazines was studied in solution according to the conditions recommended in the first version of the document issued by ICH. The substances analyzed were irradiated with a high-pressure mercury lamp (HBO-50). The samples were irradiated with wavelengths corresponding to the Soret and Q bands, selected by the use of appropriate filters.The method used for evaluation of porphyrazine photodecomposition was subjected to a validation procedure by determination of linearity, LOD, LOQ and precision. The photodegradation appeared to follow first-order kinetics. Quantitative evaluation of the photochemical decomposition was performed on the basis of the photodegradation parameters. Furthermore, quantum yields have been estimated using the quinine solution as a chemical actinometer. The experimental quantum yields were extrapolated to the initial concentration of porphyrazine to obtain the actual quantum yields. The photochemical stability of the PzMg(II) hexapropyl(selenadiazole)porphyrazine complex was found to be greater than that of the PzZn(II) complex and the demetallated Pz2H.The photosensitizing activity of the porphyrazines was evaluated by application of 1,3-diphenylisobenzofuran (DPBF) as a singlet oxygen chemical quencher. The values of singlet oxygen generation obtained for the compounds were compared with zinc phthalocyanine (ZnPc), used as a standard. The results revealed that the PzZn(II) derivative is the most efficient sensitizer. The quantum yield of singlet oxygen generation was φ = 0.85, 0.67 and 0.17 for PzZn, PzMg and Pz2H, respectively.     

New promising porphyrazine-based agents for optical theranostics of cancer

New porphyrazine bases containing peripheral benzyloxyphenyl groups have been synthesized by the template method. The procedure includes condensation of aromatic aldehydes with malononitrile, transformation of arylmethylidenemalononitriles to arylethenetricarbonitriles, template assembly of porphyrazine macrocycle on bis(indenyl)ytterbium(II) complex, and removal of the central metal ion. Luminescence properties of the synthesized porphyrazines and their dependence on the viscosity of the medium were studied, and the light and dark toxicities of the porphyrazines have been estimated. The obtained results suggest the possibility of using these porphyrazines as optical theranostic agents of new generation.     

Synthesis and spectral properties of 1,2,5-thiadiazolo-, 1,2,5-selenadiazolo-, and benzo-fused β-phenyl-substituted porphyrazines

Cross cyclotetramerization of trans-2,3-diphenylbutanedinitrile with 1,2,5-thia(selena)diazole-3,4-dicarbonitriles or phthalodinitrile in the presence of magnesium butoxide gave mixtures of Mg(II) porphyrazine complexes which were treated with trifluoroacetic acid to isolate unsymmetrical hexaphenyl-substituted 1,2,5-thia(selena)diazolo-and benzo-fused porphyrazines together with diphenyltribenzoporphyrazine. Their ¹H NMR and electronic absorption spectra (in the UV and visible regions) were recorded. The effect of benzene and heteroring fusion on the electronic and steric structure and spectral properties of porphyrazine derivatives was studied in terms of the molecular orbital perturbation theory and semiempirical quantum-chemical calculations (AM1, PM3, ZINDO/S, CNDO/S).     

ROM polymerization-capture-release: application to the synthesis of unsymmetrical porphyrazinedithiols and peripherally metalated derivatives

Crossover Linstead macrocyclization of a doubly norbornenyl-functionalized dimercaptomaleonitrile with dipropylmaleonitrile gave a crude mixture of porphyrazines containing the hexapropylporphyrazinedithiol magnesium complex. The mixture was subjected to ring-opening metathesis polymerization to yield the insoluble porphyrazinedithiol-functionalized polymers. Cleavage from the polymer backbone using mercury(II) acetate followed by reaction with electrophiles gave access to a range of thioporphyrazinedithiol derivatives including solitaire porphyrazines. Studies into the possible uses of hexapropyl-2,3-di-(carboxymethylthio)porphyrazine in sensing metal cations in solution are described.     

