EPR, resonance Raman, and DFT calculations on thiolate- and imidazole-bound iron(III) porphyrin complexes: Role of the axial ligand in tuning the electronic structure

Article abstract of DOI:10.1021/ic3016035

Iron(III) porphyrin complexes bearing covalently attached imidazole and thiolate axial ligands are investigated using resonance Raman, electron paramagnetic resonance, and cyclic voltammetry. The thiolate ligand stabilizes a low-spin ground state in solve

Full text of DOI:10.1021/ic3016035

Article
pubs.acs.org/IC
EPR, Resonance Raman, and DFT Calculations on Thiolate- and
Imidazole-Bound Iron(III) Porphyrin Complexes: Role of the Axial
Ligand in Tuning the Electronic Structure
Pradip Kumar Das, Sudipta Chatterjee, Subhra Samanta, and Abhishek Dey*
Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, Kolkata, India 700032
S
* Supporting Information
ABSTRACT: Iron(III) porphyrin complexes bearing cova-
lently attached imidazole and thiolate axial ligands are
investigated using resonance Raman, electron paramagnetic
resonance, and cyclic voltammetry. The thiolate ligand
stabilizes a low-spin ground state in solvent-bound six-
coordinate species, weakens the Fe−Npyr bonds, and shifts
the FeIII/II potential more negative by ∼500 mV relative to an
imidazole-bound species. Density functional theory calcula-
tions reproduce the experimental observation and indicate that
the covalent charge donation from thiolate to iron reduces the
Z
eff on the iron. This increases the Fe3d orbital energies, which
changes the bonding interaction present in these complexes
significantly. In particular, the increase of the Fe3d energies
activates an iron-to-porphyrin π*-back-bonding interaction not present in the imidazole-bound complex.
INTRODUCTION
■
Thiolate-bound iron porphyrin cofactors are found in several
metalloenzymes, e.g., cytochrome P450 (cyt P450), NO
synthase, and chloroperoxidase.1−6 Out of these, cyt P450 has
been of particular interest to the catalysis community because
of its capability of oxidizing inert C−H bonds using molecular
O2.2 The remarkable reactivity of this heme enzyme is mostly
attributed to the presence of the proximal thiolate ligand in the
active site, which is proposed to exert a “push effect”.7−13 The
Fe center in the active site of cyt P450 in its resting form
(Figure 1) is best described as a six-coordinate (6C), low-spin
(LS; S = 1/2) FeIII.14,15 Upon substrate binding, a five-
5
coordinate (5C), high-spin (HS; S = /2) FeIII site is formed
and is reduced to generate a HS (S = 2) FeII active form that
binds O2.16−18 The “push effect” of the thiolate ligand has been
proposed to lower the FeIII/II reduction potential, weaken the
axial ligand binding, and affect the heterolytic O−O bond
cleavage of a FeIII-OOH species (compound 0)4 without
requiring an acidic proton to drive it, resulting in the formation
of a highly oxidizing species known as compound I.8,16−25
Several investigations, both theoretical and experimental, have
focused on the nature of the “push effect”, and both
electrostatic (thiolate is an anionic ligand) and orbital overlap
(Fe−S bonds are very covalent) have been invoked to play
roles.13,14,17,26−32 However, it is difficult to quantitatively
evaluate these effects in the protein active site because of the
possible involvement of second-sphere interactions, e.g.,
hydrogen bonding, steric, etc.33,34 Rather, well-defined
synthetic models offer a simpler platform to investigate these
effects.
Figure 1. Active site structure of a cyt P450 enzyme (pdb id: 1AKD).
The synthesis of a thiolate-bound iron(III) porphyrin
complex is complicated by the 2FeIII + RS ⇄ 2FeII + RS−SR
equilibrium. So far, few synthetic models of an oxidized cyt
P450 active site are reported that mimic the axial thiolate
coordination to an iron(III) porphyrin.35−41 Some models bear
aromatic thiolate ligands and are HS in a noncoordinating
solvent like CH2Cl2.42−44 On the contrary, the aliphatic/
benzylic thiolate-coordinated models offer a 6C LS complex
Received: May 14, 2012
Published: September 26, 2012
© 2012 American Chemical Society
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with a solvent molecule bound to the iron as the sixth ligand.45
Some of these models are known to hydroxylate C−H bonds of
intermediate strength using peracids/peroxides.42 Most of these
synthetic models are extremely unstable under O2 even in their
oxidized ferric state.44,46 Previous studies demonstrated that the
nature of the Fe−S bond in the cyt P450 active site and related
synthetic model complexes is much more covalent relative to
that of a neutral ligand.43
Thiolate is a weak-field ligand because it can act as σ and π
donors. Imidazole (most abundant heme-coordinating residue
in nature), on the other hand, is a strong-field ligand because it
mainly acts as a strong σ donor. However, many water (H2O)-
bound histidine (imidazole headgroup)-coordinated ferric
heme sites are, in fact, HS, whereas the H2O-bound cysteine
(thiolate headgroup)-coordinated ferric heme sites are LS,
which is counterintuitive.47 The same is true for synthetic
model complexes; i.e., imidazole-coordinated H2O/solvent-
bound complexes are HS, whereas thiolate-coordinated H2O/
solvent complexes are LS. This, however, is not the case for
nonheme systems.48 The 6C active site of superoxide reductase
(SOR), which bears an axial cysteine ligand, is HS in both
resting and several ligand-bound states.49 This implies the
presence of an unusual bonding phenomenon in thiolate-ligated
heme complexes that needs to be understood.
(98%), 2,4,6-collidine (99%), and chloroform-d (99.8%) were
purchased from Aldrich Chemical Company. Tetrahydrofuran
(THF), acetonitrile (CH3CN), dimethylformamide (DMF), dichloro-
methane (DCM), methanol (MeOH), diethyl ether, acetic acid,
stannous chloride (SnCl2·2H2O), and anhydrous Na2SO4 were
purchased from Merck. All solvents were purified by standard
procedures. Pyrrole and 2,4,6-collidine were distilled directly before
use. meso-Mono(o-aminophenyl)triphenylporphyrin50 and meso-tetra-
(α,α,α,α-o-aminophenyl)porphyrin (TAPP)37 were synthesized using
reported methods. Insertion of the iron into porphyrins followed
known routes.37 Column chromatography was done on 60−120 mesh
silica gel, purchased from SRL. Thin-layer chromatography (TLC) was
done on commercially prepared silica gel or alumina plates purchased
from Merck.
