Conversion of electron configuration of iron ion through core contraction of porphyrin: Implications for heme distortion

Article abstract of DOI:10.1021/ol303419b

It was demonstrated experimentally that nonplanar iron porphyrins can be induced to undergo a conversion in their electronic configuration to form a cross-hybrid transition by compressing the macrocyclic core size for the central metal ion. A series of mo

Full text of DOI:10.1021/ol303419b

ORGANIC
LETTERS
2013
Vol. 15, No. 3
606–609
Conversion of Electron Configuration
of Iron Ion through Core Contraction
of Porphyrin: Implications for Heme Distortion
Zaichun Zhou,* Qiuhua Liu, Ziqiang Yan, Ge Long, Xi Zhang, Chenzhong Cao,* and
Rongqing Jiang
School of Chemistry and Chemical Engineering, and Key Laboratory of Theoretical
Chemistry and Molecular Simulation of Ministry of Education, Hunan University of
Science and Technology, Xiangtan 411201, China
zhouzaichun@hnust.edu.cn; czcao@hnust.edu.cn
Received December 15, 2012
ABSTRACT
It was demonstrated experimentally that nonplanar iron porphyrins can be induced to undergo a conversion in their electronic configuration to
form a cross-hybrid transition by compressing the macrocyclic core size for the central metal ion. A series of monostrapped iron porphyrins were
used as model systems, and their electronic properties were probed using electron spin resonance and differential spectral analyses. These
results indicate that the formation of a cross-hybrid transition stage is related to the stability of the high-valence state and potent oxidizing ability
of the central iron ion.
For some time, it was generally believed that the func-
tions of the heme depended on the peripheral environment
of the macrocycle,1,2 and very little attention was given to
the impact of changes in the macrocycle itself. Recent
studies, however, have suggested that conformational
changes in the heme macrocycle may play a more impor-
tant role in heme function than that of the surrounding
environment.3,4 The nonplanarity of heme has been
recognized as a structural feature that is conserved in
specific proteins.5 The potent oxidizing ability of heme
is capable of hydroxylating inactivated CÀH bonds.6
The nonplanarity of porphyrins has received considerable
attention because of its significance in proteins,7 and
nonplanar porphyrins also exhibit a significant number of
specific properties including catalytic ability,8 tunable axial
binding,9 and significant spectral red shifts.10 Distortions of
this type are energetically unfavorable, suggesting that they
are crucial to the functions of heme and porphyrins.11
In our more recent report,12 we clarified the role of the
macrocyclic deformation modes and distortion degree in
heme for a series of ruffle-type 5,15-10,20-distrapped free-
base porphyrins and a dome-type capped porphyrin. The
results indicated that the free 4-N core in these two types of
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Biochemistry 2005, 44, 12690–12699.
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r
10.1021/ol303419b
Published on Web 01/16/2013
2013 American Chemical Society