Peripherally metalated secoporphyrazines: a new generation of photoactive pigments

Base-catalyzed cross condensation of dipropylmaleonitrile 1 with bis(dimethylamino)maleonitrile 2 in an equimolar ratio afforded the porphyrazines 3a, 4a, 5a, 6a and 7a. Subsequent demetalation of 5a with TFA followed by remetalation with Zn(OAc)(2) gave ligand 5c in good yield. Compound 5c was, in turn, selectively oxidized and further peripherally functionalized using Pt(PhCN)(2)Cl(2) and PdCl(2) to yield the novel seco solitaire porphyrazines 10a and 10b. The photophysical profiles of the seco solitaire porphyrazines 10a and 10b were evaluated by means of absorption, emission, and transient absorption spectroscopy. The new pigments 10a and 10b were found to be photochemically more stable than the solitaire complexes 3d and 3e and mediated the generation of singlet oxygen with quantum yields of 0.59 and 0.45, respectively.     

Synthesis and Characterisation of Unsymmetrical Porphyrazines Containing Bis(hydroxyethylthio) Substituents

Summary. Unsymmetrical porphyrazines bearing a single peripheral bis(hydroxyethylthio) moiety were synthesised by mixed condensation of bis(2-hydroxyethylthio)maleonitrile and phthalonitrile. Complexation of the thioether groups of metal-free porphyrazine with PdCl₂ further lowered the intensity of the Q-band absorption of the porphyrazine core. The new compounds were characterised by elemental analyses, IR, ¹H NMR, UV-Vis, and mass spectra.     

Synthesis and Characterisation of Unsymmetrical Porphyrazines Containing Bis(hydroxyethylthio) Substituents

Unsymmetrical porphyrazines bearing a single peripheral bis(hydroxyethylthio) moiety were synthesised by mixed condensation of bis(2-hydroxyethylthio)maleonitrile and phthalonitrile. Complexation of the thioether groups of metal-free porphyrazine with PdCl₂ further lowered the intensity of the Q-band absorption of the porphyrazine core. The new compounds were characterised by elemental analyses, IR, ¹H NMR, UV-Vis, and mass spectra.     

Comparative studies of photophysical and photochemical properties of solketal substituted platinum(II) and zinc(II) phthalocyanine sets

A complete set of platinum(II) solketal substituted phthalocyanines has been synthesized and characterized. To evaluate their potential as Type II photosensitizers for photodynamic therapy, comparative studies of their photophysical and photochemical properties with analogous zinc(II) series have been achieved: electronic absorption, fluorescence quantum yields, lifetimes, and fluorescence quenching by benzoquinone, as well as singlet oxygen generation and photodegradation. It appears that platinum(II) phthalocyanines are worth being used as Type II photosensitizers, as they exhibit good singlet oxygen generation and appropriate photodegradation.     

Bis(dimethylamino)porphyrazines: synthetic, structural, and spectroscopic investigations

The synthesis and isolation of unsymmetrical porphyrazines bearing two, four, and six bis-(dimethylamino) functionalities has been achieved via the base-catalyzed cross-condensation of 1,2-dicyanobenzene 8 and bis(dimethylamino)maleonitrile 7. In addition, the benzo-fused hexaaminoporphyrazine dimer 10 was prepared from condensation of dinitrile 7 (in excess) with benzenebis(1,3-diiminopyrroline) 9. Electrochemical studies reveal that all porphyrazines may be readily oxidized. The X-ray structures of porphyrazines 2b and 5a and the cis isomer 3a are presented. The latter is the first structure of a porphyrazine having a cis-type substitution pattern. The extended pi-conjugation in dimer 10 causes a approximately 100 nm red-shifted Q-band in the electronic absorption spectrum.     

Photophysics and photochemistry of tetraanthraporphyrazines; attempts to obtain a new generation of photosensitizers

Linearly benzo-annulated copper porphyrazines, such as octaphenyltetraanthraporphyrazinato-copper and octapentoxytetranaphthoporphyrazinato-copper, with absorption maxima at about 880 nm, were synthesized. These compounds exhibit very low-lying triplets with an energy below the activation energy of singlet oxygen. Therefore they do not generate singlet oxygen. The transient absorption spectra of the T₁—T_x transition were measured. The solvent dependence of the photophysical parameters in the triplet manifold is discussed. On irradiation in the presence of CBr₄, π-cation radicals are formed.     

