Synthesis, cellular uptake of, and cell photosensitization by a porphyrin bearing a quinoline group

A tetraphenyl porphine linked to a 7-chloroquinoline (5,10,15,20-tetraphenyl-1-3-[4-(4-aminobutyl)7-chloroquinoline] propioamidoporphine, TPPQ) was synthesized and examined as a potential photosensitizer for photodynamic therapy (PDT) of proliferative diseases. With respect to haematoporphyrin, TPPQ is a good in vitro photodynamic sensitizer producing singlet oxygen in 1% Triton X100 solutions. As with other hydrophobic porphyrins used in PDT, blood lipoproteins strongly bind TPPQ. Thus one low density lipoprotein (LDL) can incorporate 25 TPPQ molecules and 17 TPPQ molecules are taken up by one high density lipoprotein (HDL). Cell delivery of TPPQ using HDL or human serum albumin (HSA) as carrier is rather weak. However, an efficient TPPQ delivery to human skin fibroblasts is observed, partly aided by receptor-mediated endocytosis of LDL. Fluorescence spectroscopy shows that the cellular localization of TPPQ is both carrier and time dependent. During its delivery with LDL, TPPQ does not significantly impair the endocytosis of LDL-receptor complexes. After delivery with LDL, TPPQ is as efficient as other haematoporphyrin derivatives used in the PDT of cancers in photosensitizing human skin fibroblasts.     

PHOTOINITIATED VECTORIAL TRANSMEMBRANE ELECTRON TRANSFER IN BILAYERS SENSITIZED BY A FACE TO FACE TRIPORPHYRIN ACTING AS A MOLECULAR ELECTRONIC DEVICE. AMPLIFICATION DUE TO IONIC COUPLING

Under light excitation transmembrane electron transfer is observed when a stacked Zn-Cu-Zn triporphyrin is incorporated in a bilayer between aqueous redox phases. The electric polarization of the membrane due to the photoinduced transmembrane charge flux drives ion transport. This effect increases the net charge transfer across the system, giving rise to an amplification similar to a field effect transistor. Thus this system can be considered an organic phototransistor.     

Synthesis of new meso-tetrakis (glycosylated) porphyrins

The synthesis of a new family of meso-tetrakis (glycosylated) porphyrins is reported. Unfortunately, the porphyrins 4 and 5 bearing glycosyloxymethylene substituents are unstable.     

Nonplanar distortions of bis-base low-spin iron(II)-porphyrinates: absorption and resonance Raman investigations of cross-trans-linked iron(II)-basket-handle porphyrin complexes

Electronic absorption and Soret-excited resonance Raman (RR) spectra are reported for bis-N-alkylimidazole and bis-pyridine complexes of various cross-trans-linked iron(II)-"basket-handle" porphyrins (Fe(II)-BHP) in methylene chloride. These compounds enable us to characterize the spectroscopic properties of ruffled six-coordinated low-spin Fe(II)-porphyrin complexes. The visible absorption spectra show that the Q and B bands are progressively red-shifted when the handles are shortened and/or when the steric hindrance of the axial ligands is increased. This effect is accompanied by both a decrease in RR frequency of the nu(2) mode and an increase in frequency of the nu(8) and nu(s)(Fe-ligand(2)) modes. More precisely, an inverse linear correlation is found between the frequencies of the nu(2) and nu(8) modes. For each ligation state, the positions of the absorption bands are also linearly correlated with the frequency of the nu(2) or nu(8) mode. All of these spectroscopic data reveal that the degree of ruffling of the Fe(II)-BHP complexes is increased by the N-methylimidazole --> pyridine axial substitutions, presumably because the mutual steric strains between the axial ligand rings, the porphyrin macrocycle and the porphyrin handles are increased. The present study provides a first basis for discerning ruffled conformations from planar and other nonplanar structures in ferrous heme proteins.     

13C CP/MAS NMR Studies of Hemoprotein Models with and without an Axial Hindered Base: (13)C Shielding Tensors and Comparison with Hemoproteins and X-ray Structural Data

13C cross-polarization magic-angle-spinning (CP/MAS) NMR spectra of several carbonmonoxide (93-99% (13)C enriched) hemoprotein models with 1,2-dimethylimidazole (1,2-diMeIm) and 1-methylimidazole (1-MeIm) as axial ligands are reported. This enables the (13)CO spinning sideband manifold to be measured and hence the principal components of the (13)CO chemical shift tensor to be obtained. Negative polar interactions in the binding pocket of the cap porphyrin model and inhibition of Fe-->CO back-donation result in a reduction in shielding anisotropy; on the contrary, positive distal polar interactions result in an increase in the shielding anisotropy and asymmetry parameter in some models. It appears that the axial hindered base 1,2-dimethylimidazole has little direct effect on the local geometry at the CO site, despite higher rates of CO desorption being observed for such complexes. This suggests that the mechanism by which steric interactions are released for the 1,2-diMeIm complexes compared to 1-MeIm complexes does not involve a significant increase in bending of the Fe-C-O unit. The asymmetry of the shielding tensor of all the heme model compounds studied is smaller than that found for horse myoglobin and rabbit hemoglobin.     

