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Carlo Floriani - One of the best experts on this subject based on the ideXlab platform.
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Artificial Porphyrins Containing Cyclopropane Units Functioning as Electron Shuttles
ChemInform, 2010Co-Authors: Carlo FlorianiAbstract:The absence of the meso-hydrogen atoms in meso-octaalkylPorphyrinogens enable the generation of novel forms of the oxidized Porphyrinogen, “artificial porphyrin”. A stepwise four electron oxidation of meso-octaalkylPorphyrinogen transition metal complexes led to an unusual aromatization of the Porphyrinogen with the loss of four hydrogen atoms and the introduction of one, followed by two cyclopropane units into the Porphyrinogen frame. Such oxidized forms of Porphyrinogen function as two electron shuttles via the formation and cleavage of the cyclopropane unit. Furthermore, the appropriate site opening of the cyclopropane may lead to important modifications of the Porphyrinogen frame.
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Acetylenes Rearranging on Ruthenium-Porphyrinogen and Leading to Vinylidene and Carbene Functionalities This work was supported by the "Fonds National Suisse de la Recherche Scientifique" (Grant No. 20-61 246.00).
Angewandte Chemie, 2001Co-Authors: Lucia Bonomo, Euro Solari, Christine Stern, Rosario Scopelliti, Carlo FlorianiAbstract:: Through a proton-transfer reaction a Porphyrinogen assists the transformation of terminal acetylenes into Ru-vinylidenes, which are the entry point to a variety of Ru-carbenes and Ru-cumulenes. The scheme (in which the Porphyrinogen is stylized) shows the reversible interconversion of an acetylide into a divinylidene unit.
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acetylenes rearranging on ruthenium Porphyrinogen and leading to vinylidene and carbene functionalities
Angewandte Chemie, 2001Co-Authors: Lucia Bonomo, Euro Solari, Christine Stern, Rosario Scopelliti, Carlo FlorianiAbstract:Through a proton-transfer reaction a Porphyrinogen assists the transformation of terminal acetylenes into Ru-vinylidenes, which are the entry point to a variety of Ru-carbenes and Ru-cumulenes. The scheme (in which the Porphyrinogen is stylized) shows the reversible interconversion of an acetylide into a divinylidene unit.
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A theoretical analysis of the fundamental stepwise six-electron oxidation of Porphyrinogen to porphyrins: the energetics of porphodimethene and artificial porphyrin intermediates
Journal of The Chemical Society-dalton Transactions, 2001Co-Authors: Paola Belanzoni, Lucia Bonomo, Marzio Rosi, Antonio Sgamellotti, Carlo FlorianiAbstract:Density functional calculations have been carried out on a series of model hypothetical intermediates in the six-electron oxidation of Porphyrinogen (5,10,15,20,22,24-hexahydroporphyrin) to porphyrin. Two possible reaction pathways have been investigated: the conventional one, supposed to be followed both in the chemical synthesis and the biosynthesis of porphyrins, and the unconventional one, which has been discovered on studying the oxidation of a stable form of Porphyrinogen, namely meso-octaalkylPorphyrinogen. The energetics of both pathways have fully been investigated for the free Porphyrinogen. The conventional route is strongly preferred with respect to the unconventional one. The metal-assisted six-electron oxidation of Porphyrinogen to porphyrin was also investigated by density functional calculations on several nickel and cobalt model complexes. The metal does not seem to be able to force the system to follow a different route; the conventional route is even more preferred with respect to the unconventional one.
