Factor F430 from Methanogenic Bacteria: Structure of the Porphninoid Ligand System



A structure is proposed for F430M, a non-cristalline methanolysis product of isolates of the nickel-containing, porphinoid factor F430 from Methanobacterium thermoautotrophicum.



Crucial to the structure determination are five incorporation experiments with M. thermoautotrophicum (strain Marburg) in which the specifically mono-13C-labeled biosynthetic precursors (2-13C), (3-13C), (4-13C)-, (5-13C) ALA (ALA = δ-amino-levulinic acid) and L-(methyl-13C)methionine were incorporated into F430 with high efficiency. The 13C-NMR,-spectra of the specifically labeled F430M samples derived therefrom, together with the UV./VIS. spectral data of F430M, contain all the information necessary for the deduction of the constitution of the F430M chromophore, assuming the established pattern of porphinoid biosynthesis to be operative in F430 biosynthesis. 1H-NMR. spectroscopy and, in particular, 1H-NMR.-NOE-difference spectroscopy corroborates and completes the constitutional assignments and, furthermore, makes possible an almost complete derivation of the molecule's relative configuration. Schemes 3 and 4 summarize the results of 1H-NMR. spectroscopy, presenting them within the context of the proposed structure for F430M. The assignment of absolute configuration implied in the formula is given preference because of F430M's very close structural and (assumed) biosynthetic relationship to sirohydrochlorin and vitamin B12 (with respect to ring C, the assignment is based on degradative evidence).



According to the proposed structure, the nickel complex F430M possesses an uroporphinoid (Type III) ligand skeleton with an additional carbocyclic ring and a chromophore system not previously encountered among natural porphinoids. It can be considered to be a (tetrahydro) derivative of the corphin system, combining structural elements of both porphyrins and corrins.

Zur Kenntnis des Faktors F430 aus methanogenen Bakterien: Struktur des porphinoiden Ligandsystems

Die im Anschlus an die Arbeiten zur Synthese des Vitamins B12 begonnene Suche nach einer potentiell biomimetischen Dunkelvariante der photochemischen A/D-Secocorrin → Corrin-Cycloisomerisierung hat seinerzeit zur Auffindung einer ganzen Familie von (A→D)-Cyclisierungsvarianten gefuhrt; nach den heutigen Kenntnissen uber den Verlauf der Vitamin-B12-Biosynthese kommt in der Tat einer dieser Varianten der Rang eines chemischen Modells der Reaktionsstufe zu, durch welche die Biosynthese den kritischen Schritt der Corrinbildung vollzieht. Durch diese chemischen Studien zum Problem der Vitamin-B12-Biosynthese lies sich experimentell die Tatsache aufdecken, das die fur das Corrinsystem typische A/D-Ringverknupfung, welche zu Beginn der B12-Arbeiten als die schwierigste Hurde einer chemischen Vitamin-B12-Synthese gegolten hatte, in Wahrheit ein Strukturelement ist, das sich unter strukturgerechten Voraussetzungen auf vielfaltige Weise und mit groser Leichtigkeit bildet. Analoges gilt, wie nun neuere Folgeuntersuchungen zeigen, auch fur andere spezifische Strukturelemente des Vitamin-B12-Molekuls; hierzu gehoren die charakteristische Anordnung der Doppelbindungen im Corrinchromophor, die spezielle Grose des Makroringes des Corrinliganden, die spezifische Haftung des Nucleotidringes an der Propionsaure-Seitenkette des Ringes D, sowie das (allerdings nicht nur fur Vitamin B12, sondern fur alle uroporphinoiden Cofaktoren charakteristische) Substitutionsmuster der Seitenketten an der Ligandperipherie. Alle diese zunachst komplex erscheinenden Strukturelemente erweisen sich unter strukturgerechten Voraussetzungen in uberraschendem Ausmas als selbstkonstituierend, das heist sie benotigen zu ihrer Bildung ein im Hinblick auf ihre Komplexitat und Spezifitat erstaunlich geringes Mas an externer Instruktion. Wir betrachten diese Befunde als Stationen auf dem Wege zu einer chemischen Rationalisierung der Vitamin-B12-Struktur, deren Ziel wir darin sehen, das dem Strukturtyp des Vitamins B12 immanente Potential zur Selbstkonstituierung experimentell zu erfassen. Es ist dieses Potential einer Cofaktorstruktur, welches zusammen mit deren spezifischer Reaktivitatsveranlagung fur das Faktum der biologischen Selektion dieser Struktur mitverantwortlich ist. Die chemische Rationalisierung von Biomolekulstrukturen ist eine Aufgabe der organischen Naturstoffchemie. Die Forschungsdisziplin der Naturstoffsynthese bietet problemgerechte konzeptuelle und methodische Mittel, um diese Aufgabe experimentell anzugehen.

