Reactivity of mono-meso-substituted iron(II) octaethylporphyrin complexes with hydrogen peroxide in the absence of dioxygen. Evidence for nucleophilic attack on the heme.

Treatment of the mono-meso-substituted iron(II) octaethylporphyrin complexes, (py)2Fe(II)(meso-NO2-OEP), (py)2Fe(II)(meso-CN-OEP), (py)2Fe(II)(meso-HC(O)-OEP), (py)2Fe(II)(meso-Cl-OEP), (py)2Fe(II)(meso-OMe-OEP), (py)2Fe(II)(meso-Ph-OEP), and (py)2Fe(II)(meso-n-Bu-OEP), with hydrogen peroxide in pyridine-d5 at -30 degrees C in the strict absence of dioxygen has been monitored by 1H NMR spectroscopy. The product oxophlorin complexes are stable as long as the samples are protected from exposure to dioxygen. Hydrogen peroxide reacts cleanly with mono-meso-substituted iron(II) porphyrins in pyridine solution under an inert atmosphere to form mixtures of three possible oxygenation products, (py)2Fe(cis-meso-R-OEPO), (py)2Fe(trans-meso-R-OEPO), and (py)2Fe(OEPO). The yields of (py)2Fe(OEPO), which results from replacement of the unique meso substituent, as a function of the identity of the meso substituent decrease in the order NO2 > HC(O) approximately equal to CN approximately equal to Cl > OMe > Ph, Bu, which suggests that the species responsible for attack on the porphyrin periphery is nucleophilic in nature. A mechanism involving isoporphyrin formation through attack of hydroxide ion on a cationic iron porphyrin with an oxidized porphyrin ring is suggested. The identity of the unique meso functionality also affects the regiospecificity of substitution when the unique meso group is retained. Although random attack at the two different meso sites is expected to yield a cis/trans product ratio of 2, the observed ratios vary in the following order: cyano, 5.0; n-butyl, 4.9; chloro, 3.2; formyl, 2.6; methoxy, 1.9; phenyl 1.4.

Verdoheme reactivity. Remarkable paramagnetically shifted (1)H NMR spectra of intermediates from the addition of hydroxide or methoxide with Fe(II) and Fe(III) verdohemes.

Studies of the reaction of 5-oxaporphyrin iron complexes (verdohemes) with methoxide ion or hydroxide ion have been undertaken to understand the initial step of ring opening of verdohemes. High-spin [ClFe(III)(OEOP)] undergoes a complex series of reactions upon treatment with hydroxide ion in chloroform, and similar species are also detected in dichloromethane, acetonitrile, and dimethyl sulfoxide. Three distinct paramagnetic intermediates have been identified by (1)H NMR spectroscopy. These reactive species are formed by addition of hydroxide to the macrocycle and to the iron as an axial ligand. Treatment of low-spin [(py)(2)Fe(II)(OEOP)]Cl (OEOP is the monoanion of octaethyl-5-oxaporphyrin) with excess methoxide ion in pyridine solution produces [(py)(n)()Fe(II)(OEBOMe)] (n = 1 or 2) ((OEBOMe), dianion of octaethylmethoxybiliverdin), whose (1)H NMR spectrum undergoes marked alteration upon addition of further amounts of methoxide ion. An identical (1)H NMR spectrum, which is characterized by methylene resonances with both upfield and downfield paramagnetic shifts, is formed upon treatment of [Fe(II)(OEBOMe)](2) with methoxide in pyridine solution and results from the formation of [(MeO)Fe(II)(OEBOMe)](-).

25,27-dithiasapphyrin and pyrrole-inverted isomer of 21,23-dithiaporphyrin from condensation of pyrrole and 2,5-bis(p-tolylhydroxymethyl)thiophene.