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The Porphyrinogen−Porphodimethene Relationship Leading to Novel Synthetic Methodologies Focused on the Modification and Functionalization of the Porphyrinogen and Porphodimethene Skeletons
Journal of the American Chemical Society, 2000Co-Authors: Lucia Bonomo, Euro Solari, Carlo Floriani, Rosario Scopelliti, Nazzareno ReAbstract:The general synthetic methods presented in this paper make available, on a preparative scale, unprecedented Porphyrinogen-derived skeletons, including their functionalization at the meso positions. The stepwise dealkylation of meso-octaalkylPorphyrinogen R8N4H4 [R = Et, 1; R = Bun, 2] was chemically, mechanistically, and structurally followed until the formation of porphomethene and porphodimethene derivatives 5−13, obtained with a sequential use of SnCl4. In particular, the porphodimethene derivative [(Et6N4)SnCl2], 9, was reductively transmetalated using Li metal to Et6N4Li2, 14, subsequently hydrolyzed to Et6N4H2, 15. The porphodimethene−nickel complex [(Et6N4)Ni], 16, was used for studying the reactivity and the ligand modification of the porphodimethene skeleton. The reactivity of 16 toward nucleophiles led to otherwise inaccessible meso-substituted-meso-functionalized Porphyrinogens [(Et6N4R2)NiLi2], [R = H, 18; R = Bun, 19; R = CH2CN, 20], thus exemplifying a general methodology to meso-functionali...
Jonathan P. Hill - One of the best experts on this subject based on the ideXlab platform.
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Stable pseudotetrahedral supermolecules based on an oxoPorphyrinogen
Tetrahedron Letters, 2010Co-Authors: Jan Labuta, Jonathan P. Hill, Mark R J Elsegood, Katsuhiko ArigaAbstract:Abstract Topologically asymmetric compounds, important as chiral nanoscale building blocks, were synthesized using stepwise N-alkylation on tetrakis (3,5-di- t -butyl-4-oxocyclohexadien-2,5-yl) Porphyrinogen as revealed by X-ray crystallographic studies on a Porphyrinogen molecule bearing four different N-substituents.
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Highly effective electrochemical anion sensing based on oxoPorphyrinogen
Elsevier, 2007Co-Authors: Amy Lea Schumacher, Jonathan P. Hill, Katsuhiko Ariga, Francis D’souzaAbstract:The effect of anion binding on the oxidation potential of an anion receptor, N21,N23-dibenzyl-5,10,15,20-(3,5-di-t-butyl-4-oxo-cyclohexa-2,5-dienylidene)Porphyrinogen, 1 in o-dichlorobenzene is reported. The anion binding site of 1, at its inner pyrrolic amine hydrogens, is an integral part of the highly conjugated macrocycle, thus predicting larger potential shifts upon anion binding. Accordingly, cathodic shifts up to 600 mV are observed upon anion binding and such potential shifts correlate well with the anion binding constants. Keywords: Electrochemical anion sensing, Porphyrinogen, Cathodic shift, Recognitio
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Chromogenic indicator for anion reporting based on an N-substituted oxoPorphyrinogen.
Inorganic Chemistry, 2006Co-Authors: Jonathan P. Hill, Amy Lea Schumacher, Francis D'souza, Jan Labuta, Masaru Aoyagi, Takashi Nakanishi, Carl Redshaw, Mark R J Elsegood, Katsuhiko ArigaAbstract:5,10,15,20-Tetrakis-3,5-di-tert-butyl-4-oxocyclohexadienylidene Porphyrinogen and its di-N-benzylated derivative are solvatochromic dyes capable of binding anionic species. The influence of solvent polarity and hydrogen bonding on their electronic absorption spectra was observed. Hydrogen bonding by the Porphyrinogen amine protons of acetone solvent molecules could be observed in the solid state. The acetone solvate of N21N23-dibenzyl-5,10,15,20-tetrakis-3,5-di-tert-butyl-4-oxocyclohexadienylidene Porphyrinogen crystallized under anhydrous conditions in the space group P1 with cell dimensions a = 12.1693(11) A, b = 17.5849(13) A, c = 21.0965(17) A, α = 69.870(4)°, β = 78.140(4)°, γ = 82.865(5)°. These Porphyrinogens are capable of binding a variety of anions and can be used to distinguish fluoride chromogenically from the other halide anions. Solvatochromism was combined with anion binding in an attempt to provide more selective tests for anions. The anion binding properties were investigated using UV/vi...
