Heme Protein Models Research Articles

Insight into Heme Protein Redox Potential Control and Functional Aspects of Six-Coordinate Ligand-Sensing Heme Proteins from Studies of Synthetic Heme Peptides

We describe detailed studies of peptide-sandwiched mesohemes PSMA and PSMW, which comprise two histidine (His)-containing peptides covalently attached to the propionate groups of iron mesoporphyrin II. Some of the energy produced by ligation of the His side chains to Fe in the PSMs is invested in inducing helical conformations in the peptides. Replacing an alanine residue in each peptide of PSMA with tryptophan (Trp) to give PSMW generates additional energy via Trp side chain-porphyrin interactions, which enhances the peptide helicity and stability of the His-ligated state. The structural change strengthened His-FeIII ligation to a greater extent than His-FeII ligation, leading to a 56-mV negative shift in the midpoint reduction potential at pH 8 (Em,8 value). This is intriguing because converting PSMA to PSMW decreased heme solvent exposure, which would normally be expected to stabilize FeII relative to FeIII. This and other results presented herein suggest that differences in stability may be at least as important as differences in porphyrin solvent exposure in governing redox potentials of heme protein variants having identical heme ligation motifs. Support for this possibility is provided by the results of studies from our laboratories comparing the microsomal and mitochondrial isoforms of mammalian cytochrome b5. Our studies of the PSMs also revealed that reduction of FeIII to FeII reversed the relative affinities of the first and second His ligands for Fe (K2III > K1III; K2II < K1II). We propose that this is a consequence of conformational mobility of the peptide components, coupled with the much greater ease with which FeII can be pulled from the mean plane of a porphyrin. An interesting consequence of this phenomenon, which we refer to as "dynamic strain", is that an exogenous ligand can compete with one of the His ligands in an FeII-PSM, a reaction accompanied by peptide helix unwinding. In this regard, the PSMs are better models of neuroglobin, CooA, and other six-coordinate ligand-sensing heme proteins than of stably bis(His)-ligated electron-transfer heme proteins such as cytochrome b5. Exclusive binding of exogenous ligands by the FeII form of PSMA led to positive shifts in its Em,8 value, which increases with increasing ligand strength. The possible relevance of this observation to the function of six-coordinate ligand-sensing heme proteins is discussed.

Porphyrin cored hyperbranched polymers as heme protein models

The single step synthesis of an Fe(II) porphyrin cored hyperbranched polymer, possessing similar size and topology to the natural heme containing proteins, is reported: UV spectroscopy successfully demonstrated the ability of this polymer to reversibly bind oxygen.

Host—Guest Interactions of Cyclodextrins and Metalloporphyrins: Supramolecular Building Blocks Toward Artificial Heme Proteins

AbstractFor Abstract see ChemInform Abstract in Full Text.

Host-guest interactions of cyclodextrins and metalloporphyrins: supramolecular building blocks toward artificial heme proteins

Cyclodextrins are versatile building blocks for a variety of macromolecules due to the inclusion complexes that are formed with hydrophobic organic molecules. Cyclodextrin-porphyrin interactions are of particular interest since cyclodextrins can serve as a non-covalent binding pocket while metalloporphyrins could serve as the heme analogs in the construction of heme protein model compounds. Various approaches to the design and assembly of biomimetic porphyrin constructs are compared and contrasted in this minireview with a particular emphasis on self-assembled and porphyrin-cyclodextrin systems. Several recent advances from our laboratories are described in this context. A sensitive fluorescent binding probe, 6A-N-dansyl-permethylated-β-cyclodextrin (Dan-NH-TMCD), was found to form 2:1 complexes with the meso-tetraphenylporphyrins Mn(III)TCPP , Mn(III)TPPS and Mn(III)TF 4 TMAP with high binding constants. A perPEGylated cyclodextrin, heptakis(2,3,6-tri-O-2-(2-(2-methoxyethoxy)ethoxy)ethyl)-β-cyclodextrin (TPCD), has been shown by 1 H NMR spectroscopy to form a 1:1 complex with H 2 TCPP with a binding constant above 108M-1. Such a strong binding constant is the largest found for a 1:1 complex between a monomeric cyclodextrin and a guest. TPCD was also found to bind Mn(III)TCPP with a binding constant of 1.2 × 106 M -1. A novel, self-assembled hemoprotein model, hemodextrin is also described. The molecular design is based on a PEGylated cyclodextrin scaffold that bears both a heme-binding pocket and an axial ligand that binds an iron porphyrin. The binding constant for Fe (III) TPPS (iron(III) meso-tetra(4-sulfonatophenyl)porphyrin) by py-PPCD was determined to be 2 × 106 M -1. The pyridyl nitrogen of py-PPCD was shown to ligate to the iron center by observing signal changes in the Fe(II) -porphyrin 1 H NMR spectrum. This hemodextrin ensemble, a minimalist myoglobin, was shown to bind dioxygen reversibly and to form a stable ferryl species.

