Stable Iron Porphyrin Intramolecularly Coordinated by Alcoholate Anion

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Stable Iron Porphyrin Intramolecularly Coordinated by Alcoholate Anion: Synthesis and Evaluation of Axial Ligand Effect of Alcoholate on Spectroscopy and Catalytic Activity Yoshinori Shirakawa, Yuuki Yano, Yuki Niwa, Kanako Inabe, Naoki Umezawa, Nobuki Kato, Yosuke Hisamatsu, and Tsunehiko Higuchi* Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan

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S Supporting Information *

ABSTRACT: We synthesized intramolecularly aliphatic alcoholate-coordinated iron porphyrins (1a, 1b) that retain their axial coordination in the presence of another ligand or oxidant. The electron-donative character of alcoholate was less than that of thiolate, and the coordination ability of a sixth ligand to 1a and 1b was very much lower than in the case of the thiolate-coordinated compounds. Density functional theory calculations indicated that the marked difference in coordination ability could be explained in terms of thermodynamic and steric factors. The catalytic oxidizing ability of the thiolate-coordinated compound, SR complex, was much higher than that of 1a.

1. INTRODUCTION Cytochrome P450s catalyze various types of oxidative reactions involved in steroid biosynthesis, fatty acid metabolism, and detoxification of xenobiotic compounds, most of which are monooxygenase-type NADPH/NADH- and O2-dependent reactions.1 Because of the extremely strong oxidizing ability of cytochrome P450 enzymes, much interest has been focused on their chemistry, and identification of the reactive intermediate responsible for oxygen atom transfer to the substrate in the catalytic oxidation reaction has been a major goal in bioinorganic chemistry.1 Cytochrome P450 and NO synthase (NOS) have strong oxidizing ability and unusual structure among heme enzymes, in that their heme iron has thiolate coordination. Consequently, attention has mainly been focused on their structure−function relationship. We previously synthesized the first thiolate-coordinated iron porphyrin (named SR complex (Figure 1)) that retains its thiolate coordination during catalytic oxidizing reactions, and compared the effects of axial thiolate, imidazole, and chloride ligands on the catalytic oxidation reaction mediated by the SR complex.2 On the other hand, heme of catalase is coordinated by phenolate, which has relatively high ligand field strength, and several model complexes having iron porphyrin coordinated by phenolate have been reported.3 Electrons of the oxyanion of phenolate conjugate with the π-electron system of the attached benzene ring. On the other hand, alcoholate, in which an oxy anion is attached to a saturated carbon atom,4 does not conjugate with any π-electron system, as the case of the sulfur anion of thiolate ligand of P450. Therefore, it is of interest to compare the relative axial ligand effects of thiolate © XXXX American Chemical Society

and alcoholate. This issue has not previously been studied, and so the basis for the emergence of thiolate as an axial ligand of heme of cytochrome P450 during the course of evolution, rather than alcoholate, remains unclear. Another reason for the present work was to establish how axial coordination of alcoholate affects the structure and function of iron porphyrin. In addition, we wished to test the validity of a reported prediction (see below) that heme alcoholate complex would be a more active oxidation catalyst than heme thiolate. A number of iron porphyrins coordinated by external alkoxide anion have been prepared, and their physico-chemical properties such as UV−vis,5a EPR,5b electrochemistry,5c and crystal structure5d,e have been investigated. Morishima et al. predicted that heme alcoholate complex would be a more active catalyst for oxidation with peroxide than heme thiolate, based on the results of their density functional theory (DFT) calculations.6 However, the relative effects of the axial alcoholate ligand on coordination chemistry and catalytic oxidizing activity have never been evaluated by using an isolable heme alcoholate complex. This is probably because the highly basic alcoholate ligand is usually exchangeable by another ligand or acidic hydroperoxide as a result of protonation to form a weak alcohol ligand with an acidic component. Furthermore, previously reported heme alcoholate complexes needed an excess of highly basic alcoholate anion, which seriously affects evaluation of the chemical properties. Interestingly, Dawson and coauthors have reported preparation Received: December 4, 2018

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DOI: 10.1021/acs.inorgchem.8b03384 Inorg. Chem. XXXX, XXX, XXX−XXX

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Figure 1. Structures of SR complex, SR-HB complex, and heme alcoholates 1a and 1b.

