Opposing influences of ruffling and doming deformation on the 4-N cavity size of porphyrin macrocycles: The role of heme deformations revealed

Article abstract of DOI:10.1002/chem.201200722

Ruffle- and dome-type porphyrins were developed as model systems to investigate the role of deformation mode and degree of distortion in heme. Their crystal structures revealed that as the degree of distortion increases, cavity size can be contracted in t

Full text of DOI:10.1002/chem.201200722

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DOI: 10.1002/chem.201200722
Opposing Influences of Ruffling and Doming Deformation on the 4-N Cavity
Size of Porphyrin Macrocycles: The Role of Heme Deformations Revealed
Zaichun Zhou,* Min Shen, Chenzhong Cao, Qiuhua Liu, and Ziqiang Yan[a]
Nonplanar heme distortion has been recognized as a con-
served structural feature of particular proteins.[1,2] Most
recent computational study suggested that large-scale con-
formational change may play a more important role in the
biomolecular function of the B12-dependent enzyme than
was previously thought.[3] Although such conformational
changes are necessary for heme catalysis,[4,5] they are ener-
getically unfavorable,[1,6] and can lead to changes in the
oxygen affinity of heme proteins.[7,8] Furthermore, it can sta-
bilize the unligated low-valent iron(II) oxidation state and
generate a high-valent iron(V)–oxo complex,[9,10] which is
Nonplanar porphyrins show an observable out-of-plane
feature, and the occurrence of the out-of-plane deformations
is generally accompanied with the formation of in-plane
components in the macrocycle.[27] The ruf- and dom-type
porphyrins, taking on a typical out-of-plane deformation,
will also induce an in-plane change. According to geometric
analysis of the porphyrin macrocycle, the size of the 4-N
cavity will be contracted in the ruffling system, as the
degree of macrocyclic distortion increases (Figure 1). In con-
trast, the size of the cavity will be expanded in a doming de-
formation under the same increase of distortion degree.
a potent oxidant involved in the hydroxylation of inactivat-
[11]
À
ed C H bonds.
The role of heme distortion and its functional occurrence
remains complicated and unclear. For this reason, significant
attention has been focused on exploring the distortion prop-
erties of porphyrins, including their photophysical,[12–15] axial
ligation,[16–18] electron transfer,[19,20] molecular stimula-
tion,[4,21] redox potential,[22] and catalytic properties.[23] How-
ever, the impact of these deformations on the chemical
properties of porphyrins remains unclear.
The size change of 4-N cavity in heme macrocycle may
play a critical role in the functional occurrence. Several de-
formation modes of the heme macrocycle have been identi-
fied, including the dominant ruffling (ruf-), saddling (sad-),
occasional waving (wav-), doming (dom-), and propeller-like
(pro-) modes.[17,24] In all of these distortion modes, the dis-
tance among central four N atoms is inevitably changed due
to the deviation of pyrrole rings from their original copla-
narity. The ruf- and sad-deformation systems are commonly
used as model ones to simulate the role of heme distortion
and investigate spectral properties.[12,25,26] The dom-deforma-
tion, which is possibly short of a suitable sample with dom-
feature, however, has rarely been studied.[27]
Figure 1. The influence of ruffling (ruf-) and doming (dom-) deformation
modes on the 4-N cavity size in porphyrin macrocycles. The circle repre-
sents the free size of complexed metal ion.
À
The free M N (M=Mn, Fe, Co, Ni, Cu, or Zn ion with
a general valency) bond lengths were in the range of 1.97–
2.06 ꢀ,[28–30] providing a 4-N cavity of LNN =3.94–4.12 ꢀ
after complexation (LNN =average length of diagonal N
atoms in the porphyrin macrocycle). A planar porphyrin can
readily complex a M ion because of its large cavity size (LNN
ꢀ4.10 ꢀ). However, the question is, whether can the cavity