ELECTRON AND PROTON PHOTOTRANSPORTS IN A BILAYER MEMBRANE. ACIDIC PORPHYRIN AND SUPEROXIDE ION AS ΔpH SENSITIVE CHARGE CARRIERS

Abstract— Glycerolmonooleate planar bilayer membranes containing a zinc-mesotetraphenyl l-[3-propionic acid] porphyrin separate two buffered aqueous phases, an oxidizing and a reducing one. Under illumination stationary photocurrents are recorded, that depend on the respective acidities of the aqueous phases. A strong enhancement is observed when the oxidizing solution is more acidic than the reducing solution. This phenomenon is attributed to the double role of the acidic porphyrin acting as an electron and a proton carrier. A second mechanism, also pH dependent, intervenes concurrently. The excited zinc-porphyrin reduces oxygen and the resulting superoxide ion translocates through the membrane lipidic core.     

Glycosylated Porphyrins: Characterization of Association in Aqueous Solutions by Absorption and Fluorescence Spectroscopies and Determination of Singlet Oxygen Yield in Organic Media

The behavior of a series of porphyrins substituted at meso positions by para -phenyl-β- d -glucose groups is examined in aqueous solutions by absorbance and fluorescence spectroscopies. This series includes tetra-, tri- and diglycosylated compounds, the last being substituted at adjacent or opposite meso positions. The other subsituents are alkyl chains and, in one case, a fluorophenyl group. Although all these compounds dimerize in aqueous solutions, the dimerization constants span over four orders of magnitiude (K _d = 1.3 × 10⁵–1.9 × 10⁹ M⁻¹). The dimer stability is strongly dependent on the nature and the arrangement of the substituents. The diglycosylated derivative substituted at adjacent meso positions yields the most stable dimer that is likely to present an offset stacked geometry. The dimer structures expected from the symmetry of the various compounds correlated well with the optical spectra that display exciton splitting in the Soret band. The fluorescence of the dimers is quenched in all derivatives with the noticeable exception of the adjacent diglycosylated derivative. All the compounds studied photosensitize the formation of singlet oxygen with yields ranging between 0.54 and 0.81. A fairly linear correlation between the yield and the number of aryl groups at meso positions is observed.     

PHOTOINDUCED VOLTA POTENTIAL IN A PORPHYRIN MONOLAYER

Abstract— When spread on an oxidizing aqueous subphase, an amphipathic basket handle zinc porphyrin (P) monolayer gives rise to a photoinduced Volta potential change. This surface photopotential is interpreted on the basis of an interfacial electron transfer in the interphase; upon light excitation, electrons are transferred from the chromophores in the monolayer to electron acceptors diffusing from the subphase. A kinetic model for charge separation and stabilization is proposed to account for the influences of the electron acceptor concentration, the pH of the subphase and the light intensity.     

Proton magnetic resonance in four-coordinated ferrous porphyrins

The N.M.R. spectra of ferrous four-coordinated octaethylporphyrin, deuteroporphyrin IX dimethylester, meso-tetraphenylporphin and mesotetra(αααα-o-pivalamidophenyl)porphin (the so-called ‘picket fence’ porphyrin) show that these paramagnetic complexes are in the same spin state in non-polar solvents. The isotropic paramagnetic shifts have been analysed using fluorine substituted tetraphenylporphins as probes for the estimation of the pseudocontact contribution to the observed shifts. The anisotropy of the pseudocontact interaction and the distribution pattern of the contact hyperfine interaction suggest that the spin state of these complexes corresponds to S=1. The electronic relaxation time for this configuration is very short, (T ₁=5 × 10^-13s), enabling the observation of high resolution spectra for these axially non-coordinated ferrous prophyrins.     

Definitive evidence for a proximal effect of pyridine in the NaOCl/Mn(porphyrin)x / pyridine catalytic oxygenation system

Using pyridine-attached manganese porphyrins, it has been possible to obtain definitive evidence that pyridine behaves as a proximal ligand in the NaOCl/Mn(porphyrin)X catalytic oxygenation system.