Instrumentation. UV−vis absorption data were obtained from an
Agilent Technologies model 8453 spectrophotometer fitted with a
1
diode-array detector. All of the H NMR spectra were recorded on a
Bruker DPX-300 or DPX-500 spectrometer at room temperature. The
EPR spectra were recorded on a JEOL instrument. The mass spectra
were recorded by a QTOF Micro YA263 instrument. All electro-
chemical experiments were performed using a CH Instruments model
CHI710D electrochemical analyzer. rR data were collected using a
413.1 nm excitation wavelength from a Kr+ ion source (Coherent,
Sabre Innova SBRC-DBW-K) and a Trivista 555 triple spectropho-
tometer (gratings used in the three stages were 900, 900, and 1800
grooves/mm) fitted with a Pixis CCD camera (Princeton Instru-
ments). The optics (e.g., plano−convex lenses, mirrors, etc.) for
collection of the rR data were purchased from Sigma-koki, Japan.
Electrochemical Measurements. The CV experiments were
performed on CH Instruments bipotentiostat models 700D and 610D.
A glassy carbon electrode was used as the working electrode. A
platinum wire was used as the counter electrode. The measurements
were made against an Ag/AgCl reference electrode with scan rates
varying from 50 to 500 mV. The solutions were comprised of 1 mM
complex and 100 mM tetrabutylammonium perchlorate (TBAP) as
the supporting electrolyte.
In our pursuit of a synthetic analogue of cyt P450, we have
been able to synthesize two thiolate-bound iron(III) porphyrin
complexes in which the porphyrin macrocycle and thiolate
functional group are held by a flexible linker (PSR or PPSR;
Figure 2). One of the 5C molecules (PPSR; Figure 2) has the
Synthesis and Characterization. The synthetic strategy is
described in detail in Scheme 1.
1. meso-Mono(o-5-bromovaleramidophenyl)triphenylporphyrin
(1). 5-Bromovaleroyl chloride (26 μL, 1.2 equiv) was dissolved in 5
mL of dry THF, added dropwise over a period of 30 min to a solution
of meso-mono(o-aminophenyl)triphenylporphyrin50 (100 mg, 0.158
mmol) in 20 mL of dry THF, and cooled to 0 °C. When the addition
was complete, the resulting solution turned green. Aqueous ammonia
was added dropwise until the solution became purple. The solution
was then poured into a separating funnel. A total 50 mL of CH2Cl2
was added and washed with 2 × 30 mL of 10% NaHCO3 and 2 × 30
mL of H2O. The organic layer was collected and dried over anhydrous
Na2SO4. The solvent was then evaporated on a rotary evaporator, and
the residue was purified by chromatography on a column packed with
60−120 mesh silica gel in hexane using 80% DCM/hexane mixture as
the eluent. Yield: 119.62 mg (∼95%).
Figure 2. Schematic diagrams of the PSR, PPSR, and PIM complexes.
Anal. Calcd for C49H38BrN5O: C, 74.24; H, 4.83; N, 8.83. Found:
1
C, 73.34; H, 4.95, N, 8.72. H NMR (CDCl3): δ −2.72 (s, 2H), 1.07
thiolate arm sterically protected in a hydrophobic environment,
and the other has the thiolate arm exposed (PSR; Figure 2). To
understand the effect of thiolate on the properties of the Fe
center, an analogous complex is synthesized in which the same
linker bears an imidazole headgroup (PIM; Figure 2) instead of
a thiolate.50−52 In this study, we use electron paramagnetic
resonance (EPR), resonance Raman (rR), cyclic voltammetry
(CV), and density functional theory (DFT) calculations to
investigate the electronic structure of these complexes.
(m, 2H), 1.19 (m, 2H), 1.34 (m, 2H), 2.75 (t, 2H, J = 6.6 and 6.3 Hz),
6.74 (s, 1H), 7.54 (t, 1H, J = 7.2 and 7.5 Hz), 7.83 (m, 10H), 8.06 (d,
1H, J = 7.5 Hz), 8.23 (m, 6H), 8.72 (d, 1H, J = 8.4 Hz), 8.78 (d, 2H, J
= 4.8 Hz), 8.89 (s, 6H). ESI-MS (positive-ion mode, MeOH): m/z
792.34 (90%; [M]+).
2. meso-Mono(o-5-thioacetatovaleramidophenyl)-
triphenylporphyrin (2). Potassium thioacetate (17.2 mg, 1.2 equiv)
was added to the solution of 1 (100 mg, 0.126 mmol) taken in 25 mL
of dry and degassed DMF, and the reaction was refluxed for 8 h in the
dark under N2 atmosphere. The formation of the desired product was
monitored by TLC. After quenching the reaction mixture with H2O,
diethyl ether was added to collect the product in the organic layer.
Then it was dried over anhydrous Na2SO4. After removal of the
solvent, the product was purified by column chromatography using a
1% MeOH/DCM mixture as the eluent. Yield: 92.44 mg (∼93%).
EXPERIMENTAL DETAILS
■
Materials. Benzaldehyde (99%), 2-nitrobenzaldehyde (98%),
pyrrole (98%), 5-bromovaleroyl chloride (97%), 5-chlorovaleroyl
chloride (96%), potassium thioacetate (98%), ferrous bromide
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Scheme 1. General Synthetic Procedure
Anal. Calcd for C51H41N5O2S: C, 77.74; H, 5.24; N, 8.89. Found: C,
76.78; H, 5.62; N, 8.69. H NMR (CDCl3): δ −2.72 (s, 2H), 0.86−
0.96 (m, 4H), 1.35 (m, 2H), 1.872 (s, 3H), 2.2 (t, 2H, J = 4.2 Hz),
6.77 (s, 1H), 7.52 (t, 1H, J = 4.2 and 4.5 Hz), 7.69−7.89 (m, 10H),
8.04 (d, 1H, J = 4.2 Hz), 8.18−8.24 (m, 6H), 8.71 (d, 1H, J = 4.8 Hz),
8.78 (d, 2H, J = 2.7 Hz), 8.89 (s, 6H). ESI-MS (positive-ion mode,
CH3CN): m/z 788.35 (100%; [MH]+).
