Molecular complexes of amino acids with porphyrins as possible precursors of pigment-protein systems

The present communication gives experimental results of the studies of catalytic and photochemical properties of peptide-like compounds containing metalloporphyrins (hemoproteinoids and molecular complexes obtained through adsorption of porphyrins and amino acids on volcanic ash). The data suggest that molecular complexes of amino acids with porphyrins could have evolved in the course of chemical evolution and were intermediated between abiogenically synthesized molecules of amino acids and porphyrins and pigment-protein systems of living organisms.     

Magnesium porphyrins as possible photosensitizers of macroergic phosphate bonds formation during prebiotic evolution

The paper presents experimental data on the light-induced ATP synthesis in the model systems containing chlorophyll adsorbates on aluminium or silicon oxides. The mechanism of phosphorylation observed in this system is based on the photosensitized electron transfer, where phosphate ion plays the role of an electron donor. Chlorophyll is a representative of magnesium porphyrins, which are known as photosensitizers. The formation of magnesium porphyrins in the prebiotic conditions seems to be quite probable, e.g. as a result of volcanic activity. During arising of life, magnesium porphyrins could participate in the formation of macroergic phosphate bonds of the dehydrating agents, which are necessary for the synthesis of biologically significant compounds.     

Chloroalkyl piperazine and nitrogen mustard porphyrins: synthesis and anticancer activity

Fifteen new chloroalkyl piperazine and nitrogen mustard porphyrins have been synthesized by the direct condensation of chloroalkyl piperazine, nitrogen mustard benzaldehyde, and pyrrole. Each porphyrin bears 1-4 chloroalkyl piperazine or nitrogen mustard moieties, which have been used as drugs. The Lindsey method was modified to synthesize chloroalkyl piperazine and nitrogen mustard porphyrins. To successfully synthesize chloroalkyl piperazine and nitrogen mustard porphyrins, catalyst acidity was proved to be the key factor, while the ratio of pyrrole to aldehyde had great influence on product yield. The synthetic chloroalkyl piperazine and nitrogen mustard porphyrins were characterized by elementary analysis, MS, (1)H NMR, IR, and UV-vis. Their anticancer activity to bel-7404 liver cancer cells was tested by the MTT assay. Most of the synthetic porphyrins had good anticancer activity toward bel-7404 liver cancer cells in the absence of light. These compounds might be potential anticancer medicines.     

Synthesis of corrins and related macrocycles based on pyrrolic intermediates.

Intermediate in structure between porphyrins and corrins are the corroles and 1-methyltetradehydrocorrins. These ring systems, like the porphyrins, can be obtained by cyclization of linear tetrapyrrolic compounds, reactions which have been shown to proceed by orbital symmetry-allowed electrocyclic processes, and examples will be quoted. Thermolysis of nickel 1-methyltetradehydrocorrins causes a migration of the methyl group whereas similar treatment of nickel 1,19-dimethyltetradehydrocorrin salts yields porphyrin derivatives; the mechanisms of these transformations have been elucidated. Stepwise hydrogenation of metal tetradehydrocorrin salts (10 double bonds) yields a series of macrocycles containing 9, 8, 7, 6 and 5 double bonds and conditions necessary to obtain corrins have been established.     

Inhibitory effect of porphyrins on the proliferation of mouse spleen lymphocytes in vitro

The influence of various porphyrins (deuteroporphyrin IX, mesoporphyrin IX, protoporphyrin IX, hematoporphyrin) and two related compounds (hemin, biliverdin) on the spontaneous proliferation of mouse spleen lymphocytes has been estimated in vitro by the 3H-thymidine uptake assay. It has been found that porphyrins (endogenous ligands for the mitochondrial benzodiazepine receptor) produce a concentration-dependent inhibition of 3H-thymidine incorporation into the DNA of these cells. Metalloporphyrin-hemin has been observed to evoke a weak inhibitory effect, in a high concentration (10(-4)M), whereas biliverdin, a porphyrins degradation product, was inactive in the same experimental conditions. Those findings indicate that endogenous porphyrins, presumably acting through the mitochondrial benzodiazepine receptor, could regulate the proliferation of mouse spleen lymphocytes in vitro.     