nonplanar systems exhibited an opposing trend as the
degree of distortion increased, in that they took on a larger
size range than the free diameter of the iron ion.13
compressing the 4-N core in size. The electronic properties
of six monostrapped iron porphyrins have been probed
using the differential spectra and electron spin resonance
(ESR) method. A radical occurred when a 4-N electron
pair partially occupied the 3dz2 orbital of the central iron
ion, leading to the formation of a cross-hybrid transition.
These findings revealed that the occurrence of the transi-
tion stage was related to the stability of the high-valence
state and potent oxidizing ability of the central iron ion.
These findings provided some theoretical understanding
as to how distorted heme can stabilize the unligated Fe(II)
oxidationstate14 and alsogeneratethehigh-valentiron(V)-
oxo complex15 by changing its deformation modes and
adjusting its distortion degree. Unfortunately, however,
these synthetic distrapped-type porphyrins cannot be met-
alized under the existing conditions because the two straps
block this process, and changes to the electronic properties
of the central metal following core contraction can there-
fore not be explored experimentally.12
Scheme 1. Model Compounds: Free-Base Porphyrins 1À6,
Their Iron 1-Fe to 6-Fe and Zinc Complexes 1-Zn to 6-Zn
Figure 1. Differential spectra of the strapped iron porphyrins
1-Fe to 6-Fe to the corresponding zinc complexes 1-Zn to 6-Zn
at the Soret band in a CHCl3 solution (∼2.0 Â 10À6 M) at 293 K.
aΔλmax is the spectral shift of the maxima between each iron
porphyrin (e.g., 1-Fe) and its corresponding zinc one (1-Zn).
The dotted line represents the predicted trend.
The differential spectra obtained from a comparison of
the iron and zinc porphyrins can systematically deduct
their spectral shift from size difference of metals.19 The
conversion process was reflected in their absorptive
spectra.20 The spectral shift of a distorted porphyrin
provides a means of following changes in the ground
energy level.10 For the iron porphyrins, 1-Fe to 6-Fe, the
spectral shifts did not exhibit a continuous trend and
present an inflection point at nC = 4.
The differential value, Δλmax, represents the spectral
shift between the iron porphyrin and the corresponding
zinc porphyrin (Figure 1). For compounds 2-Fe to 6-Fe,
the electronic spectra showed a regular red shift under a
low degree of distortion (nC > 4), whereas compound 1-Fe
exhibited a ∼5 nm deviation from the extended trend line
based on the curve for compounds 2-Fe to 6-Fe. This
deviation indicated an increase of ∼3 kJ/mol for the energy
level. Inspection of the graph revealed that the line can also
be divided into three sections (I, II, and III).
We developed an interest in what would happen if the
core sizebecamelessthanthe minimum value ofthe central
free metal ions. The macrocyclic distortion and resulting
core contraction can result in changes in the electronic and
magnetic properties of the central iron ion16 and a spectral
shift for the porphyrin ring.17,18 Three series of mono-
strapped nonplanar porphyrins10 in their free-base forms
1À6, their iron complexes 1-Fe to 6-Fe, and their zinc
complexes 1-Zn to 6-Zn (Scheme 1) were selected as
replaceable model systems of the ruffle-type porphyrins
for the above target.
In the current report, we have demonstrated experimen-
tally that nonplanar iron porphyrins can be induced to
generate a conversion in the electronic configuration and
form a cross-hybrid transition of the central metal ion by
(13) Haynes, W. M. Handbook of Chemistry and Physics, 91st ed.;
CRC Press: Boca Raton, FL, 2010; section 9, p 18, and section 12, p 11.
(14) Olea, C., Jr.; Boon, E. M.; Pellicena, P.; Kuriyan, J.; Marletta,
M. A. ACS Chem. Biol. 2008, 3, 703–710.
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J. A.; Horner, J. H.; Makris, T. M.; Sligar, S. G. J. Am. Chem. Soc. 2006,
128, 4580–4581.
The crystal structures of the model compounds revealed
that their macrocycles adopted a ruffle-like deformation
due to the shrinkage caused by the straps, and the core size
became smaller as the straps were shortened. Furthermore,
(16) Christoforidis, K. C.; Louloudi, M.; Milaeva, E. R.; Deligiannakis,
Y. J. Catal. 2010, 270, 153–162.
˚
the cavity diameter of compound 1-Fe was 3.930 A and
(17) Groves, J. T.; Haushalter, R. C.; Nakamura, M.; Nemo, T. E.;
Evans, B. J. J. Am. Chem. Soc. 1981, 103, 2884–2286.
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(19) Kulcsar, A.; Saltiel, J.; Zimanyi, L. J. Am. Chem. Soc. 2001, 123,
3332–3340.
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Org. Lett., Vol. 15, No. 3, 2013
607