[see structure]. A novel aromatic isomer of 5,10,15,20-tetra(p-tolyl)-21,23-dithiaporphyrin (S2TTP) with an inverted pyrrole ring, 5,10,15,20-tetra(p-tolyl)-2-aza-21-carba-22,24-dithiaporphyrin (S2CTTP), and 5,10,15,20-tetra(p-tolyl)-25,27-dithiasapphyrin (25,27-S2TTSH), have been obtained by a condensation of 2,5-bis((p-tolyl)hydroxymethyl)thiophene and pyrrole. A conformational equilibrium, unique in a sapphyrin class, between two S(27)-thiophene-flipped and planar structures of neutral 25,27-S2TTSH was detected by 1H NMR.

Palladium (II) complexes of oxybenziporphyrin.

8,19-Dimethyl-9,13,14,18-tetraethyloxybenziporphyrin coordinates palladium(II) to form the four-coordinate anionic complex [(OBP)Pd(II)](-). The NMR data provide evidence for the retention of macrocyclic aromaticity and coordination via a carbon sigma-donor. Protonation of the external oxygen atom to give [(HOBP)Pd(II)] switches the molecule to a less aromatic phenol-like state, which is manifested by a significant reduction of the macrocyclic ring current. [(AcOBP)Pd(II)] and [(TsOBP)Pd(II)], two ester derivatives of [(OBP)Pd(II)](-), are similar to the protonated species, and their benzenoid character is more pronounced. However, reaction of [(OBP)Pd(II)](-) with methyl iodide leads to selective methylation of the coordinating C(22) atom to form a novel organopalladium complex (OBPMe)Pd(II). The strong shielding of the inner Me(22) (delta((1)H) -2.00 ppm in CDCl(3)) indicates that the aromaticity of the macrocycle has been retained. At the same time the (13)C chemical shift of C(22) (44 ppm) shows that the palladium-bound carbon has undergone a drastic hybridization change. Alkylation with n-BuI yields a mixture of the O-substituted [(n-BuOBP)Pd(II)] and the C-substituted [(OBP-n-Bu)Pd(II)], which confirms the ambident nucleophilicity of [(OBP)Pd(II)](-). DFT calculations carried out for six tautomers of oxybenziporphyrin and the 22-methylated palladium species provide further insight into the electronic structure of the ligand and its complexes. Relative energies of the tautomers, increasing in the order [CH,NH,N,NH,O] < [CH,N,NH,N,OH] < [CH(2),N,NH,N,O] < [CH(2),N,N,N,OH], have been used to estimate the accessibility of four limiting delocalization modes postulated for oxybenziporphyrin and its derivatives. The state of macrocyclic aromaticity observed experimentally in the free base and the phenolic aromaticity of the O-protonated tautomer are the most favorable, and the latter has its energy higher by only 13 kcal/mol. The peculiar bonding situation in (OBPMe)Pd(II), which can be inferred from the NMR data, is also predicted by the DFT methods, which show a strongly distorted tetrahedral environment of C(22).

Figure-eight tetrathiaoctaphyrin and dihydrotetrathiaoctaphyrin.