Porphyrins and metalloporphyrins: versatile circular dichroic reporter groups for structural studies

During the last few years, porphyrins and metalloporphyrins have attracted widespread attention as chromophores for studies in circular dichroism (CD), an indispensable chiroptical tool for monitoring chiral interactions. This review summarizes the multifaceted properties of porphyrins and metalloporphyrins, powerful CD chromophores that are characterized by their intense and red-shifted Soret band, propensity to undergo pi-pi stacking, facile incorporation of metals, and ease in varying solubility. Such attributes make porphyrins one of the most attractive and sensitive chromophores used in CD studies. They offer possibilities for studying the stereochemistry of chiral porphyrin assemblies, large organic molecules, biopolymers, and compounds available in miniscule quantities. The tendency of porphyrins to undergo pi-pi stacking and zinc porphyrins to coordinate with amines enable the CD exciton chirality method to be extended to configurational assignments of flexible compounds containing only one stereogenic center. Various artificial porphyrin receptors have been synthesized for the recognition of biologically important chiral guests such as carbohydrates, amino acids, and their derivatives. The induced CD of the host porphyrin Soret band reflects the identity of guests and binding modes of host/guest complexation with high sensitivity.     

The Evolution of Oxygen As a Biosynthetic Reagent

The biosynthesis of certain cell constituents: monounsaturated fatty acids, tyrosine, and nicotinic acid, is oxygen-dependent in many higher organisms. The same compounds can be synthesized by different, oxygen-independent pathways in lower organisms. The general outlines of these pathways are described and the importance of the compounds synthesized is discussed. An examination of the distribution of these pathways among living organisms reveals that oxygen-dependent pathways replaced the "anaerobic" pathways at different branch points on the evolutionary tree. Other groups of compounds are discussed, which are not distributed as widely among living organisms, but are found in all higher organisms. These compounds have specialized functions and their biosynthesis requires molecular oxygen. The oxygen-dependent portions of the biosynthetic pathways leading to porphyrins, quinone coenzymes, carotenoids, sterols, and polyunsaturated fatty acids are summarized. The distribution and functions of these compounds are also considered and an attempt is made to place them in the framework of evolution. While sterols and polyunsaturated fatty acids are found exclusively in the higher Protista and multicellular organisms, carotenoids, porphyrins, and quinones are also found in bacteria. The possibility of oxygen-independent mechanisms for their biosynthesis is discussed.     

Investigation on glyoxalase I inhibitors

Several classes of compounds - flavones, coumarins, S- and N-substituted glutathione analogs, transition state analogs, porphyrins, nucleotides and nucleosides - have been reported to inhibit the enzyme gloxalase I. In the current study, examination of some of the aforementioned compounds has revealed that squaric acid does not function as an inhibitor of glyoxalase I and several other compounds are much less effective in this regard than previously reported. Several new potent inhibitors of yeast glyoxalase I have been identified. Compounds containing the tropolone structure were especially inhibitory. Glutathione adducts of benzoquinone and naphthoquinone were also inhibitory and may be of particular interest with regard to the toxicology of normal aromatic metabolites in vivo.     

The phenomenon of formation of prebiological compounds in volcanic processes

Organic matter has been found in the juvenile ash of seven volcanoes in Kamchatka, the Kurile Islands and Indonesia. Its amount in one eruption is of the order of 1 00 000 tons. This matter constitutes a multicomponent mixture (more than 150 components) of, mainly, high boiling (b.p. over 250 degrees C) organic compounds of a complex structure. These are represented by hydrocarbons of saturated and aromatic nature, and, among them, polycyclic hydrocarbons, amino acids, amino sugars and other heteroatomic molecules, also containing N, O, S and C1. The formation of the above mentioned organic compounds is associated with volcanic processes--with abiogenous synthesis taking place in ash-gas clouds and, possibly, in the entrails of the Earth (hydrocarbons and their heteroatomic derivatives have also been found in volcanic bombs). On the strength of these facts, volcanic phenomena are regarded as the process which serves as the starting point of the chemical evolution from the inanimate to the animate matter.     

The phenomenon of formation of prebiological compounds in volcanic processes

Organic matter has been found in the juvenile ash of seven volcanoes in Kamchatka, the Kurile Island and Indonesia. Its amount in one eruption is of the order of 100 000 tons. This matter constitutes a multicomponent mixture (more than 150 components) of, mainly, high-boiling (b.p. over 250°C) organic compounds of a complex structure. These are represented by hydrocarbons of saturated and aromatic nature, and, among them, polycyclic hydrocarbons, amino acids, amino sugars and other heteroatomic molecules, also containing N, O, S and Cl. The formation of the above mentioned organic compounds is associated with volcanic processes—with abiogenous synthesis taking place in ash-gas clouds and, possibly, in the entrails of the Earth (hydrocarbons and their heteroatomic derivatives have also been found in volcanic bombs). On the strength of these facts, volcanic phenomena are regarded as the process which serves as the starting point of the chemical evolution from the inanimate to the animate matter.     