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cover picture structures spectral and electrochemical properties of n naphth 2 ylmethyl appended Porphyrinogens eur j org chem 14 2005
European Journal of Organic Chemistry, 2005Co-Authors: Jonathan P. Hill, Amy L Mccarty, Katsuhiko Ariga, Wolfgang Schmitt, Francis D SouzaAbstract:The cover picture shows the X-ray crystal structures of the compounds obtained by the alkylation of a conjugated Porphyrinogen precursor at its macrocyclic nitrogen atoms with 2-(methylenenaphthyl) groups. The presence of the N-alkyl groups introduces intermolecular π−π stacking interactions which culminate in a 1-dimensional stacked array for the fully N-substituted derivative. The N-alkylation enhances the ability of the compounds to form anion radical and cation radical species and permits “tuning” of the electrochemical properties of the core Porphyrinogen. Details are discussed in the article by J. P. Hill et al. on p. 2893 ff.
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Cover Picture: Structures, Spectral and Electrochemical Properties of N‐(Naphth‐2‐ylmethyl)‐Appended Porphyrinogens (Eur. J. Org. Chem. 14/2005)
European Journal of Organic Chemistry, 2005Co-Authors: Jonathan P. Hill, Amy L Mccarty, Katsuhiko Ariga, Wolfgang Schmitt, Francis D′souzaAbstract:The cover picture shows the X-ray crystal structures of the compounds obtained by the alkylation of a conjugated Porphyrinogen precursor at its macrocyclic nitrogen atoms with 2-(methylenenaphthyl) groups. The presence of the N-alkyl groups introduces intermolecular π−π stacking interactions which culminate in a 1-dimensional stacked array for the fully N-substituted derivative. The N-alkylation enhances the ability of the compounds to form anion radical and cation radical species and permits “tuning” of the electrochemical properties of the core Porphyrinogen. Details are discussed in the article by J. P. Hill et al. on p. 2893 ff.
Lucia Bonomo - One of the best experts on this subject based on the ideXlab platform.
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acetylenes rearranging on ruthenium Porphyrinogen and leading to vinylidene and carbene functionalities
Angewandte Chemie, 2001Co-Authors: Lucia Bonomo, Euro Solari, Christine Stern, Rosario Scopelliti, Carlo FlorianiAbstract:Through a proton-transfer reaction a Porphyrinogen assists the transformation of terminal acetylenes into Ru-vinylidenes, which are the entry point to a variety of Ru-carbenes and Ru-cumulenes. The scheme (in which the Porphyrinogen is stylized) shows the reversible interconversion of an acetylide into a divinylidene unit.
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Acetylenes Rearranging on Ruthenium-Porphyrinogen and Leading to Vinylidene and Carbene Functionalities This work was supported by the "Fonds National Suisse de la Recherche Scientifique" (Grant No. 20-61 246.00).
Angewandte Chemie, 2001Co-Authors: Lucia Bonomo, Euro Solari, Christine Stern, Rosario Scopelliti, Carlo FlorianiAbstract:: Through a proton-transfer reaction a Porphyrinogen assists the transformation of terminal acetylenes into Ru-vinylidenes, which are the entry point to a variety of Ru-carbenes and Ru-cumulenes. The scheme (in which the Porphyrinogen is stylized) shows the reversible interconversion of an acetylide into a divinylidene unit.
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A theoretical analysis of the fundamental stepwise six-electron oxidation of Porphyrinogen to porphyrins: the energetics of porphodimethene and artificial porphyrin intermediates
Journal of The Chemical Society-dalton Transactions, 2001Co-Authors: Paola Belanzoni, Lucia Bonomo, Marzio Rosi, Antonio Sgamellotti, Carlo FlorianiAbstract:Density functional calculations have been carried out on a series of model hypothetical intermediates in the six-electron oxidation of Porphyrinogen (5,10,15,20,22,24-hexahydroporphyrin) to porphyrin. Two possible reaction pathways have been investigated: the conventional one, supposed to be followed both in the chemical synthesis and the biosynthesis of porphyrins, and the unconventional one, which has been discovered on studying the oxidation of a stable form of Porphyrinogen, namely meso-octaalkylPorphyrinogen. The energetics of both pathways have fully been investigated for the free Porphyrinogen. The conventional route is strongly preferred with respect to the unconventional one. The metal-assisted six-electron oxidation of Porphyrinogen to porphyrin was also investigated by density functional calculations on several nickel and cobalt model complexes. The metal does not seem to be able to force the system to follow a different route; the conventional route is even more preferred with respect to the unconventional one.