The acid-catalyzed condensation of pyrrole and 2,5-bis(p-tolylhydroxymethyl)thiophene yields two novel giant heteroporphyrins: 5,10,15,20,25,30, 35,40-octa(p-tolyl)-41,43,45,47-tetrathia[36]octaphyrin(1.1.1.1.1.1.1.1) (S4OP) and 5,10,15,20,25,30,35,40-octa(p-tolyl)-dihydro-41,43,45,47-tetrathia[38]octaphyrin(1.1.1.1.1.1.1.1) (S4OPH2). These tetrathiaoctaphyrins are interconvertible through dihydrogenation or dehydrogenation processes. Both compounds possess helical figure-eight geometry with two thiophene rings for S4OP or two pyrrole rings for S4OPH2 in the ribbon-crossing center as shown by NOESY experiments. The synthesis of the figure-eight tetrathiaoctaphyrin implies a prearrangement process to form helical M or P dithiatetrapyrromethanes. The P-P or M-M condensation leads to the figure-eight molecule in competition with an intramolecular ring closure. Two dithiaporphyrin-like pockets of S4OP or S4OPH2 behave as independent proton acceptors. The stepwise process yields symmetric or asymmetric cationic species that depends on whether an even or odd number of NH protons are added. Dihydrotetrathiaoctaphyrin contains 38 pi electrons in its conjugation pathway, which corresponds to the formal [4n + 2] Hückel type pi-electron formulation that is consistent with a modest diatropic ring current effect in their 1H NMR spectra. The formal 4n type pi-electron formulation for tetrathiaoctaphyrin accounts for the residual paratropic shifts. A figure-eight conveyor-belt-like movement of the whole macrocyclic ring without a racemization step is proposed to account for the dynamic properties of S4OP. The molecule shuttles between two degenerate configurations. A S4OP-S4OPH2 couple may be considered as a molecular element which, while preserving the overall figure-eight geometry, "chooses" pyrrole or thiophene rings as spacers as a function of the macrocyclic oxidation state.

Tetraphenylbenziporphyrin--a ligand for organometallic chemistry.

6,11,16,21-Tetraphenylbenziporphyrin (TPBPH)H, an analogue of tetraphenylporphyrin with one of the pyrrole groups replaced by a benzene ring, is formed in good yield in the condensation of the appropriate precursor with pyrrole and benzaldehyde. (TPBPH)H gives organometallic complexes with palladium(II) and platinum(II), [(TPBP)PdII] and [(TPBP)PtII], in which the metal ion is bound in the macrocyclic cavity by three pyrrolic nitrogen atoms and a carbon atom of the benzene ring. In the reaction with silver(I) acetate benziporphyrin does not yield a stable complex but undergoes selective acetoxylation at the internal carbon atom. (TPBPH)H is reversibly reduced to 6-benziphlorin and reacts with a water or methanol molecule to give 6-hydroxy- or 6-methoxy-6-benziphlorin, respectively.

Pyrrole-inverted isomer of 5,10,15,20-tetraaryl-21-selenaporphyrin

A novel 5,10,15,20-tetraaryl-21-selenaporphyrin isomer with an inverted pyrrole ring, i.e., 5,10,15, 20-tetraaryl-2-aza-21-carba-22-selenaporphyrin (SeC-TArPH) has been produced by a [3 + 1] condensation of 2, 5-bis(phenylhydroxymethyl)selenophene and 5,10-ditolyltripyrrin. The reaction yielded 5,20-diphenyl-10,15-bis(p-tolyl)-21-selenaporphyrin Se-DPDTPH (19%) and its isomer with an inverted pyrrole ring, i.e., 5,10-diphenyl-15,20-bis(p-tolyl)-2-aza-21-carba-22-selenaporphyrin, SeC-DPDTPH (1%). Mechanistically the synthesis of SeC-DPDTPH requires one beta-condensation at the pyrrole moiety of 5, 10-ditolyltripyrrin instead of the stereotypical alpha-condensation. The identity of inverted selenaporphyrin has been confirmed by high-resolution mass spectrometry and (1)H NMR spectroscopy. A saddle distortion mode for the inverted selenaporphyrin macrocycle SeC-DPDTPH has been determined by X-ray crystallography. NMR spectra are consistent with the existence of tautomeric equilibria that involve three tautomeric species of the neutral form of SeC-DPDTPH. The preference for the tautomer with the labile proton located at the peripheral N(2) nitrogen atom has been detected in pyridine-d(5) solution. The density functional theory (DFT) has been applied to determine the molecular and electronic structure of three tautomers of 2-aza-21-carba-22-selenaporphyrin: 2-N, 23-N, 24-NH, 2-N, 23-NH, 24-N, and 2-NH, 23-N, 24-N formally created from SeC-DPDTPH by a replacement of phenyl and tolyl groups with hydrogen. The total energies calculated using the B3LYP/6-311G//B3LYP/6-311G approach, demonstrate that relative stability of postulated tautomers decreases in the order 2-N, 23-NH, 24-N > 2-N, 23-N, 24-NH > 2-NH, 23-N, 24-N. The small energy differences between tautomeric species suggests their simultaneous presence in equilibrium.