Dithiacrown Ether Substituted Porphyrazines: Synthesis, Single-Crystal Structure, and Control of Aggregation in Solution by Complexation of Transition-Metal Ions

The synthesis of novel magnesium, copper, and metal-free porphyrazines, peripherally substituted with dithia-7-crown-2 (MPz(7)), dithia-15-crown-5 (MPz(15)), and dithia-18-crown-6 (MPz(18)) macrocycles is reported. These compounds are prepared starting from dicyanoethylene containing crown ethers 3, 2(1), and 2(2), respectively, which contain sulfur as well as oxygen heteroatoms. The "crowned" porphyrazines bind silver(I) and mercury(II) perchlorates. UV/vis spectroscopy and electron paramagnetic resonance measurements reveal that addition of the transition-metal ions leads to dimerization of the porphyrazine complexes. In the case of the dithia-18-crown-6-substituted porphyrazines, the dimers break up to form monomeric 6:1 guest-host complexes when more than 2 equiv of the metal ion is added. The single-crystal structures of the crown ether 2(2) and the porphyrazine MgPz(18) are presented. Compound C(14)H(20)N(2)O(4)S(2) (2(2)) crystallizes in the monoclinic space group P2(1)/c with a = 10.9310(13) ?, b = 19.383(3) ?, c = 8.6976(14) ?, beta = 108.898(11) degrees, V = 1743.5(5) ?(3), and Z = 4. The structure refinement converged to R = 0.0366 and R(w) = 0.0504. Compound C(56)H(82)MgN(8)O(17)S(8) (MgPz(18)) crystallizes in the triclinic space group P&onemacr; with a = 9.584(3) ?, b = 17.672(2) ?, c = 19.620(4) ?, alpha = 84.904(14) degrees, beta = 85.21(2) degrees, gamma = 89.29(2) degrees, V = 3298.4(13) ?(3), and Z = 2. The structure refinement converged to R1 = 0.0839 and wR2 = 0.2196. The electrical properties of H(2)Pz(18) have been studied by complex impedance spectroscopy. The bulk electrical conductivity of this compound is approximately 1 order of magnitude higher than that of the corresponding 18-crown-6 phthalocyanine.     

Synthesis, characterization and spectroscopic properties of novel periphery – functionalized unsymmetrical porphyrazines containing mixed dithienylpyrrolyl and dimethylamino groups

Following our previous report on a novel class of C₄ symmetric porphyrazines bearing 2,5-dimethylpyrrolyl and methyl(3-pyridylmethyl)amino groups in the periphery, here we report the synthesis and characterization of unsymmetrical porphyrazines with peripheral 2,5-di(2-thienyl)pyrrolyl and dimethylamino groups that break the molecular C₄ symmetry. The porphyrazines were prepared via macrocyclization reactions of a dinitrile precursor. Variable-temperature ¹H NMR experiments, single crystal X-ray work and UV–Vis spectra in different solvents of the unsymmetrical magnesium porphyrazine provided information on the structural and electronic features of the entire macrocyclic system. A detailed discussion of the UV–Vis spectra in different solvents emphasizes the role played by the extended peripheral 2,5-di(2-thienyl)pyrrolyl substituent.     

Electronic structure and optical properties of a tin-encapsulated nickel porphyrazine compound

The recently synthesized metal-encapsulated porphyrazine compound, [Sn(t-Bu)₂]₄-star-Ni(porphyrazine)-S₈, shows very interesting structural and optical absorption features compared with other metal-centered porphyrazines, e.g., metal phthalocyanines (Pc). Using self-consistent-field local density theory, we studied the ground-state and excited-state electronic structure of this molecule and compared it with its metal phthalocyanine analog NiPc. The theoretical optical spectra including oscillator strengths are in good agreement with experimental absorption and show that the characteristic transitions at the so-called Soret band in NiPc are red-shifted in the new compound. © 1994 John Wiley & Sons, Inc.     

Porphyrazines as molecular scaffolds: flexible syntheses of novel multimetallic complexes

Reductive deselenation of selenodiazole-fused porphyrazines, followed by acylation of the resultant labile porphyrazinediamines, was used to prepare macrocycles bearing two Collins ligands, two oxamido residues, or two quinoline-2-carboxamido units. Peripheral coordination of copper(II) to the di-(quinoline-2-carboxamido)-porphyrazine gave a metal-linked face-to-face porphyrazine dimer array. Sequential derivatization of the two amino groups in the porphyrazinediamines was used to prepare mixed peripheral ligand systems including a dimetallic picolinamido-Schiff base porphyrazine. Such systems exhibit strong metal-metal spin coupling and are anticipated to be of value in the synthesis of novel electronic and magnetic materials.     