Figure 2. Crystal structures of compounds 1-Fe to 6-Fe (strap is from (CH2)3 to (CH2)8). The symbol, LNN, is the averaged length between
the diagonal N atoms in the porphyrin center. The substituents, tert-butyl group, and peripheral protons have been omitted for clarity.
therefore less than the minimum value of free diameter
(LNN = 3.94 A) of a iron ion.13 The cavity parameters for
˚
the six compounds, 1-Fe to 6-Fe, are shown in Figure 2.
An early report demonstrated that the porphyrin core
can be expanded or contracted by regulating the spin state
of the nickel(II) ion within the porphyrin.21,22 It remained
unclear, however, whether the electronic spin state of the
metal ion could, in turn, be converted during the contrac-
tion of the core. For the iron(III) porphyrins 1-Fe to 6-Fe,
the core size tended to increase as the nC value increased, as
evidenced by a plot of LNN against nC (Figure 3). The size
contraction appeared as two independent trends depending
on whether there was an odd or even number of carbon
˚
atoms in the strap. The core size of compound 1-Fe (3.930 A)
˚
appeared as a clear deviation (∼0.02 A) from the trend line
Figure 3. Relationship of the core size (LNN) to the number of
derived from the two curves. A transition stage occurred
between 1-Fe and 2-Fe, outlining a change in the trend
(black line), which also implied that that a core size value
carbon atoms (nC) in the straps according to the crystal struc-
tures of compounds 1-Fe to 6-Fe in Figure 2. The dotted line
represents the predicted trend.
˚
of ∼3.95 A represented a critical size in the conversion of the
electron configuration of the iron ion. The black trend line
was subsequently divided into three separate stages that
corresponded to the outer (I), inner (II), and cross-hybrid
stages (III), which was completely consistent with three
stages encountered during the differential spectra (Figure 1).
Any conversion in the electronic configuration in this
context inevitably leads to a change in some of the spectral
properties.16,23 Further information relating to the impact
of the core size on the conversion of the electronic config-
uration and formation of a cross-hybrid transition was
obtained from the ESR results. ESR measurements for the
toluene solution of 1-Fe to 6-Fe were performed in inert
gas at 130 K, effectively avoiding intermolecular electron
exchange interactions.
occurred, resulting in the formation of a cross-hybrid
transition in the central metal ion (Figure 4). A possible
electron exchange between the outer 4dxy orbital and the
inner 3dz2 one will take place under full core contraction;
that is, a lone pair electrons occupied in the 4dxy orbital is
transferred to the 3dz2 one, and the original unpaired
2
electron in the 3dz orbital is repelled to either localize
in the 4dxy one or delocalize in the conjugation macro-
cycle. A marked radical signal (* in Figure 4) was
obtained for compound 1-Fe and can be attributed to
the delocalization of the unpaired electron. It was
thought that the 4-N unit effectively maintained the
outer sp2d hybrid mode in compounds 3-Fe to 6-Fe
and completely changed to the inner dsp2 form in com-
pound 1-Fe. A new signal (g = 2.2), however, was observed
exclusively in compound 1-Fe, which can be attributed to
the repulsion of the 4-N electron pair to the 3d electron
resulting in the formation of a metastable state. For com-
pound 2-Fe, it can be thought that the 4-N unit existed in a
mixed sp2dTdsp2 form.
The ESR results for the six current compounds indicated
that the conversion of the electronic configuration
(21) Duval, H.; Bulach, V.; Fischer, J.; Weiss, R. Inorg. Chem. 1999,
38, 5495–5501.
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J.-P.; Nelson, N. Y.; Smith, K. M.; Fajer, J. Res. Chem. Intermed. 2002,
28, 741–759.
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The ESR spectra of all of the samples contained
the high-spin (HS) Fe(III) (S = 5/2) feature (marked
608
Org. Lett., Vol. 15, No. 3, 2013