Preface

Dr. Gilda H. Loew, 70, president and founder of the Molecular Research Institute in Mountain View, California, passed away on January 5, 2001, after a long and valiant struggle against breast cancer. Born and raised in Brooklyn, New York, Dr. Loew attended Erasmus Hall High School and then earned a Bachelor's Degree in Chemistry at New York University. After completing a Master's Degree in Chemistry at Columbia University, she subsequently earned a doctorate in Chemical Physics from the University of California, Berkeley. In a succession of positions during the 1950s and 1960s, Dr. Loew was a pioneer in the application of computational chemistry to problems in the biological sciences. She began a long association with Stanford University in 1969. In 1979, Dr. Loew formed the Molecular Research Institute (MRI), where she led the efforts of a team of scientists for the next two decades. Establishing MRI was an expression of Dr. Loew's independent spirit, her persistence, and her desire to contribute successfully and productively to responsible science on her own terms. Dr. Loew is best known for the computational investigation of the structural and functional aspects of heme proteins and enzymes, to which she devoted more than four decades. She studied the electronic structure and electromagnetic properties, the mechanisms of heme-catalyzed reactions, substrate metabolism by heme enzymes, and her laboratory constructed and used the first three-dimensional models of heme proteins. In addition, her research interests covered such diverse topics as the mechanisms by which drugs such as opioids and anxiolytics stimulate receptors in the brain, the computer-aided risk assessment of chemical carcinogens, multicomponent chemical systems, and prebiotic synthesis and interstellar molecules. As listed in this volume, her publications include over 300 scientific articles, reviews, and book chapters co-authored with many associates in many countries and from many disciplines. Her co-authors were often young scientists whom she mentored with care and prepared for successful independent careers. The tireless support of these colleagues and the pride she took in their successes are most memorable. Dr. Loew was an enthusiastic and stimulating participant in the activities of many professional organizations, demonstrating the breadth of her interests and her ability to cross disciplines. She was a longstanding member of the American Chemical Society and was also a member of the American Physical Society, the Biophysical Society, the International Society of the Origin of Life, the International Society of Quantum Biology & Pharmacology, the New York Academy of Science, and American Women in Science. She served these societies in many leadership positions as a dedicated member of key committees and task forces that enhanced the lives and activities of thousands of her colleagues. She was president of the International Society of Quantum Biology and Pharmacology from 1990 to 1992 and served on numerous editorial boards as well as review and policy committees for the National Institutes of Health, National Science Foundation, the Department of Energy, the Environmental Protection Agency, and the National Aeronautical and Space Administration. Dr. Loew was a passionate conversationalist and debater of ideas and a favorite participant in professional and social gatherings of scientific colleagues and intellectuals around the world. Her personality and interactions were driven and sustained by her great passion for literature, the arts, dancing, politics, and travel. She leaves an unfillable void in the hearts and minds of all who knew her. This issue celebrates Gilda Loew's remarkable achievements as a researcher and scholar, and her boundless enthusiasm for science. This could be achieved only with the help of her many colleagues, students, and associates whose contributions help highlight the diversity of scientific areas in which she was active. Dr. Loew was particularly fond of the Sanibel Symposia organized yearly by the Quantum Theory Project and published in the International Journal of Quantum Chemistry (IJQC). We are therefore especially grateful to the Editors of IJQC for making this special issue possible.

N-hydroxyguanidines as new heme ligands: UV-visible, EPR, and resonance Raman studies of the interaction of various compounds bearing a C=NOH function with microperoxidase-8.

