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Abstract: We have designed anion receptor 4 based on
a conformationally labile bispyrrolylbenzene framework, the
conformation of which can be changed by appropriate
anionic stimuli. In the absence of fluoride anion, the pyrrole
moieties rotate freely at room temperature. However, when
the concentration of fluoride anion exceeds 2 equivalents,
the rotation of the pyrrole units slows down and the confor-
mation of the receptor changes to anti-anti. DFT calculations
have shown that this change is due to binding of a third
fluoride anion through CÀH interaction. Anion receptor 4
can also serve as a molecular logic gate. Anionic inputs such
as fluoride and dihydrogenphosphate allow the realization
of INHIBIT and NAND logic gate functions with absorption
and fluorescence as readouts, respectively.
Introduction
the hydrogen-bond donors became cooperatively directed to-
wards the anion. A similar mechanism was observed for boron
[16]
Recently, many attempts have been made to produce synthetic
molecules that can change conformation upon the application
complexes of dipyrrolyldiketones.
Motivated by the above considerations, we decided to
design a new conformationally labile anion-binding platform,
the conformation of which could be switched by appropriate
anionic stimuli. We anticipated that further functionalization of
[
1]
[2]
[3]
of various external stimuli, such as temperature, light, pH,
[
4]
or guest molecules. Molecules that can change conformation
are expected to find a broad range of applications in molecular
[
5]
[6]
[17]
machines, information processing at the molecular level,
the previously reported bispyrrolylbenzene building block
[
7]
[8]
catalysis, sensing, and so on. Many cellular processes are
controlled by receptors, which, after binding an appropriate
guest, undergo a conformational change, triggering a cascade
of biochemical processes. A typical example can be found in
with two additional hydrogen-bond donors (two amide
groups) would provide a flexible functional unit showing
guest-dependent conformation. Moreover, due to the four hy-
drogen-bond donors capable of switching, this system should
be effective even in a demanding solvent such as DMSO.
[
9]
the growth hormone receptor. A conformational change is
also crucial in the induced-fit model of enzyme–substrate inter-
[
10]
action. In this model, the initially weakly bound substrate
causes a conformational change of the enzyme, strengthening
its binding until the substrate is completely bound, thus stabi-
lizing the transition state of the catalyzed reaction. This differs
from the typical mechanism of guest-induced conformational
switching, in which the binding event causes the conforma-
tional change, and the degree of conformational change de-
pends on the guest concentration. Moreover, several enzymes
are activated in similar ways by binding additional small mole-
Results and Discussion
The bispyrrolylbenzene anion receptor 4 is readily available by
a short reaction sequence from commercially available 5-me-
thoxyisophthalic acid (Scheme 1). In the first step, the acid di-
chloride was generated from 5-methoxyisophthalic acid by
treatment with thionyl chloride; reaction of this acid dichloride
with allylamine yielded diamide 1 in 91% overall yield. Com-
pound 1 was then reacted with phosgene, and the product
was immediately treated with potassium tert-butylate to afford
the bispyrrolylbenzene derivative 2 in 49% yield. Compound 2
was acylated with trichloroacetyl chloride to form compound
[
11]
cules (cofactors).
Switches that can operate by reversible hydrogen binding of
an anionic stimulus seem to be particularly interesting in this
[12]
regard, owing to the importance of anions in Nature.
A
common anion-binding motif consists of hydrogen-bond
[
13]
donors, such as amide, urea, pyrrole, or indole. It has previ-
ously been shown that for diphenylacetylenes with both intra-
molecularly hydrogen-bonded urea and carbonyl groups, the
addition of chloride anion resulted in cleavage of the intramo-
lecular hydrogen bond and a change in the conformation of
[
14]
[15]
the receptor. Gale and co-workers investigated 2,7-disub-
stituted indole-based receptors, which, after the addition of
anionic guests, underwent a conformational change such that
[a] J. M. Granda, Dr. O. Staszewska-Krajewska, Prof. J. Jurczak
Institute of Organic Chemistry
Polish Academy of Sciences
Kasprzaka 44/52, 01-224 Warsaw (Poland)
Fax: (+48)22-632-66-81
E-mail: janusz.jurczak@icho.edu.pl
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201403116: Details of the experimental pro-
1
cedures and spectral data for new compounds, including images of H and
1
3
C NMR spectra, titration experiments and Job plots, and conformational
studies in solution.
Scheme 1. Synthesis of bispyrrolylbenzene anion receptor 4.
Chem. Eur. J. 2014, 20, 12790 – 12795
12791
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim