Selenoureas for anion binding as molecular logic gates

Article abstract of DOI:10.1039/c7cc07148e

The first example of a molecular logic gate based on selenourea/anion host-guest interaction that performs a ternary logic operation using an ¹H-NMR easy to read response output is described here. Selenoureas are very versatile receptors for anion binding, capable of forming both mono- and bi-coordinated adducts at room temperature in solution.

Full text of DOI:10.1039/c7cc07148e

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Selenoureas for anion binding as molecular logic gates.
Arianna Casula,a Paloma Begines,b Alexandre Bettoschi,a Josè G. Fernandez-Bolaños,b Francesco
Isaia, a Vito Lippolis,a Óscar López,b Giacomo Picci,a M. Andrea Scorciapino,c* and Claudia
Caltagironea*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
The first example of molecular logic gate based on selenoureas/ of 21-digit decimal numbers.9 Jurczak proposed a novel
anions host-guest interaction, that performs a ternary logic strategy for the classification of guest chirality based on the
operation using a 1H-NMR easy to read response output is combination of artificial neural networks and anion-receptor
described here. Selenoureas are very versatile receptors for anion chemistry using 1H-NMR spectroscopy.10
binding, capable of forming at room temperature in solution both Urea and thiourea moieties have been widely used for the
mono- and bi-coordinated adducts.
design of artificial receptors for anion binding and sensing.11-13
Recently, we proposed for the first time selenoureas as a new
binding motif for anion recognition and sensing.14 Normally,
ureas and thioureas act, at least in solution, as bidentate
ligands for anions forming eight-membered ring with
oxoanions or six-membered rings with spherical anions such as
halides,15, 16 while , to the best of our knowledge, stable mono-
coordinated adducts are unknown. Following our interest in
the development of selenourea-based receptors for anion
binding, we designed and synthesised a new family of aromatic
Classic molecular logic gates are based on molecules which are
able to perform a logic operation when one (or more) chemical
process acts as input and one (or more) easily detectable
analytical signal acts as output. The first pioneering works in
this field were reported by Aviram1 and de Silva2 almost 30
years ago. In particular, de Silva et al., realised that the binary
notation, zeros and ones, and the principles of Boolean
language, could be applied to chemical systems and they
reported the first molecular logic AND gate using protons and
sodium ions as chemical inputs and fluorescence as optical
output.2 Since then, many examples of molecular logic gates
have been developed and the complexity of the realized logic
functions has dramatically increased.3-8 Most of the described
molecular logic gates are based on fluorescent chemosensors
because the “OFF” or “ON” fluorescent status can be
straightforwardly translated into the “0” or “1” Boolean
operations. Nevertheless, Keinan et al. demonstrated that
selenoureas L1
properties with those of the corresponding thioureas (L4
and ureas (L7
L9) using 1H-NMR spectroscopy in DMSO-d6 (Fig.
-L3 and we compared their anion binding
-L6
)
-
1). We wanted to explore the possibility for selenoureas of
forming mono-coordinated adducts in solution along with
classic bi-coordinated ones and, therefore, the possibility to
construct molecular logic gates based on the nature of the
adduct formed, as illustrated hereinafter.
Se
Se
Se
N
N
N
H
N
N
N
1
H
H
H
H
H
chemical shift and peak integration in H-NMR spectra can be
L3
L1
L2
efficiently used as measurable parameters to develop an
infochemical device able to perform three different
operations, i) text encoding, ii) encryption of 21-digit binary
numbers and their addition and subtraction, and iii) encryption
S
S
S
N
H
N
H
N
H
N
H
N
H
N
H
L6
L5
L4
O
O
O
N
H
N
H
N
H
N
N
N
H
H
H
L8
L9
L7
Fig. 1 Receptors presented in the paper.
The synthesis of the selenoureas L1
of phenyl isoselenocyanate (for L1
isoselenocyanate (for L2 and L3) with aniline (for L1 and L2
-
L3 is based on the reaction
)
or 1-naphtyl
)
and 1-naphtylamine (for L3) in a 1:1 mixture of dry DCM and
EtOH under inert atmosphere in the dark at room temperature
to give the desired product in good yields (84%, 79%, and 55%,
for L1
,
L2, and L3, respectively, see ESI for synthetic details).
