Recognition of imidazoles by strapped zinc(II) porphyrin receptors: Insight into the induced-fit mechanism

Article abstract of DOI:10.1021/ic701590x

Imidazole-porphyrin coordination has become an important tool in the design of self-assembled materials. A combination of spectrophotometric and stopped-flow techniques has been used to gain insight into the control of imidazole binding in the distal pocket of phenanthroline-strapped porphyrins. The binding studies of a variety of imidazole substrates in combination with both hindered and accessible receptors have permitted the determination of the thermodynamic and kinetic parameters associated with the imidazole binding.

Full text of DOI:10.1021/ic701590x

Inorg. Chem. 2007, 46, 9534−9536
Recognition of Imidazoles by Strapped Zinc(II) Porphyrin Receptors:
Insight into the Induced-Fit Mechanism
Jeremy Brandel,† Ali Trabolsi,† Fre´de´ric Melin,‡ Mourad Elhabiri,† Jean Weiss,*,‡ and
Anne-Marie Albrecht-Gary*,†
Laboratoire de Physico-Chimie Bioinorganique, ULP-CNRS (UMR 7177), Institut de Chimie,
ECPM, 25 rue Becquerel, 67200 Strasbourg, France, and Laboratoire de Chimie des Ligands a`
Architecture Controˆle´e, ULP-CNRS (UMR 7177), Institut de Chimie, 4 rue Blaise Pascal,
67000 Strasbourg, France
Received August 9, 2007
Imidazole
−
porphyrin coordination has become an important tool
Once established, the recognition of imidazoles offered
an opportunity to gain insight into the self-assembly process,
especially its thermodynamic and kinetic parameters. Thus,
2,9-diphenyl-1,10-phenanthroline-strapped porphyrins ZnL1
and ZnL2 and substituted imidazoles S1-S5 were chosen
to identify the key parameters controlling the proximal/
distal10 recognition of the substrates (Figure 1).2 The resor-
cinol ether L2 was initially prepared as a synthetic interme-
diate and offered the opportunity to address the influence of
in the design of self-assembled materials. A combination of
spectrophotometric and stopped-flow techniques has been used
to gain insight into the control of imidazole binding in the distal
pocket of phenanthroline-strapped porphyrins. The binding studies
of a variety of imidazole substrates in combination with both
hindered and accessible receptors have permitted the determination
of the thermodynamic and kinetic parameters associated with the
imidazole binding.
(2) For recent examples, see: (a) Nomoto, A.; Mitsuoka, H.; Oseki, H.;
Kobuke, Y. Chem. Commun. 2002, 1074-1075. (b) Nomoto, A.;
Kobuke, Y. Chem. Commun. 2002, 1104-1105. (c) Phillips-
McNaughton, K.; Groves, J. T. Org. Lett. 2003, 5, 1829-1832. (d)
Kuramochi, Y.; Satake, A.; Kobuke, Y. J. Am. Chem. Soc. 2004, 126,
8668-8669. (e) Takahashi, R.; Kobuke, Y. J. Org. Chem. 2005, 70,
2745-2753. (f) Furutsu, D.; Satake, A.; Kobuke, Y. Inorg. Chem.
2005, 44, 4460-4462. (g) Hwang, I. W.; Park, M.; Ahn, T. K.; Yoon,
Z. S.; Ko, D. M.; Kim, D.; Ito, F.; Ishibashi, Y.; Khan, S. R.;
Nagasawa, Y.; Miyasaka, H.; Ikeda, C.; Takahashi, R.; Ogawa, K.;
Satake, A.; Kobuke, Y. Chem.sEur. J. 2005, 11, 3753-3761. (h)
Shoji, O.; Tanaka, H.; Kawai, T.; Kobuke, Y. J. Am. Chem. Soc. 2005,
127, 8598-8599. (i) Hajjaj, F.; Yoon, Z. S.; Yoon, M. C.; Park, J.;
Satake, A.; Kim, D.; Kobuke, Y. J. Am. Chem. Soc. 2006, 128, 4612-
4623. (j) Wytko, J. A.; Weiss, J. In N4-Macrocyclic Metal Complexes;
Zagal, J., Bedioui, F., Dodelet, J. P., Eds.; Springer: New York, 2006;
Vol. 18, pp 63-250. (k) Satakea, A.; Shojia, O.; Kobuke, Y. J.
Organomet. Chem. 2007, 692, 635-644.
