Threading of a double-calix[6]arene system with dialkylammonium axles

Article abstract of DOI:10.1080/10610278.2013.872248

The threading of a double-calix[6]arene system (4) with dialkylammonium axles (2 and 3) has been investigated in the presence of the superweak tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (TFPB) anion. NMR and ESI(+)-mass spectrometry analyses showed that singly and doubly threaded pseudorotaxanes can be stepwise formed under appropriate conditions. The directional threading of an alkylbenzylammonium axle with double-calix[6]arene 4 occurs with an endo-alkyl preference in accordance with the endo-alkyl rule. DFT calculations confirmed this preference and evidenced that the pseudo[3]rotaxane complexes are characterised by an anti-conformation around the O^calix-CH ^bridge₂ bonds, which led to a spatial divergence of the two calix-cavities.

Full text of DOI:10.1080/10610278.2013.872248

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Threading of a double-calix[6]arene system with
dialkylammonium axles
Roberta Ciaoa, Carmen Talottaa, Carmine Gaetaa & Placido Neria
a Dipartimento di Chimica e Biologia and NANO_MATES Research Center, Università di
Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano (Salerno), Italy
Published online: 17 Jan 2014.
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To cite this article: Roberta Ciao, Carmen Talotta, Carmine Gaeta & Placido Neri (2014) Threading of a double-calix[6]arene
system with dialkylammonium axles, Supramolecular Chemistry, 26:7-8, 569-578, DOI: 10.1080/10610278.2013.872248
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Supramolecular Chemistry, 2014
Vol. 26, Nos. 7–8, 569–578, http://dx.doi.org/10.1080/10610278.2013.872248
Threading of a double-calix[6]arene system with dialkylammonium axles
Roberta Ciao, Carmen Talotta, Carmine Gaeta* and Placido Neri*
`
Dipartimento di Chimica e Biologia and NANO_MATES Research Center, Universita di Salerno,
Via Giovanni Paolo II 132, I-84084 Fisciano (Salerno), Italy
(Received 23 October 2013; accepted 21 November 2013)
The threading of a double-calix[6]arene system (4) with dialkylammonium axles (2 and 3) has been investigated in the
presence of the ‘superweak’ tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (TFPB) anion. NMR and ESI(þ)-mass
spectrometry analyses showed that singly and doubly threaded pseudorotaxanes can be stepwise formed under appropriate
conditions. The directional threading of an alkylbenzylammonium axle with double-calix[6]arene 4 occurs with an endo-
alkyl preference in accordance with the ‘endo-alkyl rule’. DFT calculations confirmed this preference and evidenced that the
pseudo[3]rotaxane complexes are characterised by an anti-conformation around the OcalixZCH2bridge bonds, which led to a
spatial divergence of the two calix-cavities.
Keywords: double-calixarene; directional threading; TFPB superweak anion; pseudorotaxane
1. Introduction
corresponding interlocked counterparts such as [2 and 3]
rotaxane (15) and [2]catenane (16) systems. Recently, we
have also shown that the larger 32-membered calix[8]arene
macrocycle gives through-the-annulus threading with
dialkylammonium axles only upon partial pre-organisation
of the native macroring by 1,5-intrabridging to generate
two smaller subcavities (17). Our study showed that such
1,5-bridged calix[8]arene hosts gave pseudo[2]rotaxanes
in which only one dialkylammonium axle was threaded
into one of the two subcavities, leaving the other
unoccupied.
Rotaxanes and catenanes (1) have gained a prominent
position in the field of nanotechnology wherein they have
been used as molecular machines (2) or molecular
electronics (3). In addition, novel and fascinating functions
have been shown in the last couple of years for these
interpenetrated architectures. For example, a prototypical,
rotaxane-based, artificial ribosome has been reported by
Leigh and coworkers, which is able to perform a sequence-
specific synthesis of a peptide (4).
Rotaxane and catenane architectures can be efficiently
obtained through a template-directed synthesis (5) by
exploiting the threading of a linear axle through a
macrocycle to form a pseudorotaxane complex, which can
be considered the most common precursor to both
rotaxanes and catenanes. One of the early applications of
this strategy provides the use of dialkylammonium ions as
axles and macrocycles such as crown ethers (6),
cyclodextrins (7) and cucurbiturils (8).
Concerning the hosts with multiple cavities or rings,
spectacular interpenetrated architectures have been
obtained by double-threading through systems in which
two macrocycles are covalently linked to one another in a
handcuff-like fashion (18) (e.g. double-crown ethers or
amide-based double macrocycle). In particular, non-trivial
‘handcuff’ catenane (19) architectures have been reported
where two covalently linked macrocycles have a single
larger macrocycle passing through both rings.
In the last few years, we have shown (9) that the
through-the-annulus threading of simple calix[6]arene
hosts (e.g. 1, Chart 1) (10) with dialkylammonium axles (e.
g. 2þ and 3þ) can be obtained through the inducing effect
of the superweak tetrakis[3,5-bis(trifluoromethyl)Phenyl]
borate (TFPB) anion (11) that gives free ‘naked’
dialkylammonium cations (12). Thus, through this ‘super-
weak anion approach’, we have obtained interesting
examples of stereoprogrammed (13) and self-sorting (14)
calixarene-based pseudorotaxane architectures and the
Regarding double-calixarene systems (e.g. 4) (20),
their threading with dialkylammonium ions was unex-
plored until very recently (21) when our group obtained
the first examples of ‘handcuff’ architectures 62þ by
double-threading double-calix[6]arene
4 with bis
(ammonium) axle 52þ (22). As a complement to that
preliminary report, we have extended our study to the
threading features of 4 with dialkylammonium axles 2þ
and 3þ and we report the obtained results here.
*Corresponding authors. Email: cgaeta@unisa.it; neri@unisa.it
q 2014 Taylor & Francis

