A triazole-bearing picket fence type nickel porphyrin as a cyanide selective allosteric host

Article abstract of DOI:10.1039/c5cc00809c

A triazole-bearing picket fence type nickel porphyrin (1) has been synthesized as a host compound for anion binding. Among the various anionic species examined, cyanide was the only one that affected a spectral change of 1. Moreover, 1 exhibited strong homotropic positive allosterism against cyanide binding due to an electronic effect as well as multiple hydrogen bonds formed between cyanide and the triazole groups. This journal is

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A Triazole-bearing picket fence type nickel porphyrin as a
cyanide selective allosteric host
Cite this: DOI: 10.1039/x0xx00000x
Kyeong-Im Hong, Hongsik Yoon, and Woo-Dong Jang*
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
www.rsc.org/
of the allosteric effect to signal amplification has scarcely been
established. In this communication, we report the design of a
triazole-bearing picket fence type nickel porphyrin (1; scheme 1) as
an allosteric host, which was utilized for the selective detection of
cyanide ion.
A triazole-bearing picket fence type nickel porphyrin (1) has
been synthesized as a host compound for anion binding.
Among various anionic species examined, cyanide was the
only one that affected a spectral change of 1. Moreover, 1
exhibited strong homotropic positive allosterism against
cyanide binding due to electronic effect as well as multiple
hydrogen bonds formed between cyanide and the triazole
groups.
Allosteric control is the most important and essential regulatory
mechanism for maintaining homeostasis in biological systems.1
Proteins with multiple guest-binding sites often display allosteric
binding phenomena.2 In this process, the first guest binding induces
a conformational change in the host protein, which influences the
binding affinity of additional guests. The binding of molecular
oxygen to hemoglobin is a representative example. Hemoglobin is an
assembly of four globular protein subunits. When the first oxygen
binds to a certain subunit, conformational rearrangement of the
whole protein is initiated, and the binding affinities of other subunits
to molecular oxygen are enhanced. Therefore, the oxygen binding
isotherm to hemoglobin becomes
a
sigmoidal curve.3 Such
cooperative binding is of great interest in the design of functional
materials.4 Chemists have tried to synthesize multiple guest binding
host systems to establish synthetic receptors displaying positive
allosterism because such positive allosteric systems could be utilized
for signal amplification.5 Recently, we have reported several
porphyrin-based allosteric host systems. Among these hosts, a
porphyrin-based molecular tweezer exhibited strong heterotopic
positive allosterism, while a porphyrin-based macrocycle exhibited
homotopic positive allosterism, which could be modulated by the
addition of additional guests.6 Although several porphyrin-based
allosteric host systems have been successfully designed, application
Scheme 1. Synthesis of 1. Reagents and conditions: i) n-BuLi, diisopropyl amine,
DMF, THF, -78 oC, 40 min; ii)TMS-acetylene, CuI, Pd(PPh3)2Cl2, Et3N, THF, in N2,
reflux; iii) propionic acid, reflux, 2 h; iv) Zn(OAc)2, CH2Cl2/MeOH, 25 oC, 6h; v)
tetrabutylammonium fluoride, THF, 25 oC,
2 h; vi) CuSO4 • 5H2O, sodium
ascorbate, THF/H2O, reflux, vii) TFA, CH2Cl2, 25 oC, 3 h; viii) Ni(II) acetylacetonate,
Toluene, reflux, 24 h.
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ChDeOmI:ic1a0.l10C3o9m/Cm5CuCn0i0c8a0t9ioCns
The synthesis of 1 is outlined in scheme 1. Briefly, a formyl group Therefore, we would expect 1:2 host-guest complex formation
was introduced to 1,3-dibromobenzene to obtain 3. A Sonogashira between 1 and cyanide ions, and the continuous variation method
coupling reaction between 3 and trimethylsilyl (TMS)-acetylene was (Job’s plot) indicated 1:2 binding of cyanide ions to 1 (Figure 1d).
conducted to obtain 4. Subsequently, the acid catalyzed condensation The strong binding affinity of cyanide to 1 can be explained by the
reaction of 4 with phenyldipyrrolemethane and subsequent oxidation formation of multiple C-H hydrogen bondings between triazole
resulted in the TMS-acetylene-bearing porphyrin (5). After groups and cyanide. To confirm the effect of triazole groups, cyanide
introduction of zinc ion (6) and deprotection of the TMS groups (7), was titrated to the tetraphenyl nickel porphyrin (NiTPP; Figure 2),
methyl-4-(azidomethyl)benzoate was introduced using
a CuI- structural analog of 1 without triazole groups. As result, NiTPP
catalyzed alkyne-azide click reaction to obtain 8. Finally, the central exhibited almost negligible absorption changes even 1000 eq. of
zinc ion of 8 was removed by acid treatment, and then nickel ion was cyanide addition in CH2Cl2, indicating the cooperative effect of
introduced to obtain 1.
hydrogen bondings to the coordination of cyanide (Figure S1).
Figure 2. Structure of
2 and NiTPP
Figure 1. Absorption and visual change of
1
by addition of anions in 0.5%
M) in the presence of various anions
(50 eq.), b) UV/Vis titration of CN- (0-50 eq.) to
(inset: binding isotherm
monitored at 442 nm), c) visual change by addition of various anions (50 eq.) to
d) Job’s plot of
with CN-.
H2O/MeCN. a) absorption spectra of
1 (6 µ
1
1
,
1
Figure 3. a) Concentration changes of
addition of cyanide, b) Hill plot of with cyanide.
1, 1 1
•CN-, and •2CN- upon successive
The UV/Vis absorption of 1 in 0.5% H2O/MeCN was measured. 1
exhibited strong Soret absorption at 416 nm and weak Q band