Synthesis,G-quadruplexes DNA binding,and photocytotoxicity of novel cationic expanded porphyrins

Intensive reports allowed the conclusion that molecules with extended aromatic surfaces always do good jobs in the DNA interactions. Inspired by the previous successful researches, herein, we designed a series of cationic porphyrins with expanded planar substituents, and evaluated their binding behaviors to G-quadruplex DNA using the combination of surface-enhanced raman, circular dichroism, absorption spectroscopy and fluorescence resonance energy transfer melting assays. Asymmetrical tetracationic porphyrin with one phenyl-4-N-methyl-4-pyridyl group and three N-methyl-4-pyridyl groups exhibit the best G4-DNA binding affinities among all the designed compounds, suggesting that the bulk of the substituents should be matched to the width of the grooves they putatively lie in. Theoretical calculations applying the density functional theory have been carried out and explain the binding properties of these porphyrins reasonably. Meanwhile, these porphyrins were proved to be potential photochemotherapeutic agents since they have photocytotoxic activities against both myeloma cell (Ag8.653) and gliomas cell (U251) lines.     

Synthesis of beta-substituted cationic porphyrins and their interactions with DNA

The beta-substituted cationic porphyrins (7, 8 and 10) have been synthesized and their interactions with plasmid DNA investigated. We found that substituents at the beta-position of porphyrins (7 and 8) have apparently affected their interactions with DNA compared with non-beta-substituted porphyrins (10).     

Different patterns of hepatic microsomal enzyme activity produced by administration of pure hexachlorobiphenyl isomers and hexachlorobenzene

Three hexachlorobiphenyl isomers, 2,2′,4,4′,5,5′-hexachlorobiphenyl (I), 2,2′,3,3′,4,4′-hexachlorobiphenyl (II) and 2,2′,3,4,4′,5′-hexachlorobiphenyl (III), have been administered to rats and the effects of these three compounds upon hepatic microsomal drug metabolism and upon hepatic porphyrins have been studied. Comparisons have been made with hexachlorobenzene and a commercial polychlorinated biphenyl mixture, Aroclor 1254. From measurements of activities of microsomal drug oxidations in vitro, the durations of pharmacological actions of certain drugs in vivo and spectral shifts associated with cytochrome P-450 it is shown that the three pure hexachlorobiphenyl isomers initially produce changes in hepatic microsomal activity which resemble those seen after treatment with phenobarbitone (PB). In contrast, following chronic feeding of the isomers, compounds II and III but not I produce a pattern of hepatic microsomal enzyme activity which shows some characteristics of the 3-methylcholanthrene (3-MC) and some characteristics of the phenobarbitone classes of inducer. Also, compounds II and III, but not I, cause accumulation in the liver of porphyrins containing either seven or eight carboxyl groups. These two responses are similar to those observed following hexachlorobenzene treatment and suggest that a relationship may exist between the mixed pattern of enzyme induction and the onset of hepatic porphyrin accumulation.     

Photogeneration of singlet molecular oxygen by the components of hematoporphyrin IX derivative

The photosensitized luminescence of singlet molecular oxygen has been studied in aqueous and alcoholic solutions of hematoporphyrin IX (HP) and di- and oligomeric components of "hematoporphyrin derivative" (photofrin II) which is known to be used as a drug in photodynamic tumor therapy. The quantum yields of 1O2 generation (gamma delta) by these compounds have been determined. It was found that the highest gamma delta values are characteristic of alcoholic and micellar detergent aqueous solutions. In detergent-free aqueous solutions containing mainly associated porphyrin molecules, gamma delta is much lower (5-30%), polymeric photofrin components being considerably less active than HP. Both localization of porphyrins in hydrophobic loci and high photosensitizing activity in lipid phase are supposed to play the key role in tumor photodestruction.     

Suppression of singlet oxygen luminescence by porphyrins and metalloporphyrins

The luminescene of 1O2 (1270 nm) has been observed upon illumination of air saturated solutions of different porphyrins and their complexes with Zn in CCl4. In solutions of Co-, Cu-, Ni- and Fe-porphyrins this luminescence has not been revealed. All the porphyrins studied have shown to quench 1O2, the rate constants of the "physical" and "chemical" quenching being measured. The physical way of quenching is found to be much more effective. The quenching activity of the pigments depends greatly on the presence and nature of the central metall atom incorporated into porphyrin (H2 less than Cu less than Zn less than Co approximately Ni approximately Fe) increases with hydrogenation of the semiisolated double bonds (porphyrins are less active than chlorins and bacteriochlorins).     