570
R. Ciao et al.
N
H2
N
H2
O
O
O
O
O
O
+
2
+
3
F
C
C
C F
3
C F
1
3
3
F
F
C
3
3
3
3
-
B
C
F
C F
C F
3
O
O
O
O
O
O
O
O
TFPB– Anion
O
O
O
O
N
R
4
H2
O
O
H2
N
52+
R
R = CH2(CH2)3CH3
O
O
O O
O
O
O
H
N
H
N
H
O
H
O
O
O
O
O
O
-
6
2+. 2TFPB
Chart 1. (Colour online) Structures of calix[6]arene hosts 1 and 4, alkylammonium axles 2þ, 3þ and 52þ, TFPB anion, and pseudo[2]
rotaxane 62þ.
2. Results and discussion
(Figure 1). In fact, upon addition of 1 equiv. of
2þ·TFPB2 salt, a new set of signals emerged (Figure 1
(c)) due to the formation of the singly threaded pseudo[2]
rotaxane ion 2þ,4 (Scheme 2). Under these conditions
(1 equiv. of axle 2þ), the formation of a singly threaded
pseudo[2]rotaxane ion 2þ,4 (Scheme 2) was ascertained
Double-calix[6]arene 4 was synthesised exploiting the
reaction sequence shown in Scheme 1 (23). In particular,
p-H-calix[6]arene 7 (24) was monobenzylated with
benzylbromide and K2CO3 to give 8 in 40% yield (25),
which was exhaustively methylated with MeI in the
presence of Cs2CO3 as the base to give 9 in 90% yield.
This derivative was then subjected to hydrogenolysis with
Pd/C to give pentamethoxycalix[6]arene-mono-ol 10 in
45% yield, which was reacted with 1,3-bis(bromomethyl)
benzene in the presence of NaH to give double-calix[6]
arene 4 in 33% yield.
1
The H NMR spectrum (400 MHz, CDCl3) of 4 at
298 K (Figure 1, bottom) shows sharp signals indicating a
fast conformational interconversion. This is due to the
small dimension of both the methoxy groups at the lower
rim and the p-H ‘substituents’ at the upper rim, which
allow the through-the-annulus passage of both rims (26).
Therefore, at room temperature, double-calix[6]arene 4 is
conformationally mobile.
2.1. Threading of double-calix[6]arene 4 with di-n-
pentylammonium axle 21
1
Figure 1. (Colour online) H NMR spectra (400 MHz,þ298 K,
CDCl3) of: (a) 4 (2.6 £ 1023 M); (b) 4 and 0.5 equiv. of 2 ; (c)þ4
and 1 equiv. of 2þ; (d)4 and 2 equiv. of 2þ; (e) 4 and 3 equiv. of 2 ;
(f) significant portion of the ESI(þ)-MS of a mixture of 4 and
1 equiv. of 2þ.
Interestingly, the addition of di-n-pentylammonium salt
2þ·TFPB2 to a CDCl3 solution of double-calix[6]arene 4
caused dramatic changes in its 1H NMR spectrum