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The Porphyrinogen−Porphodimethene Relationship Leading to Novel Synthetic Methodologies Focused on the Modification and Functionalization of the Porphyrinogen and Porphodimethene Skeletons
Journal of the American Chemical Society, 2000Co-Authors: Lucia Bonomo, Euro Solari, Carlo Floriani, Rosario Scopelliti, Nazzareno ReAbstract:The general synthetic methods presented in this paper make available, on a preparative scale, unprecedented Porphyrinogen-derived skeletons, including their functionalization at the meso positions. The stepwise dealkylation of meso-octaalkylPorphyrinogen R8N4H4 [R = Et, 1; R = Bun, 2] was chemically, mechanistically, and structurally followed until the formation of porphomethene and porphodimethene derivatives 5−13, obtained with a sequential use of SnCl4. In particular, the porphodimethene derivative [(Et6N4)SnCl2], 9, was reductively transmetalated using Li metal to Et6N4Li2, 14, subsequently hydrolyzed to Et6N4H2, 15. The porphodimethene−nickel complex [(Et6N4)Ni], 16, was used for studying the reactivity and the ligand modification of the porphodimethene skeleton. The reactivity of 16 toward nucleophiles led to otherwise inaccessible meso-substituted-meso-functionalized Porphyrinogens [(Et6N4R2)NiLi2], [R = H, 18; R = Bun, 19; R = CH2CN, 20], thus exemplifying a general methodology to meso-functionali...
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the Porphyrinogen porphodimethene relationship leading to novel synthetic methodologies focused on the modification and functionalization of the Porphyrinogen and porphodimethene skeletons
Journal of the American Chemical Society, 2000Co-Authors: Lucia Bonomo, Euro Solari, Rosario Scopelliti, Carlo FlorianiAbstract:The general synthetic methods presented in this paper make available, on a preparative scale, unprecedented Porphyrinogen-derived skeletons, including their functionalization at the meso positions. The stepwise dealkylation of meso-octaalkylPorphyrinogen R8N4H4 [R = Et, 1; R = Bun, 2] was chemically, mechanistically, and structurally followed until the formation of porphomethene and porphodimethene derivatives 5−13, obtained with a sequential use of SnCl4. In particular, the porphodimethene derivative [(Et6N4)SnCl2], 9, was reductively transmetalated using Li metal to Et6N4Li2, 14, subsequently hydrolyzed to Et6N4H2, 15. The porphodimethene−nickel complex [(Et6N4)Ni], 16, was used for studying the reactivity and the ligand modification of the porphodimethene skeleton. The reactivity of 16 toward nucleophiles led to otherwise inaccessible meso-substituted-meso-functionalized Porphyrinogens [(Et6N4R2)NiLi2], [R = H, 18; R = Bun, 19; R = CH2CN, 20], thus exemplifying a general methodology to meso-functionali...
Euro Solari - One of the best experts on this subject based on the ideXlab platform.
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acetylenes rearranging on ruthenium Porphyrinogen and leading to vinylidene and carbene functionalities
Angewandte Chemie, 2001Co-Authors: Lucia Bonomo, Euro Solari, Christine Stern, Rosario Scopelliti, Carlo FlorianiAbstract:Through a proton-transfer reaction a Porphyrinogen assists the transformation of terminal acetylenes into Ru-vinylidenes, which are the entry point to a variety of Ru-carbenes and Ru-cumulenes. The scheme (in which the Porphyrinogen is stylized) shows the reversible interconversion of an acetylide into a divinylidene unit.