absorptions around 527 and 560 nm. As reported in our previous
paper, the triazole-bearing picket fence zinc porphyrin exhibited
very strong binding affinities to anionic guest species through the
cooperative effects of C-H hydrogen bonds and an axial ligation
interaction with the central zinc ion.7 Because a nickel ion in the
porphyrin center has relatively weaker Lewis acidic character than
zinc ion, we expected that the binding affinity of anionic species
would be relatively weaker with 1 than our previously reported
triazole-bearing picket fence type zinc porphyrin. To confirm the
binding affinities of anions to 1, various anions were added to 1 in
0.5% H2O/MeCN. As expected, most of the anionic species did not
show a UV/Vis absorption change upon addition of a large excess of
the anion (Figure 1a). Very interestingly, only the addition of
cyanide ion caused a strong spectral shift of 1, and in a UV/Vis
titration study, the Soret and Q band absorptions gradually red-
shifted with clear isosbestic points at 389, 428, 508, and 543 nm
(Figure 1b). The binding of cyanide to 1 could also be observed with
the naked eye due to a pronounced color change of the solution. As
shown in Figure 1c, the cyanide containing solution exhibited a
definite color change while the other solutions did not show any
color change. Unlike the zinc porphyrin, the nickel porphyrin can
accommodate two axial ligands to form a hexa-coordinate state.
1
Upon cyanide binding to 1, the binding isotherm exhibited a
sigmoidal curve (inset of Figure 1b), indicating positive allosteric
behavior in the binding of cyanide to 1. Figure 3a shows
concentration changes of 1, 1•CN-, and 1•2CN- upon successive
additions of cyanide, where the concentrations were estimated by
spectral analysis using commercially available Hypspec software.
This graph also clearly indicates 1 has a strong positive allosterism
for cyanide binding. The cyanide binding profile was analysed using
the nonlinear curve fitting method and the Hill equation: log(y/(1-y))
= n log[CN-] + log K, where y, K, and n are the fractional saturation
of host, the association constant, and the Hill coefficient,
respectively.8 The Hill plot (Figure 3b) showed a linear correlation
between log(y/(1-y)) and log[CN-] with a Hill coefficient of 1.96;
indicating a strong positive allosteric effect exists in cyanide binding.
The strong positive allosteric effect can be explained by electronic
effect as well as structural changes of 1. By the axial coordination of
CN-, 1 becomes paramagnetic hexacoordination state via less stable
square pyramidal pentacoordiation state. On the other hand, because
the triazole groups are attached to the meso phenyl rings of
porphyrin, the initial cyanide binding may change the dihedral
angles between the meso phenyl rings and the porphyrin plane to
form stable hydrogen bonds between cyanide and the triazole groups.
2 | Chem. Commun., 2015, 00, 1-3
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DOI: 10.1039/C5CC00809C
Such structural alteration would provide suitable space for access of
In summary, a triazole-bearing picket fence type nickel porphyrin
a second cyanide guest on the opposite face of the porphyrin. has been designed as a host compound for anion binding. The
Therefore, the binding affinity of the second cyanide may be greatly porphyrin exhibited strong homotropic positive allosterism with
enhanced. In fact, the first and second binding constants for cyanide cyanide binding due to multiple hydrogen bonds formed between
binding to 1 were estimated to be 2.4 x 104 and 6.8 x 104 M-1, cyanide and triazole groups. Such hosts exhibiting strong binding
respectively, using Hypspec. To confirm the effect of hydrogen affinity and an allosteric mechanism could be utilized for further
bonding on the second guest binding, we newly synthesized 2 applications in signal amplification.
(Figure 2), which has only two triazole groups in same face of nickel
porphyrin. Therefore, the first guest binding takes place with the aid
of C-H hydrogen bonding. However, the second guest binding
should be taken place without aid of hydrogen bonding. The first and
second binding constants and Hill coefficient for cyanide binding to
2 were estimated to 1.9 x 103, 1.2 x 103 and 1.22, respectively
(Figure S2 and Table S1). This result indicates that the electronic
effect also exist in the positive allosterism of CN- binding to 1 and 2.
Because 1 exhibited significantly increased Hill coefficient than 2,
the result obviously evidences the contribution of C-H hydrogen
bonding.
One merit of porphyrins is a typically strong extinction coefficient,
which enables colorimetric detection of cyanide ions at a low
detection limit. In figure 1b, the UV/Vis absorption spectrum of 1
continuously changed with respect to the concentration of cyanide
from 2 to 10 µM. From this data, a calibration curve for
quantification of cyanide concentration could be constructed. More
importantly, the change of Q band (from 510 to 580 nm) absorption
showed clear symmetry, which could be utilized for ratiometric
Notes and references
Department of Chemistry, Yonsei University, 50 Yonsei-ro, Seodaemun-
gu, Seoul 120-749, Korea, E-mail: wdjang@yonsei.ac.kr.
†
This work was supported by the Mid-Career Researcher Program
(2014R1A2A1A10051083) funded by the National Research Foundation
(NRF) of Korea.
Electronic Supplementary Information (ESI) available: [experimental
details]. See DOI: 10.1039/c000000x/
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Figure 4. NMR spectra of a)
1 and b) 1 with cyanide (10 eq.) in CD3CN, 400 MHz.
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