Na2SO4 and was purified by column chromatography using a 95:5 dry
DCM/MeOH mixture in a N2 atmosphere. Yield: 86 mg (∼90%).
Anal. Calcd for C49H37BrFeN5OS: C, 66.90; H, 4.24; N, 7.96.
Found: C, 65.84; H, 4.90; N, 7.26. ESI-MS (positive-ion mode,
CH3CN): m/z 799.06 (10%; [M]+), 840.98 (25%; [M]+ + CH3CN),
683 (100%; [M]+ − tail linker).
1
UV−vis (THF): λmax/nm = 372, 418, 508, 579.
UV−vis (THF): λmax/nm = 418, 515, 550, 595, 650.
5 . m e s o - M o n o ( o - 5 - t h i o l a t e v a l e r a m i d o p h e n y l ) -
triphenylporphyrinatoiron (PSR; 5). Thiol-functionalized porphyrin
4 (86 mg, 0.107 mmol) was dissolved in 15 mL of dry and degassed
MeOH in the presence of activated K2CO3. The solution was stirred
overnight in a glovebox. The reaction mixture was then filtered using
Whatmann 40, and the filtrate was evaporated and dried using a
vacuum pump inside the glovebox. Yield: 77 mg (∼90%).
3. meso-Mono(o-5-thioacetatovaleramidophenyl)-
triphenylporphyrinatoiron(III) Bromide (3). Thioacetate-function-
alized porphyrin 2 (100 mg, 0.126 mmol) was dissolved in 15 mL
of dry and degassed THF. 2,4,6-Collidine (34 μL, 2 equiv) was added
to this solution followed by the addition of FeBr2 (109 mg, 4 equiv).
The solution was stirred overnight in a glovebox in the dark. The
reaction mixture was quenched by H2O followed by the addition of
DCM. The organic layer was washed with a brine solution and was
collected and dried over anhydrous Na2SO4. The solvent was removed
on a rotary evaporator, and the residue was separated by
chromatography on a column packed with 60−120 mesh silica gel
in CH2Cl2. The column was eluted with a 4% MeOH/CH2Cl2
mixture. Yield: 98 mg (∼92%).
UV−vis (THF): λmax/nm = 332, 414, 574.
6. meso-Mono[o-5-(N-imidazolyl)valeramidophenyl]-
triphenylporphyrin (6). Collman et al. first reported an imidazole
tail porphyrin.50 Here we synthesized PIM by a different approach. 1
(100 mg, 0.125 mmol) was dissolved in 10 mL of degassed DMF
under N2 atmosphere. A solution of 18 mg of imidazole in 2 mL of
DMF was added in the presence of K2CO3, and the resulting solution
was allowed to reflux under a N2 atmosphere in the dark for 8 h. The
solution was then poured into 100 mL of diethyl ether, washed with
100 mL of H2O, and dried over anhydrous Na2SO4. The solvent was
evaporated on a rotary evaporator and the residue separated by flash
chromatography (5% MeOH in CH2Cl2). Yield: 90 mg (90%).
Anal. Calcd for C52H41N7O: C, 80.08; H, 5.30; N, 12.57. Found: C,
Anal. Calcd for C51H39BrFeN5O2S: C, 66.46; H, 4.26; N, 7.60.
Found: C, 66.06; H, 4.52; N, 7.12. ESI-MS (positive-ion mode,
CH3CN): m/z 841.24 (100%; [M]+).
UV−vis (THF): λmax/nm = 345, 414, 508, 576.
4 . m e s o - M o n o ( o - 5 - t h i o l v a l e r a m i d o p h e n y l ) -
triphenylporphyrinatoiron(III) Bromide (4). Thioacetate-function-
alized iron porphyrin 3 (100 mg, 0.118 mmol) was taken in 15 mL
of a degassed mixture of concentrated HCl and MeOH (1:14). The
solution was then refluxed under N2 atmosphere in the dark. The
reaction mixture was worked up with H2O and DCM. The organic
layer was washed with a brine solution. It was dried over anhydrous
1
77.94; H, 5.95, N, 10.72. H NMR (CDCl3): δ −2.64 (s, 2H), 0.2−3
[8H, −(CH2)4−], 7.7−7.79 (m, 15H), 7.8 (5H), 8.83 (3H), 8.79
(1H), 8.9 (7H), 8.96 (1H). ESI-MS (positive-ion mode, MeOH): m/z
780 (20%; [M]+).
UV−vis (CH2Cl2): λmax/nm = 420, 516, 551, 591, 647.
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7. meso-Mono[o-5-(N-imidazolyl)valeramidophenyl]-
triphenylporphyrinatoiron(III) Bromide. This compound was pre-
pared as described above for 3. Anal. Calcd for C52H39BrFeN7O: C,
68.36; H, 4.30; N, 10.73. Found: C, 67.05; H, 5.10; N, 9.94.
UV−vis (CH2Cl2): λmax/nm = 320, 416, 510, 567.
solution was stirred overnight in a glovebox. The reaction mixture was
filtered, and the filtrate was evaporated and dried by a vacuum pump
inside the box. Yield: 70 mg (90%). ESI-MS (positive-ion mode,
MeOH): m/z 1093.5742 (100%; [M]+).
Computational Details. All calculations were performed at the
IACS computer cluster using Gaussian 03 software.53 Both BP86 and
B3LYP functionals were used, and a mixed basis set with 6-311g* on
the Fe, N, O, and S atoms and 6-31g* on the C and H atoms was used
for optimization.54−57 For the final energy and ground-state
calculations, a 6-311+g* basis set on all atoms was used. Frequency
calculations were performed using the basis set used for optimization,
and no negative frequencies were found for the structures reported.
The Mulliken populations were analyzed using QMforge software.
1H NMR (CDCl3): δ −5.32 to −0.83 (−CH2− proton), 79.11−
81.12 (β-pyrrole proton).