Vitamin B12: Experimente zur Frage nach dem Ursprung seiner molekularen Struktur

"We'll never be able to know" is a truism that leads to resignation with respect to any experimental effort to search for the chemistry of life's origin. But such resignation runs radically counter to the challenge imposed upon chemistry as a natural science. Notwithstanding the prognosis according to which the shortest path to understanding the metamorphosis of the chemical into the biological is by way of experimental modeling of "artificial chemical life", the scientific search for the route nature adopted in creating the life we know will arguably never truly end. It is, after all, part of the search for our own origin.

Etiology of Potentially Primordial Biomolecular Structures: From Vitamin B12 to the Nucleic Acids and an Inquiry Into the Chemistry of Life's Origin: A Retrospective

The Saddle Conformation of Hydroporphinoid Nickel(II) Complexes: Structure, Origin, and Stereochemical Consequences



Thirteen crystal structures document the general phenomenon of coordination-hole contraction in hexahydro- and tetrahydroporphinoid ligands of complexes with small metal ions such as low-spin Ni(II). The contraction is characterized by a deformation of the ligand system towards a saddle-shaped, ruffled conformation of approximate S4 symmetry. The central metal ion is coplanar with the four coordinating N-centers whereas the four C(meso)-atoms are situated alternately above and below this coordination plane. Increasing steepness of the saddle (parameter dm) is associated with decreasing metal-N distances. For metal pyrrocorphinates, dm increases in the order Cu(II) < (pyridine) Co(II) < Ni(II), for Ni(II) complexes it does so in the order porphyrin < chlorin < bacteriochlorin < isobacteriochlorin < pyrrocorphin. In the saddle conformation of hydroporphinoid Ni(II) complexes, the hydropyrrole rings assume half-chair conformations whereby the individual half-chairs are conformationally constrained in such a way that the inclination of their peripheral single bond parallels the inclination of the ligand saddle (W-conformation of the ensemble of 5-membered ring half-chairs). There are only two such conformations available for a given complex; they interrelate by saddle inversion with concomitant inversion of the ensemble of half-chairs. The coordination-hole contraction of hydroporphinoid ligands is expected and observed experimentally to exert control on the stereochemistry and reactivity of the ligand periphery as well as on the axial electrophilicity of the central metal ion. Tetracoordinate nickel(II) pyrrocorphinates are found to favor the tctct configuration of substituents at the ligand periphery, nickel(II) isobacteriochlorinates the tct configuration, whereas nickel(II) bacteriochlorinates are expected to favor the ttt configuration. Relative rates and regioselectivities of autoxidation of nickel(II) pyrrocorphinates to corresponding bacterio-and isobacteriochlorinates depend on the configuration and conformation of the ligand periphery. The residual axial electrophilicity of the metal ion in tetracoordinate Ni(II) complexes of the octaethyl series appears to increase in the order chlorin < isobacteriochlorin ≲ bacteriochlorin < pyrrocorphin. All hydroporphinoid metal complexes used in the X-ray structure studies were prepared as part of exploring the porphyrinogen pyrrocorphin tautomerization, a novel structural transformation of porphyrinogens.

Die Sattelkonformation der hydroporphinoiden Nickel(II)‐Komplexe: Struktur, Ursprung und stereochemische Konsequenzen

Chemistry of α-Aminonitriles I: Introduction and Pathways to Uroporphyrinogen-octanitriles.



An introduction to experimental studies on the chemistry of α-aminonitriles potentially relevant to the problems of prebiotic chemistry is presented. The framework of conditions wherein the investigation is chosen to be carried out implies both molecular oxygen and - whenever feasible - water to be excluded from reaction conditions. This study focusses on 2-amino-2-propenenitrile (3) (Scheme 6) as central starting material of reaction sequences which aim at the nitrile forms of proteinogenic amino acids as well as at the aza forms of building blocks of biological cofactor molecules as their targets (Scheme 5). Schemes 13,16,23 as well as 25 and 26 summarize reaction sequences by which 3 is transformed within the defined framework of conditions into the thermodynamic (statistically controlled) mixture of the four isomeric uroperphyrinogen-octanitriles 57–60. HPLC's of such mixtures document the dominance of the least symmetrical isomer whose constitutional pattern of peripheral substituents happens to be the one percent in all biological porphinoids. Preparative procedures for the synthesis of 3(Scheme 9), the β,β-disubstituted pyrrol-nitriles 30,53 and 54 (Scheme 19) as well as the porphyrinogenoctakis(propionitrile) and-octakis(acetonitrile) 65 and 66, respectively (Scheme 24) are given.

