A Constrained and “Inverted” [3+3] Salphen Macrocycle with an ortho-Phenylethynyl Substitution Pattern

Article abstract of DOI:10.1002/chem.201904763

A [3+3] Schiff-base salphen macrocycle (7 a) was synthesized by imine condensation between ortho-phenylenediamine and ortho-phenylethynyl-bridged bis(5-salicylaldehyde) precursors. The triangular-shaped macrocycle 7 a has a nonclassical (or “inverted”) de

Full text of DOI:10.1002/chem.201904763

A Journal of
Accepted Article
Title: A constrained and “inverted” [3 + 3] salphen macrocycle with an
ortho-phenylethynyl substitution pattern
Authors: Tomas Torres and Maxence Urbani
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.201904763
Link to VoR: http://dx.doi.org/10.1002/chem.201904763
Supported by

10.1002/chem.201904763
Chemistry - A European Journal
FULL PAPER
A constrained and “inverted” [3 + 3] salphen macrocycle with an
ortho-phenylethynyl substitution pattern
Maxence Urbani*[a,b] and Tomas Torres*[a,b,c]
properties and reactivity, making them excellent catalyst and
ion-sensors for instance. Remarkably, mononuclear Zn(II) Schiff-
base complexes are known to form dimeric structures having a
typical Zn2O2 central unit, mediated by strong intermolecular Zn–
O coordinative interactions (through μ2-phenoxo bridging).[16-18]
Salphen-type macrocycles have attracted a particular interest in
the field of supramolecular chemistry, owing to their ability to
self-assemble into organised stacks.[7‒10,19‒21] In particular, the
aggregation behaviour of multinuclear Zn(II) salphen complexes
is strongly enhanced owing to their unusual oligomeric (Zn−O)n
coordination motifs, a peculiar property that has been exploited
for the construction of self-assembled nanostructures of very
high stability.[18,22-24]
Abstract: A novel [3+3] Schiff base salphen macrocycle (7a) was
synthetized by imine condensation between ortho-phenylenediamine
and ortho-phenylethynyl-bridged bis(5-salicylaldehyde) precursors.
The triangular-shaped macrocycle 7a has a non-classical design (or
“inverted”), with the N2O2 coordination “pockets” located at the sides
instead of corners. 7a could be synthesized in a reasonably good
yield (64%) considering the steric constrains imposed by the ortho-
substitution pattern. Subsequent zinc-metalation afforded the
corresponding Zn-metallomacrocyle 7b. Spectroscopic experiments
evidenced weak (7a) to strong (7b) self-aggregation behaviour in
solution. Their ability to self-organize at the supramolecular level
was further studied in the solid state by AFM and TEM experiments,
revealing the formation of large bundles of fibers with lengths of
several microns and width of nanometers.
The reversibility character of the imine condensation within
dynamic exchange of C=N bonds meets the requirements for
dynamic covalent reactions,[ 25 ] which has been exploited to
prepare shape-persistent 2D and 3D molecular systems of high-
complexities and in high yields, such as macrocycles[26‒30] tiered-
Introduction
[32]
architectures,[31] capsules
and molecular cages.[33‒38] One of
Schiff base ligands have been widely explored for the
preparation of stable and functional coordination complexes, and
have raised interest in various fields of research, especially in
catalysis[1] and asymmetric catalysis[2], but also as colorimetric
sensors triggered by metal–ligand coordination,[ 3 ] crystalline
porous materials (CPMs),[ 4 , 5 ] molecular magnets,[ 6 ] liquid
crystals[ 7 ‒ 10 ] and energy materials[ 11 ] including organic light
emitting diodes (OLED)[ 12 , 13 ] and also more recently dye-
sensitized solar cells (DSSC).[14] They are distinguished by their
relative ease of synthesis (condensation between carbonyl and
primary-amine precursors), and tuneable denticity allowing
multiple-binding of several kinds of metal ions, thus offering a
large panel of oxidation state, tuneable optical, redox, and even
magnetic properties of their metal complexes.[15] Salen is a large
family of tetradentate Schiff base ligands prepared by
condensation between hydroxy-benzaldehyde and primary-
diamine precursors. The cooperative metal-binding effect owing
to their N2O2 pocket makes them powerful ligands for metal
complexation. Salphens are -conjugated salen systems, thus
holding several advantages in terms of stability, optical
the main synthetic challenge is to obtain selectively one type of
macrocycle within a given size and in good yield. For this
purpose, the most convenient and efficient method to prepare
symmetrical salphen macrocycles involves the condensation
between a diformyl-aromatic precursor and ortho-phenylene-
diamine derivative in a one pot-synthesis. Initially, one of the first
reports relied on the condensation between 3,6-diformylcatechol
and ortho-phenylene diamine producing almost exclusively a
