Integrative Self-Sorting of Bipyridinium/Diazapyrenium-Based Ligands into Pseudo[1]rotaxanes

Article abstract of DOI:10.1002/chem.201704540

We present here the design and synthesis of a series of multicomponent supramolecular architectures, structures formed by the Pd^II/Pt^II-directed integrative social self-sorting in aqueous media of pairs of complementary N-monoalkyl-4,4′-bipyridinium/2,7-diazapyrenium-based ligands. Out of the different potential outcomes of the processes, we have found out how the designed systems selectively enhance the production of pseudo[1]rotaxanes, hermaphroditic host–guest aggregates that maximize the strength of the occurring π–π, C?H???π, and hydrophobic interactions, as well as the number of those interactions per receptor. It is also demonstrated how both integrative social and narcissistic Pd^II-directed self-sorting can occur orthogonally and concomitantly for this type of ditopic ligands.

Full text of DOI:10.1002/chem.201704540

A Journal of
Accepted Article
Title: Integrative Self-Sorting of Bipyridinium/Diazapyrenium-Based
Ligands Into Pseudo[1]rotaxanes
Authors: Tamara Rama, Arturo Blanco-Gómez, Iago Neira, Olaya
Domarco, Marcos D. García, José María Quintela, and Carlos
Peinador
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201704540
Link to VoR: http://dx.doi.org/10.1002/chem.201704540
Supported by

10.1002/chem.201704540
Chemistry - A European Journal
COMMUNICATION
Integrative Self-Sorting of Bipyridinium/Diazapyrenium-Based
Ligands Into Pseudo[1]rotaxanes
Tamara Rama,[a] Arturo Blanco-Gómez,[a] Iago Neira,[a] Olaya Domarco,[a] Marcos D. García,*,[a] José M.
Quintela[a] and Carlos Peinador*[a]
Abstract: We present herein the design and synthesis of a series of
multicomponent supramolecular architectures, structures formed by
the Pd(II)/Pt(II)-directed integrative social self-sorting in aqueous
media of pairs of complementary N-monoalkyl-4,4’-bipyridinium/2,7-
diazapyrenium-based ligands. Out of the different potential
outcomes of the processes, we have found how the designed
systems selectively enhance the production of pseudo[1]rotaxanes,
hermaphroditic host-guest aggregates that maximize the strength of
the occurring π-π, C-H···π and hydrophobic interactions, as well as
the number of those interactions per receptor. It will be
demonstrated as well how both integrative social and narcissistic
are not only appealing synthetic targets for their intrinsic
topological beauty, but for their potential use as molecular
actuators or as synthetic models of lasso peptides.12
Crucially, the design of the synthetic partners in this work is
based on our experience on the metal directed self-assembly of
N-monoalkyl-4,4’-bipyridinium/-2,7-diazapyrenium ligands into π-
deficient metallocycles,13 receptors able to complex aromatic
substrates through π-π, C-H···π and hydrophobic forces.14
Therefore, we envisioned that the shape-complementary ligands
L114a or L314f and (±)-L2, bearing a π-excedent dioxophenyl
moiety attached to the bipyridinium ditopic ligand through a non-
Pd(II)-directed self-sorting can occur orthogonally, and concomitantly, interfering linker, would mainly produce in water, upon the
for this type of ditopic ligands.
guidance of the metal centers M1 and M2, the heteromeric
pseudo[1]rotaxanes S3a,b and S4a,b as the result of social
integrative self-sorting processes.15 Importantly, these species
would be favored, in theory, over the corresponding
homometallacycles, due to the enthalpic gain produced by the
maximization of the number of host-guest interactions per
metallacycle on S3a,b and S4a,b.