(3) (a) Paul, D.; Wytko, J. A.; Koepf, M.; Weiss, J. Inorg. Chem. 2002,
41, 3699. (b) Leray, I.; Valeur, B.; Paul, D.; Regnier, E.; Koepf, M.;
Wytko, J. A.; Boudon, C.; Weiss, J. Photochem. Photobiol. Sci. 2005,
4, 280-286.
(4) Koepf, M.; Trabolsi, A.; Elhabiri, M.; Wytko, J. A.; Albrecht-Gary,
A. M.; Weiss, J. Org. Lett. 2005, 7, 1279-1282.
(5) Froidevaux, J.; Ochsenbein, P.; Bonin, M.; Schenk, K.; Maltese, P.;
Gisselbrecht, J. P.; Weiss, J. J. Am. Chem. Soc. 1997, 119, 12362-
12363.
(6) (a) Melin, F.; Boudon, C.; Lo, M.; Schenk, K. J.; Bonin, M.;
Ochsenbein, P.; Gross, M.; Weiss, J. J. Porphyrins Phthalocyanines
2007, 11, 212-221. (b) Melin, F.; Choua, S.; Bernard, M.; Turek, P.;
Weiss, J. Inorg. Chem. 2006, 45, 10750-10757.
(7) Walker, F. A. Chem. ReV. 2004, 104, 589-616 and references cited
therein.
(8) (a) Fatin-Rouge, N.; Blanc, S.; Pfeil, A.; Rigault, A.; Albrecht-Gary,
A. M.; Lehn, J. M. HelV. Chim. Acta 2001, 84, 1694-1711. (b)
Hamacek, J.; Blanc, S.; Elhabiri, M.; Leize, E.; Van Dorsselaer, A.;
Piguet, C.; Albrecht-Gary, A. M. J. Am. Chem. Soc. 2003, 125, 1541-
1550. (c) Kalny, D.; Elhabiri, M.; Moav, T.; Vaskevich, A.; Rubinstein,
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1427.
The design of self-assembling multiporphyrin arrays and
networks makes extensive use of axial base coordination to
metalloporphyrins.1 In particular, axial imidazole binding to
zinc(II) porphyrins is an extremely powerful tool in the
formation of self-assembled, linear, and cyclic multiporphyrin
assemblies.2 Although we have described self-assembled
photodyads3 and linear porphyrin arrays,4 based on selective
distal binding of imidazole substrates in phenanthroline
(phen)-strapped porphyrins,5 these architectures were initially
designed as hemoprotein models.6 For both research fields,1
control over the fifth coordination of the metalloporphyrin
is a key parameter, and the behavior of zinc(II) porphyrins
versus nitrogen axial bases is commonly extrapolated to
pentacoordinated iron(II).7 Because of the labile nature of
the fifth N-Zn coordination bond, kinetic data, which are
essential to both deciphering the assembly mechanism8 and
understanding the distal site recognition process, are ex-
tremely scarce.9
* To whom correspondence should be addressed. E-mail: jweiss@
chimie.u-strasbg.fr (J.W.), amalbre@chimie.u-strasbg.fr (A.-M.A.-G.).
† Laboratoire de Physico-Chimie Bioinorganique.
‡ Laboratoire de Chimie des Ligands a` Architecture Controˆle´e.
(1) (a) Iengo, E.; Zangrando, E.; Alessio, E. Eur. J. Inorg. Chem. 2003,
2371-2384. (b) Wojaczynski, J.; Latos-Graz˘yn˜ski, L. Coord. Chem.
ReV. 2000, 204, 113-171. (c) Imamura, T.; Fukushima, K. Coord.
Chem. ReV. 2000, 198, 133-156. (d) Heitz, V.; Chambron, J. C.;
Sauvage, J. P. In The Porphyrin Handbook; Kadish, K. M., Smith, K.
M., Guilard, R., Eds.; Academic Press: New York, 2000; Vol. 6, pp
1-42. (e) Sanders, J. K. M. The Porphyrin Handbook; Kadish, K.
M., Smith, K. M., Guilard, R., Eds.; Academic Press: New York,
2000; Vol. 3, pp 347-368. (f) Haycock, R. A.; Hunter, C. A.; James,
D. A.; Michelsen, U.; Sutton, L. R. Org. Lett. 2000, 2, 2435-2438.
(9) Caldin, E.; Field, J. P. J. Chem. Soc., Faraday Trans. I 1982, 78,
1923-1935.
