Pyrrole Nitrogen Atoms Research Articles

Synthesis of nickel(II), copper(II), zinc(II), and cadmium(II) complexes of 2-[(2-mercaptophenyl)iminomethyl] pyrrole and 2-[(2-mercaptoethyl)-iminomethyl]pyrrole by the electrochemical cleavage of a disulphide bond: the crystal structure of bis{2-[(pyrrol-2-yl)methyleneamino]thiophenolato-S,N}zinc(II)

The electrochemical oxidation of anodic metal (nickel, copper, zinc, or cadmium) in acetonitrile solutions of the Schiff bases derived from 2-pyrrolecarbaldehyde and bis(2-aminophenyl)disulphide (H2L2) or cysteamine (H2L2′) gives compounds [ML], [ML′] or [Zn(HL)2]. The crystal structure of bis{2-[(pyrrol-2-yl)methyleneamino]thiophenolato}zinc(II) is orthorhombic, space group Pbca with a= 13.764(3), b= 17.819(1), c= 16.593(2)A, and Z= 8. The zinc atom has ZnS2N2 distorted tetrahedral stereochemistry and the pyrrolic nitrogen atoms are not co-ordinated.

Structural investigations of the dipyrromethene complexes of calcium(II), nickel(II) and copper(II)

Structures of complexes formed between calcium(II), nickel(II) and copper(II) and the ligand, 3,3′,4,4′-tetrachloro-5,5′-dicarbethoxy-2,2′-dipyrromethene have been determined. The Ni(II) and Cu(II) ions are six-coordinate, with a distorted octahedral configuration consisting of the four pyrrole nitrogen atoms and two oxygen atoms of the ligand. The Ca(II) ion is eight-coordinate with a distorted dodecahedral geometry involving four pyrrole nitrogen atoms and the four carbonyl oxygen atoms of the carbethoxy groups. For each metal complex, oxygen coordination results in distortion away from the tetrahedral conformation of the ligand nitrogen donors. The Ca(II) chelate is monoclinic, space group P2 1/ n, Z = 4, a = 11.381(2), b = 24.916(4), c = 13.410(2) Å, β = 94.31(1)°, V = 3792(1) Å 3. The Ni(II) and Cu(II) complexes are isostructural, triclinic, space group P 1 , Z = 2. For the Ni(II) chelate, a = 12.574(4), b = 14.608(3), c = 10.634(2) Å, α = 96.42(2), β = 100.05(2), γ = 108.89(2)°, V = 1789.6(8) Å 3. For the Cu(II) chelate, a = 12.522(5), b = 14.493(6), c = 10.704(6) Å, α = 96.50(5), β = 100.86(2), γ = 108.44(1)°, V = 1778.41(6) Å 3. The structures were solved by direct methods and refined by least-squares techniques to R = 0.043 (2531 independent reflections) for the Ca(II) chelate; R = 0.044 (3149 independent reflections) for the Ni(II) chelate; and R = 0.067 (2468 independent reflections) for the Cu(II) chelate.

Nitro derivatives of bi- and tri-cyclic heterocycles as potential radio-sensitizers

Two series of bicyclic compounds having a pyridinic and pyrrolic nitrogen atom in different rings have been synthesized as potential radiosensitizers of hypoxic mammalian cells. The compounds were obtained from 3-nitro-pyrrolo[2,3- b]pyridine by regioselective alkylation at the nitrogen atom in either the 5- or 6-membered rings. Partition coefficients, one electron reduction potentials, radiosensitization of Chinese hamster V79 cells and cytotoxicity were measured. Generally, the N-1 alkyl-substituted 3-nitropyrrolopyridines showed greater electron affinity than their N-7 alkyl substituted analogues. All compounds were substantially less electron affinic than the 2-nitroimidazole, misonidazole. Consistent with this, misonidazole showed the most efficient sensitizing properties. None of the compounds synthesized here showed significantly lower toxicity than misonidazole. Consequently there is likely to be no therapeutic benefit from using these novel compounds as radiosensitizers.

Solution studies on tetra( p-carboxyphenyl)porphyrin iron(II) using Mössbauer spectroscopy and electronic absorption spectroscopies

Mössbauer (78 K) and electronic absorption spectra (298 K) of tetra( p-carboxyphenyl)porphyrin iron(II) solutions are reported and discussed. Evidence for only two iron(II) complexes, the first an intermediate spin and the second a high spin complex, is found in the Mössbauer spectra. Electronic absorption spectra show a low spin complex is present at very low concentrations. It is observed from these results that the carboxy groups on the phenyl rings of this porphyrin greatly influence the chemistry. From the difference in the quadrupole splitting for the intermediate spin complex compared to that found in the tetra( p-sulphophenyl)porphyrin iron(II) system, the substituent on the phenyl ring clearly changes the electron density on the pyrrole nitrogen atoms.