Interaction between microperoxidase-8 (MP8), a water-soluble hemeprotein model, and a wide range of N-aryl and N-alkyl N'-hydroxyguanidines and related compounds has been investigated using UV-visible, EPR, and resonance Raman spectroscopies. All the N-hydroxyguanidines studied bind to the ferric form of MP8 with formation of stable low-spin iron(III) complexes characterized by absorption maxima at 405, 535, and 560 nm. The complex obtained with N-(4-methoxyphenyl) N'-hydroxyguanidine exhibits EPR g-values at 2.55, 2.26, and 1.86. The resonance Raman (RR) spectrum of this complex is also in agreement with an hexacoordinated low-spin iron(III) structure. The dissociation constants (K(s)) of the MP8 complexes with mono- and disubstituted N-hydroxyguanidines vary between 15 and 160 microM at pH 7.4. Amidoximes also form low-spin iron(III) complexes of MP8, although with much larger dissociation constants. Under the same conditions, ketoximes, aldoximes, methoxyguanidines, and guanidines completely fail to form such complexes with MP8. The K(s) values of the MP8-N-hydroxyguanidine complexes decrease as the pH of the solution is increased, and the affinity of the N-hydroxyguanidines toward MP8 increases with the pK(a) of these ligands. Altogether these results show that compounds involving a -C(NHR)=NOH moiety act as good ligands of MP8-Fe(III) with an affinity that depends on the electron-richness of this moiety. The analysis of the EPR spectrum of the MP8-N-hydroxyguanidine complexes according to Taylor's equations shows a strong axial distortion of the iron, typical of those observed for hexacoordinated heme-Fe(III) complexes with at least one pi donor axial ligand (HO(-), RO(-), or RS(-)). These data strongly suggest that N-hydroxyguanidines bind to MP8 iron via their oxygen atom after deprotonation or weakening of their O-H bond. It thus seems that N-hydroxyguanidines could constitute a new class of strong ligands for hemeproteins and iron(III)-porphyrins.

The H93G myoglobin cavity mutant as a versatile template for modeling heme proteins: ferrous, ferric, and ferryl mixed-ligand complexes with imidazole in the cavity.

One of the difficulties in preparing accurate ambient-temperature model complexes for heme proteins, particularly in the ferric state, has been the generation of mixed-ligand adducts: complexes with different ligands on either side of the heme. The difference in the accessibility of the two sides of the heme in the H93G cavity mutant of myoglobin (Mb) provides a potential general solution to this problem. To demonstrate the versatility of H93G Mb for the preparation of heme protein models, numerous mixed-ligand adducts of ferrous, ferric, and ferryl imidazole-ligated H93G (H93G(Im) Mb) have been prepared. The complexes have been characterized by electronic absorption and magnetic circular dichroism (MCD) spectroscopy in comparison to analogous derivatives of wild type Mb. The starting ferric H93G(Im) Mb state spectroscopically resembles wild-type ferric Mb as expected for a complex containing a single imidazole in the proximal cavity and water bound on the distal side. Addition of a sixth ligand to ferric H93G(Im) Mb, whether charge neutral (imidazole) or anionic (cyanide and azide), results in formation of six-coordinate low-spin complexes with MCD characteristics similar to those of parallel derivatives of wild-type ferric Mb. Reduction of ferric H93G(Im) Mb and subsequent exposure to either CO, NO, or O2 produces ferrous complexes (deoxy, CO, NO, and O2) that consistently exhibit MCD spectra similar to the analogous ferrous species of wild-type ferrous Mb. Most interestingly, reaction of ferric H93G(Im) Mb with H2O2 results in the formation of a stable high-valent oxoferryl complex with MCD characteristics that are essentially identical to those of oxoferryl wild-type Mb. The generation of such a wide array of mixed-ligand heme complexes demonstrates the efficacy of the H93G Mb cavity mutant as a template for the preparation of heme protein model complexes.

Synthesis of Chiral Amino Acid-Linked Porphyrin Protein Supramolecular Complexes and Their Novel Induced Circular Dichroism