Figure 2. Synthesis of complex 1a. Reagents and conditions: (a) NBS, BPO, hν; (b) NaOAc in DMF, 59% (2 steps); (c) TFA-AcOH, 75%; (d) (1) 2-chloro-1-methylpyridinium iodide, Et3N in THF/CH2Cl2; (2) α,α,α,α-meso-tetrakis(2-aminophenyl)porphyrin in THF/CH2Cl2, 60%; (e) pivaloyl chloride, pyridine in CH2Cl2, 65%; (f) Fe(CO)5, I2, 2,4,6-collidine intoluene, 82%; (g) sodium methoxide/MeOH intoluene, 54%.

Figure 3. Electronic absorption spectra of 1a(Fe(III)) and its reduced states and 1b(Fe(III)) at 298 K. [1] = 10 μM in toluene. (A) a: the spectrum of 1a(Fe(III)); b: the spectrum observed immediately after the addition of 1a to toluene containing an excess of NaBH4 and 15-Crown-5 under Ar; c: the spectrum 16 min after the start of reduction. (B) Electronic absorption spectrum of 1b(Fe(III)) at 298 K.

B

DOI: 10.1021/acs.inorgchem.8b03384 Inorg. Chem. XXXX, XXX, XXX−XXX

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any change of λmax, although the reason for this is unclear. We show only the spectrum of 1b (Fe(III)) in Figure 3. EPR Spectra. Both of these complexes were found to contain Fe(III) in a high-spin state from the results of EPR and electronic absorption spectroscopy. EPR spectra of 1a and 1b showed three signals assignable to Fe(III)porphyrin in a highspin state (Figure 4 and Table 2). Complex 1a was chromatographically and mass spectrometrically homogeneous. Therefore, 1a appears to be a mixture of two conformers at 4 K, although NMR data could not be used to support this idea due to the paramagnetic property of 1a. Cyclic Voltammetry. The cyclic voltammograms of 1a and 1b gave reversible redox couples (Figure S3). The E1/2 (FeII/ FeIII) of 1a (−0.63 V) was ca. 0.2 V higher than that of SR, and the E1/2 (FeII/FeIII) of 1b was similar (Figure S3 and Table 2). These results indicate that the electronic Push ef fect of alcoholate is lower than that of thiolate. FT-IR Spectroscopy of NO-1a(FeIII). N-O Stretching mode of the NO-1a(FeIII) complex was measured by FT-IR spectroscopy (Figure S4 and Table 2). The assignment was confirmed by the observation of an isotope shift when 15NO was used (1863 cm−1). The N-O stretching mode of NO-1a (1897 cm−1) was clearly lower than the mode of NO-FeIII meso-tetraphenylporphyrin axially coordinated by iso-amyl alcohol (1935 cm−1) or H2O (1937 cm−1).8a,b The difference in the two modes supports the idea that complex 1a is not a heme-alcohol form, but a heme-alcoholate form. The N-O stretching mode of NO-1a (1897 cm−1, this work) was much higher than that of the NO-SR complex (1828 cm−1).9 Electrochemistry and FT-IR both indicate that the axial alcoholate ligand is a poorer π-electron donor than thiolate toward iron porphyrin. Coordination Chemistry of 1a with 1-Methylimidazole Evaluated by Electronic Absorption Spectral Titration, DFT Calculation, and Measurement of Effective Magnetic Moment. The binding constant of 1methylimidazole (1-MeIm) as a sixth ligand to complex 1a was evaluated by electronic absorption spectral titration. Only 10 equiv of 1-MeIm was necessary for almost complete formation of the 1-MeIm-SR complex (Figure 5a). In contrast, to our surprise, addition of even 2000 equiv of 1-MeIm did not alter the absorption spectra of the 1a complex, indicating that it is in a high-spin state (at 298 K, Figure 5b), even though the ligand field strength of 1-MeIm is high. The reported 1-MeImcoordinated iron porphyrin methoxide is known to be in the low-spin state from its EPR spectra at 77 K.10 However, it was also reported that no visible spectral change was observed at room temperature when 30 equiv of 1-MeIm was added to iron meso-tetraphenylporphyrin methoxide solution.10 Our data clearly indicate that there is a very marked difference between the effect of thiolate and that of alcoholate as a fifth ligand of heme upon sixth ligand coordination. Coordination of a sixth ligand to the heme iron is a thermodynamically controlled process. We mixed 1a and 1MeIm in CH2Cl2 at 298 K and measured the heat of formation by using isothermal titration calorimetry (ITC). As expected, almost no measurable heat other than heat of dilution was observed (Figure S5). The coordination equilibrium constant depends on the energy difference between the noncoordination state and coordination state, because the chemical equilibrium obeys the Arrhenius equation. Therefore, we carried out DFT calculation for each complex in order to