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Acetylenes Rearranging on Ruthenium-Porphyrinogen and Leading to Vinylidene and Carbene Functionalities This work was supported by the "Fonds National Suisse de la Recherche Scientifique" (Grant No. 20-61 246.00).
Angewandte Chemie, 2001Co-Authors: Lucia Bonomo, Euro Solari, Christine Stern, Rosario Scopelliti, Carlo FlorianiAbstract:: Through a proton-transfer reaction a Porphyrinogen assists the transformation of terminal acetylenes into Ru-vinylidenes, which are the entry point to a variety of Ru-carbenes and Ru-cumulenes. The scheme (in which the Porphyrinogen is stylized) shows the reversible interconversion of an acetylide into a divinylidene unit.
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The Porphyrinogen−Porphodimethene Relationship Leading to Novel Synthetic Methodologies Focused on the Modification and Functionalization of the Porphyrinogen and Porphodimethene Skeletons
Journal of the American Chemical Society, 2000Co-Authors: Lucia Bonomo, Euro Solari, Carlo Floriani, Rosario Scopelliti, Nazzareno ReAbstract:The general synthetic methods presented in this paper make available, on a preparative scale, unprecedented Porphyrinogen-derived skeletons, including their functionalization at the meso positions. The stepwise dealkylation of meso-octaalkylPorphyrinogen R8N4H4 [R = Et, 1; R = Bun, 2] was chemically, mechanistically, and structurally followed until the formation of porphomethene and porphodimethene derivatives 5−13, obtained with a sequential use of SnCl4. In particular, the porphodimethene derivative [(Et6N4)SnCl2], 9, was reductively transmetalated using Li metal to Et6N4Li2, 14, subsequently hydrolyzed to Et6N4H2, 15. The porphodimethene−nickel complex [(Et6N4)Ni], 16, was used for studying the reactivity and the ligand modification of the porphodimethene skeleton. The reactivity of 16 toward nucleophiles led to otherwise inaccessible meso-substituted-meso-functionalized Porphyrinogens [(Et6N4R2)NiLi2], [R = H, 18; R = Bun, 19; R = CH2CN, 20], thus exemplifying a general methodology to meso-functionali...
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the Porphyrinogen porphodimethene relationship leading to novel synthetic methodologies focused on the modification and functionalization of the Porphyrinogen and porphodimethene skeletons
Journal of the American Chemical Society, 2000Co-Authors: Lucia Bonomo, Euro Solari, Rosario Scopelliti, Carlo FlorianiAbstract:The general synthetic methods presented in this paper make available, on a preparative scale, unprecedented Porphyrinogen-derived skeletons, including their functionalization at the meso positions. The stepwise dealkylation of meso-octaalkylPorphyrinogen R8N4H4 [R = Et, 1; R = Bun, 2] was chemically, mechanistically, and structurally followed until the formation of porphomethene and porphodimethene derivatives 5−13, obtained with a sequential use of SnCl4. In particular, the porphodimethene derivative [(Et6N4)SnCl2], 9, was reductively transmetalated using Li metal to Et6N4Li2, 14, subsequently hydrolyzed to Et6N4H2, 15. The porphodimethene−nickel complex [(Et6N4)Ni], 16, was used for studying the reactivity and the ligand modification of the porphodimethene skeleton. The reactivity of 16 toward nucleophiles led to otherwise inaccessible meso-substituted-meso-functionalized Porphyrinogens [(Et6N4R2)NiLi2], [R = H, 18; R = Bun, 19; R = CH2CN, 20], thus exemplifying a general methodology to meso-functionali...
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Porphodimethene–Porphyrinogen relationship: the generation of unprecedented forms of Porphyrinogen†
Chemical Communications, 1999Co-Authors: Lucia Bonomo, Euro Solari, Carlo Floriani, Rosario Scopelliti, Mario LatronicoAbstract:The electrophilic reactivity of the porphodimethene skeleton towards nucleophiles led the establishment of a synthetic methodology to unprecedented forms of Porphyrinogen containing the vinylidene substituents as well as other functionalities in the meso-positions
Timothy D Lash - One of the best experts on this subject based on the ideXlab platform.