Supramolecular synthesis1 has traditionally focused on
mimicking Nature,2 making use of relatively simple components
programmed to connect via weak intermolecular forces.3
Nevertheless, abiotic (self)assembly utilizes in most of the cases
identical building blocks, with less attention being paid to the use
of structurally-diverse constituents and, consequently, on the
development of synthetic strategies based on integrative social
self-sorting.4 Such approach would be highly attractive for the
construction of desymmetrized supramolecules, which can in
turn render new functional complex chemical systems.5,6
In this regard, directional intermolecular interactions, such as
hydrogen bonding7 or metal-ligand bonding,8 have been
extensively used in order to achieve control over self-sorted
systems. Conversely, non-directional interactions have been
scarcely employed,9 with the use of hydrophobic forces being
particularly unappreciated,10 especially if we consider their
importance on the design and development of functional
supramolecular systems able work in aqueous media.11
N
N
N
O
N
H2
N
ONO2
ONO2
Et3P
ONO2
ONO2
Pd
Pt
O
N
N+
N
Et3P
N
N
H2
N+
N
N
O
O
N
N
N
O
N
N
O
=
=
M1
M2
Pd
Pt
L3·NO3
L1·NO3
L2·NO3
L4·2NO3
In an attempt to implement metal-directed self-assembly, π-π
interactions and hydrophobic forces on multicomponent
supramolecular synthesis, we present herein the integrative self-
sorting of a series of ditopic ligands L1-L3, intended to produce
scorpionand-shaped metallacycles S3a,b-S4a,b upon the
guidance of Pd(II)/Pt(II) metal centers M1 and M2 (Figure 1).
Such aggregates, named in the literature as pseudo[1]rotaxanes,
self-inclusion complexes, hermaphroditic host-guest compounds
or molecular lassos, are exotic supramolecular structures that
·6
S3a NO3 from M1
·6
S3b NO3 from M2
·6
S4a
S4b
NO3 from
·6
M
1
·6
S2a NO3 from M1
·6
S2b NO3 from M2
M
NO3 from
2
Figure 1. Schematic depiction of the building blocks (L1-L4, M1 and M2), and
new supramolecular structures (S2a,b-S4a,b), discussed in this work.
Firstly, in separated experiments, we proceeded to monitor by
NMR the self-assembly in D2O of L1 and (±)-L2 with the Pd(II)
center M1. As expected, the results pointed out the formation,
respectively, of the homometallacycles S1a14a and S2a as sole
reaction products assembling instantaneously on the
concentration window 5‒0.3 mM. In the case of S2a, the 1H
NMR, the spectrum of the mixture certainly supports its
formation, with two separate broad resonances (∂ = 4.15 and ∂ =
5.56 ppm), attributable to two dioxoaryl moieties positioned,
respectively, in and out of the cavity of the metallacycle (Figure
[a]
T. Rama, A. Blanco-Gómez, I. Neira, O. Domarco, Prof. M. D.
García, Prof. C. Peinador, Prof. J. M. Quintela. Departamento de
Química and Centro de Investigacións Científicas Avanzadas
(CICA). Facultade de Ciencias, Universidade da Coruña, 15071,
A
Coruña,
Spain.
E-mail:
carlos.peinador@udc.es;
marcos.garcia1@udc.es.
Supporting information for this article is given via a link at the end
of the document.
This article is protected by copyright. All rights reserved.

10.1002/chem.201704540
Chemistry - A European Journal
COMMUNICATION
2). Furthermore, 1D and 2D NMR experiments allowed us to
assign protons Ha, Hf, and Hg, which are clearly deshielded as
a result of the coordination to the metal centers, and Hc, Hb and
Hd, shielded as a consequence of the inclusion of one aromatic
ring within the cavity of the receptor. VT H NMR experiments
showed that S2a is the main resulting from the reaction even at
4.05 ppm, with the characteristic shielding effect provoked by
the insertion of the aromatic pendant on the cavity assembled by
the two ligands. Furthermore, other diagnostic resonances could
be assigned: Hc, Hb and Hd shielded as a result of the
autocomplexation of the dioxoaryl; and Ha, Hf, and Hg,
deshielded by effect both of the coordination of the ligands to the
Pd(II) center and the occurrence of C-H···π interactions between
the short sides of the metallacyclic cavity and the dioxoaryl
subunit (Figure S27). DOSY experiments at room temperature
(Figure S26), further support the formation of S3a, with all the
components of the mixture diffusing as a whole.