of a P450 mutant (ΔC436S CYP2B4) that is indicated to have a heme-alcoholate coordination structure judging from magnetic circular dichroism (MCD) data and electronic absorption spectra.7 However, the protein has not been fully characterized, e.g., in terms of vibration spectroscopy, electrochemical properties, and catalytic activity. Here we report the synthesis of the first isolable alcoholatecoordinated iron porphyrins (1a and 1b in Figure 1) that retain their axial ligands during catalytic oxidation. We also describe their chemical properties including catalytic oxidization activity.

2. RESULTS AND DISCUSSION Synthesis. We expected that the synthetic method of SR complexes that we developed2a would be directly applicable to the heme alcoholate complex (Figure 2). Indeed, the coupling reaction of (o-acetoxymethylphenoxy)acetic acid (4a) and an amino group of α,α,α,α-meso-tetrakis(2-aminophenyl)porphyrin, and the subsequent synthetic steps proceeded as in the case of the SR complex.2a Complex 1a was successfully purified by silica gel column chromatography under air, even though alkoxide anion is highly basic and should be protonated by acidic silanols on silica gel. The reason for the axial coordination stability is probably that the alkoxide oxygen is deeply buried in bulky pivalamido groups of the porphyrin, and therefore, alkoxide and silanol cannot come into direct contact. We also prepared 1b, an alcoholate-coordinated iron porphyrin with a NH−O hydrogen bond on the axial ligand analogously to our previous synthesis of SR-HB, an iron porphyrin coordinated by thiolate with a NH−S hydrogen bond (Figure S1).2d High-resolution mass (ESI) spectra of 1a (m/z 1166.4135 [M + Na]+) and 1b (m/z 1223.4353 [M + Na]+) together with the results of elemental analysis supported these structures. Electronic Absorption Spectra. The electronic absorption spectra of 1a(Fe(III)) and 1a(Fe(II)) were measured (Figure 3 and Table 1). The spectral pattern of 1a(Fe(III)) Table 1. Electronic Absorption Spectra of Complexes 1a and 1ba complex 1a(Fe(III)) 1a(Fe(II)) 1b(Fe(III))

band maxima, nm (ε, M−1 cm−1 × 10−3) 349 (32.7), 418 (80.3), 481 (sh, 20.3), 581 (11.9), 637 (sh, 6.66) 438 (94.5), 536 (10.8), 570 (12.2), 636 (sh, 6.73) 350 (33.3), 420 (88.6), 500 (sh, 12.3), 594 (5.92), 649 (3.46)

a

Toluene, 298 K. sh: shoulder.