8 . m e s o - M o n o ( o - 5 - c h l o r o v a l e r a m i d o p h e n y l ) -
triaminophenylporphyrin (8). To a solution of TAPP37 (100 mg,
0.148 mmol) taken in 20 mL of dry THF was added dropwise 5-
chlorovaleryl chloride (23 μL, 1.2 equiv), and the reaction mixture was
stirred for 1 h. To this reaction mixture were added dropwise DCM
and aqueous ammonia, and after workup, the organic layer was
collected, dried over anhydrous Na2SO4, and purified by column
chromatography using a 90% DCM/hexane mixture as the eluent.
Yield: 82 mg (∼70%).
RESULTS
■
Anal. Calcd for C64H65ClN8O4: C, 73.51; H, 6.27; N, 10.72. Found:
C, 72.25; H, 6.75; N, 10.35. ESI-MS (positive-ion mode, CH3CN): m/
z 793 (100%; [M]+).
A. EPR. The X-band EPR data of the PSR, PIM, and PPSR
complexes in weakly coordinating solvents like THF or DCM
9 . m e s o - T r i s ( α , α , α - o - p i v a l a m i d o p h e n y l - α - o - 5 -
chlorovaleramidophenyl)porphyrin (9). To the solution of 8 (100
mg, 0.125 mmol) in 20 mL of dry THF, (1.2 equiv × 3) of pyridine
was added followed by the dropwise addition of pivolyl chloride (70
μL, 4.5 equiv) and the reaction mixture was stirred for 1 h. DCM and
aqueous ammonia were added to this reaction mixture and after
workup, the organic layer was collected, dried over anhydrous Na2SO4,
and purified by column chromatography using a 1% MeOH/DCM
mixture as the eluent. Yield: 105 mg (∼80%).
Anal. Calcd for C64H65ClN8O4: C, 73.51; H, 6.27; N, 10.72. Found:
C, 72.25; H, 6.75; N, 10.35. ESI-MS (positive-ion mode, CH3CN): m/
1
z 1045 (100%; [M]+). H NMR (CDCl3): δ −2.62 (s, 2H), 0.06 (s,
6H), 0.25 (s, 18H), 0.4 (s, 3H), 1.87 (m, 4H), 2.8 (m, 4H), 7.1 (m,
2H), 7.47 (m, 6H), 7.93 (m, 8H), 8.71 (m, 4H), 8.84 (s, 8H).
1 0. me s o- T r is ( α, α , α -o-pi v al am id op henyl - α - o -5 -
thioacetatovaleramidophenyl)porphyrin (10). To the solution of 9
(100 mg, 0.095 mmol) taken in 20 mL of dry and degassed acetone,
potassium thioacetate (13 mg, 1.2 equiv) was added and the reaction
was stirred for 8 h under N2 atmosphere. After evaporation of the
solvent in a rotary evaporator, the reaction was quenched with H2O,
and DCM was added to collect the product in the organic layer. It was
dried over anhydrous Na2SO4 and purified by column chromatography
using a 5% MeOH/DCM mixture. Yield: 72.67 mg (∼70%).
Anal. Calcd for C66H68N8O5S: C, 73.04; H, 6.31; N, 10.32. Found:
C, 72.05; H, 6.80; N, 10.02. ESI-MS (positive-ion mode, MeOH): m/z
1085.37 (100%; [M]+).
Figure 3. X-band EPR data of the PSR, PIM, and PPSR complexes in
THF at 77 K, 10 mW power, and gain 1 × 104.
show an axial HS signal at g = 6 (Figure 3), indicative of a S =
5/2 ground state (GS). The EPR data of the precursor thiol
complex (PSHR) also shows a HS signal under the same
conditions (Figure S-17 in the Supporting Information).58
In a coordinating solvent like MeOH, the PIM complex
shows an axial EPR signal with rhombic distortion (g = 6.2 and
5.4), suggesting the formation of a MeOH-bound complex
5
(PIM/MeOH) but retaining its S = /2 GS (Figure 4, green).
1 1. me s o- T r is ( α, α , α -o-pi v al am id op henyl - α - o -5 -
thioacetatovaleramidophenyl)porphyrinatoiron(III) Bromide (11).
To the solution of thioacetate-functionalized porphyrin 10 (100 mg,
0.092 mmol) in 15 mL of dry and degassed THF, 2,4,6-collidine was
added (25 μL, 2 equiv) followed by the addition of FeBr2 (80 mg, 4
equiv) to this solution. The solution was stirred overnight in a
glovebox. The reaction mixture was worked up by H2O followed by
the addition of DCM. The organic layer was washed with a brine
solution and collected. It was dried over anhydrous Na2SO4 and
purified by column chromatography using a 93:7 dry DCM/MeOH
mixture in a N2 atmosphere. Yield: 89 mg (85%).
1 2. me s o- T r is ( α, α , α -o-pi v al am id op henyl - α - o -5 -
thiolvaleramidophenyl)porphyrinatoiron(III) Bromide (12). Thioa-
cetate-functionalized iron porphyrin 11 (100 mg, 0.087 mmol) was
dissolved in 15 mL of a degassed mixture of concentrated HCl and
MeOH (1:14) and refuxed overnight under N2 atmosphere in the
dark. The reaction mixture was poured into H2O followed by the
addition of DCM. The organic layer was collected and dried over
anhydrous Na2SO4. It was purified by column chromatography using a
95:5 dry DCM/MeOH mixture in N2 atmosphere. Yield: 77 mg
(80%).
Figure 4. X-band EPR data of the PSR, PPSR, and PIM complexes in
MeOH at 77 K, 10 mW power, and gain 1 × 104.