Crystal structure analysis and refinement at 2·5 Å of hexameric C-phycocyanin from the cyanobacterium Agmenellum quadruplicatum: The molecular model and its implications for light-harvesting

The crystal structure of the light-harvesting protein-pigment complex C-phycocyanin from the cyanobacterium Agmenellum quadruplicatum has been determined by Patterson search techniques on the basis of the molecular model of C-phycocyanin from Mastigocladus laminosus. The crystal unit cell (space group P321) contains three (alpha beta)6 hexamers centred on the crystallographic triads. The hexamer at the origin of the unit cell exhibits crystallographic 32 point symmetry. The other two hexamers (independent of the former) show crystallographic 3-fold and local 2-fold symmetry. The 3-fold redundancy of the asymmetric unit of the crystal cell was used in the refinement process, which proceeded by cyclic averaging, model building and energy-restrained crystallographic refinement. Refinement was terminated with a conventional crystallographic R-value of 0.20 with data to 2.5 A resolution. The two independent hexamers of the unit cell are identical within the limits of error at all levels of aggregation. Two trimers, which closely resemble the M. laminosus C-phycocyanin, are aggregated head-to-head to form the hexamer. Both trimers fit complementarily and are held together by polar and ionic interactions. Conservation of the amino acid residues involved in protein-chromophore and intermonomer interactions suggests common structural features for all biliproteins. Most probably, the hexameric aggregation form present in the crystals is closely related to the discs of native phycobilisome rods. All tetrapyrrole chromophores are extended but with different geometries enforced by different protein surroundings. In particular, interactions of the propionic side-chains with arginine residues and of the pyrrole nitrogen atoms with aspartate residues define configuration and conformation of the chromophores. Relative chromophore distances and orientations have been determined and a preferential pathway for the energy transfer suggested. Accordingly, within a hexamer the absorbed energy is funneled to chromophore B84 and then transduced via B84 chromophores along the phycobilisome rods.

Luminescence of porphyrins and metalloporphyrins VIII: luminescence and hydrogen photogeneration from porphyrin conjugate diacids

Porphyrin conjugate diacids are formed by addition of two extra protons to the pyrrole nitrogen atoms of the porphyrin ring and the compounds derived from tetraphenylporphine absorb strongly at wavelengths above 600 nm. The absorption and fluorescence properties depend on inductive effects of any substituents on the phenyl rings. No phosphorescence was detected although the diacids show relatively long-lived triplet states at room temperature. The diacids photosensitize the dissociation of formic acid into hydrogen and CO 2 although the rates of hydrogen formation are slow.

ChemInform Abstract: PROTECTING GROUPS FOR THE PYRROLE NITROGEN ATOM. THE 2‐CHLOROETHYL, 2‐PHENYLSULFONYLETHYL, AND RELATED MOIETIES

AbstractDie Chlorethylgruppe wird als eine unter vielseitigen Bedingungen verwendbare Schutzgruppe des Pyrrolstickstoffs vorgestellt.

Protecting groups for the pyrrole nitrogen atom. The 2-chloroethyl, 2-phenylsulfonylethyl, and related moieties

The 2-chloroethyl and 2-phenylsulfonylethyl moieties are versatile protecting groups for the pyrrole nitrogen atom. The 2-chloroethyl group is easily attached under phase transfer conditions using 1,2-dichloroethane. The 2-phenylsulfonylethyl moiety is readily appended under both phase transfer and homogeneous solution conditions using 2-phenylsulfonylcthyl chloride 5. Deprotection of the N-(2-chloroethyl)pyrroles is accomplished by means of efficient three-step, one-pot sequences via the N-vinyl compounds 3 and subsequent degradation of the N-(1-hydroxyethyl) compounds 4 or the acctoxymercuration derivatives 5 obtained therefrom. The 2-phenylsulfonylethyl group is excised by a reverse Michael reaction using sodium hydride or DBN as the base.The utility of the 2-chloroethyl protecting group is exemplified in a synthesis of benzyl cyclopenta[b] |pyrrole-5-carboxylate 13 from 1-(2-chloroethyl)-4-oxotetrahydroindolc 2d.