of a distorted porphyrin can be reduced to be smaller than
the minimum size (LNN <3.94 ꢀ) or enlarged to be larger
than the maximum size (LNN >4.12 ꢀ).
[a] Dr. Z. Zhou, M. Shen, Prof. C. Cao, Q. Liu, Z. Yan
School of Chemistry and Chemical Engineering,
Key Laboratory of Theoretical Chemistry, and
Molecular Simulation of Ministry of Education
Hunan University of Science and Technology
Taoyuan Road, Xiangtan, 411201(P.R. China)
Fax : (+)86-731-58290509
The macrocyclic deformation modes and the degree of
distortion in natural heme can be exactly adjusted with ease
by the coordination of its prosthetic group[31] and the regula-
tion of its side chains in proteins.[18,32] Whilst the develop-
ment of artificial nonplanar systems, including the distorted
E-mail: zhouzaichun@hnust.edu.cn
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201200722.
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periphery-crowded porphyrins[33,34] and the strapped (or bas-
keted) ones,[35,36] gave compounds with reliable deformation
modes capable of producing enough distortion, they cannot
meet the specificity of conformation and the invariability of
distortion degree required in this field. This significantly
limits a systematic investigation into the relationship of the
unique functions of heme to the deformation modes and dis-
tortion degree.
In this paper, we clarify the role of macrocyclic deforma-
tion modes and distortion degree in heme for a series of
5,15-10,20-di-strapped free-base porphyrins 1–5 and
a capped porphyrin 6 shown in Scheme 1, which have been
Scheme 1. Model compounds 5,15-10,20-di-strapped free-base porphyrins
1–5 and the capped porphyrin 6 with its copper(II) complex 6-Cu.
developed as model compounds with the ruf- and dom-de-
formation modes, respectively, to investigate the influence
of macrocyclic deformation on 4-N cavity size. Results indi-
cated that the free cavity in the two types of nonplanar por-
phyrins showed an opposing trend, as the degree of distor-
tion increased, implying a larger size range than that of the
free-metal ions in the fourth period. Furthermore, we found
that the spectral redshift of the nonplanar porphyrins was
closely related to the size of the macrocyclic cavity for of
the same deformation mode, providing an effective way to
track changes in macrocyclic cavity in size.
The crystal structures of the model compounds revealed
that the di-strapped macrocycles adopt a typical ruf-defor-
mation mode, whereas the capped examples adopt a typical
dom-form (Figure 2). These structures effectively avoid dis-
turbances due to substituent effects, and the exchange of
conformations is similar to those reported for peripherally
crowded porphyrins.[37] This represents a unique feature that
makes these structures distinguishable from many previously
reported artificial nonplanar systems.[12,38–40]
Figure 2. The crystal structures of compounds 3 (top), 5 (middle), and 6
(bottom).
size could completely exceed the free diameter of the cen-
tral metal ions (for fourth-period metals). For the di-strap-
ped porphyrins 1–5, the shorter alkyl straps induced a greater
degree of macrocyclic distortion. The length of the straps
could be flexibly adjusted by changing the number of
carbon atoms (NC from 8 to 4) providing a variation in the
LNN of 3.87 to 4.10 ꢀ (Table 1). A cavity size less than the
minimum value (LNN =3.94 ꢀ) could be achieved in the di-
strapped porphyrins 1 and 2. For the capped porphyrin 6,
the LNN was 4.17 ꢀ, which is a larger cavity size than the
maximum value (LNN =4.12 ꢀ).
The 4-N-cavity size could be reduced in the ruf-type mac-
rocycle and enlarged in the dom-type example by increasing
the degree of distortion. Furthermore, the variable cavity
The spectral redshift observed for the distorted porphyrin
is believed to originate from the hybrid orbital-deformation
effect.[12] The redshifts of the tetrapyrrole macrocycles are
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Chem. Eur. J. 2012, 18, 7675 – 7679