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The synthesis of the isoselenocyanates was previously characterized by a remarkably lower frequency than trans NH
reported by Fernández-Bolaños et al.17 Receptors L4
-L9 were protons.
already described in the literature.18-22
In order to evaluate the anion binding modes of L1
-L3, as well
as those of the other receptors, 1D-NMR titrations in DMSO-d6
were performed with chloride, dihydrogenphosphate, acetate,
and benzoate as their tetrabutylammonium salts. Resonances
due to the selenourea NHs protons were found to shift from
10-11 ppm to higher frequencies as a consequence of the
anion coordination event. Additionally, the appearance of
multiple resonances in the range 10-12 ppm and of new
resonances both in the aromatic range and at lower
frequencies (5-6 ppm), was observed in a number of instances,
suggesting the presence of more than one adduct species in
solution. In order to rationalize this behaviour and to assign
the new resonances, both 1D and 2D-NMR experiments were
carried out in DMSO-d6, starting from the case of the
structurally asymmetric L2 and acetate as guest anion species.
This prototypical study case was chosen because during the
Fig. 2 a) 1H-NMR spectra of free L2, upon addition of 0.5 equivalents of TBAAcO
(tetrabutylammonium acetate), and in the presence of 2.5 equivalents of TBAAcO in
DMSO-d6; b) structures of the proposed mono and bi-coordinated adducts. Colour
code: purple indicates bi-coordinated adduct, red and light blue indicate mono-
coordinated adducts and the corresponding 1H-NMR signals.
titration, for
a relatively wide range of anion added
equivalents, four 1H singlets were simultaneously present in
the 10-12 ppm range together with two new singlets in the 5-6
ppm range (Fig.2a, Fig. S1 for a complete stack plot).
At room temperature, rotation around C-N bonds was fast
enough to observe only a single time averaged resonance but,
by decreasing the temperature, the two separate signals were
visible in the spectrum, after the coalescence regime was
overcome.23 It was also demonstrated that by moving from
oxygen to sulfur, the coalescence temperature increased as
well as the frequency separation between cis and trans NH
proton signals.23 Our results seem to be consistent with this
evidence and show that the trends (coalescence temperature
and frequency separation) on changing the chalcogen continue
also by moving further along the 16 group down to selenium.
In fact, even increasing the temperature up to 330 K to speed
up the rotation around the C-N bonds, we did not reach the
coalescence regime for L2 (it should also be noted that our
substituents in the selenourea moiety are bulkier than Robert
methyls).
Due to the asymmetric structure of L2 the two signals
observed at ~10 ppm in the free receptor are due to the two
selenourea NHs protons. After the coalescence regime at the
beginning of the titration, up to six different singlets
attributable to NHs protons were observed (Fig. 2a) which
could be categorized into three couples of resonances on the
basis of their frequency: high (>10.5 ppm), intermediate (9.5-
10.5 ppm) and low (4.5-6.0 ppm) (Fig. S2). g-COSY, TOCSY and
ROESY were carried out on L2 in DMSO-d6 in the presence of
2.5 equivalents of acetate (in this condition all the six singlets
were well-resolved, see ESI and Fig S2 for
a detailed
description) with the aim of identifying all the species present
in solution. From the results of these experiments we
concluded that three different adduct species were present in
solution:
a
bi-coordinated and two different mono-
After these findings, we moved on to evaluate the effect of the
chalcogen on the binding modes by using the asymmetric
coordinated adducts of L2 with acetate as shown in Fig. 2.