(spectrum a in Figure 3, λmax = 418 nm) was similar to that of Fe(III) meso-tetramesitylporphyrin methoxide.5a Next, the complex 1a in toluene was reduced with NaBH4-15-Crown-5 couple. The spectrum of the reduced product showed a bathochromically shifted Soret band (spectrum b, λmax = 438 nm), but gradually changed to spectrum c (λmax = 432 nm). Spectrum c is similar to the spectrum obtained when Fe(III) meso-tetraphenylporphyrin chloride (Fe(III)(TPP)Cl) was reduced in the same manner (λmax = 425 nm, Figure S2). Therefore, spectrum b should be that of 1a(Fe(II)) and spectrum c would be that of Fe(II) porphyrin coordinated by alcohol or crown ether as the fifth ligand. In the case of 1b, reaction with NaBH4-15-Crown-5 caused a considerable decrease of intensity throughout the whole spectrum without C

DOI: 10.1021/acs.inorgchem.8b03384 Inorg. Chem. XXXX, XXX, XXX−XXX

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Figure 4. EPR Spectra of 1a (a) and 1b (b). [1a], [1b]: 100 μM in toluene at 4 K.

Table 3. Calculated Energy and Coordination Heata

Table 2. EPR, Cyclic Voltammogram of Iron(III)porphyrin Thiolate or Alcoholate Axial Ligand and N-O Stretching Mode of the NO-Coordinated Complex Fe(Por)

axial ligand

SR

R-S−

1a

R-O−

SR-HB

R-S−

1b

R-O−

EPR at 4 K

E1/2 (FeII/FeIII)

ν (N-O) of ON-Fe(Por)a

gx = 1.96 gy = 2.21 gz = 2.32 g = 1.9, 5.5, 6.0 gx = 1.96 gy = 2.20 gz = 2.32 g = 2.1, 5.4, 6.1

−0.81 V

1828 cm−1

−0.63 V

1897 cm−1

−0.70 V

1837 cm−1

−0.50 V

n.d.

ν (N-O) data of ON-SR and ON-SR-HB: ref 9.

a

Fe porphyrin

energy of 5coordinate Fe porphyrin (A) [spin state S = 5/2]

energy of 1-MeIm-Fe porphyrin (6-coordinate) (B) [spin state S = 1/2]

heat formed by 1-MeIm coordination (C)

1a SR complex Fe(Por)OMe* Fe(Por)SMe*

−4780.9022 −5103.7762 −2367.1415 −2690.0928

−5046.3011 −5369.1662 −2632.7216 −2955.7058

0.0112 −0.0201 −0.0708 −0.1037

Unit: hartree. Energy of 1-MeIm: −265.4101 hartree (D). Heat (C) was calculated by an equation: C = B − (A + D). DFT Calculation: Geometry optimization with ωB97X-D/6-31G*, then single point energy with M06-2X/6-31G* in the cases of 1a and SR complex. * Geometry optimization with ωB97X-V/6-311+G(2df,2p) in the cases of Fe(Por)OMe and Fe(Por)SMe (1-MeIm: −265.5093 hartree).

a

obtain the energy difference. Coordination of 1-MeIm to the SR complex was exothermic (Table 3). In contrast, coordination of 1-MeIm to 1a was endothermic. This endothermicity in the case of 1a may explain why 1-MeIm hardly coordinated to 1a. Next, we calculated simple iron

Figure 5. (a) Electronic absorption spectral changes of SR (10 μM in CH2Cl2 at 298 K) with increasing 1-MeIm concentration. [1-MeIm] (μM): 0 (black), 20 (red), 100 (blue). (b) Electronic absorption spectral changes of 1a (10 μM in CH2Cl2 at 298 K) with increasing 1-MeIm concentration. [1-MeIm] (μM): 0 (solid line), 20 000 (dashed line). D