A chiral amino acid has been covalently linked to (5-(2-carboxylphenyl)-10,15,20-triphenylporphinato)zinc(II) via amide formation. As a heme protein model, the resulting chiral amino acid-linked porphinatozinc(II) complex, AA-COTPPZn (AA = amino acid residue), was designed to investigate the relationship of the induced circular dichroism (ICD) of heme protein and the intramolecular interaction. The synthesized porphinatozinc(II) complexes exhibited split ICD in the Soret region. The ICD of AA-COTPPZn in the Soret region also indicates that an amino acid residue interacts with a porphyrin plane and the intramolecular interaction makes the conformation of an amino acid residue relatively fixed. Electronic absorption spectra demonstrate that a hydroxyl group of the amino acid residue coordinates to a Zn atom of the porphinatozinc(II) complex in Thr-COTPPZn (Thr = threonine) and Ser-COTPPZn (Ser = serine) and the coordination interaction between the amino acid residue and a porphyrin moiety is weakin Leu-COTPPZn (Leu = leucine). ICD studies indicate that the stronger intramolecular interaction increases the ICD intensity of these chiral porphinatozinc(II) complexes and that the different direction of intramolecular interaction would make the disposition of the ICD different. AA-COTPPZn represents a unique system which allows us to investigate the CD (CD = circular dichroism) features which arise from the heme moiety directly rather than from heme protein model compounds, as was done previously.

The Role of the Distal and Proximal Protein Environments in Controlling the Ferric Spin State and in Stabilizing Thiolate Ligation in Heme Systems: Thiolate Adducts of the Myoglobin H93G Cavity Mutant

Recently, heme protein cavity mutants have been engineered in which the proximal coordinating amino acid has been replaced by a smaller, noncoordinating residue leaving a cavity that can be filled by exogenous axial ligands. This approach was pioneered by Barrick (Biochemistry 1994, 33, 6546−6554) with H93G sperm whale myoglobin where the coordinating histidine is replaced by glycine and the proximal cavity is filled with imidazole. In the present study, models for cysteine thiolate-ligated ferric cytochrome P450 have been prepared using H93G myoglobin containing thiolate ligands in the cavity. Despite the availability of water to serve as a distal ligand as occurs in both ferric wild type myoglobin and ferric H93G myoglobin with imidazole in the cavity, the ferric H93G thiolate complexes spectroscopically resemble five-coordinate high-spin substrate-bound ferric P450, which contains a thiolate proximal ligand and lacks a water distal ligand. Thus, the distal protein environment plays a crucial role in controlling whether a five-coordinate thiolate-ligated ferric heme binds water or not. Two advantages pertain to the present thiolate-ligated heme protein model relative to purely synthetic thiolate-ligated ferric porphyrins: (a) aliphatic thiols can form complexes without reduction of the ferric iron and (b) mixed ligand complexes that are stable at ambient temperatures can be prepared with a neutral ligand such as imidazole trans to thiolate. However, when anionic ligands are added to the ferric thiolate adduct in an attempt to prepare mixed ligand complexes with two anionic ligands, the thiolate ligand is displaced (or lost) without formation of a stable mixed ligand derivative. Further, reduction of the ferric-thiolate complex leads to loss of the thiolate ligand even in the presence of CO. The data presented for the thiolate adducts of ferric H93G myoglobin are analyzed in the context of the spectrally related H93C myoglobin mutants. The inability of the thiolate adducts of H93G myoglobin to accommodate a second anionic ligand in the ferric state or to remain thiolate-ligated in the ferrous state is likely due to the lack of (a) correctly positioned hydrogen bond donating groups and (b) a properly oriented helix dipole to stabilize the thiolate ligand as occurs in the proximal protein environment of P450. The present results illustrate the important role of the distal and proximal heme environments in controlling the ferric spin state and in stabilizing thiolate ligation in heme systems, respectively.

Time-Resolved X-ray Absorption Determination of Structural Changes following Photoinduced Electron Transfer within Bis-porphyrin Heme Protein Models

Time domain energy dispersive X-ray absorption spectroscopy provides a powerful probe of changes in molecular structure that occur during photoinduced electron transfer reactions. In this study a diporphyrin model for electron transfer within modified heme proteins is examined using this technique. Transient optical absorption experiments show that photoinduced electron transfer from the lowest excited triplet state of a Zn porphyrin attached at a fixed 25 {angstrom} distance by means of a long spacer molecule to an Fe(III) porphyrin occurs with a 6 ms time constant at 77 K. Time domain X-ray absorption measurements are consistent with transient reduction of Fe(III) to Fe(II) that is accompanied by substantial weakening of the bond between the Fe atom and a pyridine molecule ligated to it. Coupling of ligand loss to reduction of Fe(III) to Fe(II) provides a means of stabilizing the reduced intermediate.