1
353 K (Figure S14).
Figure 2. 1H NMR (500 MHz, D2O, 298K) spectrum of 5 mM (±)-L2·NO3 and
S2a·6NO3 (5 mM (±)-L2·NO3 and M1).
In order to bypass the kinetic lability of the Pd(II)-N(pyridine)
bonds on the obtained concentration-dependent species S2a,
and with the aim of gaining further structural information by
means of mass spectrometry, we prepared the Pt(II) analogue
S2b by reaction of (±)-L2 and M2,16,17 which instantaneously
produced an 1H NMR in D2O similar to that of S2a (Figure S19).
Ion methatesis of this nitrate salt, S2b·6NO3 with KPF6 allowed
the isolation of a solid by precipitation, which was redisolved in
acetone and submitted to HR ESI-MS,18 showing a peak at m/z
1376.4909 for [S2b−2PF6]+2, with and isotopic distribution
matching that calculated for the proposed structure in solution
(Figure S16).
Figure 3. Observed (bottom), and theoretical (top), isotopic distributions for
the fragments [S3b−2PF6]2+ (left) and [S4b−2PF6]2+ (right).
The Pt(II) analogue S3b could be obtained by reaction of L1, (±)-
1
L2 and M2, instantaneously showing after mixing an H NMR in
D2O at r.t. similar to that of S3a and, therefore, in good
agreement with the formation of the corresponding
pseudo[1]rotaxane (Figure S34). As explained for S2b, HR ESI-
MS allowed us in this occasion to detect a peak at m/z =
1172.7963 [S3b−2PF6]+2 supporting the formation of the
proposed integrative species (Figure 3).
It should be noted that, upon formation of S3a,b and S2a,b, a
color change of the aqueous solutions of the corresponding
ligands arises when the metallic center is added, a fact
attributable to charge-transfer bands (λmax = 445 and 430 nm,
respectively), appearing as a result of the insertion of the
aromatic pendants on the cavities of the metallacycles. In both
cases, linear correlations could be stablished between the
concentrations of S3a (Figure S30) or S2a (Figure S15) and the
absorbance at the maxima of the charge-transfer bands,
ensuring that those are the result of unimolecular processes,
rather than other potential situations involving oligomeric
species.19
In an analogous fashion to that described for the synthesis of
S3a, pseudo[1]rotaxane S4a could be also prepared in water by
reaction, in this occasion, of the diazapyrenium-based ligand
L3,14f (±)-L2 and M1 (Figure 1). The 1H NMR of the mixture,
recorded just after the mixture of the components, clearly
supports again the integrative self-sorting of the ligands (Figure
S42), with a splitting in this case of the signals of L3 as a result
Scheme 1. Cartoon representation of the integrative self-sorting process
leading to S3a.
With this information on S1 and S2 in our hands, we proceeded
to study by NMR spectroscopy, in D2O at r.t., the ternary mixture
of the complementary ligands L1·and (±)-L2 with the Pd(II)
center M1, (Scheme 1). The reaction instantaneously yielded a
new main species, different to S1a and S2a, and with a 1H NMR
(Figure 4), in good agreement with the expected
pseudo[1]rotaxane S3a as main reaction product on the
concentration window 2.5-0.08 mM. VT 1H NMR showed this
species to persist on the temperature range 298-353 K (Figure
S29). 1D and 2D NMR experiments allowed us to assign the
resonances for protons of the dioxoaryl moiety at δ = 4.23 and
This article is protected by copyright. All rights reserved.

10.1002/chem.201704540
Chemistry - A European Journal
COMMUNICATION
of impeded rotation of the diazapyrenium ring along its N-N axis.