N-alkylation of the haem moiety of cytochrome P-450 caused by substituted dihydropyridines. Preferential attack of different pyrrole nitrogen atoms after induction of various cytochrome P-450 isoenzymes

1. 3,5-Diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethylpyridine (4-ethyl-DDC) gives rise to N-ethylprotoporphyrin in the liver of rats by donating its 4-ethyl group to one of the pyrrole nitrogen atoms of haem. Four structural isomers are obtained, depending on which pyrrole nitrogen is alkylated. 2. When rats are pretreated with an inducer of cytochrome P-450, the production of N-ethylprotoporphyrin caused by 4-ethyl-DDC is greater, both in the whole animal and in hepatocytes incubated with the drug in vitro. 3. Pre-incubation of hepatocytes with 2-allyl-2-isopropylacetamide decreases the yield of N-ethylprotoporphyrin due to 4-ethyl-DDC, an effect largely reversed by adding exogenous haem. 4. The isomeric composition of N-ethylprotoporphyrin produced in vivo and in vitro depends on the cytochrome P-450 isoenzyme that predominates at the time of treatment, suggesting a role for the apo-cytochrome in directing alkylation on to one of the pyrrole nitrogens.

Inactivation of cytochrome P-450 and production of N-alkylated porphyrins caused in isolated hepatocytes by substituted dihydropyridines : Structural requirements for loss of haem and alkylation of the pyrrole nitrogen atom

Drugs with unsaturated side chains and certain dihydropyridines both convert liver haem into Nalkylated porphyrins, but the underlying mechanisms differ in the two cases. With unsaturated drugs, for example 2-allyl-2-isopropylacetamide (AIA), a monooxygenated derivative of the drug becomes bound [l] onto one of the pyrrole nitrogen atoms [2-41 of liver haem; whereas with 3,5diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) only the 4-methyl substituent of the drug is transferred onto the pyrrole nitrogen atom [5-71 and the product, N-methyl protoporphyrin, is a powerful inhibitor of ferrochelatase (EC 4.99.1.1) [8,9]. There is strong evidence that the N-alkylated porphyrins produced by unsaturated compounds all originate from the haem of cytochrome P-450 [ 10-121, but it is less clear from which pool of hepatic haem N-methyl protoporphyrin originates after treatment with DDC; and the detailed mechanism of the transmethylation reaction involved has not yet been elucidated. The aim of the experiments described in this paper has been to clarify wether N-methyl protoporphyrin originates from the haem of cytochrome P450 and whether exogenous haem can be utilized

Thiocyanate‐assisted demetallation of α,β,γ,δ‐tetra(p‐sulfophenyl)porphinatoindium(III) in aqueous media

AbstractThe rate law for the demetallation of the title indium(III)‐porphin complex in aqueous acidic thiocyanate media at 3.00M ionic strength was found to be of the form where [H4P2−] is the concentration of the diacid product formed, [InP]t is the total concentration of all forms of indium(III)‐porphin complex present, and a and b are constants. The constant a is a pseudo‐third‐order rate constant with the value (0.057 ± 0.005)M−2 s−1 and b has the value 0.704M−2 at 50.5°C. If the mechanism for demetallation involves ringpuckering with the attachment of two H+ ions, then 1/b can be identified with the product K1K2 for the stepwise dissociation of two protons from two ring pyrrolic nitrogen atoms of H2InP−. In the sulfonated tetraphenylporphin used for these studies the ring pyrrolic nitrogen atoms seem to be the most probable sites for protonation. If this identification is correct, the value of 1.42 ± 0.13 found for the product K1K2 shows the enormous effect that the presence of the In3+ center has on the ionization constants of these two protons. That the kinetic studies show saturation effects with respect to proton addition to InP3− may result from the fact that In3+ sits about 0.6 Å above the porphin ring.

Resolution enhancement of EPR spectra using the Fourier transform technique. Analysis of nitrosyl cytochrome c oxidase in frozen solution

A computer program is described which applies the Fourier transform technique to electron paramagnetic resonance spectroscopy, in order to improve the signalto-noise ratio and to differentiate or integrate the EPR spectra. Resolution enhancement is performed by transforming the lineshape from Lorentzian to Gaussian and by computing higher derivatives using the experimental first derivative spectrum. This procedure avoids overmodulation of the spectrum when higher derivatives are measured. Furthermore, a simulation procedure for spectra of randomly oriented anisotropic systems is combined with these Fourier transform facilities. As an example, the complete determination of the EPR parameters of nitrosyl cytochrome c oxidase complexes was accomplished. The hexacoordinated and the pentacoordinated complexes (without axially bound histidine) show hyperfine constants in the x and y directions (heme plane) which are equivalent for nitrosyl and pyrrole nitrogen atoms, respectively. Both complexes show a larger hyperfine splitting of 15NO in the z direction than in the x and y directions. The interaction of the electron spin with the pyrrole nitrogens influences the resonances in the x and y directions significantly whereas the contribution to the resonances in the z direction seems to be very small. The hexacoordinated complex exhibits splitting constants of N ϵ of the histidine in all principal directions; the largest splitting is found in the z direction.