Hemoprotein models based on a covalent helix-heme-helix sandwich 4. Discrimination of paramagnetic Fe(III)-Mimochrome I Δ and Λ isomers by NMR spectroscopy

A 1H NMR study of the paramagnetic Fe(III)-Mimochrome I, a porphyrin peptide compound based on a covalent helix-porphyrin-helix sandwich, prototype of a new class of heme-protein models, is reported. The study demonstrates that Fe(III)-Mimochrome I exists, in d 7-DMF solution at millimolar concentration, as two hexacoordinated Δ and Λ isomers. It represents the first observation of two isomeric forms of a bis-histidine Fe(III)-porphyrin peptide adduct. 1H NMR studies in d 7-DMF solution of the paramagnetic Fe(III) deuteroporphyrin dimethylester (DPDME), either as acetate (Ac) or chloride salts, are also reported for comparison. In the acetate form this compound gives detectable different mixed-ligand isomers by imidazole addition, while the chloride form gives preferentially the bis-imidazole complex.

Dendrimers with Porphyrin Cores: Synthetic models for globular heme proteins

AbstractDendritic iron porphyrins were synthesized as functional mimics of globular electron‐transfer heme proteins. The cascade molecules 1 · Zn−3 Zn of first to third generation were obtained starting from the (meso‐diarylporphyrin) zinc 6 · Zn which contains four carboxylate arms for attachment of the poly(ether‐amide) dendritic branches by peptide‐coupling methodology (Scheme 1). Generation 3 compound 3 · Zn with 108 methyl‐carboxylate end groups has a molecular weight of 19054. D, and computer modeling suggests that its structure is globular and densely‐packed, measuring ca. 4 nm in diameter and, therefore, similar in dimensions to the electron‐transfer protein cytochrome‐c. Starting from the generation 1 poly(carboxylic acid) 11 · Zn and the generation 2 analog 12 · Zn the dendritic ZnII porphyrins 4 · Zn and 5 · Zn, respectively, were obtained by esterification with triethyleneglycol monomethyl ether (Schemes 3 and 4). Demetallation followed by insertion of FeII and in situ oxidation afforded the water‐soluble dendritic iron porphyrins 4 FeCl and 5 FeCl. The electrochemical behavior of esters 1 · Zn−3 · Zn in organic solvents changed smoothly with increasing dendritic generation (Table 1). Progressing from 1 · Zn to 3 · Zn in THF, the first porphyrin‐centered oxidation and reduction potentials become more negative by 320 and 210mV, respectively. These changes were attributed to strong microenvironmental effects imposed on the electroactive core by the densely packed dendritic surroundings. The electrochemical properties of 4 · FeCl and 5 · FeCl were investigated by cyclic voltammetry in both CH2Cl2 and H2O (Tables 2 and 3). Progressing from 4 · FeCl to 5 · FeCl in CH2Cl2, the redox potential of the biologically relevant FeIII/FeII couple remained virtually unchanged, whereas in aqueous solution, 5 FeCl exhibited a potential 420 mV more positive than did 4 FeCl. The large difference between these potentials in H2O was attributed to differences in solvation of the core electrophore. Whereas the relatively open dendritic branches in 4 · Fecl do not impede access of bulk solvent to the central core, the densely packed dendritic superstructure of 5 · FeCl significantly reduces contact between the heme and external solvent. As a result, the more charged FeIII state is destabilized relative to FeII, and the redox potential is strongly shifted to a more positive value.

Deformability of Fe(II)CO and Fe(III)CN groups in heme protein models: nonlocal density functional theory calculations

High-quality nonlocal density functional calculations have been carried out on the deformability of Fe(II)CO and Fe(III)CN units in model compounds of heme proteins. The results confirm our previous finding with a local functional that the Fe(II)CO unit is significantly deformable with respect to tilting and bending. This deformability stems in large part from a large, negative interaction constant between the FeC tilt and FeCO bend coordinates. The Fe(III)CN unit is also significantly deformable, but in this case the deformability results from a very small Fe(III)CN bend force constant and the ability of the cyano nitrogen to act as a hydrogen bond acceptor. The prediction that the energetic penalty associated with deforming the Fe(II)CO unit is relatively modest indicates that such deformations are unlikely to be the dominant contributor to myoglobin's discrimation against CO in favor of O2.