9534 Inorganic Chemistry, Vol. 46, No. 23, 2007
10.1021/ic701590x CCC: $37.00
© 2007 American Chemical Society
Published on Web 10/12/2007

COMMUNICATION
taken as an example of N1-substituted analogues, whereas
ZnTPP is a reference porphyrin receptor.
In agreement with previous reports, in the case of ZnTPP,
the data collected in Figure 2 mostly reflect electronic effects
of the substituents on the N3-heteroatom, which binds to
zinc(II). The association constants increase in the same order
as the pKa values.12 Substrates S3 and S4 are representative
examples because the electron-donating methyl group in S3
enhances the stability of the corresponding ZnTPP-S3
complex [log KZnTPP-S3 ) 4.9(1)]. The electron-withdrawing
phenyl substituent of S4 strongly destabilizes the ZnTPP-
S4 species [log KZnTPP-S4 ) 2.54(6)], confirming general
trends in the stability constants of zinc porphyrins with
N-axial bases.
Figure 1. Chemical structures of the phen-strapped zinc(II) receptors ZnL1
and ZnL2 and of the imidazole substrates S1-S5.
Imidazole S2 without a substituent either in position 2 or
in position 5 and substrate S5 with a bulky substituent in
position 5 are both stabilized in their interactions with ZnL1
and ZnL2 compared to those with ZnTPP (Figure 2).
Substrates S3 and S4, which are substituted in position 2,
also lead to more stable ZnL1 and ZnL2 complexes than with
ZnTPP (Figure 2).
Clearly, N1-unsubstituted imidazoles are strongly stabilized
by at least 1 order of magnitude in the presence of the phen
strap in both receptors ZnL1 and ZnL2 with respect to
ZnTPP. The binding of S2-S5 within the strap is shown
by the spectrophotometric changes at about 250-370 nm,
where the phen absorbs (see the Supporting Information).5,13
On the other hand, the binding of S1 by ZnL1 and ZnL2
does not affect the electronic spectra of the phen subunit
(see the Supporting Information). These data confirm the
proximal recognition of the N1-methyl derivative that is
unable to establish bifurcated hydrogen bonds with the phen
nitrogen atoms in the strap. The global trend is a significant
decrease in the stability of the complexes formed between
S1 and ZnL1 or ZnL2 in comparison to that of the S1-
ZnTPP complex (Figure 2).
Interestingly, comparison of the stabilities of ZnL1 and
ZnL2 imidazole complexes shows that the smallest substrate
S2 is more stable by about 1 order of magnitude with ZnL2
compared to ZnL1. This result accounts for an enhanced
inertness due to the bulky stoppers in meso positions (Figures
1 and 2). The low stability constant for ZnL2-S4 clearly
indicates that the fitting of the strapped porphyrins is reduced
when bulky 2-phenyl-1H-imidazole (S4) is combined with
the ZnL2 receptor. Although previous attempts to modulate
the affinity of the phen-strapped porphyrins for exogen
substrates were unsuccessful,13 destabilization by a factor of
nearly 50 is therefore observed when bulkiness is increased
both at the receptor’s meso position and at the imidazole’s
2 position. Thus, for the first time, the proximity of the bulky
resorcinol meso substituents, which control access to the
distal site, tunes the influence of the bifurcated hydrogen
bond established between the imidazole N1-H and the phen
strap. In the ZnTPP, ZnL1, and ZnL2 series, tools to control
the imidazole binding are gradually introduced with N-
coordination, hydrogen-bond positioning, and steric hin-
drance, all of which provide insight about their respective
role in the molecular recognition process.
Figure 2. Stability constants (log KZnL-S) of imidazoles S1-S5 with
strapped receptors ZnL1 and ZnL2. Solvent: 1,2-dichloroethane. T ) 25.0(2)
°C. Stability constants determined from UV-vis absorption and fluorescence
spectrophotometric titrations (see the Supporting Information). Uncertainties
) 3σ.
steric hindrance around the distal cavity, which was not
possible with previously obtained systems bearing meso-xylyl
substituents.13 Prior to detailed studies, previous studies
performed in dichloromethane were reproduced in 1,2-
dichloroethane. The latter solvent was preferred because of
its greater stability upon irradiation at high energies. Previous
studies in dichloromethane confronted us with the protonation
of free base porphyrins during UV-vis studies.3 As stated
hereafter, slightly higher stability constants were obtained
in dichloroethane, and the trend remains unchanged in the
case of L1 and valid in the case of L2.