Copper(II) complexes of inverted porphyrin and its methylated derivatives.

The inverted porphyrins 2-aza-5,10,15,20-tetraphenyl-21-carbaporphyrin (CTPPH2) and its methylated derivatives 2-aza-2-methyl-5,10,15,20-tetraphenyl-21-carbaporphyrin (2-NCH3CTPPH) and 2-aza-2-methyl-5,10,15,20-tetraphenyl-21-methyl-21-carbaporphyrin (2-NCH3-21-CH3CTPPH) stabilize the rare organocopper(II) complexes (CTPP)CuII (1), (2-NCH3CTPP)CuII (2), (CTPPH)CuIIX (3-X), (2-NCH3CTPPH)CuIIX (4-X) (X = Cl-, TFA), and (2-NCH3-21-CH3CTPP)CuIICl (5). The EPR spectra recorded for 1, 2, 4, and 5 revealed typical features diagnostic of the copper(II) electronic structure. The superhyperfine coupling pattern indicates a presence of three nitrogen donors in the first coordination sphere. An addition of HX acid to 1 and 2 to yield the species 3-X and 4-X. The reaction mechanism includes protonation of the inner C(21) carbon accompanied by an axial coordination of anion. Methylation of (2-NCH3CTPP)CuII (2) with methyl iodide resulted in formation of (2-NCH3-21-CH3CTPP)CuIICl (5) which implies an existence of a sigma-carbanion-copper(II) bond in 2. The 2H NMR investigations carried out for the pyrrole deuterated derivatives (CTPP-d7)CuII, (2-NCH3-21-CH3CTTP-d7)CuIICl, and the methyl deuterated (2-NCH3-21-CD3CTPP)CuIICl one confirmed independently the copper(II) electronic structure with the considerable dx2-y2 metal orbital contribution to the SOMO. The redox properties of copper(II) inverted porphyrins were studied by the cyclic and differential pulse voltammetry. The halfwave potentials indicate a metal-centered oxidation of 1 (390 mV) and 2 (343 mV). The dimethylated homologue 5 reveals the reduction process at -224 mV attributed to the CuII/CuI transformation.

Reactions of nickel(II) 2,21-dimethyl-2-aza-21-carbaporphyrin with phenyl Grignard reagents, phenyllithium, and n-butyllithium.