Attribution of the NHs signals for the two mono-coordinated
adducts, which are marked in red and blue in Figure 2, is
inherently ambiguous, but it is important to stress here that
the presence of the bi-coordinated adduct is clearly
demonstrated by the presence of resonances above 11 ppm,
while the presence of mono-coordinated species is
unambiguously supported by resonances in the 4.5-6.0 ppm
range. Among the two signals assigned to each mono-
coordinated adduct, the one at higher frequency (10-10.5
ppm) is attributed to the selenourea NH proton coordinating
the anion, the one at the lower frequency is attributed to the
non-coordinating NH (see ESI, Fig. S3).
receptors L2, L5, and L8 and acetate as anion (see ESI Figs. S1
and S4). In the case of L8, upon addition of increasing amounts
of acetate, the usual progressive shift of the two NHs signals
was previously reported,21 which clearly indicated the
formation of a bi-coordinated adduct and the fast (on the NMR
time scale) exchange rate between the adduct and the free
receptor. In the case of L5, the behaviour appeared the same
(Fig. S4) but the system immediately showed a coalescence
regime, indicating that the exchange rate significantly
decreased when compared to L8. As reported above, in the
case of the L2 (Fig. S1), we observed the formation of both the
bi- and mono-coordinated adducts in equilibrium with a slow
exchange rate. In the light of the above-mentioned evidence
from the literature (and the correlations we found with
substituents’ size in the receptors as reported hereinafter), the
This interpretation is also strongly supported by a previous
study reported by Roberts et al.23 on the interaction of simple
urea, thiourea, 1,1-dimethylurea and 1,1-dimethylthiourea
with acetate. It was demonstrated that the resonance
frequency of the urea protons depended on their localization
in space with respect to the chalcogen, with cis NH protons
observed differences between L8, L5, and L2, could be
reasonably explained considering the increasing size of the Van
der Waals radius of the chalcogen, which could change the
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rotation barrier around the C-N bonds following the order Finally, we evaluated the effect of the substituents size in the
L2 L5 L8. The effect of the chalcogen on the binding modes receptors on the anion binding ability of selenoureas L1 L3, by
was also confirmed in the case of the symmetric diphenyl- using acetate as prototypical anion. The results are
substituted L1 L5, and L7 (see ESI, Fig. S5). summarised in Table 2 and in the stack plots in the ESI (Fig. S9
We then evaluated the role of the anion size and geometry on and S10).
the coordination modes of selenoureas L1 L3 by comparing
>
>
-
,
-
Table 2 Type of adducts observed for L1-L3 with acetate in DMSO-d6.
chloride, dihydrogenphosphate, acetate, and benzoate. Results
obtained for the prototypical case of L2 are summarised in
Table 1 and in the stack plots in the ESI (Fig. S6). Results for L1
and L3 are shown in Figs. S9 and S10, respectively.
Receptor
Mono-coordination
Bi-coordination
L1
L2
L3
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢀ
Table 1 Type of adducts observed for L2 with different anions in DMSO-d6.
Both in the case of the di-phenyl (L1) and phenyl-naphthyl (L2
)
Anion
Mono-coordination
Bi-coordination
substituted receptors, resonances corresponding to both
mono- and bi-coordinated adducts were observed, with the
difference in the total number of NH singlets simply due to the
symmetry of the receptor itself (Fig. S8a and S8b). Differently,
in the case of 1,3-dinaphtylselenourea L3 we observed only
the mono-coordinated species (Fig. S8c). In the light of all the
collected evidence, this difference is clearly due to the
increased steric hindrance provided by the two aryl
substituents, making the formation of the bi-coordinated
adduct particularly unfavourable. We performed 1H-NMR
Cl-
ꢀ
ꢀ
ꢁ
ꢁ
ꢁ
ꢁ
-
H2PO4
AcO-
BzO-
ꢁ
ꢁ
In the case of the relatively small and spherical chloride anion,
the usual progressive shift of the two selenourea NHs to higher
frequency was observed only at high anion equivalents added,
indicating a low binding affinity. No coalescence regime was
observed, while the resonance shift presumably reflected the
fast exchange rate between the free receptor and the bi-
coordinated adduct.
titrations also with receptors L4-L9 and all the anions
considered and we observed only the formation of the bi-
coordinated adducts. It is worth noticing that we did not
observed any relevant variation in the Uv-Vis and the
In the case of dihydrogenphosphate, after a first coalescence
regime the two signals reappeared in the spectrum but located
at lower frequency than those of the free receptor. Upon
addition of further increasing amounts of anion, the
progressive shift of the two NHs was observed, up to
frequency values higher than those observed for the free
receptor. This peculiar behaviour can be explained with a fast
exchange rate between the two possible mono-coordinated
species and the bi-coordinated adduct. The absence of
resonances in the 4.5-6.0 ppm range, characteristic of mono-
coordinated adducts, showed that the bi-coordinated species
is the dominating one, to which dihydrogenphosphate anion
can evolve very rapidly from any of the two mono-coordinated
forms. This is absolutely reliable if one considers the
tetrahedral geometry of the anion. The presence of four
oxygen atoms pointing to different directions should be able to
facilitate the second coordination event even if the receptor
adopts a “distorted” non-planar conformation.
fluorescent properties of receptors L1-L3 upon addition of the
anions investigated.
