Journal of Porphyrins and Phthalocyanines

We have developed a comprehensive methodology that affords regioisomerically pure trans-A₂B-corroles bearing substituents with basic nitrogen atoms at meso positions. The corrole formation reaction involves the acid-catalyzed condensation of a dipyrromethane (DPM) and an aldehyde followed by oxidation with DDQ. The optimal conditions for this process were identified by extensive modifications of the previously developed conditions for the synthesis of trans-A₂B-corroles with aromatic substituents. In particular three distinct sets of conditions were identified for various specific cases. Pyridine, quinoline and quinoxaline derived aldehydes as well as other aromatic aldehydes with tertiary amine groups in different positions were succesfully used in the condensation involving sterically hindered dipyrromethanes under the following conditions: (First step: CH₂Cl₂, [DPM] = 33 mM, [aldehyde] = 17 mM, [TFA] = 50 mM, 1h, room temperature, second step: neutralization with Et₃N, CH₂Cl₂, dilution 26 times, 1.5 or 1.3 eqs. of DDQ versus DPM). A different set of conditions was developed for the condesation involving sterically unhindered dipyrromethanes: (first step: CH₂Cl₂, [DPM] = 33 mM, [aldehyde] = 17 mM, [TFA] = 17 mM, 5h, room temperature, second step: neutralization with Et₃N, CH₂Cl₂, dilution 26 times, 1 eq of DDQ versus DPM). In this case only aldehydes with the formyl group directly adjacent to the heterocylic ring are efficient substrates; for the remaining aldehydes an extensive scrambling was observed. The condensation of pyridyldipyrromethanes with aldehydes bearing electron-withdrawing substituents (first step: CH₂Cl₂, [DPM] = 33 mM, [aldehyde] = 17 mM, [TFA] = 67 mM, 1h, room temperature, second step: neutralization with Et₃N, CH₂Cl₂, dilution 26 times, 1 eq of DDQ versus DPM) leads to corroles in 2-11 % yield depending on the position of the nitrogen atom. Finally, 10-(4-formylphenyl)-5,15-dimesitylcorrole was obtained and reacted with mesityldipyrromethane, giving the symmetrical corrole dyad in 14% yield. A total of 21 new corroles of type trans-A₂B were prepared.

The synthesis of thiol-derivatized cobalt phthalocyanine complex, 2,3,9,10,16,17,23,24-octa (butylthiophthalocyaninatocobalt(II) (CoOBTPc) is described. Cyclic voltammetric data of this complex in DMF showed five quasi-reversible and reversible, diffusion-controlled redox couples, comprising both the phthalocyanine ring and central metal redox processes. The CoOBTPc complex forms a self-assembled monolayer (SAM) on gold electrode. The investigation of the integrity of this SAM, using the established cyclic voltammetric methods in aqueous alkaline solutions, gave evidence about the formation of a stable and easily reproducible monolayer. However, due to its susceptibility to destruction via oxidative and reductive desorptions, its potential application as an electrochemical sensor in alkaline pH is limited to a potential window of between −0.20 and +0.55 V vs Ag/AgCl.

The gel-like films obtained from the homoassociation of diprotonated meso-tetrakis(4-sulfonatophenyl)porphyrin show structural changes depending on their water content, which is determined by the affinity for water of the ionic species segregated from the homoassociation process. These materials, in which NaCl or H₂SO₄ are segregated, were studied and their electrochemical behavior at several water contents was examined. The behavior of humid films was clearly different from dry films. The p_H2O value, which determines the separation between the dry and humid behavior, depends on the type of the ionic species segregated in the homoassociation. This is briefly discussed in relation to the design of humidity sensors.

The reaction of PcMCl₂ (M = Zr, Hf) with β-diketones is reported. ¹H NMR and elemental analysis suggest the substitution of two Cl atoms for two β-diketone fragments takes place as a result of this reaction and the complexes PcM(β-dik)₂ are formed. All obtained complexes are stable and highly soluble in most organic solvents. The data from ¹H and ¹⁹F NMR, and UV-vis spectroscopy suggest the coordination of two β-diketone ligands in a cis geometry about the central atom of the macrocycle. It was shown bis(β-diketonato)zirconium(IV) and hafnium(IV) phthalocyanines containing β-diketones with donor or acceptor groups or with bulky substituents can be obtained.

Amphiphilic phthalocyanines are used as potential photosensitizers in photodynamic therapy. The low water solubility of most of these dyes is the reason that different kinds of vehicles are employed as endogenous carriers. Due to the photophysical inactivity of the phthalocyanine aggregates, it is important to improve their solubility in order to study dyes in solid tumor models. On the other hand, the photodynamic therapy activity depends on the location of phthalocyanines in the cell and the interaction of cellular components. In this work, the photophysical properties of tetrasubstituted Zn(II) phthalocyanines with different lipophilic properties are incorporated into liposomes of L-α-dimyristoylphosphatidylcholine (DMPC). The fluorescence quantum yields, the association constants and their localization in the membranes are reported.

A new class of porphyrins bearing natural polyamines has been designed in order to target the photosensitizers towards malignant cells. We report here the synthesis of spermidine and spermine porphyrins. The photocytotoxicity of these compounds against K562 human chronic myelogenous leukemia cells has been evaluated and compared to Photofrin II^®.

Ni, Zn, Pd and Pt tetra(pentafluorophenyl)porpholactone (TFPL) were synthesized and identified by their optical and mass spectra. The lactone ring was produced from the parent free-base porphyrin using silver nitrate and oxalic acid with a yield of 73%, and the metals were inserted by standard procedures from metal salts. The compounds show intense Soret Bands in the region 390-420 nm. The longest wavelength visible absorbance peaks, in the region 572-608 nm, are weaker than the Soret peaks by a factor of only ~3 for the Ni, Pd, and Pt complexes but a factor of ~10 for the free-base and Zn complexes. As found with other metalloporphyrins the Ni complex is dark, Zn shows fluorescence and Pd and Pt complexes show strong phosphorescence. The Pd complex also shows a weak fluorescence not quenched by oxygen. The phosphorescence lifetimes of Pd and Pt complexes of TFPL in 3-methylpentane at 77 K are, respectively, ~1 ms and ~70 μs, about 60% that of the TFPP complexes. The wavelengths of phosphorescence emission, 733 nm and 758 nm for PtTFPL and PdTFPL, respectively, are sufficiently red-shifted so that these pressure sensitive luminophors can be included in the same pressure sensitive paint (PSP) as Eu complexes, whose emission at ~615 nm can serve as a temperature sensor. The fluorescences of Mg, Zn, and Y(TFPP) show weak origin bands, making them suitable as unquenched references for PSP.

A series of β,β-dihydroxychlorins derived from meso-tetraphenylporphyrins (TPPs) have been synthesized. Their in vitro cytotoxicity has been measured and compared to BPDMA (verteporfin). Under the assay conditions BPDMA had an LD₅₀ (lethal dose to kill 50% of cells) value of 0.007 μM (5 ng/mL). The LD₅₀ values for the TPP derivatives varied from 1.7 × 10^-2 to 9.9 μM depending upon the substituents and their position on the phenyl groups. One example of the dihydroxychlorin prepared from unsubstituted 5,15-diphenylporphyrin was examined and this exhibited an LD₅₀ of 2.4 × 10^-3 μM!