Therefore, the PIM complex mimics the coordination and spin-
state properties of histidine-coordinated enzyme active sites,
e.g., hemoglobin, cytochrome c oxidase, etc.; i.e., the 5C and
solvent-bound 6C states are both HS. On the contrary, both
thiolate-bound complexes, PSR and PPSR, show an S = 1/2 GS
at 77 K in a coordinating solvent like MeOH (Figure 4, blue
1 3. me s o- T r is ( α, α , α -o-pi v al am id op henyl - α - o -5 -
thiolatevaleramidophenyl)porphyrinatoiron(III) (13). To the sol-
ution of thiol-functionalized porphyrin 12 (77 mg, 0.069 mmol) in 15
mL of dry and degassed MeOH, activated K2CO3 was added. The
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and red). The HS 5C PSR and PPSR complexes are also readily
converted to their LS analogue upon the addition of 5−10%
MeOH (v/v) to their THF solutions. The g values of the LS
PSR and PPSR complexes are similar to those reported for
several cyt P450 models and the oxidized resting state of cyt
P450 (Table 1).59 The rhombicity of the LS S = /2 signal,
1
Table 1. EPR Parameters for the Heme Thiolate Complexes
spin
g1
g2
g3
V/λ
1
cyt P450
/
2.45
2.49
2.50
2.26
2.16
2.16
1.91
1.90
1.89
4.59
4.07
3.94
2
1
PPSR in MeOH
PSR in MeOH
/
2
1
/
2
calculated using the Taylor analysis,60 is similar to those
calculated for resting cyt P450 and is consistent with the
presence of a strong π-aniosotropic ligand like thiolate.61 Thus,
5
PSR and PPSR form S = /2 species in a weakly coordinating
1
solvent and S = /2 in a coordinating solvent like MeOH. This
mimics the GS property of cyt P450, where the 5C substrate-
bound state is S = 5/2, while the resting 6C H2O-bound state is
1
S = /2. Because the linker used to attach the thiolate and
1
imidazole are the same in these complexes, the S = /2 GS of
the 6C MeOH-bound PSR/PPSR complexes relative to the S =
5/2 GS of the PIM/MeOH complex must derive from an
intrinsic electronic structure difference between these com-
plexes (vide infra).
Figure 5. rR data in the (A) high-energy region (1300−1600 cm−1)
and rR data in the (B) low-energy region (300−800 cm−1). Laser
excitation wavelength = 413.1 nm; power = 10 mW.
B. rR. rR is a powerful tool that has been extensively used to
diagnose the oxidation state, ligation, and spin state of iron
porphyrin complexes.62 Exciting the intense Soret transition
observed in the chromophores yields vibrational information of
this macrocycle. Further, the direct coordination of a ligand can
be established by observing the corresponding metal−ligand
vibration. Only a very few reports of Fe−S vibrations in
thiolate-bound iron(III) porphyrin complexes exist in the
literature.63
The low-temperature (77 K) rR data of the PSR complex in
THF show that the oxidation- and spin-state marker ν4 and ν2
bands are at 1361 and 1554 cm−1 (Figure 5A, red), respectively.
The rR data of the PIM complex in DCM show that the ν4 and
ν2 bands are at 1360 and 1550 cm−1 (Figure 5A, black),
respectively.64 However, the rR spectrum of the PSR complex
in MeOH shows that the ν4 and ν2 bands are at 1369 and 1567
cm−1, respectively (Figure 5A, blue). These values indicate that
the Fe center in the PIM and PSR complexes in THF are HS
FeIII, while the Fe center in PSR in MeOH is LS FeIII,
consistent with the EPR data (Figure 4).62
Table 2. Selected Fe−S Modes of Synthetic Heme Thiolate
Models and Native P450 Complexes
complex
PSR in THF
HS/LS
νFe−S (cm−1
)
ref
HS
HS
HS
HS
LS
369
366
350
356
this work
42
Higuchi’s complex SR
cyt P450cam (substrate-bound)
cyt P450BM3
66, 67
65, 68
this work
42
PSR in MeOH
361, 421, 465
394
Higuchi’s complex 1
LS
in DCM and the S = 5/2 PSR in THF complexes, respectively.69
The Fe−Npyr vibration reflects the relative donor strengths of
the axial ligands between complexes having the same spin
5
states. The data suggest that the S = /2 PIM complex, which
has an axial imidazole ligand, has a stronger Fe−Npyr vibration
5
(400 cm−1) relative to the S = /2 PSR (391 cm−1) complex,
which has a thiolate axial ligand, indicating that the thiolate is a
much better donor than imidazole. DFT calculations have been
utilized to understand this effect in detail (vide infra).
In the low-frequency region, new vibrations are observed for
the thiolate-bound S = /2 PSR/MeOH complex (Figure 5B,
Note that, in general, Fe−S vibrations have only been
observed by using excitation in the UV region (330−360
nm).42,65 However, here the rR data suggest that the Fe−S
vibrations are possibly observed by exciting the Soret band.
This implies mixing of the porphyrin and the Fe−S bonding
orbitals in these complexes (vide infra).
C. CV. The PSR complex in MeOH shows two oxidation
reduction processes (Figure 6, red). The quasi-reversible wave
with E1/2 of −0.49 V (i.e., −0.3 V vs NHE) represents the
FeIII/II couple, consistent with the values reported for the
resting cyt P450 (−0.2 V vs NHE) and related LS
models.15,42,70 There is also a one-electron process at −1.09
V, possibly representing the reduction of the porphyrin ring (P)
to an anion radical species (P•−).71 In THF solvent, the FeIII/II
E1/2 of the PSR complex is −0.56 V. The P/P•− process is
irreversible in this solvent and is observed around −0.9 V. The
1
blue), at 340, 361, 421, 465, 676, and 770 cm−1, which are not
observed for the MeOH-bound PIM complex. This suggests
that these vibrations possibly originate because of thiolate
coordination to iron(III) porphyrin. The vibrations in the range
of 350−470 cm−1 may have contribution from the FeIII−S
stretching mode (Table 2), while those in the range of 650−
800 cm−1 may have contribution from the C−S stretching
mode.42,65,63 While confirmed assignment of these vibrations
will require isotopic substitution, DFT calculations support
5
these tentative assignments (vide infra). Similarly, the S = /2
PSR complex in THF shows additional vibrations at 336 and
369 cm−1 and at 624, 679, and 765 cm−1. The ν8 vibrations,
which represent the Fe−Npyr (Fe−pyrrole nitrogen) symmetric
5
stretch, are observed at 400 and 391 cm−1 for the S = /2 PIM
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and these values do not vary significantly between func-
tionals.19,42,44,45,74 The optimized bond lengths of PIM agree
reasonably well with the values reported for HS imidazole-
bound iron porphyrin complexes.61 In general, the Fe−Npyr and
Fe−L (where L = axial ligand) distances are shorter in the LS
complexes. The Fe−Npyr bonds are longer by 0.03 Å in the HS
thiolate-bound PSR complex relative to the HS imidazole-
bound PIM complex, indicating a weaker Fe−Npyr bond in the
former.