Influences of Macrocyclic Deformation on the Porphyrin Core
Table 1. The core size and the maxima of six model compounds.
COMMUNICATION
ly difficult, as the degree of distortion in a contraction-type
(e.g., ruf-) macrocycle increases.
Compound
1
2
3
4
5
6
LNN [ꢀ][a]
3.869[b]
446.2
3.929[b]
438.6
4.027
429.8
4.065[b]
422.8
4.099
423.6
4.168
432.0
A larger cavity (LNN >4.12 ꢀ) facilitates complexation in
an expansion-type (e.g., dom-) system, but both the expand-
ed cavity and the complexed metal ion tend to maintain
their original size. The copper(II) complex 6-Cu was pre-
pared to assess changes in the 4-N cavity size of dom-type
systems before and after complexation.[42] The crystal struc-
ture revealed contraction of the cavity (LNN =4.01 ꢀ) after
complexation, with a difference of 0.16 ꢀ (Figures 2 and 4).
lmax [nm][c]
[a] LNN is the averaged length between diagonal N atoms in the porphy-
rin center. [b] The values were acquired from DFT computation by ap-
plying the B3LYP hybrid functional with a 6-31G basis set (see the Sup-
porting Information). [c] lmax is the maxima at Soret band.
potentially useful indicators of ring nonplanarity. The elec-
tronic spectra of the model porphyrins 1–5 are significantly
redshifted (Figure 3). Their maxima were observed to red-
Figure 4. The crystal structure of compound 6-Cu. LNN is described in
Figure 2.
In recent report, the cavity contraction of another in-plane
type (sad-) copper(II) porphyrin complex (LNN =3.96 ꢀ) re-
vealed metal-ion shrinkage.[43] These facts illustrate that in
compound 6-Cu is a force balance between contraction of
the 4-N cavity and expansion of the copper ion. The crystal
structures of the synthetic porphyrins were further analyzed
by using a normal structural decomposition method for
quantifying their out-of-plane and in-plane distortions. (see
Figure S3 in the Supporting Information).
Changes in the size of the 4-N cavity directly influence
the electron cloud density of the complexed metal ion. The
smaller cavity presses against the central metal ion leading
to an increase in electron density (Figure 5 left), whereas an
expanded cavity relaxes the central ion leading to a reduc-
tion in density (Figure 5 right). When the change in density
reaches a certain level, an electron transfer including possi-
ble electronic rearrangement and transition in d orbitals,
occurs. The change in the electron-cloud density is easily de-
termined by DFT computation. As a consequence, the va-
Figure 3. Comparison of absorption spectra of the di-strapped porphyrins
1–5 and the capped porphyrin 6 at the Soret band in a CHCl3 solution
(ꢀ2.0ꢂ10À6 m) at 293 K.
shift over the range of l=422.8 to 446.2 nm (from 4, 5, 3, 2
to 1) at the Soret band, as the degree of distortion in-
creased. A good linear correlation was found between the
maxima and the LNN values for the ruf-type compounds (see
the Supporting Information). The maxima in the dom-type
compound
6 was observed at l=432.0 nm, implying
a degree of macrocyclic distortion between compounds 2
and 3 (Figure 3). The LNN value of these compounds
(4.17 ꢀ), however, was much greater than the maximum
value observed in the above described ruf-type compounds
and other planer-type compounds reported in the litera-
ture.[41] Therefore, changing size of the 4-N cavity cannot be
followed solely by the spectral redshift, and the deformation
mode of the macrocycle must also be considered. These
findings afford an indispensable additional tool in monitor-
ing the degree of distortion in porphyrin macrocycles.
In general, the size of the 4-N cavity can change during
complexation to match the ionic size of the metal. At the
same time, the complexing metal ion changes (including
compression or enlargement) to match the changed 4-N
cavity size. Theoretically, the complexation of metal ions to
the pressed cavity (LNN <3.94 ꢀ) should become increasing-
Figure 5. Stretching in the in-plane direction of the central metal ion (M
of the fourth period) in differential nonplanar modes.
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This work was supported by the National Natural Science Foundation of
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Keywords: biomimetic synthesis
·
heme proteins
·
macrocycles · metalloenzymes · porphyrinoids
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Received: March 4, 2012
Published online: May 15, 2012
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