High-spin ferrous porphyrin complexes as models for deoxymyoglobin and -hemoglobin. A proton nuclear magnetic resonance study

Goff, Harold M.; Gn, La Mar

doi:10.1021/ja00462a022

Cited by 117 publications

(55 citation statements)

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“…[25][26][27][28][29][30] The energy of the closed-shell singlet state (first column of the table) then corresponds to the spin pairing energy ∆E sp (cf. eq 1).…”

Section: Resultsmentioning

confidence: 99%

Binding of CO, NO, and O₂ to Heme by Density Functional and Multireference ab Initio Calculations

2008

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Using the CASSCF/CASPT2 approach, along with several DFT methods (PBE0, B3LYP, BP86, OLYP), we have investigated the bonding of CO, NO, and O2 molecules to two model heme systems: an iron(II) porphyrin with and without an axial imidazole ligand. The experimentally available binding energies are best reproduced by the CASPT2 method and with the OLYP functional. The other functionals considered perform much worse, either severely overbinding (BP86) or underbinding (B3LYP, PBE0). Significant discrepancies between the different density functionals are observed, not only for the energetics but sometimes also for structure predictions. This confirms our viewpoint that a balanced treatment of the electronic exchange and correlation is vital to describe the weak metal-ligand bond between heme and CO, NO, or O2. The binding energies DeltaEb were split into two contributions: the so-called spin-pairing energy DeltaE sp and the "inherent" binding energy DeltaEb0, and both contributions were analyzed in terms of method and basis set effects. We have also investigated the spin density distributions resulting from the bonding of the NO molecule (a noninnocent ligand) to heme. Our analysis at the DFT and CASSCF level shows that, while various density functionals predict qualitatively very different spin distributions, the CASSCF spin populations most closely correspond to the results obtained with the pure BP86 or OLYP rather than with the hybrid functionals.

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“…[25][26][27][28][29][30] The energy of the closed-shell singlet state (first column of the table) then corresponds to the spin pairing energy ∆E sp (cf. eq 1).…”

Section: Resultsmentioning

confidence: 99%

Binding of CO, NO, and O₂ to Heme by Density Functional and Multireference ab Initio Calculations

2008

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“…However, the 1 H-NMR spectrum of these species is not as well-defined as with CObound or O 2 -bound species (33,34) suggesting that multiple species with different spin states may be present. Upon drying the sample by azeotropic distillation with toluene the following observations were made: (i) paramagnetic signals develop first at 15 ppm then at 50-60 ppm corresponding to the signals of ␤-pyrrole protons (35)(36)(37)(38) and (ii) the 4 band of a high spin species develops (1,342 cm Ϫ1 ) to give a 3:7 ratio 4 band(HS)/4 band(LS). However, washing a dry sample with water resulted in the disappearance of both the 1 H-NMR paramagnetic signals and the resonance Raman 4 high spin marker band.…”

Section: Resultsmentioning

confidence: 99%

Water may inhibit oxygen binding in hemoprotein models

Collman

Decréau²,

Dey³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Three distal imidazole pickets in a cytochrome c oxidase (CcO) model form a pocket hosting a cluster of water molecules. The cluster makes the ferrous heme low spin, and consequently the O2 binding slow. The nature of the rigid proximal imidazole tail favors a high spin/low spin cross-over. The O2 binding rate is enhanced either by removing the water, increasing the hydrophobicity of the gas binding pocket, or inserting a metal ion that coordinates to the 3 distal imidazole pickets.spin cross-over ͉ tris-imidazole pocket ͉ water cluster H emoglobin (Hb), myoglobin (Mb) and cytochrome c oxidase (CcO) are hemoproteins that bind O 2, subsequently transporting or reducing it in a 4e-/4Hϩ process (1, 2). The kinetics of oxygen binding to the active sites of these biomolecules are tuned by stabilizing interactions between the oxygen complex and the immediate environment (3, 4). In monometallic proteins such as myoglobin or hemoglobin, a distal histidine stabilizes the oxygen complex by hydrogen bonding (5, 6). A distal copper tris-imidazole ligand in CcO also provides enthalpic stabilization (7). In addition to structural factors affecting oxygen adduct stability in Mb and Hb, it has been suggested that the molecules of water present in the binding pocket could contribute to the relative oxygen affinities (4, 8, 9) in a model dubbed the ''water displacement model.'' This proposed model could logically be extended to CcO where water is the product of the 4e-/4Hϩ reduction of O 2 . Water is expected to be present in larger quantities in CcO than in Hb or Mb, and it is removed from the binding site by water channels (10-13). Here, we describe well-defined biomimetic hemoprotein models 1-4 ( Fig. 1) that demonstrate the role of water in slowing the binding of O 2 . The rates of reaction correlate with the hydrophobicity of the distal pocket (tris-pivalamido-or picket fence in 2, tris-imidazole in 3) and the presence or absence of a distal bound metal [Cu(I) or Zn(II) in 4ab]. Results and DiscussionThe reaction of oxygen with ferrous porphyrins 1-4 was carried out by injecting an anaerobic solution of porphyrin into O 2 -saturated dichloromethane solution (10 mM) under 1 atm of O 2 . Under the initial conditions of the reaction it is assumed, based on earlier studies (15), that the ligand association rate k on (O 2 ) is several orders of magnitude faster than the ligand dissociation rate k off (O 2 ) and consequently the dissociation rate can be assumed negligeable. The O 2 binding rates were obtained by monitoring the change in of the Soret and Q bands in the UV/Vis spectrum (Fig. 2) that shifted from 426 nm to 421 nm, and from 535 nm to 550 nm, respectively. The oxygen complex was characterized at various stages of the reaction by 2 resonance Raman stretches: (i) an oxygen isotope sensitive band observed at 570/544 cm Ϫ1 that corresponds to the Fe-O stretch and (ii) a 4-band (a spin state and redox state marker band) at 1,370 cm Ϫ1 that is typical of a ferric-superoxo species (16)(17)(18)(19). Second order k on (O 2 ) ra...