triangular and shaped-persistent [3+3] macrocycle and in
remarkable high yield (up to 91%).[39,40] Latter on, incorporation
of different linear spacers into their backbone allowed to access
macrocycles with tuneable size and optical properties, as for
instance, phenyleneethynylene linkers pioneered by MacLachlan
and co-workers.[41] By changing the geometry (length, curvature)
and/or nature of the diformyl-aromatic precursor, several
macrocycles of different size and shape could be prepared in
high yields following a similar strategy: [3+3],[41‒45] [4+4],[7‒9] and
[6+6].[46] Several examples of soluble triangular-shaped [3+3]
Schiff-base macrocycle of different size have been reported,
including salen (triangleimine) and salphen types.[41‒44]
Nonetheless, it is worth to notice that all of them are constructed
in a similar fashion, that is by condensation of a bis(4-
substituted-2-hydroxybenzaldehyde) precursor (linearly linked)
and an o,o-substituted diamino derivative. Consequently, they
posses the three N2O2 pocket coordination sites located at each
corners of the triangle (Chart 1.a, left). To our knowledge, the
only example of a [3+3] salphen-type macrocycle with an
“inverted configuration”, that is three N2O2 pocket located at the
sides instead of corners of the triangle (Chart 1.b, right), was
reported by MacLachlan and co-workers.[47] In their work, two
macrocycles with regioisomeric backbones were reported, one
constructed in a classical way and the other one in a non-
[a]
Dr. M. Urbani, Prof. T. Torres
Departamento de Química Orgánica, Universidad Autónoma de
Madrid, Cantoblanco, 28049 Madrid, Spain
E-mail: maxence.urbani@uam.es, tomas.torres@uam.es
Dr. M. Urbani, Prof. T. Torres
IMDEA-Nanociencia, Campus de Cantoblanco, 28049 Madrid,
Spain
[b]
[c]
Prof. T. Torres
Institute for Advanced Research in Chemical Sciences (IAdChem)
Universidad Autónoma de Madrid, 28049 Madrid, Spain.
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.201904763
Chemistry - A European Journal
FULL PAPER
conventional (or inverted) fashion. To achieve such designs, two
isomeric 2-hydroxy-benzaldehyde (or salicylaldehyde) units
substituted either at the 4- or 5- position, were attached to a
linear- (180º) or a 60º- linker, respectively, and subsequently
condensed with the same diamino precursor. Most importantly,
they observed drastic differences regarding their aggregation
behaviour, one regioisomeric macrocycle being strongly
aggregated in solution whereas the other one was not (or
weakly), which they ascribed to what they called “social or
antisocial” arrangement. In this work, we report the synthesis of
a novel triangular-shaped [3+3] Schiff base salphen macrocycle
(7a) constructed in a non-conventional fashion (inverted) and
having an ortho-type substitution pattern, and subsequent Zn-
metallation into metallomacrocycle 7b. These macrocycles
display weak - (7a) to strong- (7b) tendency to undergo
aggregation in solution as supported by NMR and UV-visible
spectroscopy experiments. The ability of these macrocycles to
self-organize at the supramolecular level was further studied in
the solid state by AFM and TEM experiments.
Scheme 1. Synthesis of macrocycle 7a. Reagents and conditions: i) TMSA (4
eq), Pd(PPh3)4, CuI, Et3N, sealed tube, 85°C, 4 days (60 %); ii) TBAF 1 M in
THF, THF, 0 °C, 2 h (98%); iii) 5-bromosalicylaldehyde (2.4 eq), Pd(PPh3)4,
CuI, Et3N, 75 °C, 10 h (32%); iv) CHCl3/AcCN (1:1), reflux, 24 h (64%); v)
Zn(OAc)2, THF/EtOH (4:1), 45 °C, 2.5 h (quant.).
in mixtures of solvents CHCl3/EtOH (1:1), AcCN/EtOH (2:1), or
CHCl3/AcCN (8:2), at reflux for 1‒2.5 days and concentration of
reagents ([3] = [6] = 1 mM or 12 mM). Under these conditions,
we systematically obtained intensively colored crude of reactions
(orange/red) fully soluble in common organic solvent (e.g.:
CHCl3). However, MS and 1H NMR analysis of these crudes
revealed complex mixtures of open-forms (oligomers) and/or
macrocyles in various proportions, with only traces of the
desired [3+3] macrocycle. The identified macrocycles by MS
analysis were the [1+1] as the major product, followed by [2+2],
[3+3], [4+4] as minor products. Changing the conditions to a
refluxing mixture of CHCl3/AcCN (1:1) at ca. 85‒90 ºC for 24 h,
and a concentration of 12 mM ([3] = [6]), we observed this time
the formation of an orange precipitate during the course of the
reaction as the major product. MS analysis of the insoluble
fraction identified the [3+3] macrocycle, confirming its successful
formation under these conditions, while that of the supernatant
(fully soluble material) revealed the presence of the [1+1] and
[2+2] macrocycle as major products (see Figures S3 and S4 in
the ESI). In fact, 7a is poorly soluble in most of common organic
solvents despite the presence of six peripheral octyl chains (ca.