Structural and Electronic Factors That Influence Oxygen Affinities: A Spectroscopic Comparison of Ferrous and Cobaltous Oxymyoglobin

Various structural and electronic factors that result in similar rates of oxygen association (kon) and differing rates of oxygen dissociation (koff) for ferrous (FeMb) and cobaltous (CoMb) myoglobin have been investigated. Similar values for kon indicate similar barriers to oxygen binding for CoMb and FeMb. Through optical spectroscopy, we have found that the stable quantum yields of photolysis for CoMbO2 (0.55 +/- 0.05) and FeMbO2 (0.50 +/- 0.05) at 10 K are the same. The X-ray absorption near edge spectra (XANES) of CoMb and FeMb reveal similar metal-heme displacements for the deoxy, oxy, and low temperature photoproduct states of CoMb and FeMb. Thus, similar barriers to ligand binding, indicated by similar kon's and photoproduct yields for CoMb and FeMb, correlate with the metal-heme displacements for the oxy, deoxy, and low temperature photoproduct states of CoMb and FeMb. Lower values of koff for FeMbO2 versus CoMbO2 imply different barriers to oxygen release for the two species. X-ray edge positions of CoMb and FeMb indicate a substantial transfer of electron density from the metal to the ligand upon oxygenation. The distribution of electron density throughout the M-O-O moiety differs for CoMbO2 and FeMbO2. Resonance Raman spectroscopy has demonstrated that the Co-O bond is weaker when compared to Fe-O [Tsubaki, M., & Yu, N. T. (1981) Proc. Natl. Acad. Sci., U.S.A. 78, 3581]. We have used photolyzed/unphotolyzed Fourier Transform Infrared (FTIR) difference spectra of CoMb16O2, CoMb18O2, FeMb16O2, and FeMb18O2 to show that the dioxygen stretching frequency, v(O-O), in CoMbO2 (approximately 1138 cm-1) is higher than FeMbO2 (approximately 1131 cm-1). The dioxygen stretching frequency in CoMbO2 is closer to that of heme protein models lacking a hydrogen bond to the distal histidine, suggesting that formation of the hydrogen bond in FeMbO2 provides a greater effect on the distribution of electron density throughout the Fe-O-O... HN moiety, potentially stabilizing a more ionic Fe-O-O bond. These findings demonstrate important electrostatic differences in the distal environments of CoMbO2 and FeMbO2, resulting in different barriers to oxygen release.

Binding of O 2 and CO to heme protein models

UV-Vis studies of two heme protein models differing only by two carbons show unexpected oxygen and carbonmonoxide affinities and in one case a partition coefficient M = 105 which can be compared favorably with hemoprotein values.

Hydrogen bonding to the proximal imidazole in heme protein model compounds: effects upon oxygen binding and peroxidase activity

Hydrogen bonding to the proximal imidazole in heme protein model compounds: effects upon oxygen binding and peroxidase activity

ChemInform Abstract: NUCLEAR MAGNETIC RESONANCE OF PARAMAGNETIC METALLOPORPHYRINS

The present article reviews and discusses proton magnetic resonance studies on metalloporphyrins which provide good models for heme proteins in their physical and chemical properties. Emphasis is given on the discussion of the1Hnmr work done in our laboratory.

Electron exchange in models for heme proteins

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectron exchange in models for heme proteinsDabney White Dixon, Michael Barbush, and Ataollah ShiraziCite this: J. Am. Chem. Soc. 1984, 106, 16, 4638–4639Publication Date (Print):August 1, 1984Publication History Published online1 May 2002Published inissue 1 August 1984https://doi.org/10.1021/ja00328a068RIGHTS & PERMISSIONSArticle Views50Altmetric-Citations16LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (318 KB) Get e-Alerts Get e-Alerts

Nuclear magnetic resonance of paramagnetic metalloporphyrins

The present article reviews and discusses proton magnetic resonance studies on metalloporphyrins which provide good models for heme proteins in their physical and chemical properties. Emphasis is given on the discussion of the1Hnmr work done in our laboratory.

Steric control of CO binding in a totally synthetic heme protein model

A family of totally synthetic models for the carbon monoxide adducts of heme proteins has been synthesized and applied to the elucidation of the role of steric effects in the relative detoxification of carbon monoxide. The complexes are designed such that a sheltered void of controllable dimensions encompasses the CO binding site. Systematic variations in the available space for the iron-bound CO produce a wide range of equilibrium binding constants (K(CO)). An x-ray structure determination of a CO adduct complex having a crowded CO site reveals that the Fe-C identical withO linkage is bent, and further, the distortion involves both displacement of the Fe-C vector from the normal to the N(4) plane and bending of the Fe-C-O angle.