Journal of Porphyrins and Phthalocyanines

Manganese(III) complexes of isomeric tetrakis(N-alkylpyridyl)porphyrins (N-alkyl = N-methyl, M or N-ethyl, E), MnTM(E)-2(3,4)-PyP⁵⁺, are being developed as superoxide dismutase (SOD) mimics. Simultaneously, techniques for their purification, identification and characterization are being pursued. Electrospray mass spectrometry (ESMS) proved to be an excellent method for identification and characterization of this group of water-soluble cationic porphyrins. The multiply charged parent ion is observed for both the metal-free ligands and their corresponding manganese complexes. The other major peaks in the mass spectra result from loss of N-alkyl groups, reduction of the metal center, axial coordination of chloride or hydroxo ion in the case of the Fe porphyrin, loss of metal and deprotonation of pyrrolic nitrogens. As a result of inductive and resonance effects, which stabilize the ortho isomer, almost no loss of N-alkyl groups from the manganese complex or from its parent ligand was observed. The relative intensity of the multiply charged molecular ion Mn^IIITM-3(4)-PyP⁵⁺/5 was 100% in the case of the meta and para isomers. Although manganese porphyrins display a low preference toward axial ligation, favorable electrostatics at the metal center of the ortho isomer gives rise to 100% relative intensity of the species that has chloride axially ligated at the manganese site, Mn^IIITM(E)-2-PyPCl⁴⁺/4. When the stronger preference of iron porphyrins toward axial ligation combines with the ortho effect, the monohydroxo iron porphyrin Fe^IIITM-2-PyP(OH)⁴⁺/4 dominates the ESMS of an aqueous acetonitrile solution at pH 7.8.

5,15-Diphenylporphyrin was regiospecifically halogenated in high yield to give 5-iodo-15-bromo-10,20-diphenylporphyrin, which was then subjected to Heck and Stille-type coupling reactions to form unsymmetrically substituted porphyrins. The regioselectivity of the iodination of diphenylporphyrins and subsequent formation of amphiphilic porphyrins via palladium-based methodology was also studied. The utility of this method for the synthesis of photodynamic sensitisers has been demonstrated on AR4-2J rat pancreatic carcinoma cells.

A convenient procedure for the synthesis of polyphenylene porphyrin dyads is described. The dyads consist of a meso-nitrophenylporphyrin covalently linked to a polyphenylene chain by an amide bond. The final phenyl group in the chain bears electron donor methoxy groups. The π-conjugated chain was obtained in excellent yield via a Wittig–Horner reaction, which produces a new double bond (E isomer) incorporating either —COOCH₃ or E isomer) incorporating either —CON(OCH₃)(CH₃) functional groups. Expansion of the conjugated chain involves the reduction of these groups to aldehydes followed by a second Wittig–Horner reaction. 5-(4-Aminophenyl)-10,15,20-tris(4-nitrophenyl)porphyrin was synthesized from meso-(4-nitrophenyl)dipyrromethane. The E isomer) incorporating either —NO₂ groups in para positions of the peripheral phenyl rings give extra electron-withdrawing character to the porphyrin macrocycles. Coupling of the polyphenylene acids with aminoporphyrin results in the desired dyads. These dyads have moieties with different electron donor–acceptor properties. This present strategy may be easily used for preparation of other similar dyad derivatives. These compounds can be suitable for photodynamic therapy.

Tin complexes of meso-substituted synthetic porphyrins, namely Sn⁴⁺-meso-tetraphenyl- porphyrin (Sn-TPP) and Sn⁴⁺-meso-tetrakis(N-methyl-3-pyridyl)porphyrin tetratosylate (Sn-TMe-3-PyP), efficiently decrease the serum bilirubin level when injected subcutaneously at a dose of 100 μM kg⁻¹ body weight into mice. These compounds are active during hyperbilirubinemia, induced by phenylhydrazine, hemin and tetrachloromethane, and also during autoimmune hemolytic anemia. In the latter case a decrease in serum bilirubin content was observed, as well as a decrease in the amount of blood reticulocytes which reflects a milder course of the disease. The Sn complexes under study induce, in vivo, cytochrome P-450, inhibit microsomal heme oxygenase and decrease the intensity of lipid peroxidation. At the same time, in vitro the hepatic and splenic heme oxygenase activity is blocked only when a 0.1 μM concentration of Sn-TMe-3-PyP or Sn-protoporphyrin IX is added to the incubation mixture. Sn-TPP does not affect the activity of this enzyme in vitro.

Planar 1,2-naphthalocyanines present four different geometrical isomers of C_4h, C_2v, D_2h and C_s symmetries. In the case of magnesium complexes these four isomers have been isolated and characterized for the first time. The C_4h and C_s isomers of the magnesium complexes have been transformed in two steps into the corresponding lutetium mononaphthalocyanines 1,2-NcLuX.