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normal and abnormal heme biosynthesis part 7 synthesis and metabolism of coproPorphyrinogen iii analogues with acetate or butyrate side chains on rings c and d development of a modified model for the active site of coproPorphyrinogen oxidase
Bioorganic & Medicinal Chemistry, 2011Co-Authors: Timothy D Lash, Teresa R Lamm, Andy J Schaber, Wenhsiang Chung, Eric K Johnson, Marjorie A JonesAbstract:Abstract Analogues of coproPorphyrinogen-III have been prepared with acetate or butyrate groups attached to the C and D pyrrolic subunits. The corresponding porphyrin methyl esters were synthesized by first generating a,c-biladienes by reacting a dipyrrylmethane with pyrrole aldehydes in the presence of HBr. Cyclization with copper(II) chloride in DMF, followed by demetalation with 15% H 2 SO 4 –TFA and reesterification, gave the required porphyrins in excellent yields. Hydrolysis with 25% hydrochloric acid and reduction with sodium-amalgam gave novel diacetate and dibutyrate Porphyrinogens 9 . Diacetate 9a was incubated with chicken red cell hemolysates (CRH), but gave complex results due to the combined action of two of the enzymes present in these preparations. Separation of uroPorphyrinogen decarboxylase (URO-D) from coproPorphyrinogen oxidase (CPO) allowed the effects of both enzymes on the diacetate substrate to be assessed. Porphyrinogen 9a proved to be a relatively poor substrate for CPO compared to the natural substrate coproPorphyrinogen-III, and only the A ring propionate moiety was processed to a significant extent. Similar results were obtained for incubations of 9a with purified human recombinant CPO. Diacetate 9a was also a substrate for URO-D and a Porphyrinogen monoacetate was the major product in this case; however, some conversion of a second acetate unit was also evident. The dibutyrate Porphyrinogen 9b was only recognized by the enzyme CPO, but proved to be a modest substrate for incubations with CRH. However, 9b was an excellent substrate for purified human recombinant CPO. The major product for these incubations was a monovinylPorphyrinogen, but some divinyl product was also generated in incubations using purified recombinant human CPO. The incubation products were converted into the corresponding porphyrin methyl esters, and these were characterized by proton NMR spectroscopy and mass spectrometry. The results extend our understanding of substrate recognition and catalysis for this intriguing enzyme and have allowed us to extend the active site model for CPO. In addition, the competitive action of both URO-D and CPO on the same diacetate Porphyrinogen substrate provides additional perspectives on the potential existence of abnormal pathways for heme biosynthesis.
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use of di and tripropionate substrate analogs to probe the active site of human recombinant coproPorphyrinogen oxidase
Medical Science Monitor, 2008Co-Authors: Justin B. Morgenthaler, Reyna L Barto, Timothy D Lash, Marjorie A JonesAbstract:Background: Defects in the enzyme coproPorphyrinogen oxidase result in accumulation of porphyrins which may affect the severity of a subset of porphyrias. Thus evaluation of this enzyme for substrate selectivity is of value. Kinetic evaluations of recombinant human coproPorphyrinogen oxidase have been undertaken using six di- and tripropionate analogs of the natural substrate coproporphyrin-ogen-III. These substrate analogs were modified by having alkyl groups in place of one or both of the ring 13- or 17-propionate moieties. Material/Methods: Cloned human enzyme was incubated with analogs under apparent first order conditions and with various substrate concentrations. The kinetic values, K m and V max , were determined. Results: Relative to the authentic substrate, the K m values for the 13-ethyl, dimethyl and diethyl Porphyrinogens were very comparable whereas the K m values were much higher using dipropyl and dibutyl Porphyrinogen and much lower for the 17-ethyl analog. For the dipropionate analogs, the V max values were an apparent function of the carbon length of the substituent on the C and D rings, with longer carbon length severely reducing product formation by some 4-5 orders of magnitude. Also, the two isomeric tripropionates that were tested indicated that it was more detrimental to have an ethyl group at the 13-position for both binding and catalysis. Conclusions: This work extends our understanding of porphyrin ring substituent effects reported by Cooper et al. (2005). The substituents on both the C and D rings have significant effects on both the substrate binding and catalysis by this important enzyme.