In situ assessment of porphyrin photosensitizers in Propionibacterium acnes

Porphyrins are known to be efficient photosensitizer molecules and the combined action of light and porphyrins in Propionibacterium acnes have a lethal action on the cells. Identification and quantification of in situ porphyrins in P. acnes have been done using an integrating sphere connected to an ordinary absorption spectrophotometer, and the amounts of porphyrins in the cells were quantified by measuring scattering free absorption spectra of the cell suspensions. The concentration of porphyrins in P. acnes cells were increased in either of two ways; by the addition of delta-aminolevulinic acid (ALA), which lead to the formation of coproporphyrin III under the incubation conditions used in these experiments, or by the addition of protoporphyrin IX (PPIX) to the cell suspension. In the latter case, PPIX molecules are taken up by the cells in a membrane-mediated uptake mechanism, and accumulate in the cells either on a monomeric or a particular aggregate form. The fraction of porphyrins on aggregate form increased with increasing PPIX additions. In the case of ALA induced porphyrin production, only monomeric porphyrins were stored in the cells. In both cases, the cells have a limited binding capacity of monomeric porphyrins, which is estimated to be 3 x 10(5) molecules/cell, or one porphyrin molecule to every 100st lipid molecule in the cell membrane.     

Assessment of the relevance of supported planar bilayers for modeling specific interactions between glycodendrimeric porphyrins and retinoblastoma cells

Glycodendrimeric porphyrins seem promising photosensitizers usable in photodynamic therapy. Evidence of their ability to interact with an artificial supported bilayer membrane exhibiting a model sugar receptor has been previously shown. In the present work, the interaction of the glycodendrimeric porphyrins with retinoblastoma cells bearing the actual sugar receptor has been assessed by both classical cell cultures and an original approach using the quartz crystal microbalance (QCM-D). Our results showed that unlike cell cultures, QCM-D allowed analyzing the mechanism of interaction of the glycodendrimeric porphyrins with the sugar receptor. Not only was molecular recognition demonstrated, but our methodology also proved efficient to discriminate between the studied compounds, depending on the presence of carbohydrate, and the spacer length.     

Spectroscopic and electrochemical studies of novel model compounds for cytochrome c oxidase

Different metalated porphyrin compounds were studied as model complexes for cytochrome c oxidase. All models contain a tyrosine molecule and a copper binding site. Two of the compounds are bearing an axial pyridine ligand that could possibly coordinate with Fe porphyrins. All complexes were studied using NMR and UV-Vis spectroscopies and it was found that the coordination of the axial ligand is possible only in one of the porphyrins. Moreover, the synthesized catalysts were studied as promising enzyme mimics using a rotating disc electrode in the presence of molecular oxygen.     

Analyses of the returned lunar surface fines for porphyrins

In the present studies, no porphyrins were found in the lunar surface fines collected from the Sea of Tranquillity by the Apollo 11 mission, from the Ocean of Storms by the Apollo 12 mission, and from the nonmare Fra Mauro Formation by the Apollo 14 expedition under the conditions in which porphyrins would have been detected had they been present in amounts as small as 10^–14 mole.     

Syntheses and preliminary biological studies of four meso-Tetra[(nido-carboranylmethyl)phenyl]porphyrins

Two meso-tetra[(nido-carboranylmethyl)phenyl]porphyrins (para- and meta-regioisomers) and their corresponding Zn(II) complexes have been synthesized with the aim of studying the effect of carborane distribution and metalation on the biological properties of this series of compounds. In vitro cell toxicity, uptake/efflux, and subcellular localization using rat 9L, mouse B16 and/or human U-373MG cells were evaluated. All four amphiphilic porphyrins display very low cytotoxicities and time- and concentration-dependent uptake by cells, which is influenced by serum proteins. Preliminary subcellular localization studies suggest that one of these compounds localizes in close proximity to the cell nucleus. All four nido-carboranylporphyrins show promise as boron-carriers for the boron neutron capture therapy of cancers, particularly the metal-free nido-carboranylporphyrins 5 and 12, which are able to deliver higher amount of boron to cells in vitro than the corresponding zinc complexes.