1.5‒2 mg/ml in CHCl3). Based on the geometry-optimized
structures (see ESI, Table S1), only the [3+3] macrocycle 7a
should be able to adopt a conformation with enough planarity to
allow aggregation by - stacking (Figure 1), which should not
be possible for the smaller [1+1], [2+2] and larger [4+4] ones.
This explains well why experimentally, oligomers (open-forms)
and mixture of macrocycles ([1+1], [2+2] and [4+4]) were soluble
in the crude (supernatant), while the [3+3] one (7a) precipitate
Chart 1. Schematic representation of triangular-shaped [3+3] Schiff base
macrocycles with regioisomeric backbones (note the 1,2,4 and 1,2,5 isomeric
positions); black dots represent the location of the coordination sites, so-called
“salphen pockets”.
Results and Discussion
Synthesis
The synthesis of macrocycle 7a relies on an imine condensation
between
a
di-salicylaldehyde precursor (3) and 4,5-
bis(octyloxy)benzene-1,2-diamine (6) (Scheme 1). Detailed
synthesis and characterization of the precursors are provided in
the Supporting Information. The conditions of reaction for the
formation of the [3+3] macrocycle were found crucial. Initially,
several conditions were unsuccessfully attempted to obtain 7a:
This article is protected by copyright. All rights reserved.

10.1002/chem.201904763
Chemistry - A European Journal
FULL PAPER
during the course of the reaction. As Zhang and Moore[28]
discussed in details for a typical [3+3] salphen macrocycle
reported by MacLachlan and collaborators,[41] the [3+3] one
should be, in principle: 1) enthalpically favored over the smallest
[1+1] and [2+2] ones because of less angle strain, and 2)
entropically favoured over the larger [4+4] ring. Geometry-
optimized structure predicted by DFT calculations suggests that
7a is able to adopt a pseudo-planar configuration (though
relatively distorted) despite the steric repulsion between the
inner CH-phenylene protons (see Figure 1). The above results
and experimental observations, suggest that the formation of
macrocycle 7a might not be solely thermodynamically-driven but
also governed by solubility (precipitation of the aggregates).
Under optimal conditions, 7a was obtained in a reasonable 64%
yield, which lies in the range of reported values for [3+3] Schiff-
base macrocycles (40‒90%).[42‒44]
Finally, the zinc-
metallomacrocyle 7b was obtained by metalation of 7a with an
excess of Zn(OAc)2 (3.4 eq) in THF/EtOH (4:1) at 45 °C for 2.5 h.
Figure 1. Geometry-optimized structures of 7a and 7b in vacuum predicted
with DFT calculations at the B3LYP (6-31G*) level of theory (n-octyl chains
have been replaced by methyl groups in the calculations; grey: carbon, white:
hydrogen, red: oxygen, blue: nitrogen, and pink: zinc atoms).
NMR and UV-visible spectroscopy
1
To further support that the observed H NMR spectra of 7a at
As commented before, 7a displays a relative poor solubility in
most common organic solvents and tend to precipitate
progressively in solution after relatively short period of times,
indicative of aggregation. Thus, it rendered difficult
characterization by NMR since poor solubility and tendency to
undergo aggregation imposed to work at low concentration. At a
concentration below ca. 1 mM, a well-defined 1H NMR spectrum
of 7a in CDCl3 solution could be recorded (Figure 2), showing in
particular, a unique single singlet signal for both the phenolic
(upshifted at H = 13.39 ppm) and iminic (H = 8.32 ppm) protons,
characteristic of the salphen pocket. 1H NMR spectra of 7a were
also recorded in d8-THF and d6-DMSO solutions (see Figures
S26, S72 and S73 in the ESI). In d8-THF, the solubility was
slightly improved but no significant differences were observed in
the NMR spectrum with respect to that recorded in CDCl3. The
1H NMR spectrum of 7a in dilute d6-DMSO solution (0.75 mM)
was much less resolved than in CDCl3 or d8-THF but is
qualitatively the same with the exception of the quasi-
disaperance of the PhOH protons signals, similarly than
low concentration range (1 mM) does correspond to the
monomeric species in solution and, in addition, to estimate the
size of the macrocycle, DOSY 1H NMR experiments were
performed both in CDCl3 and d8-THF solutions. As exemplified
for the 2D-DOSY spectrum of 7a in d8-THF depicted in Figure 3,
the NMR signals belong to a unique specie diffusing in solution,
with average diffusion coefficients (D) ranging from 4.4‒4.7 × 10-
10
m2/s in d8-THF to 4.6‒5.1 × 10-10 m2/s in CDCl3 (see Figures
S28‒S31 in the ESI). It is worth to notice that the phenolic
protons signal systematically gave slightly greater diffusion
coefficient values (+ 5‒10%) than the other ones, which can be
reasonably explained by PhOH-imine proton-exchange
phenomena.[ 48 ] Given the experimental margin errors for the
determination of the absolute values of diffusion coefficients,