As for S3a, the signals corresponding to the dioxoaryl moiety of
(±)-L2 are clearly deshielded as a result of the self-complexing
process, enhanced in this occasion by the highly shielding effect
promoted by the 2,7-diazapyrene ring. The Pt(II) analogue S4b,
was also prepared using metal center M2, with an 1H NMR in
D2O good agreement with that of the Pd(II) species, but showing
in this case the splitting of all of the signals of L2 and L3 (Figure
S49). As for S2b and S3b, mass spectrometry on the
hexafluorophosphate salt of S4b, supported the formation of the
displacement experiment shown in Scheme 2, by adding 0.5 eq.
of L3 to a 1.25 mM solution of S3a. From the NMR data (Figure
S50), it can be estimated that ligand L3 displaces 62% of L1 out
of S3a to form S4a, showing how the self-sorting process yields,
as the main product, not only the pseudo[1]rotaxane that
optimizes the number of π-π and hydrophobic interactions per
receptor, but the one that ensures a better donor-acceptor
complementarity.
supramolecule, with
a peak found at m/z 1196.7903 for
[S4b−2PF6]+2, matching that calculated (Figure 3).
Scheme 2. Cartoon representation of the competitive experiment designed to
assess the selectivity of the integrative self-sorting processes involving ligand
(±)-L2.
As a final corollary of the previously discussed observations, we
proceeded to evaluate the outcome of the reaction between four
different N-monoalkyl-4,4’-bipyridinium/2,7-diazapyrenium-based
ligands (L1-L4) in presence of M1. As shown in Figure 5, the 1H
NMR of a 1:2:1:2:6 mixture of L1-L4 and M1, shows how the
reaction simultaneously, and orthogonally, produces the
integrative social self-sorting of L1-L3 into S3a and S4a (guided
by the optimization of the number and strength of hermaphroditic
host-guest interactions), and the narcissistic self-sorting of L4
into S5a (based on the lack of shape complementarity with the
other three ligands).
Figure 4. 1H NMR (500 MHz D2O) spectra of: a) 2.5 mM S1a (5 mM L1 and 5
mM M1), b) 2.5 mM (±)-L2, c) 2.5 mM L1, d) 2.5 mM S3a (2.5 mM (±)-L2 and
L1, 5 mM M1), e) 2.5 mM S1a (5 mM L1 and M1), 2.5 mM (±)-L2, following
the color code for each spectrum, in e) the signals corresponding to the
different components on the mixture are highlighted as colored circles.
If we consider S3a,b and S4a,b as the most stable products of
the corresponding reactions in water, that would imply that any
system including the ternary mixtures (L1 or L3 plus (±)-L2 and
M1 or M2), should evolve to assemble the corresponding
pseudo[1]rotaxane independently of the starting conditions. In
order to check this fact, we designed the competition experiment
shown in Figure 4 for S3a: to a 2.5 mM solution of the
homometallacycle S1a in D2O, 0.5 eq. of (±)-L2 were added.
The resulting 1H NMR is in good agreement with the formation of
the pseudo[1]rotaxane S3a and, crucially, with the excess of L1
appearing on the spectra as free ligand. This fact implies the
disassembly of the homomeric metallacycle to produce the
integrative species S3a, by displacing L1 by (±)-L2 on the initial
mixtures. Form the relative integration of the signals of the two
species in each spectrum, it could be estimated that (±)-L2
displaces 99% of L1 out of the corresponding homometallacycle,
to form the matching pseudorotaxane S3a. Identical results were
found for the competition between ligands L3 and (±)-L2 for the
metal center M1 (Figure S45).
Figure 5. 1H NMR (500 MHz D2O) spectra of: a) S5 (5 mM L4 and 5 mM M1),
b) S3 (2.5 mM L1 and L2, 5 mM M1), c) S4·6NO3 (2.5 mM L3 and L2, 5 mM
M1), d) 1.25 mM L1 and L3, 2.5 mM L2 and L4, 7.5 mM M1).
Furthermore, considering the higher π-acceptor character and
hydrophobicity of L3 compared to L1, we carried out the ligand
This article is protected by copyright. All rights reserved.

10.1002/chem.201704540
Chemistry - A European Journal
COMMUNICATION
[10] See, for instance: N. A. Schnarr, A. J. Kennan J. Am. Chem. Soc. 2003,
125, 667.
In summary, we have discussed herein the Pd(II)/Pt(II)-directed
integrative social self-sorting in aqueous media of pairs of
[11] G. V. Oshovsky, D. N. Reinhoudt, W Verboom Angew. Chem. Int. Ed.