Addition of a phenyl Grignard reagent to a toluene solution of the nickel(II) chloride complex of a dimethylated inverted porphyrin, (2-NCH3-21-CH3CTPP)NiIICl (1), at 203 K results in the formation of a rare paramagnetic (sigma-phenyl)nickel(II) species, (2-NCH3-21-CH3CTPP)NiIIPh (2). The coordination of the sigma-phenyl in 2 is determined by a unique pattern of three sigma-phenyl resonances (ortho 375.0 ppm; meta 108.94 ppm; para 35.68 ppm (at 283 K)) in the 1H NMR and 2H NMR spectra. The (sigma-phenyl)nickel(II) compound 2 is in the high-spin ground electronic state (dxy)2(dxz)2(dyz)2(dz2)1(dx2-y2)1, as confirmed by similarity of the NMR spectra of the equatorial ligand in 1 and 2. Titration of 1 with phenyllithium produces (2-NCH3-21-CH3CTPP)NiIIPh (2). One-electron reduction with excess PhLi yields [(2-NCH3-21-CH3CTPP)NiIIPh]- (3), which can be also generated by independent routes, e.g., by reduction of (2-NCH3-21-CH3CTPP)NiIIPh using lithium triethylborohydride or tetrabutylammonium borohydride. The spectroscopic data indicate that (2-NCH3-21-CH3CTPP)NiIIPh (2) undergoes one-electron reduction without a substantial disruption of the molecular geometry. The presence of two paramagnetic centers in 3, i.e., the high-spin nickel(II) and the carbaporphyrin anion radical, produces remarkable variations in a spectral patterns, such as the upfield and downfield positions of pyrrole resonances (103.78, 96.66, -25.35, -50.97, -92.15, -114.83 ppm (at 253 K)) and sign alternations of the meso-phenyl resonances (ortho -77.81, -79.34 ppm; meta 48.77, 48.04 ppm; para -85.65, -86.46 ppm (at 253 K)). A single species, 4, is detected in the 1H NMR titration of 1 with n-butyllithium. The formation of one- or two-electron-reduced species, [(2-NCH3-21-CH3CTPP)NiBu]- or [(2-NCH3-21-CH3CTPP)NiBu]2-, respectively, is considered to account for the spectroscopic properties of 4 (pyrrole 17.33, 15.45, -5.79, -7.74, -14.62, -58.14 ppm; 21-CH3 3 ppm (at 203 K)). The temperature dependence of the hyperfine shifts of 4 demonstrates pronounced anti-Curie behavior, interpreted in terms of a temperature-dependent spin equilibrium between diamagnetic and paramagnetic states with diamagnetic properties approached as the temperature is lowered. Warming of 2-4 results in complete decomposition via homolytic/heterolytic cleavage of an axial nickel-apical carbon bond. In the case of 2 or 3, the process yields a mixture of two compounds, 5 and 6, which are detected by EPR spectroscopy, demonstrating the anisotropy of the g tensor (5, g1 = 2.237, g2 = 2.092, g3 = 2.090; 6, g1 = 2.115, g2 = 2.030, g3 = 1.940 (in frozen toluene solution at 77 K)).

Peroxo and ferryl intermediates detected by 1H NMR spectroscopy during the oxygenation of iron(II) porphycene.

The iron(III) 2,7,12,17-tetra-n-propylporphycene (TPrPc)FeIIICl is reduced using aqueous sodium dithionite or zinc amalgam to produce (TPrPc)FeII. The 1H NMR spectrum of (TPrPc)FeII (293 K; delta (ppm): pyrrole, -37.52; meso, 71.56; alpha-CH2, 27.47; beta-CH2, 8.92; gamma-CH3, 5.55) can be accounted for by the planar unligated iron(II) porphycene with an S = 1 ground electronic state. Introduction of dioxygen into a toluene-d8 solution of (TPrPc)FeII at 203 K results in the formation of the (mu-peroxo)diiron(III) porphycene (TPrPc)FeIII-O-O-FeIII(TPrPc). The value of the chemical shift of the pyrrole resonances (17.99 ppm at 203 K) of this species and its distinct non-Curie behavior imply strong antiferromagnetic iron(III)-iron(III) coupling via a mu-peroxo bridge. The (TPrPc)FeIII-O-O-FeIII(TPrPc) intermediate is stable at 203 K, but it converts into the (mu-oxo)diiron complex (TPrPc)FeIII-O-FeIII(TPrPc) upon warming above 203 K. Reaction of (TPrPc)FeIII-O-O-FeIII(TPrPc) with a nitrogen bases (B: pyridine-d5, 1-methylimidazole) results in a homolytic cleavage of the mu-peroxo bridge to form the ferryl porphycene complex B(TPrPc)FeIVO (1H NMR (223 K), delta (ppm): pyrrole, -1.32; meso, 11.80). B(TPrPc)FeIVO reacts with triphenylphosphine at 223 K to yield triphenylphosphine oxide.

An integrated approach to the mid-spin state (S = 3/2) in six-coordinate iron(III) chiroporphyrins.