Thus, the stability constants of a series of N1-unsubstituted
imidazoles (S2-S5; Figure 2) with zinc porphyrin receptors
ZnL1 and ZnL2 were determined using both absorption and
emission spectrophotometry (see the Supporting Informa-
tion).11 The substrates were selected to examine the effect
of substituent bulkiness in positions 2 and 5. Substrate S1 is
(10) For definition of distal and proximal binding sites, see: (a) Sage, J.
T.; Champion, P. M. Small Substrate Recognition in Heme Proteins.
In ComprehensiVe Supramolecular Chemistry; Suslick, K. S., Ed.;
Pergamon Press: Oxford, U.K., 1996; Vol. 5, pp 177-218. (b)
Momenteau, M.; Reed, C. A. Chem. ReV. 1994, 94, 659-698.
(11) Nappa, M.; Valentine, J. S. J. Am. Chem. Soc. 1978, 100, 5075-
5080.
(12) (a) Kadish, K. M.; Shiue, L. R.; Rhodes, R. K.; Bottomley, L. A.
Inorg. Chem. 1981, 20, 1274-1277. (b) Kadish, K. M.; Shiue, L. R.
Inorg. Chem. 1982, 21, 1112-1115. (c) Ogoshi, H.; Mizutani, T.;
Hayashi, T.; Kuroda, Y. The Porphyrin Handbook; Kadish, K. M.,
Smith, K. M., Guilard, R., Eds.; Academic Press: New York, 2000;
Vol. 6, pp 279-340.
(13) For ligand synthesis and X-ray characterization of several inclusion
complexes, see: Paul, D.; Melin, F.; Hirtz, C.; Wytko, J. A.;
Ochsenbein, P.; Bonin, M.; Schenk, K.; Maltese, P.; Weiss, J. Inorg.
Chem. 2003, 42, 3779-3787.
Inorganic Chemistry, Vol. 46, No. 23, 2007 9535

COMMUNICATION
Table 1. Stability and Rate Constants Relative to Pentacoordinated
Complexes with ZnL1 and ZnL2 a
strong steric interactions between S4 and the 2,6-dimethoxy-
phenyl groups lead to more labile complexes. In contrast,
the complexes formed with S3 and S5 are 1-2 orders of
magnitude more inert than those formed with ZnL1 because
of the stopper effect of the 2,6-dimethoxyphenyl substituents.
Substrate S4 exhibited the most striking behavior; there-
fore, the activation parameters for the ZnL1-S4 and ZnL2-
S4 complexes will be presented. For ZnL2, the activation
enthalpies for the formation and dissociation are comparable
with ∆Hq ) 74(4) kJ mol-1 and ∆Hq ) 71(3) kJ mol-1,
receptor
ZnL1
kf (M-1 s-1
ZnL2
log K kf (M-1 s-1
sub-
strate log K
)
kd (s-1
)
)
kd (s-1
)
S3 7.6(4)b
7.7(5)b
6.2(3)c 2.2(9) × 107 16(8)
7.6(4)c 3(2) × 106
0.07(3)
S4 3.92(7)b
2.3(3)b
3.2(2)c 2.0(7) × 104
1.4(2) 2.1(3)c 4.9(1) × 102 4.3(3)
S5 5.3(4)b
5.14(4)b
4.04(7)c 1.54(8) × 105 14(2)
4.5(1)c 2.0(3) × 104 0.65(9)
f
d
a Solvent: 1,2-dichloroethane. T ) 25.0(2) °C. Uncertainties ) 3σ. See
whereas the activation entropies are significantly different
the Supporting Information for detailed experiments. b Titrations. c Kinetics.
[∆Sq ) 53(12) J mol-1 K-1 and ∆Sqd ) 4(9) J mol-1 K-1].
f
The reaction is therefore entropically driven with ∆∆Sq )
49(15) J mol-1 K-1. An opposite and interesting situation is
found for the ZnL1-S4 complex, for which the formation
[∆Hq ) 42(2) kJ mol-1 and ∆Sq ) -26(6) J mol-1 K-1]
This prompted studies on the formation kinetics for
complexes formed between receptors ZnL1 and ZnL2 and
substrates S3-S5 (see the Supporting Information). For
substrates S1 and S2, the reactions were too fast to be
measured by the stopped-flow technique, in agreement with
kinetic data reported elsewhere9 for ZnTPP and S2 (kf )
3.2 × 109 M-1 s-1) in chlorobenzene. However, a single rate-
limiting step was observed for S3-S5 and led to the
determination of the bimolecular formation rate constant kf
and of the monomolecular dissociation constant kd. It is
noteworthy that the ratio kf/kd agrees well with the stability
constants of the corresponding complexes (Table 1).