Chemie der α-Aminonitrile 1. Mitteilung Einleitung und Wege zu Uroporphyrinogen-octanitrilen

The Pyrrocorphin Ligand System: Synthesis of 2,2,7,7,12,12,17-Heptamethyl-2,3,7,8,12,13-hexahydroporphyrin



Reaction Schemes 4 and 6 summarize the synthesis of the title compound, a representative of a recently described novel type of hexahydroporphinoid ligand system (‘pyrrocorphin’). Pyrrocorphins incorporate structural elements of both corrins and porphyrins and are chemically closely related to the tautomeric non-pyrrolic corphins (Scheme 1).



The synthesis exemplifies a methodology for constructing pyrrolic hydro-porphinoids with the methods of corrin instead of porphyrin synthesis. An X-ray analysis of 2-(cyanomethyl)-2-methyl-3-oxobutanamide has been carried out.

Das Pyrrocorphin‐Ligandsystem: Synthese des 2,2,7,7,12,12,17‐Heptamethyl‐2,3,7,8,12,13‐hexahydroporphyrins. Kurzmitteilung

Experiments on a simulation of the photochemical A/D-secocorrin corrin cycloisomerization by redox processes. Electrochemical oxidation of nickel(II)-1-methylidene-2,2,7,7,12,12-hexamethyl-15-cyano-1,19-secocorrinate perchlorate



Can the act of light excitation in the photochemical A/D-secocorrin corrin cycloisomerization be replaced by redox reactions in the dark? Electrochemical oxidation of nickel(II)-A/D-secocorrinate 4 in acetonitrile containing a trace of water produces the secocorrinoxide–nickel-complex 5 (structure determined by X-ray analysis) in almost quantitative yield. This two-electron oxidation involves a hydrogen shift from the methylene group C(19) in ring D to the methylidene carbon atom at ring A in the radical cation intermediate. Since the same type of hydrogen shift occurs in the photochemical A/D-secocorrin corrin cycloisomerization, a close parallelism in their chemical reactivity seems to exist between electronically excited A/D-secocorrins and corresponding radical cations. Formation of the corrin complex 2 (M = Ni+) could be achieved (so far only in modest yields) by electrochemical one-electron oxidation of 4 in acetonitrile/acetanhydride/acetic acid 8:1:1 followed by one-electron reduction. – The transformation of the oxide nickel complex 5 to the corrinoid complex 10 – a new member in the family of dehydrocorrins – is also recorded.

Versuche zur Redox-Simulation der photochemischen A/D-Secocorrin Corrin-Cycloisomerisierung. Elektrochemische Oxydation von Nickel(II)-1-methyliden-2,2,7,7,12,12-hexamethyl-15-cyan-1,19-secocorinat-perchlorat. Vorläufige Mitteilung†

Corrin Synthesis via A→D Ring Closure. The Construction of A/D-Secocorrin Chromophore Systems by the ‘Sulfide Contraction’ Method and the Photochemical A/B-Secocorrin→Corrin Cycloisomerization

Novel (5R,8S,10R)-6-(allyloxy)- and (5R,8S,10R)-6-(propyloxy)ergolines have been synthesized by use of a Meisenheimer [2,3]-sigmatropic rearrangement of a (5R,8S,10R)-6-allyl-ergoline N6-oxide as key step.

Synthesis of (5R,8S,10R)‐6‐(Allyloxy)‐ and (5R,8S,10R)‐6‐(Propyloxy)ergolines from the 6‐Methyl Precursors

The title compound 7 and two related novel ergolines have been synthesised from (5R,8R,10R)-8-(methyl-thiomethyl)ergoline-6-carbonitrile (4). The guanidine function of 7 induces a boat conformation of ergoline-ring D, as demonstrated by a careful NMR spectroscopic analysis of 7 and its N-hydroxy congener 6. Diphenylphosphinodithioic acid has been used to convert the cyanamide function of 4 into the thiourea function at (5R,8R,10R)-8-(methylthiomethyl)ergoline-6-thiocarboxamide (5).

René Nordmann

Papers

Das Pyrrocorphin‐Ligandsystem: Synthese des 2,2,7,7,12,12,17‐Heptamethyl‐2,3,7,8,12,13‐hexahydroporphyrins. Kurzmitteilung

Versuche zur Redox-Simulation der photochemischen A/D-Secocorrin Corrin-Cycloisomerisierung. Elektrochemische Oxydation von Nickel(II)-1-methyliden-2,2,7,7,12,12-hexamethyl-15-cyan-1,19-secocorinat-perchlorat. Vorläufige Mitteilung†

Corrin Synthesis via A→D Ring Closure. The Construction of A/D-Secocorrin Chromophore Systems by the ‘Sulfide Contraction’ Method and the Photochemical A/B-Secocorrin→Corrin Cycloisomerization

Synthesis of (5R,8S,10R)‐6‐(Allyloxy)‐ and (5R,8S,10R)‐6‐(Propyloxy)ergolines from the 6‐Methyl Precursors

Synthesis and Conformation of (5R,8R,10R)‐8‐(Methylthiomethyl)ergoline‐6‐carboxamidine