An intermediate-spin state very close to the mid-spin state (S = 3/2) can be stabilized in a ferric porphyrin by an integrated approach which combines the favorable effects of a weak axial field strength and of a small macrocycle hole. Axial ligand exchange by reaction of chloroiron(III)tetramethylchiroporphyrin [(TMCP)FeCl] with silver perchlorate in ethanol-chloroform leads to ethanol-ligated ferric chiroporphyrins. Two distinct crystalline products containing a bisethanol complex [[(TMCP)FeIII(EtOH)2]ClO4] and three variants of a mixed ethanol-water complex [[(TMCP)FeIII(EtOH)(H2O)]ClO4] have been structurally characterized in the solid state. The small hole of the ruffled chiroporphyrin and the weak axial oxygen ligation result in strongly tetragonally distorted complexes. The six-coordinate species exhibit long axial Fe-O bond distances (2.173(5)-2.272(4) A) and the shortest equatorial Fe-N(av) distances (1.950(5)-1.978(7) A) found as yet in a ferric porphyrin, reflecting a singly occupied dz2 orbital and a largely depopulated dx2-y2 orbital. An intriguing case of bond-stretch isomerism is seen for the axial Fe-O bonds in two crystallographically independent mixed ethanol-water species, and it is accounted for by their distinct intra- and intermolecular hydrogen-bond arrays. The Mössbauer spectrum (delta = 0.35(1) mm s-1 and delta EQ = 3.79(1) mm s-1 at 77 K) indicates a strong tetragonal distortion around the ferric ion, in agreement with the structural data. The value of the magnetic moment (mu eff = 3.8 mu B in the range 50-300 K) strongly supports a mid-spin state (S = 3/2). The EPR spectrum at 80 K (g perpendicular approximately 4.0, g parallel approximately 2.00) is consistent with a nearly pure mid-spin state (4A2) with little rhombic distortion. The 1H NMR spectra in CDCl3-EtOH exhibit upfield-shifted resonances for the pyrrole protons (delta approximately -30 ppm) which are consistent with the depopulated iron dx2-y2 orbital. Solution equilibria with water and various alcohols, and the spin state of the corresponding species, are discussed on the basis of the NMR data. The bisethanol and ethanol-water species are potential models of unknown hemoprotein ligation states such as Tyr(OH)/Tyr(OH) or Tyr(OH)/H2O that could be obtained by site-directed mutagenesis.

New potent sensitizers for photodynamic therapy: 21-oxaporphyrin, 21-thiaporphyrin and 21,23-dithiaporphyrin induce extensive tumor necrosis.

New sensitizers for photodynamic therapy (PDT) are reported. These compounds, namely 21-thiaporphyrin, 21,23-dithiaporphyrin and 21-oxaporphyrin, reveal some of the properties required for such therapy. Their physicochemical, chemical and pharmacological features meant that we could use them in the treatment of transplantable BFS1 fibrosarcoma in Balb/c mice. New sensitizers and the well-known chlorin e6 (Ce6) were used in doses of 2.5, 5.0, 7.5 and 10.0 mg/kg body weight, given intraperitoneally and followed by light irradiation, the total light doses being 50, 100 and 150 J/cm(2) within 24 h after injection. The effectiveness of new sensitizers in PDT was evaluated with in terms of tumor necrosis intensity, the survival time of treated animals, the rate of tumor response (complete/partial/no response), and skin photosensitivity. These results were compared to results obtained in analogous conditions after Ce6-PDT. Distribution studies revealed that the highest concentration of new compounds occurred within 24 h after injection. The results of these experiments confirmed that 21-thiaporphyrin, 21,23-dithiaporphyrin and 21-oxaporphyrin can be considered as potent tumor photosensitizers that do not exert any unwanted effects, primarily skin photosensitization. We suggest that these porphyrins are possible sensitizers to be applied in clinical PDT.