2007, 46, 2366.
complementary
N-monoalkyl-4,4’-bipyridinium/2,7-
diazapyrenium-based ligands. Out of the different potential
outcomes of the processes, we have found how the designed
systems enhance the production of pseudo[1]rotaxanes,
hermaphroditic host-guest aggregates that maximize the
strength of the occurring π-π, CH-π and hydrophobic
interactions, as well as the number of those interactions per
metallacyle. As far as we know, these supramolecules are the
firt examples of pseudo[1]rotaxanes self-assembled from
multiple components, rather than obtained by clasical covalent
synthesis.12 We have demonstrated as well how the
multicomponent reaction in aqueous media of four different, but
structurally-related, ligands with a Pd(II) metal center, produces
only heteromeric species, with the remaining non-integrated
ligands self-assembling in a narcisistic manner to produce
homometallacyclic species.
[12] See, for instance: Y. Wang, J. Sun, Z. Liu, M. S. Nassar, Y. Y. Botros, J.
F. Stoddart, Chem. Sci. 2017, 8, 2562, and references cited therein.
[13] C. Peinador, V. Blanco, M. D. García, J. M. Quintela, PdII and PtII
Metal-Directed Self-Assembly of Supramolecular Structures Based on
N-Monoalkyl-4,4′-Bipyridinium Derivatives, in Molecular Self-Assembly:
Advances and Applications, Ed.: A. D. Q. Li, Pan Stanford Publishing,
Singapore, 2012, p. 351; b) M. D. García, C. Alvariño, E. M. López-
Vidal, T. Rama, C. Peinador, J. M. Quintela, Inorg. Chim. Acta 2014,
417, 27.
[14] a) M. Chas, C. Platas-Iglesias, C. Peinador, J. M. Quintela,
Tetrahedron Lett. 2006, 47, 3119; b) C. Peinador, E. Pía, V. Blanco, M.
D. García, J. M. Quintela, Org. Lett. 2010, 12, 1380; c) V. Blanco, M.
D.; García, C. Platas-Iglesias, C. Peinador, J. M. Quintela, Chem.
Commun. 2010, 46, 6672; d) V. Blanco, M. D. García, A. Terenzi, E.
Pía, A. Fernandez-Mato, C. Peinador, J. M. Quintela, Chem. Eur. J.
2010,16,12373; e) V. Blanco, M. D. García, C. Peinador, J. M. Quintela,
Chem. Sci. 2011, 2, 2407; f) T. Rama, E. M. López-Vidal, M. D. García,
C. Peinador, J. M. Quintela, Chem. Eur. J. 2015, 21, 9482; g) T. Rama,
C. Alvariño, O. Domarco, C. Platas-Iglesias, V. Blanco, M. D. García, C.
Peinador, J. M. Quintela, Inorg. Chem. 2016, 55, 2290.
Acknowledgements
[15] Due to the racemic nature of (±)-L2, the self-assembly of the
pseudo[1]rotaxanes S3a-b and S4a-b would produce as well
racemates. Each of the enantiomers could have in turn two up/down
conformers, as a consequence of the insertion of the dioxophenyl
moiety on the receptor, with the linkers passsing, or not, through the
plane defined by the four corners of the metallacycle. For the assembly
of the homometallacycles S2a-b, those processes would render a
mixture of syn/anti stereoisomers,14g depending on the relative
orientation of the two linkers attached to the metallacycle and, again,
each of the isomers could have in turn two up/down conformers. As the
stereoisomers and conformers discussed would certainly have a very
similar chemical environment for their protons, those were not be
detected by 1H NMR in any of the proccesses described in this work.
[16] The Pt(II) complex M2,17 was chosen on the basis of its known ability to
produce the self-assembly of bipyridine-based ligands at room
temperature in aqueous media,18 due to the trans-effect provoked by
the triethylphosphines as ancillary ligands. Altough the kinetic lability of
the Pt(II)-N(pyridine) bonds is conveniently lowered, the increased
estability of the obtained supramolecules. compared to the Pd(II)
counterparts allows for their easier characterization by means of MS.18
[17] C. J. Kuehl, F. M. Tabellion, A. M.; Arif, P. J. Stang, Organometallics
2001, 20, 1956.