Liver production of N-alkylated porphyrins caused in mice by treatment with substituted dihydropyridines : Evidence that the alkyl group on the pyrrole nitrogen atom originates from the drug

The porphyrogenic drug, 3,Sdiethoxycarbonyl1,4-dihydro-2,4,6_trimethylpyridine causes a marked inhibition of the enzyme protohaem ferro-lyase (EC 4.99.1 .l) in the liver of rats, mice and chick embryos [l-4] an effect which is thought to be responsible for the very pronounced accumulation of protoporphyrin seen in this type of experimental porphyria. We have isolated a potent inhibitor of protohaem ferro-lyase from the liver of mice made porphyric by treatment with this drug [5,6] and have identified the inhibitor as N-methyl protoporphyrin [7]. Inhibition of protohaem ferro-lyase has also been obtained both in vivo and in vitro with synthetic N-alkylated porphyrins [7-91, and the size of the alkyl group present on the pyrrole nitrogen atom has been shown to be important for the inhibitory effect, N-ethylmesoporphyrin being less active than N-methylmesoporphyrin [8]. Isotopic experiments have suggested that the N-methylated protoporphyrin produced by treatment with 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine originates from liver haem [5,6,10], but the source of the methyl group bound onto the pyrrole nitrogen atom has not yet been determined. The following findings have raised the possibility that the methyl group may originate from the 4-methyl substituent of the drug: under relatively mild chemical conditions certain dihydropyridines lose their 4-alkyl substituent on oxidation and that this alkyl group can be donated to suitable nucleophiles [ 111. A series of dihydropyridine analogues have been compared for their ability to inhibit liver protohaem ferro-lyase

ChemInform Abstract: INDOLOBENZOTHIOPHENES. 2. SOME ELECTROPHILIC SUBSTITUTION REACTIONS OF INDOLO(6,5‐D)BENZO(B)THIOPHENE

AbstractDie Acetylierung des Indolobenzothiophens (I) mit Acetanhydrid liefert die N‐Acetylverbindung (II), während bei der Mannich‐Reaktion und der Azo‐ kupplung eine Reaktion in 3‐Stellung zu (V) bzw. (VII) erfolgt.

Indolobenzothiophenes. 2. Some electrophilic substitution reactions of indolo[6,5-d]benzo[b]thiophene

The behavior of indolo[6,5-d]benzo[b]thiophene in acylation, Mannich, Vilsmeier, and diazo coupling reactions was investigated. Acylation with acetic anhydride proceeds unambiguously at the pyrrole nitrogen atom to give 1-acetylindolo[6,5-d] benzo[b]thiophene. The products of formylation are 2- and 3-formylindolo-[6,5-d] benzo[b]thiophenes. In the case of the Mannich reaction and diazo coupling substitution takes place in the 3 position of the indolobenzo[b]thiophene ring. The structures of the products obtained were proved by spectroscopic methods.

Structure of 1-vinylimidazole and the possible inversion of the pyrrole nitrogen

The three-dimensiona l structure of the 1-vinylimidazole molecule has been studied from the proton magnetic resonance spectra using paramagnetic additives and quantum-chemical calculations. It has been established that within the framework of the method of study used, agreement between the experimental and theoretical parameters is achieved by assuming that the imidazole ring has a nonplanar structure. In an analysis of the NMR spectra of diamagnetic and paramagnetic complexes of 1-vinylimidazole (VIM), it was suggested that the VIM molecule is nonplanar [1, 2]. The present paper describes a detailed study of this compound. The question of the structure of VIM is complicated. According to existing ideas, the participation of the unshared pair of the pyrrole nitrogen atom in the general v-system of the ring should stabilize the planar form of the VIM molecule. It wouldtherefore be logical to expect a coplanar arrangement of theviny[ group and the heterocyclic ring, ensuring the conjugation of their v-systems [3]. At the same time, because of steric hindrance, the vinyl group may be displaced from the plane of the ring. In this case, as a consequence of the competition of the two v-systems for conjugation with the unshared pair of the N-1 atom in the VIM molecule, inversion may take place at position 1 with deflection of the bonds N1-C 2 and N1-C 5, and also deflection of H-2 and H-5 from the C2N3C4C ~ plane on the same (scheme I) or different (scheme II) directions.