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“…(A more detailed discussion can be found elsewhere. 79,81,[94][95][96][97][98] ) Our quantitative gas titration data (Table 1) show that these azacrown-capped models ( Figure 6) manifest an even higher O 2 affinity but a much reduced CO affinity compared with Mb, resulting in M values close to 1. 94 The cyclam-capped porphyrin is particularly remarkable; while it exhibits a "normal" O 2 affinity, it does not bind CO at all (up to 1 atm of CO).…”

Section: Synthetic Models For Hemoglobin and Myoglobin Collman And Fumentioning

confidence: 99%

Synthetic Models for Hemoglobin and Myoglobin

1999

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1) Myoglobin and Hemoglobin. Dioxygen (O 2 ) binds to certain coordinatively unsaturated transition metal ions, forming O 2 complexes. Biological dioxygen carriers are reversible O 2 complexes in which the extent of binding depends on temperature, partial pressure of oxygen, and pH.Myoglobin (Mb) and hemoglobin (Hb) are the most common reversible O 2 binders in biological systems; they are responsible for the storage and transport of O 2 in most aerobic organisms. Myoglobin and hemoglobin are structurally similar. Myoglobin contains one heme prosthetic group; hemoglobin consists of four Mb-like subunits (2R + 2 ), each containing one heme prosthetic group.Myoglobin stores O 2 in muscles to permit short bursts of metabolism at rates much greater than those which would be allowed by circulatory oxygen transport. In its native deoxy form (Figure 1), the ferrous ion of the heme is in a five-coordinate high-spin state (S ) 2), with the imidazole group (His 93) serving as the axial ligand on the proximal side. Myoglobin reversibly binds molecular oxygen in the sixth, distal, vacant coordination site. Distal amino acid residues (e.g., His 64) control the immediate environment. They can induce polar, hydrophobic, or steric interactions which help regulate the affinities of the bound ligands.Hemoglobin, on the other hand, transports O 2 in blood and adjusts binding affinity to various conditions required for appropriate uptake and release of O 2 through a series of allosteric interactions. 1,2 Through the "allosteric effect", the subsequent gas binding affinity of Hb is made greater in the presence of O 2 or carbon monoxide (CO) than in their absence. Myoglobin, having only one heme site per protein, shows no such effect.(2) Control of Ligand-Binding Thermodynamics. Evidence to date suggests that the amino acid residues on the distal porphyrin face are capable of stabilizing the oxygen adduct while destabilizing the competing complex derived from binding of the endogenous toxic ligand CO. 3 Studies have shown that, in the absence of the globin protein, imidazole-ligated heme has a CO affinity much greater than that of the protein-bound heme, indicating that the protein plays a role in decreasing CO affinity. 4 The most significant distal effect invoked in the stabilization of O 2 in Hb is the hydrogen-bonding interaction between coordinated O 2 and the distal histidine, which was initially proposed by Pauling. 5 Subsequent experiments have provided evidence for H-bonding of ironbound dioxygen with the distal histidine. 6-10 A unique Hb from the bloodworm Ascaris (shown in Figure 2) has a remarkably high affinity for O 2 , nearly 10 4 times that of mammalian Hb. 11,12 The origin of this high O 2 affinity is believed to be (1) a strong H-bond between tyrosine (Tyr

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High-spin ferrous porphyrin complexes as models for deoxymyoglobin and -hemoglobin. A proton nuclear magnetic resonance study

Cited by 117 publications

References 1 publication

Binding of CO, NO, and O₂ to Heme by Density Functional and Multireference ab Initio Calculations

Binding of CO, NO, and O₂ to Heme by Density Functional and Multireference ab Initio Calculations

Water may inhibit oxygen binding in hemoprotein models

Synthetic Models for Hemoglobin and Myoglobin

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High-spin ferrous porphyrin complexes as models for deoxymyoglobin and -hemoglobin. A proton nuclear magnetic resonance study

Cited by 117 publications

References 1 publication

Binding of CO, NO, and O2 to Heme by Density Functional and Multireference ab Initio Calculations

Binding of CO, NO, and O2 to Heme by Density Functional and Multireference ab Initio Calculations

Water may inhibit oxygen binding in hemoprotein models

Synthetic Models for Hemoglobin and Myoglobin

Contact Info

Product

Resources

About

Binding of CO, NO, and O₂ to Heme by Density Functional and Multireference ab Initio Calculations

Binding of CO, NO, and O₂ to Heme by Density Functional and Multireference ab Initio Calculations