Tumor histopathology following new sensitizers: dithiaporphyrin- and sulfoxaporphyrin-mediated photodynamic therapy.

BACKGROUND: Our main aim was to evaluate tumor histopathology following new sensitizer-mediated photodynamic therapy (PDT). MATERIALS AND METHODS: In order to complete our studies we decided to use photosensitizers, i.e. dithiaporphyrin (DTP) and sulfoxaporphyrin (OXA) in combination with halogen lamp irradiation of presensitized tumors. The doses of sensitizers were: 2.5, 5.0, 7.5 and 10.0 mg/kg of body weight and total light doses were: 50, 100 and 150 J/sq.cm at the selected wavelength. Following such a treatment we have evaluated tumor necrosis of BFS1 fibrosarcoma growing on BALB/c mice. Together with tumor necrosis evaluation we have examined skin response to photodynamic treatment. RESULTS: We have found that both new sensitizers caused significant tumor damage at no skin alterations. The induction of tumor necrosis seemed to be dose dependent, i.e. higher photodynamic doses (sensitizer dose x light dose) resulted in more severe damage to the tumors than the lower doses. CONCLUSION: Our study showed that BFS1 fibrosarcoma is highly sensitive to PDT after application of new sensitizers. Both compounds can be considered as potent tumor photosensitizers in future clinical trials.

The new sensitizing agents for photodynamic therapy: 21-selenaporphyrin and 21-thiaporphyrin.

BACKGROUND: Photodynamic therapy may be a promising treatment for patients with tumors. The mechanism of its action is poorly understood and different from the cytotoxic effects induced by antitumor drugs. MATERIALS AND METHODS: New sensitizers, termed as 21-selenaporphyrin (SEP) and 21-thiaporphyrin (STSP) were studied for their photocytotoxicity in vitro against selected human cancer cell lines. This study was followed by in vivo screening of the effect of SEP using an animal tumor model. The activity of the new agents was compared with that of a known photosensitizer, namely chlorin e6. In our selection of the cell lines applied for in vitro study, the possible accessibility and effectiveness of photodynamic therapy (PDT) for treatment of colon and urinary bladder cancers, was considered. RESULTS: New compounds appeared to be not toxic for tested cells in culture, without exposure to light. The STSP exerted in vitro effects comparable with chlorin e6 photocytotoxicity, while SEP appeared to be ineffective. However, in vivo experiments performed in a BFS1 fibrosarcoma tumor model in mice showed that the SEP was at least as much effective as chlorin e6 in the induction of tumor necrosis. In contrast to chlorin e6, SEP-PDT induced no skin sensitization. CONCLUSIONS: Both new sensitizers can be applied in PDT at no risk of skin damage. The mechanism of the action of these two compounds is probably different, i.e. the 21-thiaporphyrin possibly acts directly on tumor cells and the 21-selenaporphyrin via endothelial cells of newly formed tumor vasculature.

Nickel complexes of 21-oxaporphyrin and 21, 23-dioxaporphyrin.