DOI: 10.1021/acs.inorgchem.8b03384 Inorg. Chem. XXXX, XXX, XXX−XXX

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(Fe(III)) in CDCl3 (2.47 mM) in the presence of 1.0 M 1MeIm was 4.23, which is close to that of 1a in the absence of 1MeIm. Therefore, this result also indicates that a large excess amount of 1-MeIm does not alter the spin state of 1a. Catalytic Oxidation Activity of 1a and 1b. We previously reported that the SR complex showed high catalytic activity in the O−O bond cleavage of alkyl hydroperoxides,2a peroxyacids,2b−f and endoperoxide.2g At first, cumene hydroperoxide was examined as an oxidant for 2,4,6-tri-tertbutylphenol (TBPH) in order to evaluate the catalytic activity of heme alcoholate 1a. However, no activity was observed in this case. Next, the catalytic oxidative activity of 1a for TBPH oxidation with peroxyphenylacetic acid (PPAA), a more powerful oxidant than cumene hydroperoxide, was compared with that of SR in order to evaluate the relative axial ligand effect of alcoholate (Table 4). The initial reaction rate catalyzed by 1a was 130-fold lower than the rate in the case of SR. This large difference is probably due to the small equilibrium constant of PPAA coordination to the iron of 1a and also poorer electron donation of alcoholate to iron than that of thiolate. In summary, we have succeeded in the synthesis of intramolecularly aliphatic alcoholate-coordinated iron porphyrins, which were confirmed to retain alcoholate coordination during catalytic oxidization reaction. We also evaluated their sixth ligand coordination ability. Complex 1a is simply an Osubstituted analogue of the SR complex, but notably, its chemical properties are very different from those of SR. Complex 1a in a low-spin state was hardly formed, in spite of addition of an extremely large excess of 1-MeIm, whereas SR in low-spin state was readily formed by the addition of only 10 equiv of 1-MeIm to SR. DFT calculations indicated that this marked difference in coordination ability can be explained in terms of thermodynamic and steric factors. The cyclic voltammogram of 1 and IR spectrum of 1a-NO complex indicate that the electron donation of alcoholate to heme is much weaker than that of thiolate. These results may explain why nature has selected thiolate as an axial ligand of heme in cytochrome P450, not alcoholate.

porphyrin methoxide (Fe(Por)OMe), 1-MeIm-Fe(Por)OMe, Fe(Por)SMe, and 1-MeIm-Fe(Por)SMe with a higher-level function set (ωB97X-V/6-311+G(2df,2p)) in order to examine whether or not the difference in the energy profile between 1a and SR is general (Table 3). The results indicated that Fe(Por)SMe was more exothermic than Fe(Por)OMe, although both gave exothermic profiles. These results suggest that imidazole coordination to heme thiolate is generally more advantageous than that to heme alcoholate. The difference in the heat profile between 1a and Fe(Por)OMe may be due to a difference in conformational restriction of the axial ligand linker part and/or a difference in the environment around the axial ligand. The very low coordination ability for 1-MeIm suggests that the axial orbital of iron (dz2) repels the lone pair of 1-MeIm due to its high electron density. This may be interpreted as indicating that alcoholate as an axial ligand is a high σ-electron donor to the iron dz2 orbital, in contrast to its poor π-donative character. A comparison of the structures of the two iron porphyrins obtained by the above-mentioned calculation (Figure 6)

Figure 6. Calculated structures of Fe(Por)OMe and Fe(Por)SMe obtained by geometry optimization (gas phase) using ωB97X-V/6311+G(2df,2p) function set.

indicates that the form of the porphyrin plane of Fe(Por)OMe is dome-like. This is consistent with the crystal structure of iron octaethylporphyrin methoxide.5e In contrast, the porphyrin of Fe(Por)SMe is almost completely planar. The cone angle (∠N21−Fe−N23) of the former (144.3°) is considerably narrower than that of the latter (163.9°). The narrow cone angle should sterically hinder the approach of 1-MeIm to the iron. Thus, the shape of the porphyrin plane can explain the resistance of 1a to accepting a sixth ligand. Finally, the values of effective magnetic moment (μeff) of complex 1a in the absence and presence of 1-MeIm were determined using the Evans method in order to confirm the spin state at 298 K.11 The μeff of 1a (Fe(III)) in CDCl3 was 4.68 at 298 K, showing mainly a high-spin state. The μeff of 1a

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.inorgchem.8b03384.