ii. Vibrations. The calculated vibrational frequencies (using
both BP86 and B3LYP) are listed in Table 4. The calculations
indicate that the BP86 functional reproduces (Table 4) the
experimentally observed symmetric intraligand modes for the
thiolate-bound complexes with good accuracy (within 10
cm−1). The predicted values for the imidazole linker are lower
than the experimental values by 7−30 cm−1. Note that,
although the absolute values of the error are large, the percent
errors are within 2−3% of the experimental values. The
calculations reproduce the experimentally observed increase in
the ν4 and ν2 vibrations from 1361 to 1367 cm−1 and from 1550
to 1566 cm−1 associated with the change of the spin state from
HS to LS. These also reproduce the experimentally observed
relative magnitudes in the ν8 vibrations (i.e., the Fe−Npyr
stretch) of the HS complexes, i.e., PIM > PIM/MeOH >
PSR. Thus, the BP86 functional is used for all other calculations
presented in the manuscript.
For the 5C HS PSR model, vibrations at 410, 369, and 308
cm−1 have contributions from the Fe−S stretching mode. This
suggests that the unique vibration observed at 369 cm−1 in the
rR spectrum of PSR in THF (experimentally 5C HS) may
represent a Fe−S vibration. These values are in the range of
Fe−S vibrations reported for cyt P450 and related model
complexes that vary between 300 and 360 cm−1.42,65,66 The C−
S stretching mode is calculated to be at 629 cm−1, and indeed
there are several weak vibrations observed for the PSR (not
PIM) complex in this region. The calculations indicate that
vibrations at 446, 414, 375, and 319 cm−1 have components of
the Fe−S stretching mode in the LS MeOH-bound PSR model.
The Fe−S vibrations of LS heme thiolate complexes are
reported to be between 360 and 390 cm−1, consistent with the
values observed here.42 The C−S vibration is calculated to be at
637 cm−1. Several vibrations are observed in the rR spectrum of
the PSR/MeOH complex only in these regions, consistent with
the calculations. Note that while the DFT calculations support
these tentative assignments, these assignments can only be
confirmed by appropriate isotopic substitution.
Figure 6. CV of the PSR (red) and PIM (blue) complexes in a MeOH
solvent having 100 mM TBAP as the supporting electrolyte, glassy
carbon as the working electrode, scan rate = 1 V/s, and Ag/AgCl-
saturated KCl as the reference electrode. The individual redox
processes are described in the text.
reason for this phenomenon is unclear at this point. The
difference between E1/2 observed in THF and MeOH have
contribution from the spin state (PSR is HS in THF and LS in
MeOH from the 77 K EPR data) and hydrogen bonding from
the MeOH solvent to the thiolate ligands, which are known to
tune reduction potentials up by as much as 300 mV.43,46 For
the PIM complex, in a noncoordinating THF solvent, the
FeIII/II couple is observed at −0.13 V and the one-electron P/
P•− redox couple is observed at −1.14 V (Figure 6, blue). Thus,
the presence of the axial thiolate ligand in PSR lowers the
FeIII/II potential by 0.5 V relative to the neutral imidazole ligand
in PIM. Note that the ligand framework, spin state, and solvent
remain the same between PIM and PSR; this shift in E0 mainly
reflects the effect of substituting a neutral imidazole axial ligand
with an anionic axial thiolate ligand.
D. DFT Calculations. I. Geometry. Geometry-optimized
DFT calculations provide insight into the geometric and
electronic structures of these complexes. (Geometry optimiza-
tions were performed in Gaussian 03 using both B3LYP and
BP86 functionals.54−57,73) The optimized Fe−S bond lengths
(Table 3) agree with those reported for HS (2.3−2.4 Å) and LS
(2.20−2.25 Å) thiolate-bound heme complexes and active sites,
Table 3. Optimized Bond Lengths (Å) of the Models and
Relevant Mulliken72 Charges
iii. Electronic Structure. A. 5C. The GS wave function of the
5C PIM and PSR complexes show a square-pyramidal ligand
field (Figure 8), as reported for similar complexes.19,43,75 The
Fe−
Fe−
Fe−
model
method
BP86
N/S
Npyr
Xaxial
qFe
qN/S
qpyr
2
2
dx −y orbital is calculated to be highest in energy for both of
these models because of its strong interaction with the
equatorial N atoms. The imidazole ligand forms a σ bond
S =5/2
PIM
2.08
2.05
1.52
−0.58
−0.74
S =5/2
PIM/
BP86
2.17
2.08
2.28
2.02
1.61
1.33
1.53
−0.52
−0.47
−0.49
−0.71
−0.66
−0.76
2
2
with the dz orbital (Figure 8, left). The dz orbital also has its
electron density in the XY plane, which allows overlap of the
porphyrin N atoms with it, as reflected by ∼7% porphyrin N
MeOH
S =1/2
PIM/
BP86
1.94
2.33
2.00
2.08
character in the dz orbital (Table 5).43 Note that there is ∼3%
2
MeOH
mixing between the imidazole N orbitals and the t2 orbitals on
the Fe, i.e., very weak π overlap. Alternatively, the thiolate
ligand has a π-bonding interaction with the dyz orbital and a
S =5/2
B3LYP
PSR
BP86
2.31
2.23
2.09
2.00
1.41
1.28
−0.41
−0.33
−0.71
−0.69
pseudo-σ-bonding interaction with the dz orbital.19,43 As a
2
S =1/2
PSR/
MeOH
B3LYP
2.18
2.15
result, the d orbitals with antibonding ligand contributions are
at higher energy in PSR relative to these orbitals of the PIM
complex (the energies of these orbitals are normalized with
BP86
2.19
2.00
1.16
−0.25
−0.64
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Table 4. Calculated Vibrational Frequencies (cm−1)
PSR
PSR/MeOH
BP86
PIM
PIM/MeOH
mode
rR
BP86
B3LYP
rR
B3LYP
rR
BP86
rR
BP86
ν2
1554
1451
1361
391
1551
1447
1351
378
1604
1496
1395
392
1566
1563
1458
1359
395
1615
1508
1403
392
1551
1461
1361
400
1533
1427
1353
383
1550
1446
1361
398
1526
1415
1348
382
ν3
ν4
1366
387
340
361
421
465
673
ν8
Fe−S
336
308
305
319
319
369
369
319
375
359
410
369
414
377
446
456
C−S
624
679
629
640
637
653
Figure 7. DFT-optimized structures of complexes (A) PIM, (B) PIM/MeOH, (C) PSR, and (D) PSR/MeOH.