Conversion of liver haem into N-substituted porphyrins or green pigments: Nature of the substituent at the pyrrole nitrogen atom

Conversion of liver haem into N-substituted porphyrins or green pigments: Nature of the substituent at the pyrrole nitrogen atom

Characterization of the electronic properties and geometric environment of the iron atom in the ‘myoglobin hydrogen-peroxide’ Complex by soret-excited resonance raman spectroscopy

The low temperature ( ca. 80 K) Soret-excited resonance Raman spectrum of the ‘myoglobin hydrogen-peroxide’ complex has been obtained and compared to those of Fe(II) and Fe(III) myoglobin. The RR spectra suggest that the iron atom in the ‘myoglobin hydrogen-peroxide’ complex is formally in the Fe(IV) state with a t 4 2g low-spin configuration. The ironpyrrole-nitrogen (FeN p) and ironimidazole-nitrogen (FeN im) bond lengths in the ‘myoglobin hydrogen-peroxide’ complex have been estimated from the wavenumbers of the ironpyrrole and ironimidazole stretching modes around 345 and 375 cm 1− using the FeN p and FeN im distances in Fe(II) myoglobin available from the X-ray crystallographic data in the literature. The distance from the centre of the porphyrin to the pyrrole nitrogen atoms (CtN p) was estimated from the position of the anomalously polarized band around 1560–1590 cm 1− by comparison with data in the literature on model metalloporphyrins. The FeN im', FeN p and CtN p distances for the ‘myoglobin hydrogen-peroxide’ complex were found to be 2.09, 2.08 and 2.01 Å; the distance from the iron atom to the plane of the pyrrole nitrogen atoms was determined by triangulation and found to be 0.53 +0.14 −0.18 Å. With laser lilumination of 200 mW power, the low-spin t 4 2g ‘myoglobin hydrogen-peroxide’ complex apparently undergoes a two-electron photoreduction, with a rate constant of ca. 2.5 × 10 4− s 1− at ca. 80 K, to high spin t 4 2ge 2 g Fe(II) myoglobin, since there is no evidence for Fe(III) myoglobin.

Substrate-dependent irreversible inactivation of cytochrome P-450: conversion of its haem moiety into modified porphyrins.

2-Allyl-2-isopropylacetamide and other drugs containing either an allyl, a vinyl or an ethynyl unsaturated side chain are metabolized by liver cytochrome P-450 to reactive derivatives that irreversibly inhibit the haemoprotein by a suicidal type of inactivation. The main target is the haem moiety of cytochrome P-450 which is converted into abnormal porphyrins. These have been isolated from the liver of treated rats, extensively purified and compared with model porphyrins. The abnormal porphyrins incorporate metal ions in vitro much more readily than does their parent porphyrin, protoporphyrin. They are also much more basic than protoporphyrin, and on titration with a strong acid they readily give rise to a porphyrin monocation which then requires relatively large amounts of acid for conversion to the porphyrin dication. In all these respects and also in the intensity of their bathochromic shifts these abnormal porphyrins closely resemble N-alkylated porphyrins and they markedly differ from porphyrins that are substituted at one of their meso-carbon positions or which bear electron-withdrawing substituents at the beta-positions of the pyrrole rings. This suggests strongly that reactive derivatives of the unsaturated drugs act as electrophilic reagents and alkylate one of the pyrrole nitrogen atoms of cytochrome P-450. A model centred on the apoprotein of cytochrome P-450 is considered for the degradation of liver haem caused by unsaturated drugs. The apocytochrome may accept exchangeable pools of liver haem for degradation, leading to a state of haem depletion and to activation of delta-aminolaevulinate synthase.

Significance of the pyrrolic nitrogen atom in receptor recognition ofAtta texana (Buckley) (Hymenoptera:Formicidae) trail pheromone and parapheromones

Calculations of the charge of the pyrrolic nitrogen atom in the trail pheromone ofAtta texana, methyl 4-methylpyrrole-2-carboxylate, as well as 17 analogs, showed that the most active compounds all had the same charge of −0.51 electrons on the nitrogen atom. It is suggested that the close value for this charge may be important in recognition by the receptor.