Table 4. Observed Initial Rates of TBP• Formation in the Oxidation of TBPH with Peroxyphenylacetic Acid (PPAA) Catalyzed by 1 or SR Complexa

Fe(Por)

turnover number freq (ν/s)b

νSR/νFe(Por)

SR 1a 1b

39 0.29 1.0

1 130 39

Conditions: solvent = CH2Cl2: [TBPH] = 0.2 M; [PPAA] = 5 × 10−3 M: [SR] = [1a or 1b] = 10−4 M. These reactions were carried out at 298 K under an argon atmosphere. bObserved initial rates of the reactions were based on catalysts (turnover number of catalyst/s). a

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in Oxidation Reaction Catalyzed by Synthetic Heme−Thiolate Complex Relevant to Cytochrome P450. J. Am. Chem. Soc. 2002, 124, 9622−9628. (g) Yamane, T.; Makino, K.; Umezawa, N.; Kato, N.; Higuchi, T. Extreme Rate Acceleration by Axial Thiolate Coordination on the Isomerization of Endoperoxide Catalyzed by Iron Porphyrin. Angew. Chem., Int. Ed. 2008, 47, 6438−6440. (h) Suzuki, H.; Inabe, K.; Shirakawa, Y.; Umezawa, N.; Kato, N.; Higuchi, T. Role of Thiolate Ligand in Spin State and Redox Switching in the Cytochrome P450 Catalytic Cycle. Inorg. Chem. 2017, 56, 4245−4248. (3) Iron porphyrin coordinated by a phenolate as a catalase model. (a) Garcia, B.; Lee, C. H.; Blasko, A.; Bruice, T. C. Pendant-capped porphyrins. 1. The synthesis of a biphenyl pendant-capped iron(III) porphyrin model of catalase. J. Am. Chem. Soc. 1991, 113, 8118−8126. (b) Fujii, H.; Yoshimura, T.; Kamada, H. Imidazole and pNitrophenolate Complexes of Oxoiron(IV) Porphyrin π-Cation Radicals as Models for Compounds I of Peroxidase and Catalase. Inorg. Chem. 1997, 36, 6142−6143. (c) (Recent paper) Das, P. K.; Dey, A. Resonance Raman, Electron Paramagnetic Resonance, and Density Functional Theory Calculations of a Phenolate-Bound Iron Porphyrin Complex: Electrostatic versus Covalent Contribution to Bonding. Inorg. Chem. 2014, 53, 7361−7370. (4) Definition of the term “alcoholate”: Compounds, ROM, derivatives of alcohols, ROH, in which R is saturated at the site of its attachment to oxygen and M is a metal or other cationic species. Moss, G. P.; Smith, P. A. S.; Tavernier, D. Glossary of class names of organic compounds and reactivity intermediates based on structure (IUPAC Recommendations 1995). Pure Appl. Chem. 1995, 67, 1307. (5) (a) Groves, J. T.; Quinn, R.; McMurry, T. J.; Nakamura, M.; Lang, G.; Boso, B. Preparation and Characterization of a Dialkoxyiron(IV) Porphyrin. J. Am. Chem. Soc. 1985, 107, 354−360. (b) Otsuka, T.; Ohya, T.; Sato, M. EPR Studies of the Formation of Low-Spin Dimethoxo(tetraphenylporphinato)ferrate(III) in Solution. Inorg. Chem. 1984, 23, 1777−1779. (c) Swistak, C.; Mu, X. H.; Kadish, K. M. Electrochemistry of Hydroxo- and Methoxo[tetrakis(2,4,6-trimethylphenyl)porphyrinato]iron in Dichloromethane. Electrogeneration of Iron(IV) and Iron(II) Porphyrins. Inorg. Chem. 1987, 26, 4360−4366. (d) Lecomte, C.; Chadwick, D. L.; Coppens, P.; Stevens, E. D. Electronic Structure of Metalloporphyrins. 