DOSY spectra were also recorded in the presence of mesitylene
as internal reference, in order to better estimate the
hydrodynamic radius of the macrocycle. Mean values of 15±1 Å
from d8-THF and 13.0 ± 0.7 Å from CDCl3 were extracted from
the DOSY experiments, which match fairly well the 15.6 Å
molecular radius estimated from the DFT geometry-optimized
structure (Figures S32 and Table S3 in the Supporting
Information). Surprisingly, 7b was noticeably more soluble in
organic solvent than its analogue 7a, and did not precipitate in
time at the same concentration used for NMR analysis (ca. 1
mM). In all 1H NMR spectra recorded for 7b, the phenolic proton
singlet signal (characteristic of the metal-free macrocycle) was
clearly absent, as expected if three zinc metals are bounded to
the tridentate macrocycle ligand through the N2O2 coordination
sites. However, very broad and ill-defined NMR spectra were
systematically obtained for this compound (CDCl3 or d8-THF;
see Figure S27), which, as it can be anticipated, indicate that 7b
is readily and strongly aggregated in solution at the NMR
concentration. Zinc-multimetallic salphen complexes are indeed
well-known to strongly self-assemble through oligomeric (Zn−O)n
coordination motifs with very high-stability.[22,23]
observed in
a
9:1 mixture d8-THF/d4-MeOH. At higher
concentration (1‒2 mM) in d6-DMSO, the NMR spectrum is
much less resolved and 7a precipitate realtively quickly (<1 h). In
very polar solvent such as DMSO, the intramolecular H-bonding
in 7a should be disrupted, however no change was observed
regarding the solubility or NMR features. These results suggest
that - stacking is the dominant interaction towards the self-
assembly of the metal-free macrocycle 7a.
UV-visible absorption spectroscopy experiments in solution
did not reveal any spectral changes for 7a in the 250‒2 mol/l
concentration range (either in CHCl3 or THF), which support that
7a is fully disaggregated in solution below 1 mM, and moreover,
is not affected by the nature of the solvent (see Figures S34‒
S38 in the ESI).
This article is protected by copyright. All rights reserved.

10.1002/chem.201904763
Chemistry - A European Journal
FULL PAPER
In more polar and disaggregative solvent, such as THF, 7b is
fully desaggregated at a concentration of 12 mol/L (see Figures
4.B,D), and start to aggregate at around 30 mol/L (Figure S57
in the ESI). As well, aggregation-disaggregation was also
observed at low concentrations (9 mM) in mixtures of CHCl3 and
THF solvents (see ESI, Figure S58).
These results evidence that 7b is strongly aggregated through
oligomeric (Zn−O)n coordination motifs, in contrast to the weakly
aggregated macrocycle 7a for which - stacking is the
dominant interaction. It is worth to notice that at concentrations
of- and above- 1 mM, 7b is still perfectly soluble in organic
solvent (e.g. CHCl3) despite being fully aggregated, whereas 7a
readily precipitate above this concentration. The proposed
structure of both macrocycles was confirmed by MALDI-TOF
mass spectrometry. The MS spectrum of 7a shows a unique
signal corresponding to the molecular ion peak ([7a]●+) at m/z =
2216.1, and without detection of dimeric species. In turn, the
most intense one for 7b corresponds to the dimer ([(7b)2]●+ at
m/z = 4813.7) rather than that of the monomer specie (([7b]●+ at
m/z = 2405.8), which supports the strong aggregation character
of the zinc-metallomacrocyle (see Figures S6-S9 in the ESI).
Figure 2. Partial 1H NMR spectrum (400 MHz; 298K) of 7a in CDCl3
solution ([7a] < 1 mM); *S denotes the residual CHCl3 solvent peak).
Figure 3. 2D-DOSY 1H NMR (500 MHz; 298 K) spectrum of 7a in d8-THF
solution ([7a] < 1 mM; S denote the residual signals of the THF solvent
(for nomenclature of the protons, see Figure 2); * denotes the signal of a
recurrent and residual impurity of the employed commercial d8-THF
solvent (see Figure S26 in the Supporting Information for details).
In fact, UV-visible absorption spectroscopy experiments in
solution (Figures 4 and S45-S60 in the ESI) revealed that 7b is
fully aggregated at concentrations as low as 2 mol/L in low-
polar solvent (CHCl3 or CH2Cl2). Aggregation-disaggregation of
7b was observed by UV-Visible absorption spectroscopy at
variable concentration (Figures 4.A,B) and by spectroscopic
titration with pyridine (Figures 4.C,D). Remarkably, even a large
excess of pyridine (>10,000 Eqs) was not sufficient enough to
desaggregate entirely 7b in CHCl3, and this, even at
concentration below 10 mol/L (Figure 4.C and S54).
Figure 4. Effect of the concentration (A,B) and pyridine (C,D) toward
aggregation behavior of 7b: UV-visible absorption spectra of 7b in A), C)
CHCl3 and B),D) in THF solutions.
This article is protected by copyright. All rights reserved.