The results obtained can be summarised in a truth table (Table
3) where the input are i) the nature of the chalcogen (0, 1, 2
for oxygen, sulphur and selenium, respectively), ii) the steric
hindrance of the aryl substituents at the urea moiety (0, 1, and
2 for diphenyl, phenyl-naphtyl, and di-naphtyl, respectively),
and iii) the geometry of the anion (0, 1, 2, 3, for spherical
chloride, tetrahedral dihydrogenphosphate, Y-shape acetate,
and bulky Y-shape benzoate, respectively), while the output
1
are the type of adducts formed identified on the base of H-
NMR signals (0, 1, 2, for only mono-coordinated, both mono-
and bi-coordinated, and only bi-coordinated, respectively). It is
clear, that only selenoureas are able to give multiple response
depending on the anion and on the aryl substituents
considered. The output type in Table
3 can be easily
The observation of distinct resonances for both mono- and bi-
coordinated adducts in the case of the Y-shape anions acetate
and benzoate reflected the slower exchange rate between the
different species formed in solution. The bulky selenium atom
in the receptor should limit rotations around the C-N bonds,
thus limiting the accessible conformations. As a consequence,
the complementarity between the directionality of the two
NHs hydrogen bond donors and the Y-shape of these anions is
more difficult to be achieved when selenoureas are compared
to ureas and thioureas (see ESI, Fig. S7). The bulkier benzoate,
indeed, formed only one of the two possible mono-
coordinated adducts with L2 because of its increased steric
hindrance, which determined the preferential coordination
direction on the less cluttered phenyl side of the receptor.
determined using the flowchart in Fig. 3, which also provides
the basis to implement the automatic NMR spectral analysis
for the interactions of the receptors and anions investigated in
the paper.
In conclusion, we showed that when compared to ureas and
thioureas, selenoureas appear to be more versatile receptors
for anion binding, capable of forming at room temperature in
solution both mono- and bi-coordinated adducts depending on
the geometry of the bound anion and the steric hindrance
exerted by the chalcogen itself and the substituents on the
urea moiety. This is reflected also on the increase of the NMR
coalescence temperature that facilitate the easy detection of
the mono-coordinated adduct in solution at room
temperature. As
a
consequence, on using i) the steric
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hindrance of the aryl substituents in selenoureas, and ii) the NMR Facility (University of Seville) for some of the NMR
geometry of the anion guest as inputs, a molecular logic gate experiments. PB thanks University of Seville (Plan Propio) for
can be easily developed following 1H-NMR signals of the the award of a fellowship.
adducts formed as chemical outputs.
Table
3 Truth table based on the interactions between receptors and anions
Notes and references
investigated in this work.
Input
Substituentsb
Outputd
1.
2.
3.
4.
5.
6.
7.
A. Aviram, Journal of the American Chemical Society,
1988, 110, 5687-5692.
P. A. de Silva, N. H. Q. Gunaratne and C. P. McCoy, Nature,
1993, 364, 42-44.
J. Andréasson and U. Pischel, Chemical Society Reviews,
2015, 44, 1053-1069.
A. Credi, Angewandte Chemie - International Edition,
2007, 46, 5472-5475.
B. Daly, J. Ling and A. P. de Silva, Frontiers of Chemical
Science and Engineering, 2014, 8, 240-251.
A. P. De Silva and N. D. McClenaghan, Chemistry - A
European Journal, 2004, 10, 574-586.
Madhuprasad, M. P. Bhat, H. Y. Jung, D. Losic and M. D.