2. Experimental Electron Density Distribution of (Meso-tetraphenylporphinato) Iron (III) Methoxide. Inorg. Chem. 1983, 22, 2982−2992. (e) Hatano, K.; Uno, T. Preparation and Molecular Structure of (Methoxo)(octaethylporphinato)iron (III). Bull. Chem. Soc. Jpn. 1990, 63, 1825−1827. (6) Ohta, T.; Matsuura, K.; Yoshizawa, K.; Morishima, I. The Electronic and Vibrational Structures of Iron-Oxo Porphyrin with a Methoxide or Cysteinate Axial Ligand. J. Inorg. Biochem. 2000, 82, 141−152. (7) Perera, R.; Sono, M.; Voegtle, H. L.; Dawson, J. H. Molecular Basis for the Inability of an Oxygen Atom Donor Ligand to Replace the Natural Sulfur Donor Heme Axial Ligand in Cytochrome P450 Catalysis. Spectroscopic Characterization of the Cys436Ser CYP2B4Mutant. Arch. Biochem. Biophys. 2011, 507, 119−125. (8) (a) Yi, G.-B.; Khan, M. A.; Richter-Addo, G. B. Activation of Thionitrites and Isoamyl Nitrite by Group 8 Metalloporphyrins and the Subsequent Generation of Nitrosyl Thiolates and Alkoxides of Ruthenium and Osmium Porphyrins. Inorg. Chem. 1997, 36, 3876− 3885. (b) Scheidt, W. R.; Lee, Y. J.; Hatano, K. Preparation and Structural Characterization of Nitrosyl Complexes of Ferric Porphyrinates. Molecular Structure of Aquonitrosyl(meso-tetraphenylporphinato)iron(III) Perchlorate and Nitrosyl(octaethylporphinato)iron(III) Perchlorate. J. Am. Chem. Soc. 1984, 106, 3191− 3198. (9) Suzuki, N.; Higuchi, T.; Urano, Y.; Kikuchi, K.; Uchida, T.; Mukai, M.; Kitagawa, T.; Nagano, T. First Synthetic NO−Heme− Thiolate Complex Relevant to Nitric Oxide Synthase and Cytochrome P450nor. J. Am. Chem. Soc. 2000, 122, 12059−12060. (10) Otsuka, T.; Ohya, T.; Sato, M. Electron Paramagnetic Resonance Studies of Hydrogen Bonding in Low-Spin Ferric Heme

Experimental data of synthesis, electronic absorption spectra, cyclic voltammogram, FT-IR spectrum of 1aNO, ITC of 1a with 1-MeIm, effective magnetic moment of 1a with 1-MeIm (PDF)

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Naoki Umezawa: 0000-0003-3966-2303 Tsunehiko Higuchi: 0000-0002-3586-4680 Present Address

N. Kato: Graduate School of Science, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan. Author Contributions

All authors contributed to writing the manuscript. All authors have given approval to the final version of the manuscript. Funding

This work was supported in part by Grants-in-Aid for Scientific Research (A) (No. 20249006) from the Japan Society for the Promotion of Science (JSPS). We are also grateful for support by the Platform Project for Supporting Drug Discovery and Life Science Research (No. 12760016, No. 16am0101055j0005) from MEXT, and by the Japan Agency for Medical Research and Development (AMED). Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We are grateful to Dr. Takuya Kurahashi (Institute for Molecular Science) for cooperation in EPR measurement. REFERENCES

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DOI: 10.1021/acs.inorgchem.8b03384 Inorg. Chem. XXXX, XXX, XXX−XXX

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DOI: 10.1021/acs.inorgchem.8b03384 Inorg. Chem. XXXX, XXX, XXX−XXX