10.1002/chem.201904763
Chemistry - A European Journal
FULL PAPER
The UV-visible absorption spectrum of the metal-free
macrocycle 7a in THF solution (14 M; Figure 5), shows an
intense absorption in the UV region but only a modest one in the
visible range (above 400 nm). Upon addition of three equivalents
of Zn(OAc)2, the whole absorption spectrum was significantly
redshifted, in addition to the appearance of a relatively strong
absorption band in the visible region (max = 420 nm), extending
up to ca. 550 nm. In the emission spectra, it can be remarked an
important blue-shift (max = 50 nm) of the emission band, from
595 nm to 545 nm after addition of the zinc metal salt.
Absorption and emission spectra of the -as synthesised- zinc-
metallomacrocycle 7b match those obtained from titration
experiments of 7a with Zn(OAc)2 (Figure 5). Redshift of the
absorption spectrum accompanied with appearance of a strong
absorption band in the visible region, and shorter Stoke shifts
may be indicative of a gain in planarity and hence a more
effective conjugation for the zinc-metallo (7b) with respect to the
metal-free (7a) macrocycle. Geometry-optimized structures
support this hypothesis since 7b is fairly more planar than 7a
(Figure 1). To further confirm the structure of 7a, and therefore
the three available metal- coordination sites present in the [3+3]
macrocycle, UV-Visible absorption (Figure 6) and luminescence
(see ESI, Figures S43-S44) spectrophotometric titrations of
macrocycle 7a with Zn(OAc)2 were performed in THF solutions.
The corresponding Job’s plot analyses support that macrocycle
7a is indeed able to coordinate three zinc-metal centers into its
cavities (i.e. ratio [7a]/[Zn] of 1:3). UV-visible absorption and
fluorecencece spectroscopic experiments show the ability of 7a
to bind various other metals after addition of an excess (3‒4 eq)
of the corresponding acetate metal salt at rt (M(OAc)2, with M =
Co, Cu, Ni, Mg and Mn; see Figures S69-S71 in the Supporting
Information). In this work, we focused on zinc-metallomacrocycle
(7b) owing to its well-known and peculiar property to strongly
self-assemble (through Zn-O interactions) and present also the
advantage to be highly soluble in organic media even when
strongly aggregated.
Figure 6. UV-Visible absorption spectrophotometric titration of macrocycle 7a
with Zn(OAc)2 in THF+4%EtOH; inset: Job’s plot analysis (with [Zn]Total
[Macrocycle]Total = 13.8 M and Zn: mol fraction of zinc atoms).
+
AFM and TEM imaging
Since spectroscopic (UV-Visible, NMR) and MS spectrometry
experiments clearly indicate that both macrocycles 7a and 7b
undergo aggregation in solution, we further investigated their
self-assembly in the solid state by AFM and TEM microscopies.
For AFM experiments, the samples were prepared on HOPG
substrates. The macrocycles were deposited either by drop-
casting or spin-coating solutions of 7a or 7b in CHCl3, toluene,
THF or binary mixtures of them, and at different concentrations
(see full details in the ESI, Tables S4 and S5). Regarding the
technique of deposition,
a
quite smoother and more
homogenous surface of the HOPG with reduced amount of
residual small particles were usually obtained by using spin-
coating instead of drop-casting, but no significant difference was
observed regarding the final formation of the self-assembly. On
the contrary, the size, shape and morphology of the fibers were
strongly dependent of both the solvent and concentration. At
concentrations above ca. 10‒14 M in all tested solvents (pure
or mixtures), both macrocycle materials collapse into large
amorphous domains and/or giant clusters on the surface. The
same occurred at any concentration when THF was used as the
uptake solvent. Using either CHCl3, toluene or mixtures of them,
and a concentration of macrocycle in the range of 0.5‒3 M, we
observed the formation of large bundles of fibers with lengths of
several microns, variable width (up to ca. 40 nm) and heights
(3‒40 nm) for both 7a and 7b (Figures 7 and 8, respectively).
According to our estimation of 3.0‒3.2 nm for the diameter of a
macrocycle particle (by DOSY-NMR and DFT-geometry
optimized structures), and assuming a vertical orientation of the
molecules over the surface, the height of the fibers measured by
AFM fits well with mono- to multilayer- organizations (see AFM
height profiles in the ESI, Figures S61‒S68). The minimum
Figure 5. UV-Visible absorption (solid lines) and emission (dashed lines; ex
=
420 nm) spectra in THF solutions of metal-free macrocycle 7a (blue lines),
7a+Zn(OAc)2 (3 eq.) (black lines), and as synthesized zinc-metallomacrocycle
7b (pink lines); with [7a] = [7b] = [Macrocycle]Total = 14 M.
height of 3.3‒3.5 nm can be reasonably assigned to
a
monolayer of several microfibers composed of stacked-
macrocycles.
This article is protected by copyright. All rights reserved.