Towards near-infrared photosensitisation: a photosensitising hydrophilic non-peripherally octasulfanyl-substituted Zn phthalocyanine

A Zn(II) phthalocyanine substituted with eight hydroxylated sulfanyl moieties in non-peripheral positions was designed to exhibit properties desired for photodynamic therapy: hydrophilicity, isomeric purity and near-infrared absorption in addition to high singlet oxygen generation. Photophysical and photochemical studies proved to be promising.     

Synthesis and reactions of aminoporphyrazines with annulated five- and seven-membered rings

The novel five- and seven-membered ring appended aminoporphyrazines 3 and 12 have been prepared via mixed Linstead macrocyclization. The structures of both have been unequivocally established by X-ray crystallographic studies. Reductive deselenation of selenadiazole 3 in the presence of 9,10-phenanthrenequinone or 2,3-butanedione results in the formation of pyrazines 6a,b, whereas oxidation of porphyrazine 12 gave the corresponding seco derivative 14. seco-Porphyrazine 14 mediates the generation of singlet oxygen with a quantum yield of 0.74.     

Serendipitous synthesis of trimetallic porphyrazine triads

We report the synthesis and characterization of structurally unusual porphyrazine triads with three macrocycles bound to a central pyrazine core. These trimacrocyclic complexes were accidentally discovered during studies on the peripheral metallation of porphyrazinediamines. The crystal structure of the tri-zinc porphyrazine triad is described and the spectroscopic properties including electronic absorption spectra of this complex and the corresponding magnesium, free-base, and copper derivatives are reported.     

Nipagin-Functionalized Porphyrazine and Phthalocyanine—Synthesis,Physicochemical Characterization and Toxicity Study after Deposition on Titanium Dioxide Nanoparticles P25

Aza-porphyrinoids exhibit distinct spectral properties in UV-Vis, and they are studied in applications such as photosensitizers in medicine and catalysts in technology. The use of appropriate peripheral substituents allows the modulation of their physicochemical properties. Phthalocyanine and sulfanyl porphyrazine octa-substituted with 4-(butoxycarbonyl)phenyloxy moieties were synthesized and characterized using UV-Vis and NMR spectroscopy, as well as mass spectrometry. A comparison of porphyrazine with phthalocyanine aza-porphyrinoids revealed that phthalocyanine macrocycle exhibits higher singlet oxygen generation quantum yields, reaching the value of 0.29 in DMF. After both macrocycles had been deposited on titanium dioxide nanoparticles P25, the cytotoxicities and photocytotoxicities of the prepared materials were studied using a Microtox^® acute toxicity test. The highest cytotoxicity occurred after irradiation with a red light for the material composed of phthalocyanine deposited on titania nanoparticles.     

A new approach to measuring the action spectrum for singlet oxygen production by human retinal lipofuscin

The human retinal pigment epithelial (RPE) layer contains a complex mixture of components called lipofuscin; this mixture forms with age and with various genetic disorders such as Stargardt's disease. Its presence may contribute to retinal deterioration via several mechanisms including photochemical processes. In the lipofuscin mixture, both type I and II mechanisms have been identified, with the latter consisting of the generation of singlet oxygen. Several components of that mixture have been identified, most notably a bis-retinoid pyridinium compound called A2E and its derivatives. Photo-oxidative studies on the compound A2E have revealed that its dominant photochemical mechanism is via free radical or type I processes. Because singlet oxygen is an important photooxidative intermediate in tissue, its generation in the RPE may contribute to retinal maculopathies. It is therefore necessary to determine which specific component(s) in the lipofuscin mixture produce singlet oxygen upon excitation with light. This was ascertained by evaluating the action spectrum for singlet oxygen production for the whole lipofuscin mixture using time-resolved spectroscopy. Singlet oxygen was generated by excitation of the sample at different wavelengths while maintaining a constant beam energy, and was directly detected by its phosphorescence decay at 1270 nm using a Ge photodiode. The action spectrum for singlet oxygen sensitization by the organic soluble portion of lipofuscin had an absorption maximum at ca 380 nm, which is to the blue of A2E (maximum at 430 nm). Compounds with a similar absorption maximum eluted in the HPLC earlier than A2E and were detected in human lipofuscin. The concentration of this component apparently increased in concentration in human RPE lipofuscin mixture as a function of age up to 90 years old.