Crystal and molecular structure of the ferrihemochrome bis(1-methylimidazole)(protoporphyrin IX)iron-methanol-water

Little, Robert G.; Dymock, K.; Ibers, James A.

doi:10.1021/ja00849a014

Cited by 79 publications

(31 citation statements)

References 2 publications

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“…This comparison was motivated by the observation that the imidazole plane in [Fe(Piv,C,)( 1-MeIm)] is rather "tilted" a n d makes a dihedral angle of 81.3O with the mean plane of the core. [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] In summary, the characterization of a five-coordinate iron(I1) complex bearing a sterically unhindered axial imidazole ligand has been made possible by the synthesis of a porphyrin having one severely sterically hindered face. We have carried out a systematic survey of the coordination geometry of imidazole ligands in metalloporphyrin complexes t o determine t h e extent of the "nonideality".…”

Section: Resultsmentioning

confidence: 99%

A deoxymyoglobin model with a sterically unhindered axial imidazole

Momenteau¹,

Scheidt²,

Eigenbrot³

et al. 1988

J. Am. Chem. Soc.

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Section: Resultsmentioning

confidence: 99%

A deoxymyoglobin model with a sterically unhindered axial imidazole

Momenteau¹,

Scheidt²,

Eigenbrot³

et al. 1988

J. Am. Chem. Soc.

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“…More than twenty years later, S. B. Brown et al [37] showed, thanks to absorption spectrophotometry, that Fe III PPIX can undergo dimerization in aqueous solution and first proposed this dimer to be a μ-oxo species (Figure 3) [38]. …”

Section: Thermodynamics and Structural Aspects Of Ferriprotoporphyrinmentioning

confidence: 99%

A Physico-Biochemical Study on Potential Redox-Cyclers as Antimalarial and Antischistosomal Drugs

Johann

Lanfranchi²,

Davioud‐Charvet³

et al. 2012

cpd

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The role of redox enzymes in establishing a microenvironment for parasite development is well characterized. Mimicking human glucose-6-phosphate dehydrogenase and glutathione reductase (GR) deficiencies by redox-cycling compounds thus represents a challenge to the design of new preclinical antiparasitic drug candidates. Schistosomes and malarial parasites feed on hemoglobin. Heme, the toxic prosthetic group of the protein, is not digested and represents a challenge to the redox metabolism of the parasites. Here, we report on old and new redox-cycling compoundswhose antiparasitic activities are related to their interference with (met)hemoglobin degradation and hematin crystallization. Three key-assays allowed probing and differentiating the mechanisms of drug actions. Inhibition of β-hematin was first compared to the heme binding as a possible mode of action. All tested ligands interact with the hematin π-π dimer with K D similar to those measured for the major antiparasitic drugs. No correlation between a high affinity for hematin and the capacity to prevent β-hematin formation was however deduced. Inhibition of β-hematin formation is consequently not the result of a single process but results from redox processes following electron transfers from the drugs to iron(III)-containing targets. The third experiment highlighted that several redox-active compounds (in their reduced forms) are able to efficiently reduce methemoglobin to hemoglobin in a GR/NADPH-coupled assay. A correlation between methemoglobin reduction and inhibition of β-hematin was shown, demonstrating that both processes are closely related. The ability of our redox-cyclers to trigger methemoglobin reduction therefore constitutes a critical step to understand the mechanism of action of our drug candidates.

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“…We took the initial structure of HEM from the PSII complex (PDB ID: 3ARC),[6] which was then optimized by QM for further FF parameterization (see Table 1). To validate the FF parameters, we selected three crystal structures: bis(1‐methylimidazole)‐(protoporphyrin IX)iron [Fe(1‐Me‐Im) 2 (PP‐IX)],[37] hemin chloride [Fe(Cl)(PP‐IX)],[38] and β‐hematin [(Fe‐PP‐IX) 2 ][39] (see Table 1).…”

Section: Methodsmentioning

confidence: 99%

“…S2). [37] This crystal structure has the most similar coordination compared to the HEM in the PSII complex, where the Fe atom has two axial ligands with the nitrogen atoms of the histidine (His) residues. This structure is thus useful for checking the capability of the FF in describing the intermolecular interactions between the HEM and His.…”

Section: Methodsmentioning

confidence: 99%

“…Although macrocycles in CLA and HEM are conjugated, the ring atoms are not exactly on the same plane in their crystal structures. [6, 36–39] We thus also examined if our FF parameters can sufficiently describe the relative positions of these ring atoms. Specially, we defined a plane by least‐square‐fitting of the positions of all the heavy atoms on the ring, and then computed the relative distances of individual ring atoms to the plane.…”

Section: Methodsmentioning

confidence: 99%

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Force field development for cofactors in the photosystem II

et al. 2012

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We present a set of force field (FF) parameters compatible with the AMBER03 FF to describe five cofactors in photosystem II (PSII) of oxygenic photosynthetic organisms: plastoquinone-9 (three redox forms), chlorophyll-a, pheophytin-a, heme-b, and β-carotene. The development of a reliable FF for these cofactors is an essential step for performing molecular dynamics simulations of PSII. Such simulations are important for the calculation of absorption spectrum and the further investigation of the electron and energy transfer processes. We have derived parameters for partial charges, bonds, angles, and dihedral-angles from solid theoretical models using systematic quantum mechanics (QM) calculations. We have shown that the developed FF parameters are in good agreement with both ab initio QM and experimental structural data in small molecule crystals as well as protein complexes.

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Crystal and molecular structure of the ferrihemochrome bis(1-methylimidazole)(protoporphyrin IX)iron-methanol-water

Cited by 79 publications

References 2 publications

A deoxymyoglobin model with a sterically unhindered axial imidazole

A deoxymyoglobin model with a sterically unhindered axial imidazole

A Physico-Biochemical Study on Potential Redox-Cyclers as Antimalarial and Antischistosomal Drugs

Force field development for cofactors in the photosystem II

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