10.1002/chem.201904763
Chemistry - A European Journal
FULL PAPER
Figure 7. AFM images of macrocycle 7a deposited on an HOPG surface: a)
from a drop-casted solution in a 1:9 mixture of CHCl3/toluene (1.4 M); b-d)
from spin-coated solutions: b) 0.5 M in toluene, c) 2.3 M in toluene and d)
2.7 M in a 1:4 mixture of CHCl3/toluene.
Figure 9. TEM images of 7a (top; a-c) and 7b (bottom; d-f) deposited onto a
carbon-coated grid substrate; samples were prepared by drop casting
solutions of a-c) 7a in CHCl3 [23 M], d) 7b in CHCl3 [24 M], e) 7b in THF [24
M], f) 7b in toluene [12 M], and then dried at ambient atmosphere for 24 h.
Unexpectedly, a close inspection of the TEM images revealed
bundles of helical-type aggregates organized in “stick of
liquorice”-shaped nanofibers (especially visible in Figures 9.d
and 9.f). Such helical-shaped fibers were previously reported by
MacLachlan and co-workers for dinuclear zinc(II) salphen
complexes,[49] but to our knowledge there is no such example
reported in the case of salphen macrocycles.
Conclusions
A novel [3+3] salphen macrocycle (7a) having an unusual
(inverted) design and an ortho-type substitution pattern was
prepared. Metal-free (7a) and zinc-metallo (7b) macrocycles
show weak to strong tendency to aggregate in solution,
respectively, as evidenced by different spectroscopic techniques.
This ability to self-assemble at the supramolecular level was
confirmed in the solid state by AFM and TEM experiments,
showing the formation of micrometer-sized fibers with diameter
of several nanometers composed of stacked macrocycles.
Figure 8. AFM images of metallomacrocycle 7b deposited on HOPG surface
from drop-casted solutions (2.4 M) in: a, b) CHCl3/toluene (1:9); c, d) CHCl3.
For TEM experiments, all samples were prepared on
carbon-coated grid substrates by drop-casting solutions of 7a or
7b in THF (23‒24M), CHCl3 (23‒24 M), or toluene (12 M)
(see details in the ESI, Tables S6-S11). As seen in Figures 9a-c,
metal-free macrocycle 7a gives long networks of interconnected
bunch of fibers when drop-casted from a CHCl3 solution, with
length of several micrometers and width ranging from 7 nm to
more than 80 nm. However, no self-organization was observed
neither from toluene or THF solutions, collapsing into large
clusters, droplets or amorphous domains under these conditions.
In turn, the zinc-metallomacrocycle 7b behaved far different than
its metal-free analogue. First, fibers were observed from the
three uptake solvents, and surprisingly, even when drop-casted
from THF solution (Figure 9.e) although only few of them were
observed in the latter conditions. Next, and in contrast with 7a,
only much shorter bundles of fibers (<1 m) were obtained for
7b (Figures 9.d‒f), with width of 15‒35 nm.
Experimental Section
Synthesis and characterisation
Detailed experimental procedures, synthesis and characterization of the
compounds (MS, NMR and UV-Visible spectra) are provided in the
Supporting Information.
Diffusion-Ordered NMR Spectroscopy (DOSY)
DOSY 1H-NMR experiments (500 MHz) were performed by the Servicio
Interdepartamental de Investigacion (SIdI) at the Autonoma University of
Madrid and were recorded on a Bruker TopSpin AV-500 spectrometer at
298 K. Mesitylene was used as internal reference for the estimation of
the hydrodynamic radius of the macrocycle (See detailed procedures in
This article is protected by copyright. All rights reserved.

10.1002/chem.201904763
Chemistry - A European Journal
FULL PAPER
the Supporting Information). Data analysis and automatic DOSY
processing 2D-transformation were performed using the MesReNova
14.1 software package, including the “Bayesian”- and newly implemented
“Peak Heights fits”- DOSY Transform processing methods.
Conflicts of interest
The authors declare no competing financial interests.
Keywords: Macrocyclic ligands • Salphen • Schiff bases • Self-
assembly • Supramolecular Chemistry
UV–Vis absorption and fluorescence spectroscopy
Steady-state absorption spectra were recorded on an Agilent Cary 50
UV-Visible spectrophotometer at room temperature, using either a
standard 10 mm- (for low concentration range) or a 1 mm reduced path-
(for high concentration range) UV cuvettes (QS). Fluorescence spectra
were recorded on an HORRIBA Fluorolog®-3 spectrofluorometer using a
10 mm fluorescence UV cuvette (QS).
[1]
X. Liu, C. Manzur, N. Novoa, S. Celedón, D. Carrillo, J.-R. Hamon,
Coord. Chem. Rev., 2019, 357, 144-172.
[2]
[3]
[4]
[5]
[6]
[7]
S. Matsunaga, M. Shibasaki, Chem. Commun., 2014, 50, 1044-1057.
S. Akine, J. Inclusion Phenom. Macrocyclic Chem., 2012, 72, 25-54.
A. K. Crane, M. J. MacLachlan, Eur. J. Inorg. Chem., 2012, 2012, 17-30.
J. Zhou, B. Wang, Chem. Soc. Rev., 2017, 46, 6927-6945.
E. L. Gavey, M. Pilkington, Coord. Chem. Rev., 2015, 296, 125-152.
S.-i. Kawano, Y. Ishida, K. Tanaka, J. Am. Chem. Soc., 2015, 137,
2295-2302.