Kurkuri, Chemistry - A European Journal, 2016, 22, 6148-
6178.
U. Pischel, Australian Journal of Chemistry, 2010, 63, 148-
164.
T. Ratner, O. Reany and E. Keinan, ChemPhysChem, 2009,
10, 3303-3309.
J. M. Granda and J. Jurczak, Chemistry – A European
Journal, 2014, 20, 12368-12372.
N. Busschaert, C. Caltagirone, W. Van Rossom and P. A.
Gale, Chemical Reviews, 2015, 115, 8038-8155.
P. A. Gale and C. Caltagirone, Chemical Society Reviews,
2015, 44, 4212-4227.
P. A. Gale and C. Caltagirone, Coordination Chemistry
Reviews, 2017.
A. Casula, A. Llopis-Lorente, A. Garau, F. Isaia, M. Kubicki,
V. Lippolis, F. Sancenón, R. Martínez-Máñez, A.
Owczarzak, C. Santi, M. Andrea Scorciapino and C.
Caltagirone, Chemical Communications, 2017, 53, 3729-
3732.
Chalcogena
Anion shapec
0
1
2
2
2
2
2
2
2
2
2
2
2
0, 1, 2
0,1, 2,3
2
2
2
2
1
1
2
2
1
0
2
2
0
0, 1, 2
0,1, 2,3
0
0
0
0
1
1
1
1
2
2
2
0
1
2
3
0
1
2
3
0
1
2
8.
aTernary input: 0, oxygen; 1, sulfur; 2, selenium.
9.
bTernary input: 0, di-phenyl; 1, phenyl-naphthyl; 2, di-naphthyl.
cQuaternary input: 0, spherical; 1, tetrahedral; 2, small Y-
shaped; 3, bulky Y-shaped.
10.
11.
12.
13.
14.
dTernary output: 0, only mono-coordination; 1, both mono- and
bi-coordination; 2, only bi-coordination.
15.
16.
17.
18.
V. Amendola, L. Fabbrizzi and L. Mosca, Chemical Society
Reviews, 2010, 39, 3889-3915.
A.-F. Li, J.-H. Wang, F. Wang and Y.-B. Jiang, Chemical
Society Reviews, 2010, 39, 3729-3745.
J. G. Fernández-Bolaños, Ó. López, V. c. Ulgar, I. Maya and
J. Fuentes, Tetrahedron Letters, 2004, 45, 4081-4084.
N. Busschaert, I. L. Kirby, S. Young, S. J. Coles, P. N.
Horton, M. E. Light and P. A. Gale, Angewandte Chemie -
International Edition, 2012, 51, 4426-4430.
P. P. Deohate, J. P. Deohate and B. N. Berad, Asian Journal
of Chemistry, 2004, 16, 255-260.
S. A. Kadam, K. Haav, L. Toom, T. Haljasorg and I. Leito,
Journal of Organic Chemistry, 2014, 79, 2501-2513.
S. A. Kadam, K. Martin, K. Haav, L. Toom, C. Mayeux, A.
Pung, P. A. Gale, J. R. Hiscock, S. J. Brooks, I. L. Kirby, N.
Busschaert and I. Leito, Chemistry - A European Journal,
2015, 21, 5145-5160.
Figure 3 Explicative flowchart to implement automatic spectra analysis of the receptors
L1-L3 in the presence of Cl-, H2PO4-, CH3COO- and Ph-COO-.
19.
20.
21.
The investigated series of selenoureas/anions thus, represents,
to the best of our knowledge, the first example of molecular
logic gate using the urea– based receptors for anions, that
1
performs a ternary logic operation based on a H-NMR easy to
read response.
22.
23.
A. Tarai and J. B. Baruah, Journal of Molecular Structure,
2015, 1091, 147-151.
K. A. Haushalter, J. Lau and J. D. Roberts, Journal of the
American Chemical Society, 1996, 118, 8891-8896.
The authors thank Fondazione Banco di Sardegna and Regione
Autonoma
della
Sardegna
(Progetti Biennali di Ateneo Annualità 2016), the Junta de
Andalucía (FQM134), and the European Regional Development
Fund (FEDER) for financial support. They also thank CITIUS
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