For both receptors, kf drastically decreases with increasing
bulkiness of the substituents in position 2 of the imidazoles
(S3 and S4). Differences of about 3-4 orders of magnitude
are indeed observed between S3 and S4. More moderate
effects are observed for substrate S5 substituted in position
5. The kf sequence for the various substrates with the two
porphyrin hosts is S1, S29 > S3 > S5 > S4.
Moreover, it should be noted that the increase of the
bulkiness of the meso substituents of the receptors has a
moderate effect on kf for S3 and S5 (less than 1 order of
magnitude), whereas a decrease of about 2 orders of
magnitude is observed for S4. A strong steric hindrance in
the formation of ZnL2-S4 quite drastically decreases the
corresponding rate constant kf (about 2 orders of magnitude).
Regarding substrate S5, it is remarkable that, out of the two
possible tautomers that can exist in solution, the least stable
3H tautomer is bound to the zinc-strapped receptor.14 1H
NMR data (see the Supporting Information) obtained are in
agreement with this tautomeric change, which also accounts
for the decrease in the formation rate of S5.
f
f
and the dissociation [∆Hq ) 65(4) kJ mol-1 and ∆Sq
)
d
d
-28(12) J mol-1 K-1] activation parameters lead to an
enthalpically controlled reaction [∆∆Hq ) -23(2) kJ mol-1].
In the absence of strong steric interactions between S4 and
ZnL1, the reaction proceeds through an associative and
enthalpic mechanism. In contrast, the steric hindrance in
ZnL2 imposes drastic desolvation and significant conforma-
tional changes of both substrate S4 and receptor ZnL2. The
self-assembly mechanism is consequently dissociative and
entropically driven.
In conclusion, this study provides important kinetic and
thermodynamic insight on the modulation and control of
imidazole coordination with zinc porphyrins. In the perspec-
tive of porphyrin-based materials, high binding affinities
usually required for the cohesion of self-assembled material
should be paradoxically associated with moderate inertness,
which allows self-correction and thermodynamically con-
trolled assembling processes in solution and then further
transfer of self-assembled material from the solution to the
solid state. In this regard, this work distinguishes the specific
influences of steric hindrance requirements on the receptor
and the substrate. Steric hindrance ultimately determines the
associative or dissociative character of the imidazole binding
process. The bulkiness of the substituents slows down the
rate of the recognition process, while the inertness of the
imidazole-zinc(II) porphyrin species reflects additional
intramolecular interactions.
Acknowledgment. This work has been supported by the
Centre National de la Recherche Scientifique (UMR 7177),
the Faculte´ de Chimie, and the Universite´ Louis Pasteur
(Strasbourg, France). A.T., J.B., and F.M. thank the Ministe`re
de l’Enseignement Supe´rieur et de la Recherche for Ph.D.
fellowships. Thanks are expressed to Dr. J. A. Wytko for
fruitful discussions.
Finally, the most interesting feature concerns the inertness
of the imidazolyl complexes. The sequence of kd for ZnL1
is S3 > S5 > S4. The inertness increases when the substrates
are able to develop intramolecular interactions with the
metalloporphyrin receptors. For example, S4 and S3 were
found to form more inert edifices with receptor ZnL1 than
1H-imidazole did because of the additional π-π stacking
or CH-π interactions, for which evidence was obtained from
NMR or X-ray data with meso-xylyl substituents.5,8 When
the bulkiness of the meso substituents (ZnL2) increases,
Supporting Information Available: Experimental data, stability
constants, UV-vis spectrophotometric titrations, luminescence
titrations, kinetic studies, activation parameters, and histidine
complexation. This material is available free of charge via the
Internet at http://pubs.acs.org.
(14) Reynolds, W. F.; Peat, I. R.; Freedman, M. H.; Lyerla, J. R., Jr. J.
Am. Chem. Soc. 1973, 95, 328-331.
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