Atomic Force Microscopy (AFM)
AFM measurements were carried out in a commercial AFM system
(Ntegra Prima, NT-MDT) in semicontact (dynamic) mode using scanning
by sample configuration in ambient conditions. Rectangular silicon
cantilevers HA_NC (NT-MDT) were used with a tip radius of 10 nm. Their
nominal spring constant is 3.5 N/m and its resonance frequency is
around 140 kHz. AFM samples were prepared by either drop-casting or
spin-coating a solution of the macrocycles dissolved in CHCl3, THF,
toluene or mixtures CHCl3/Toluene (1:9 or 1:4) at different concentrations
onto HOPG substrates (See Tables S4 and S5 in the Supporting
Information for details).
[8]
[9]
S.-i. Kawano, T. Hamazaki, A. Suzuki, K. Kurahashi, K. Tanaka, Chem.
- Eur. J., 2016, 22, 15674-15683.
S.-i. Kawano, M. Kato, S. Soumiya, M. Nakaya, J. Onoe, K. Tanaka,
Angew. Chem., Int. Ed., 2018, 57, 167-171.
[10] J. Jiang, R. Y. Dong, M. J. MacLachlan, Chem. Commun., 2015, 51,
16205-16208.
[11] J. Zhang, L. Xu, W.-Y. Wong, Coord. Chem. Rev., 2019, 355, 180-198.
[12] K. Li, G. S. Ming Tong, Q. Wan, G. Cheng, W.-Y. Tong, W.-H. Ang, W.-
L. Kwong, C.-M. Che, Chem. Sci., 2016, 7, 1653-1673.
[13] C.-M. Che, S.-C. Chan, H.-F. Xiang, M. C. W. Chan, Y. Liu, Y. Wang,
Chem. Commun., 2004, 1484-1485.
Transmission Electron Microscopy (TEM)
[14] G. Salassa, J. W. Ryan, E. C. Escudero-Adán, A. W. Kleij, Dalton
Trans., 2014, 43, 210-221.
TEM experiments were performed by the ICTS Centro Nacional de
Microscopía Electrónica at Complutense University of Madrid. TEM
images were obtained on a JEM1400 Transmission Electron Microscope.
Samples were prepared by drop-casting a solution of the macrocycles in
CHCl3 (23-24 M), THF (23‒24 M) or toluene (11‒12 M) onto carbon-
coated grids.
[15] P. A. Vigato, S. Tamburini, Coord. Chem. Rev., 2004, 248, 1717-2128.
[16] M. Martínez Belmonte, S. J. Wezenberg, R. M. Haak, D. Anselmo, E. C.
Escudero-Adán, J. Benet-Buchholz, A. W. Kleij, Dalton Trans. 2010, 39,
4541-4550.
[17] G. Consiglio, I. P. Oliveri, S. Failla, S. Di Bella, Inorg. Chem. 2016, 55,
10320-10328.
Geometry-optimized structures and DFT calculations
[18]
L. Leoni, A. Dalla Cort, Inorganics 2018, 6.
[19] J. K.-H. Hui, P. D. Frischmann, C.-H. Tso, C. A. Michal, M. J.
MacLachlan, Chem. - Eur. J., 2010, 16, 2453-2460.
[20] G. Salassa, A. M. Castilla, A. W. Kleij, Dalton Trans., 2011, 40, 5236-
5243.
Molecular modelling was performed with the Spartan’16 package
(Wavefunction Inc. 1991–2017) software for Windows. Minimized
geometry-optimized structures (in vacuum) were obtained by DFT
calculations at the B3LYP (6-31G*) level.
[21] A. J. Gallant, M. J. MacLachlan, Angew. Chem., Int. Ed., 2003, 42,
5307-5310.
[22] G. Salassa, M. J. J. Coenen, S. J. Wezenberg, B. L. M. Hendriksen, S.
Speller, J. A. A. W. Elemans, A. W. Kleij, J. Am. Chem. Soc. 2012, 134,
7186-7192.
[23] M. V. Escárcega-Bobadilla, G. A. Zelada-Guillén, S. V. Pyrlin, M.
Wegrzyn, M. M. D. Ramos, E. Giménez, A. Stewart, G. Maier, A. W.
Kleij, Nat. Commun. 2013, 4, 2648.
Acknowledgements
[24] G. A. Zelada-Guillén, M. V. Escárcega-Bobadilla, M. Wegrzyn, E.
Giménez, G. Maier, A. W. Kleij, Adv. Mater. Interfaces 2018, 5,
1701585.