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metabolism of pentacarboxylate Porphyrinogens by highly purified human coproPorphyrinogen oxidase further evidence for the existence of an abnormal pathway for heme biosynthesis
Bioorganic & Medicinal Chemistry, 2005Co-Authors: Christopher L. Cooper, Marjorie A Jones, Christian M Stob, Timothy D LashAbstract:Abstract An abnormal series of porphyrin tetracarboxylic acids known as the isocoproporphyrins, are commonly excreted by patients suffering from the disease porphyria cutanea tarda (PCT). These porphyrins appear to arise by bacterial degradation of dehydroisocoproPorphyrinogen that is generated by the premature metabolism of the normal pentacarboxylate intermediate (5dab) by coproPorphyrinogen oxidase (copro’gen oxidase). This Porphyrinogen can be further metabolized by uroPorphyrinogen decarboxylase to give harderoPorphyrinogen, one of the usual intermediates in heme biosynthesis. Therefore, it is possible that some of the heme formed under abnormal conditions may originate from the ‘isocopro-type’ Porphyrinogen intermediate. In order to investigate the feasibility of alternative pathways for heme biosynthesis, the four type III pentacarboxylate isomeric Porphyrinogens were incubated with purified, cloned human copro’gen oxidase at 37 °C with various substrate concentrations under initial velocity conditions. Of the four isomers, only 5dab was a substrate for copro’gen oxidase and this gave dehydroisocoproporphyrin. The structure of the related porphyrin tetramethyl ester was confirmed by proton NMR spectroscopy and mass spectrometry. The K m value for proto’gen-IX formation from copro’gen, an indicator of molecular recognition, was similar to the K m value for monovinyl product formation with 5dab, although copro’gen-III has an approximately twofold higher K cat value. Although 5dab is a slightly poorer substrate than copro’gen-III, these results support the hypothesis that an abnormal route for heme biosynthesis is possible in humans suffering from PCT or related syndromes such as hexachlorobenzene poisoning.
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the enigma of coproPorphyrinogen oxidase how does this unusual enzyme carry out oxidative decarboxylations to afford vinyl groups
Bioorganic & Medicinal Chemistry Letters, 2005Co-Authors: Timothy D LashAbstract:A new mechanism is proposed to explain how coproPorphyrinogen oxidase performs two oxidative decarboxylations on a Porphyrinogen substrate without the aid of cofactors or metal ions in the presence of molecular oxygen.
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Synthetic and biosynthetic studies of porphyrins, Part V. Evidence for an alternative pathway in the biosynthesis of haem.
International Journal of Biochemistry, 2003Co-Authors: Anthony H. Jackson, Timothy D Lash, D. J. Ryder, S.g. SmithAbstract:Abstract Patients suffering from porphyria cutanea tarda excrete relatively large amounts of porphyrins derived from intermediate Porphyrinogens between the octacarboxylic uroPorphyrinogen-III and the dicarboxylic protoPorphyrinogen-IX. The four carboxyl fraction contains a group of four porphyrins related to dehydroisocoproporphyrin which arise by the action of coproPorphyrinogen oxidase upon the pentacarboxylic precursor, before the final acetic acid residue is decarboxylated. Dehydroisocoproporphyrin, isocoproporphyrin, and desvinyldehydroisocoproporphyrin have now been synthesised and the corresponding Porphyrinogens incubated with chicken red cell haemolysates. The products have been investigated by h.p.l.c. and mass spectrometry and provide clear evidence for an alternative pathway from the normal pentacarboxylic Porphyrinogen precursor of coproPorphyrinogen-III via harderoPorphyrinogen to protoPorphyrinogen-IX and haem. The significance of our findings in relation to haem biosynthesis in normal and abnormal metabolism is also discussed.