respect to the dxy orbital, which is nonbonding in both
complexes). The molecular orbital (MO) contributions (Table
5) reveal that the dyz orbital in the PSR model has 28% S3p
Furthermore, the strong pseudo-σ-bonding interaction
between the dz orbital and the thiolate 3p orbital transfers
2
significant charge density from RS− to Fe, lowering its Zeff,
which raises its energy and allows it to mix with a low-lying π*
orbital of the porphyrin ring (Figure 8, highlighted with a green
box). Note that this mixing is also enhanced by the fact that the
Fe is ∼0.45 Å above the porphyrin plane in the optimized
structure of the PSR complex (Figure 7) relative to 0.3 Å in the
optimized structure of the PIM complex (Figure 7). This
2
mixed into it, while the dz orbital has 16% S3p mixed into it; i.e.,
there is significant covalent interaction between Fe and S (both
2
σ and π). On the contrary, the dz orbital of the PIM complex
has only 7% N contribution. Thus, the Fe−S bond is a lot more
2
2
covalent than the Fe−imidazole bond. Note that the dx −y
orbital of the PIM complex is at a higher energy than that of
the PSR complex. This reflects a weakening of the Fe−Npyr
bonds in the PSR complex relative to the PIM complex. The
calculated Mulliken charges (qFe) suggest a lower Zeff on the Fe
in the PSR complex due to the covalent donation by the
thiolate relative to the Fe in the PIM complex (Table 3; qFe).
The higher Zeff on the Fe in the PIM complex will result in
lower-energy unoccupied Fe3d orbitals and allows stronger σ-
bonding interaction with the occupied anionic porphyrin donor
ligand orbitals (in-plane pyrrole orbitals). The higher Zeff on the
Fe will also enhance its electrostatic interaction with the
dianionic porphyrin ligand. Overall, these will lead to strong
Fe−Npyr bonds in the PIM complex relative to the PSR
complex. This is evident from the shorter Fe−Npyr bond
lengths and the stronger, i.e., Fe−Npyr, vibrations.
2
mixing transfers both Fe dz and S3p (because it is involved in σ
2
bonding with the dz orbital) character into the porphyrin π*
orbital; i.e., the Fe−S σ* orbital gains some porphyrin π*
nature and vice versa. This electronic structure may explain the
observation of Fe−S and C−S vibrations upon excitation of the
porphyrin π → π* transitions (Soret band).
B. 6C. The GS wave function of the HS 6C PIM/MeOH
complex is very similar to that of the PIM complex. It has a
distorted octahedral ligand field. Compared to the 5C PIM
2
complex, the dz orbital in the 6C PIM/MeOH complex has a
slightly elevated energy because of interaction with the MeOH
ligand.
The GS wave function of the 6C LS PSR/MeOH complex
5
shows a normal t2 e0 electronic structure. The singly occupied
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structure of the 6C HS PIM/MeOH and 6C LS PSR/MeOH
complexes is the extent of back-bonding from the occupied t2
orbital to a low-lying unoccupied porphyrin π* orbital (Figure
10). In the PIM/MeOH complex ∼4.8% of the occupied Fe t2
Figure 10. Orbital overlap (PSR) between filled orbitals of Fe (dxz)
and the π* orbital of porphyrin for the 6C PSR/MeOH complex.
character is mixed into this porphyrin π* orbital, while in the
PSR/MeOH complex ∼8.2% of the occupied Fe t2 character is
mixed into this porphyrin π* orbital. This is due to the higher
energies of the Fe3d orbital of the PSR/MeOH complex relative
to the PIM/MeOH complex because greater covalent charge
donation from the anionic thiolate ligand to the Fe in the PSR/
MeOH complex (26% π + 2 × 26% σ = ∼0.8 e) lowers the Zeff
on the Fe and increases the energy of the 3d manifold. This
allows better interaction with the t2 and π* orbitals. Note that
the dyz orbital, which is raised up in energy by strong π-bonding
interaction with the thiolate, carries the unpaired electron.
Figure 8. Calculated (BP86) GS MO diagram of 5C PIM (left) and
PSR (right) complexes. Only unoccupied β orbitals are shown. The π*
orbital interacting with dz is highlighted in the center.
2
Table 5. MO Compositions of the Unoccupied β Orbitals for
the 5C HS Complexes
orbital contributions
complex
PIM
orbital
Fe3d
L
N2p
2
2
dx −y
66.51
66.6
0.00
6.69
0.91
2.29
0.08
0.00
6.51
15.87
28.64
1.03
0.42
16.49
6.19
2.89
3.1
DISCUSSION
2
dz
■
dyz
dxz
dxy
72.1
One imidazole-bound and two thiolate-bound iron porphyrin
complexes are reported. These ligands are covalently attached
to the porphyrin macrocycle using the same flexible linker.
While several imidazole- and thiolate-bound ferric models are
reported in the literature, their comparison is often complicated
by differences in their ligand structures. Here, all these
complexes have the same linker and vary only in the
coordinating headgroup, i.e., thiolate versus imidazole. The
results show that a thiolate ligand tunes the reduction potential
down by 500 mV, weakens the Fe−Npyr bond of these
complexes, and stabilizes a LS state in the 6C form relative to
an imidazole ligand.
71.22
85.49
68.01
22.74
45.34
53.48
70.54
89.47
1.32
14.92
7.17
5.84
1.8
2
2
PSR
dx −y
π*
2
dz
dyz
dxz
dxy
1.52
0.42
dyz t2 orbital forms a π bond (Figure 9, A), while the
2
unoccupied dz e orbital forms a σ bond (Figure 9, B) with the
Geometry-optimized DFT calculations are used to gain
insight into the origin of these differences. The calculations
reproduce the experimental observations, and the GS wave
function indicates that thiolate forms a strong covalent Fe−S
bond; i.e., the metal 3d orbitals are strongly mixed with S3p
orbitals. This is consistent with previous reports.43,76 As a result
of this interaction, significant electron density is transferred
from the thiolate to the Fe. This reduces the Zeff on the Fe,
which shifts the Fe 3d manifold up in energy. The increase of
the Fe3d orbital energies reduces its interaction with the
occupied donor ligand orbitals of porphyrin, i.e., a weaker Fe−
Npyr interaction. This manifests itself through longer Fe−Npyr
thiolate ligand. Because the e set of orbitals are unoccupied (in
the HS state, it is half-occupied), both Fe−S and Fe−Npyr
σ
bonds have a bond order of 1 relative to 0.5 in the HS state.