˚
LNN difference of 0.08 A between the Fe(III) and Fe(IV)
porphyrins with the same strap size (see Supporting
Information). This difference was relative to the deviation
observed in the crystal results, although the value is much
larger (Figure 3). Both of the ions possessed the d5 and d4
configurations, and their 4-N unit would consequently
adopt an outer sp2d and inner dsp2 hybrid mode. The
higher valence ion (e.g., Fe(IV)) required a smaller 4-N
cavity that could, in turn, stabilize the higher valence iron
ion Fe(IV).
Note that the deviation in the central metal ion from the
4-N plane could effectively offset any increase in the
electron cloud density in these ruffle-like strapped com-
pounds, which would be apt to maintain the Fe(III)
valence throughout the core contraction. While the occur-
renceofa deviation would be difficultinthe ruffleor saddle
porphyrins, the dominant deformations in heme, because
of the equivalent features in two sides of the macrocycle,
would effectively drive the removal of an electron to
produce a higher valence, Fe(IV).
Macrocyclic deformation of porphyrins is a nonsponta-
neous process, in that the formation of a cross-hybrid
transition is energetically unfavorable. This is the critical
difference between the current discussion and existing
organometallic theories.28,29 For example, the formation
of a cross-spin state28 can provide low-energy pathways
for otherwise difficult processes because of spin-crossing
effects. The formation of a cross-hybrid transition there-
fore requires a special deformation structure (e.g., the macro-
cyclic distortion of a porphyrin), whereas the cross-spin state
can form in common organometallic systems.
In conclusion, iron porphyrins can be induced to change
their 3d electronic configuration and form a cross-hybrid
transition by contracting their core size. The significance of
the transition stage lies in the observation that a repelled 3d
electron (as a radical) tends to leave and a stable high-
valent iron material is formed when the core contracts; the
electron willreturnto its original 3d orbital, and the central
ion maintains the low-valent state if the core recovers in
size. Our findings provide an insight into the unique
biochemical functions of heme and also add to our current
understanding of theories in bioinorganic chemistry.
Figure 4. ESR spectra of the single crystal of iron porphyrins
1-Fe to 6-Fe and the central metallic hybrid mode. The insets
represent the determined temperature and solvent, and the red
symbol (*) denotes the radical.
by g = ∼6.0).16,24,25 The signal (g = 6.0) for compound
1-Fe was derived from the complete transfer of the 4-N
electron pair to a 3dz2 orbital and the formation of a new
Fe(III) spin state, which was different from those for the
other fivecompounds. The formation ofa radical provided
evidence for the formation of an active electron under the
core contraction conditions and the occurrence of Com-
pound I, a cation radical, in the heme cycle during macro-
cyclic deformation,15,26 which guarantees the potent
oxidizing ability of the central iron ion. The ESR results
effectively consolidated these results when they were deter-
mined from the solid or from a solution at room tempera-
ture (see Supporting Information S9ÀS13).
A larger Δλmax value was related to a larger changein the
ground energy level (ΔE). These spectralshiftsandchanges
in the energy level indicated that the conversion of config-
uration required the macrocycle to possess a suitable 4-N
cavity and thatthe formation ofthe cross-hybrid transition
needed a much lower energy than that of the inner dsp2
state (Figure 1).
The formation of such a transition stage and the stability
of the high-valence central iron ions were also assessed
using DFT calculations.27 The measured Fe(IV)ÀN bond
length13 was smaller than that of a lower valence Fe(III)ÀN
bond. The computational resultsrevealedthatthere wasan
Acknowledgment. This work was supported by the
National Natural Science Foundation of China
(No. 21071051), the Key Project of Chinese Ministry of
Education (No. 211121), the Scientific Research Fund of
Hunan Provincial Education Department (No. 10B031),
and Prof. Qingxiang Guo of the University of Science and
Technology of China.
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nance “EMR of Paramagnetic Molecules”; Berliner, L. J., Reuben, J., Eds.;
Plenum Press: New York, 1993; Vol. 13, pp 1À55.
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Cador, O.; Guizouarn, T.; Boitrel, B. Inorg. Chem. 2010, 49, 7536–
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Inorg. Chem. 2010, 49, 3098–3100.
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Mechanism and Biochemistry; Ortiz de Montellano, P. R., Ed.; Plenum:
New York, 1995; pp 3À48.
Supporting Information Available. Crystal structures,
experimental procedures, and characterization of com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
(27) Liptak, M. D.; Wen, X.; Bren, K. L. J. Am. Chem. Soc. 2010, 132,
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The authors declare no competing financial interest.
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