This research was supported by the Ministerio de Economía y
Competitividad (MINECO FEDER, Grants CTQ2016-75629-P
and CTQ2013-41097-P) and Xunta de Galicia (Grant
EM2014/056). T. R. and I. N. thank the MECD (FPU program)
for financial support, O. D. thanks Fundación Gil Dávila for a
predoctoral grant.
Conflict of interest
The authors declare no conflict of interest.
Keywords: Supramolecular chemistry • Metal-directed self-
assembly • Host-guest systems • Self-sorting •
Pseudo[1]rotaxanes
[1]
[2]
a) M. C. T. Fyfe, J. F. Stoddart, Acc. Chem. Res. 1997, 30, 393; b) D. N.
Reinhoudt, M. Crego-Calama, Science 2002, 295, 2403.
[18] C. Addicott, N. Das, P. J. Stang, Inorg. Chem. 2004, 43, 5335.
[19] Y. Liu, A. H. Flood, R. M. Moskowitz, J. F. Stoddart, Chem. Eur. J. 2005,
11, 369.
M. Groll, L. Dizel, J. Lowe, D. Stock, M. Bochter, H. D. Bartunik, R.
Huber, Nature 1997, 386, 463.
[3]
[4]
D. Philp, J. F. Stoddart, Angew. Chem. Int. Ed. 1996, 35, 1155.
For recent selected reviews on integrative self-sorting, see: a) W. M.
Bloch, G. H. Clever, Chem. Commun. DOI 10.1039/c7cc03379f; b) Z.
He, W. Jiang, C. A. Schalley, Chem. Soc. Rev. 2015, 44, 779.
a) R. F. Ludlow, S. Otto, Chem. Soc. Rev. 2008, 37, 101; b) E. Mattia,
S. Otto, Nat. Nanotechnol. 2015, 10, 111.
[5]
[6]
[7]
J.-M. Lehn, Angew. Chem. Int. Ed. 2015, 54, 3276.
For recent selected examples, see: a) A. Wu, A. Chakraborty, J. C.
Fettinger, R. A. Flowers II, L. Isaacs, Angew. Chem. Int. Ed. 2002, 41,
4028; b) Y. Ma, S. V. Kolotuchin, S. C. Zimmerman, J. Am. Chem. Soc.
2002, 124, 13757; c) D. Ajami, J.-L. Hou, T. J. Dale, E. Barrett, J.
Rebek Jr., Proc. Natl. Acad. Sci. USA 2009, 106, 10430.
[8]
[9]
For a review, see reference 4a; for some recent selected examples,
see: a) N. Sinha, T. T. Y. Tan, E. Peris, F. E. Hahn, Angew. Chem. Int.
Ed. 2017, 56, 7393; b) W. M. Bloch, J. J. Holstein, W. Hiller, G. H.
Clever Angew. Chem. Int. Ed. 2017, 56, 8285.
See, for instance: T. Matsuno, S. Sato, A. Yokoyama, S. Kamata, H.
Isobe Angew. Chem. Int. Ed. 2016, 55, 15339.
This article is protected by copyright. All rights reserved.

10.1002/chem.201704540
Chemistry - A European Journal
COMMUNICATION
Entry for the Table of Contents
Layout 2:
COMMUNICATION
Tamara Rama, Arturo Blanco-Gómez,
Iago Neira, Olaya Domarco, Marcos D.
García,* José M. Quintela and Carlos
Peinador*
Page No. – Page No.
Integrative Self-Sorting of
Bipyridinium/Diazapyrenium-Based
Ligands Into Pseudo[1]rotaxanes
We present herein the Pd(II)/Pt(II)-directed integrative social self-sorting in aqueous
media of pairs of complementary N-monoalkyl-4,4’-bipyridinium/2,7-diazapyrenium-
based ligands. The obtained dynamic systems enhance the production of
pseudo[1]rotaxanes, hermaphroditic host-guest aggregates produced by
maximization of the strength of the donor-acceptor interactions, as well as the
number of those per receptor.
This article is protected by copyright. All rights reserved.