Hence, these bonds are much shorter in the LS state relative to
the HS state (Table 3). A noticeable difference in the electronic
2
2
bonds, lower Fe−Npyr vibrations (ν8), and lower dx −y orbital
energies for the PSR complex relative to the PIM complex. The
increase of the Fe3d orbital energies in the PSR complex
facilitate its oxidation (i.e., removal of an electron from the
HOMO), consistent with the experimentally observed lowering
of the FeIII/II reduction potential relative to the PIM complex.
Figure 9. MO overlap (PSR) between (A) dyz and S3p (π bonding)
and (B) dz and S3p (σ bonding) for the 6C PSR/MeOH complex.
2
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Figure 11. MO interaction between filled orbitals of metal (t2) with empty orbitals of porphyrin (π*) and S3p orbital. The green lines represent the
singly occupied 3d orbitals, the red lines represent the unoccupied 3d and π* orbitals, and the black lines represent the occupied 3d orbitals.
Another interesting consequence of thiolate coordination is
stabilization of a LS GS in the PSR/MeOH complex in contrast
to a HS GS observed in the imidazole-coordinated PIM/
MeOH complex. The same spin states are observed in the
heme active sites; histidine-bound 6C sites with a trans H2O
ligand are HS, while cysteine-bound 6C sites with a trans H2O
ligand are LS. Considering the fact that a thiolate is a weak-field
ligand (i.e., it acts as both σ and π donors), the LS state of a 6C
axial thiolate-bound iron(III) porphyrin is rather unexpected. In
fact, the 6C axial thiolate-bound nonheme active site of SOR
and its synthetic model complexes have a HS GS.48 The Fe−S
bond of this active site is quite covalent, and its covalency is
comparable to the covalency of the Fe−S bond of cyt P450 in
its resting HS state.31 The MO diagram of the 6C PSR/MeOH
complex reveals that charge transfer from thiolate to FeIII raises
the energy of the Fe3d manifold due to lowering of the Zeff of
the Fe. This allows back-bonding interaction between the
occupied t2 orbitals on the Fe and the low-lying unoccupied
porphyrin π* orbitals. The extent of back-bonding (measured
by the amount of occupied t2 character mixed into the
unoccupied ligand π* orbitals) is calculated to be 1.8 times
more in a 6C LS PSR/MeOH model relative to a 6C LS PIM/
MeOH complex. This back-bonding interaction stabilizes the t2
orbitals involved (dxz and dyz) and thus stabilizes the LS GS
state in a thiolate-bound PSR/MeOH complex. The relative
position of these porphyrin π* orbitals will definitely vary
depending on the nature of the substitution on the peripheral C
atoms. Thus, the extent of back-bonding, i.e., the extent of
stabilization of the LS GS, may vary depending on the nature of
the porphyrin ligand. Note that the back-bonding is not
observed in the HS complexes because (1) the t2 orbitals are
half-occupied and (2) the covalent charge transfer is much
more in the LS state because the Fe−S bond lengths are shorter
and the e orbitals are completely unoccupied in the LS state
and not half-occupied as in the HS state.
Thus, the thiolate ligand tunes the electronic structure of a
HS iron(III) poprphyrin via direct orbital interactions (Figure
2
11), where it raises the energy of the dz and one of the t2
orbitals (dyz in the nomenclature used here) because of pseudo-
σ- and π-bonding interactions, respectively. The covalent
charge donation from the anionic thiolate ligand also raises
the energy of the 3d manifold in general (Figure 11, middle)
relative to that of a neutral imidazole ligand. This increase of
the Fe3d manifold affects bonding interactions of the Fe3d
orbitals that the thiolate does not have any direct overlap
with it. The increase in energy of the dxy orbital (the redox-
active orbital in the HS complexes) lowers E0 of these HS
complexes (as observed experimentally), and the increase in
2
2
energy of the dx −y orbital weakens its interaction with the
occupied lower-energy porphyrin pyrrole orbitals weakening
the Fe−Npyr bond (longer Fe−N bonds in optimized structure
and lower ν8 vibration) of the HS complexes. Further, the
increase in energy of the noninteracting t2 orbital along the Fe−
S bond (dxz in the nomenclature used here) increases its back-
bonding interaction with a low-lying porphyrin π* orbital
(Figure 11, right) and lowers its energy. As a result of
destabilization of the dz2 orbital due to pseudo-σ-bonding
interaction with thiolate and the trans axial MeOH ligand and
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stabilization of the dxz orbital due to back-bonding, the 6C
thiolate-bound PSR/MeOH complex stabilizes a LS GS; an
electronic structure contribution possibly is present in many
thiolate-bound porphyrin active sites and synthetic complexes.
(26) Kumar, D.; Sastry, G. N.; de Visser, S. P. Chem.Eur. J. 2011,
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(27) de Visser, S. P.; Latifi, R.; Tahsini, L.; Nam, W.-W. Chem.
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ASSOCIATED CONTENT
* Supporting Information
■
(28) Kumar, D.; Karamzadeh, B.; Sastry, G. N.; de Visser, S. P. J. Am.
Chem. Soc. 2010, 132, 7656−7667.
S
Characterization of the complexes, EPR data of thiol
complexes, rR data of thiol complexes, and optimized
geometries. This material is available free of charge via the
Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
*E-mail: icad@iacs.res.in.
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work is funded by Council of Scientific and Industrial
Research (CSIR), India [Grant 01(2412)10/EMr-II], and the
Department of Science and Technology, India (Grant SR/IC-
35/2009). P.K.D. and S.C. acknowledge a CSIR JRF fellowship.
S.S. acknowledges the IACS integrated Ph.D. program.
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Inorganic Chemistry
Article
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