Equilibrium constants (1:1) for the reactions of cadmium(II) and lead(II) with water-soluble free base porphyrins of differing basicities (pK₃) are reported. Soft porphyrins with low pK₃ values favor the softer Cd(II), while harder porphyrins with higher pK₃ values have more affinity for the relatively harder Pb(II) ion.

The metalation of several free base porphyrins by the bismuth salts Bi(NO₃)₃ and Bi(SO₃CF₃)₃ in DMF or pyridine is described. The resulting stable Bi(III) porphyrin complexes are characterized by electrochemistry, ¹H NMR and UV-vis spectroscopy. The structure of (OEP)Bi(SO₃CF₃) was also determined by single-crystal X-ray diffraction and shows that (OEP)Bi(SO₃CF₃) exists as a dimer which is stabilized by electrostatic interactions in which the two [(OEP)Bi]⁺ cations are linked via oxygen atoms of two symmetrically related anions, leading to a heptacoordinated bismuth center. Electrochemical oxidation of (OEP)Bi(SO₃CF₃) and (TpTP)Bi(SO₃CF₃) shows that only the porphyrin macrocycles are oxidized.

Mass spectrometric studies of the composition of the gaseous phase under solid compounds of free phthalocyanine (H₂Pc) and its complexes with aluminium (AlClPc, AlFPc, (AlPc)₂O) and copper (CuPc) were performed in the temperature range up to 700 °C. It has been shown that the phthalocyanines sublime in the form of monomers, excluding one aluminium complex. All phthalocyanines under investigation sublime without thermal decomposition until 700 °C. The vapour pressure of these phthalocyanines was determined as a function of temperature by the Knudsen effusion method, in which the rate of effusion of the equilibrium vapour through a small orifice was measured. The thermodynamic parameters of the sublimation process for phthalocyanies were calculated.

In photodynamic therapy it is important to avoid undesirable side effects caused by photodynamic reactions with accumulated photosensitizers, especially in the skin. Although phthalocyanine monomers can serve as photosensitizers, aggregated phthalocyanines are inactive. In this study the aggregations of five zinc phthalocyanines (MSPc, TSPc, TX-101A, TX-105A and TX-106A) in the skin and in the tumor are compared. Every phthalocyanine was more dissociated in the tumor than in the skin. In particular, TX-101A and TX-106A remained in monomeric form in the tumor but were aggregated in the skin. The aggregation effects of phthalocyanines in organic solvents and biological materials were also investigated. These phthalocyanines were aggregated in water and ethanol and also by the addition of bovine serum albumin and ghosts of red cells. On the other hand, they were dissociated in propanol and also by the addition of low-density lipoprotein. It was found that the dissociation of these phthalocyanines depended strongly on the polarity of the solvents and on the biological microenvironment.

The study of haemin-catalysed oxidation reactions was extended to substituted aromatic rings. Both electron-donating and electron-withdrawing substituents on aromatic rings act as para- and meta-directing agents in the presence of tetrakis(2,6-dichlorophenyl)porphyrin iron(III) chloride as catalyst and m-chloroperbenzoic acid as oxidant. A new kinetic method for measuring relative rates of epoxidation of alkenes and related compounds has been developed; while steric hindrance results in decreasing the rate of hydroxylation, electron-rich and electron-withdrawing substituents were found to increase the rate of hydroxylation. A linear relationship between the logarithm of the relative rate of hydroxylation and σ Hammet is obtained, although electron-donating and electron-withdrawing substituents fit separate lines. Addition of pyridine to haemin was shown to increase the yield of epoxidation but decrease the yield of aromatic hydroxylation.

Optical oxygen-sensing systems based on the quenching of the photoexcited triplet state of platinum porphyrins—platinum octaethylporphyrin (PtOEP) and platinum tetrakis(pentafluorophenyl)porphyrin (PtTFPP)—in polystyrene (PS) using two different time-resolved spectroscopies (luminescence lifetime measurement and diffuse reflectance laser flash photolysis) have been developed. Using both spectroscopies, the same values of Stern-Volmer constant K_SV and quenching rate constant k_q (K_SV = k_qτ₀) are obtained. The decays of the luminescence and triplet-triplet reflectance of the platinum porphyrins in PS consisted of two components (faster and slower lifetimes) in the absence and presence of oxygen. For both faster and slower components the lifetime decreases with increasing oxygen concentration. For both components a Stern-Volmer plot of the platinum porphyrin-PS films exhibits linearity. However, k_q of the faster component is larger than that of the slower component (for PtOEP, three times larger; for PtTFPP, 40 times larger), indicating that two different oxygen-accessible sites exist in the platinum porphyrin-PS films. The faster and slower components are related to oxygen-accessible sites on the surface and in the bulk of the platinum porphyrin films respectively. Concerning the fractional contributions of each lifetime component, the contribution of the faster component is greater than that of the slower component, indicating that the sensing site on the surface is important for optical sensing. The contribution of different oxygen-accessible sites in platinum porphyrin-PS films for oxygen sensing is clarified by these techniques.