The nickel(I) and nickel(II) complexes of 5,20-bis(p-tolyl)-10, 15-diphenyl-21-oxaporphyrin (ODTDPPH) and 5,10,15,20-tetraphenyl-21, 23-dioxaporphyrin (O2 TPP) have been investigated. These oxa analogues of 5,10,15,20-tetraarylporphyrin, where one or two pyrrole rings are replaced by a furan moiety, have been synthesized by condensation of the respective precursors, namely 2,5-bis(arylhydroxymethyl)furan, pyrrole, and arylaldehyde. Insertion of nickel(II) into ODTDPPH or O2 TPP yielded high-spin five- and six-coordinate ([(ODTDPP)Ni(II) Cl] and [(O2 TPP)NiIICl2 ]) complexes, which can be reduced with moderate reducing reagents. The EPR spectra of [(ODTDPP)Ni(I) ] and [(O2 TPP)Ni(I) Cl] revealed the Ni(I) oxa(dioxa)porphyrin rather than a Ni(I) anion radical electronic structure. In the structures of [(ODTDPP)Ni(II) Cl], [(O2 TPP)Ni(IICl) 2 ], and [(ODTDPP)Ni(I) ], determined by X-ray diffraction, the furan ring is planar and coordinates in the η(1) fashion through the trigonal oxygen atom; the nickel ion lies in the furan plane for the latter two complexes, but slightly outside it in [(ODTDPP)Ni(II) Cl]. The Ni-N and Ni-O bond lengths decrease upon reduction of high-spin five-coordinate [(ODTDPP)Ni(II) Cl] to four-coordinate [(ODTDPP)Ni(I) ]. The pattern of downfield pyrrole resonances in (1) H NMR spectra of [(ODTDPP)Ni(IICl) ] and [(O2 TPP)-Ni(II) Cl2 ] has been established. The downfield positions of furan resonances are unusual for Ni(II) heteroporphyrins; they have been accounted for by the nearly in-plane coordination of the furan moiety as opposed to the side-on coordination found for thiophene- or selenophene-containing heteroporphyrins. An example of ion-pair formation, [(O2 TPPH)2 ][Ni(II) Cl4 ], was produced from [(O2 TPP)Ni(II) Cl2 ] by acidification with HCl.

5,20-bis(4-sulphophenyl)-10,15-bis (2-methoxy-4-sulphophenyl)-21-thiaporphyrin as a new potent sensitizer in photodynamic therapy.

The main purpose of the study was to investigate the effectiveness of a new photosensitizer for photodynamic therapy. 5,20-bis(4-sulphophenyl)-10,15-bis (2-methoxy-4-sulphophenyl)-21-thiaporphyrin (21-thiaporphyrin) was compared to chlorin e6 and tetra(m-hydroxyphenyl)porphyrin (m-THPP) for its ability to sensitize tumors and skin to light. Chlorin e6 and m-THPP induced a strong tumor and skin photosensitization. In contrast, the same doses of 21-thiaporphyrin produced no skin sensitization and gave approximately 10 mm tumor necrosis after light exposure, in comparison to the 5-6 mm necrosis induced by chlorin e6 or m-THPP under identical conditions. 21-Thiaporphyrin, tested as a potential photosensitizer, induced no skin sensitization even at doses as high as 7.5 mg/kg body weight. 21-Thiaporphyrin presents a high potency in tumor sensitizing, i.e. a feature required for an efficient photosensitizer in photodynamic therapy applications.

[Effects of para-tetra-hydroxyphenyl-porphyrin and red light on kidney clear cell carcinoma cells of Wistar rats]. / Efekty oddzialywania para-tetra-hydroksyfenyloporfiryny oraz swiatla czerwonego na komórki przeszczepialnego jasnokomórkowego raka nerki u szczurów Wistar.

Results of investigation of para-tetra-hydroxyphenyl-porphyrin and red light on treatment of kidney clear cell carcinoma in Wistar rats have been assessed. Positive influence of photodynamic therapy was confirmed.

Comment: NMR investigation of the electronic properties and magnetic states of hemes and hemoproteins: the S = 2 state in ferrous porphyrins.

The analysis of 1H NMR spectra of the high spin ferrous porphyrin with the axial base inserted in a chain bridged over one of the porphyrin face through opposite phenyl groups has been made. The possible conformational equilibria between rotamers with respect to the Fe- N axial ligand bond have allowed to account for all parameters of NMR spectra including the number of pyrrole resonances and the deviation from the Curie behaviour of the isotropic shift. The conformational model has not allowed to conclude decisively about the electronic ground state. The advantages and restriction of the previously proposed model with the settled position of the pyridine ring where the in-plane rhombic distortion splits the 5E level has also been considered. The influence of the axial ligand position on the spin density distribution has been discussed.