We are grateful for the financial support of the MINECO, Spain
(CTQ2017-85393-P). IMDEA Nanociencia acknowledges
support from the ‘Severo Ochoa’ Programme for Centres of
Excellence in R&D (MINECO, Grant SEV-2016-0686). We thank
Maite Alonso Pascual (MALDI-TOF MS), Mª Jesús Vicente
Arana (ESI-MS) and María Dolores Penín Pérez (DOSY NMR)
of the Servicio Interdepartamental de Investigación (SIdI) at the
Autonoma University of Madrid, Dr. Patricia Pedraz (AFM)
research staff at IMDEA Nanociencia Institute and Dr. Esteban
Urones Garrote (TEM) from Centro Nacional de Microscopía
Electrónica at Universidad Complutense de Madrid, for
experiments and helpful discussions.
[25] Y. Jin, C. Yu, R. J. Denman, W. Zhang, Chem. Soc. Rev., 2013, 42,
6634-6654.
[26] C. Yu, Y. Jin, W. Zhang, chapter 3: Shape‐persistent Macrocycles
through Dynamic Covalent Reactions in Dynamic Covalent Chemistry:
Principles, Reactions, and Applications, (Eds.: W. Zhang, Y. Jin), John
Wiley & Sons, Ltd, 2017, pp. 121-163.
[27] F. Mamiya, N. Ousaka, E. Yashima, Angew. Chem., Int. Ed., 2015, 54,
14442-14446.
[28] W. Zhang, J. S. Moore, Angew. Chem., Int. Ed., 2006, 45, 4416-4439.
This article is protected by copyright. All rights reserved.

10.1002/chem.201904763
Chemistry - A European Journal
FULL PAPER
[29] Z. J. Kinney, C. S. Hartley, J. Am. Chem. Soc., 2017, 139, 4821-4827.
[30] Z. J. Kinney, C. S. Hartley, Org. Lett., 2018, 20, 3327-3331.
[31] F. Ren, K. J. Day, C. S. Hartley, Angew. Chem., Int. Ed., 2016, 55,
8620-8623.
[40] A. J. Gallant, J. K. H. Hui, F. E. Zahariev, Y. A. Wang, M. J.
MacLachlan, J. Org. Chem., 2005, 70, 7936-7946.
[41] C. Ma, A. Lo, A. Abdolmaleki, M. J. MacLachlan, Org. Lett., 2004, 6,
3841-3844.
[32] A. Galán, E. C. Escudero-Adán, P. Ballester, Chem. Sci., 2017, 8,
7746-7750.
[42] S. Akine, D. Hashimoto, T. Saiki, T. Nabeshima, Tetrahedron Lett.,
2004, 45, 4225-4227.
[33] M. Mastalerz, Angew. Chem., Int. Ed., 2010, 49, 5042-5053.
[34] M. Petryk, J. Szymkowiak, B. Gierczyk, G. Spólnik, Å. Popenda, A.
Janiak, M. Kwit, Org. Biomol. Chem., 2016, 14, 7495-7499.
[35] L. Zhang, L. Xiang, C. Hang, W. Liu, W. Huang, Y. Pan, Angew. Chem.,
Int. Ed., 2017, 56, 7787-7791.
[43] C. T. L. Ma, M. J. MacLachlan, Angew. Chem., Int. Ed., 2005, 44, 4178-
4182.
[44] A. J. Gallant, M. Yun, M. Sauer, C. S. Yeung, M. J. MacLachlan, Org.
Lett., 2005, 7, 4827-4830.
[45] J. Jiang, M. J. MacLachlan, Org. Lett., 2010, 12, 1020-1023.
[46] J. K. H. Hui, M. J. MacLachlan, Chem. Commun., 2006, 2480-2482.
[47] B. N. Boden, J. K. H. Hui, M. J. MacLachlan, J. Org. Chem., 2008, 73,
8069-8072.
[36] J. C. Lauer, W.-S. Zhang, F. Rominger, R. R. Schröder, M. Mastalerz,
Chem. - Eur. J., 2018, 24, 1816-1820.
[37] G. Feng, W. Liu, Y. Peng, B. Zhao, W. Huang, Y. Dai, Chem. Commun.,
2016, 52, 9267-9270.
[48] Y. Cohen, L. Avram, L. Frish, Angew. Chem., Int. Ed., 2005, 44, 520-
554.
[38] M. Mastalerz, Chem. Commun., 2008, 4756-4758.
[39] S. Akine, T. Taniguchi, T. Nabeshima, Tetrahedron Lett., 2001, 42,
8861-8864.
[49] J. K. H. Hui, M. J. MacLachlan, Dalton Trans., 2010, 39, 7310-7319.
This article is protected by copyright. All rights reserved.

10.1002/chem.201904763
Chemistry - A European Journal
FULL PAPER
Entry for the Table of Contents
FULL PAPER
Maxence Urbani,* Tomas Torres*
Page No. – Page No.
A constrained and “inverted” [3 + 3]
salphen macrocycle with an ortho-
phenylethynyl substitution pattern
Dark side of the triangle. The synthesis and supramolecular organization of an
(inverted) triangular-shaped [3+3] salphen macrocycle is reported. Metal-free and
zinc-metallated macrocycles form nano- to micrometer- sized fibers in the solid
state.
This article is protected by copyright. All rights reserved.