Supramolecular Chemistry
571
by the ESI(þ)-mass spectrum (MS) that gave a value of
1672.4 m/z as the base peak (Figure 1(f)), corresponding to
a 1:1 host/guest stoichiometry, in which only one
dialkylammonium axle was threaded into one of the two
macrocycles of 4.
resonances at 75.4 and 74.5 ppm, which can be assigned to
OCH2 groups of the m-xylylene bridge. Naturally, these 1J
direct correlations were consistent with a singly threaded
pseudo[2]rotaxane structure.
Further addition of 1 equiv. of di-n-pentylammonium
axle 2þ led to a simplification of the 1H NMR spectrum of
the mixture of 2þ·TFPB2 and 4 (Figure 1(c),(d)). In
particular, the appearance of a new singlet at 4.98 ppm
(integrating for 4H) relative to OCH2 groups of the m-
xylylene bridge, and the presence of three singlets relative
to OMe groups were indicative of the formation of a new,
higher-symmetry, doubly threaded pseudo[3]rotaxane
(2þ)2,4 in which two axles 2þ were threaded into the
In addition, the appearance of n-alkyl resonances in the
upfield negative region of the 1H NMR spectrum of the 1:1
mixture of 2þ and 4 in CDCl3 and the formation of AX
systems for ArCH2Ar groups corroborate the formation of
the pseudo[2]rotaxane (9). The 1:1 stoichiometry was
confirmed by spectral integration. A COSY-45 spectrum
(CDCl3, 400 MHz, 298 K) of the 1:1 mixture of thread 22þ
and double-calix[6]arene 4 allowed a complete confident
assignment of all shielded alkyl resonances. Thus, a
protons at 20.02 ppm show a coupling with b methylene
group at 21.07 ppm, which presents a cross-peak with g
protons at 20.17 ppm, finally coupled with d protons at
0.37 ppm (accidentally isochronous with 1 methyl)
(Figure 2).
1
two macrocycles of 4. This was confirmed by H NMR
signal integration and by an ESI(þ)-MS of a 2:1 mixture
of 2þ·TFPB2 and 4, which gave a value of 915.5 m/z as
the base peak, corresponding to a 1:2 host/guest
stoichiometry.
DFT calculations at the B3LYP/6-31G* level of
theory (27) evidenced strongly stabilising NZH· · ·O
hydrogen bonds (Figure 4(a)) between the ammonium
threads and the calix-wheels. Interestingly, the optimised
Interestingly, a 2D HSQC spectrum (Figure 3)
revealed the presence of two cross-peaks between two
singlets at 4.99 and 4.78 ppm and two pertinent carbon
BnBr,K2CO3
dry CH3CN, reflux, 4 h
HO
HO
HO
OH
HO
HO
HO
OH
OH
OH
OH
O
7
8
MeI,Cs2CO3
Acetone, reflux,12 h
H2, Pd/C
O
O
O
O
O
O
O
O
O
O
O
CHCl3, r.t., 4 h
O
H
9
10
Br
Br
NaH, dry THF/DMF
12 h reflux
O
O
O
O
O
O
O
O
O
O
O
O
4
Scheme 1. Synthesis of double-calix[6]arene 4.

572
R. Ciao et al.
4
+ 2+·TFPB–
+
2+·TFPB–
O
O
H
O
O
H
O
O
N
O
O
O
HO
O
N
HO
O
O
ON
O
O
O
O
O
O
O
O
H
O
CDCl3
CDCl3
H
Scheme 2. (Colour online) Threading equilibria of double-calix[6]arene 4 with di-N-pentylammonium axle 2þ.
δ,ε
α
γ
β
ε
δ
γ
β
α
O
O
O
O
N
HO
O
O
O
O
O
O
O
H
2+⊂4
Figure 2. (Colour online) Significant portion of the 2D COSY spectrum (400 MHz, 298 K, CDCl3) of the 1:1 mixture of 4 and
2þ·TFPB2.
structure of the (2þ)2,4 complex (Figure 4(a)) revealed
an approximate C2 symmetry axis bisecting the m-xylyl
bridge and an anti conformation around the OcalixZCH2xylyl
bonds with dihedral angles of 168.28 and 167.28 (Figure 4
(b)). Consequently, the two calix cavities are diverging
with their main axes almost perpendicular. In particular,
the two mean planes of the calixarene oxygens form an
angle of 60.08. The preference for the anti-conformation
around the OcalixZCHx2ylyl bonds was confirmed by
molecular dynamics (MD) simulation at 500 K which
clearly evidenced that about 48% of the coconformers
sampled during the entire MD simulation (20,000 ps)
(a,b)
ε
δ
γ
β
α
O
O
O
O
O
O
O
ON
H
(b)
O
O
O
O
H
(a)
2+⊂4
Figure 3. (Colour online) Expansion of the HSQC spectrum (400 MHz, 298 K, CDCl3) spectrum of an equimolar solution of 2þ and 4.

Supramolecular Chemistry
573
Figure 4. (Colour online) (a) Energy-minimised structure of the (2þ)2,4 complex (B3LYP DFT calculations using the 6-31G* basis
set). (b) Detailed view of the predicted anti conformations around OcalixZCH2 bonds of the m-xylyl bridge. (c) Variation in the dihedral
angle between OcalixZCH2 observed during the MD simulation at 500 K (time given in ps).
showed a dihedral angle in the 150–1708 range around the
OcalixZCHx2ylyl bonds (Figure 4(c)).
we showed that encoding the appropriate alkylbenzyl
sequence along bis-ammonium axles, it was possible to
obtain a specific stereosequence (H,H or H,T in
Figure 5) of the two calix-wheels in (H,H)-122þ and
(H,T)-132þ pseudo[3]rotaxane architectures (13). Ana-
logously, the stereoprogrammed synthesis of a catenane
orientational isomer 14þ (an oriented calix[2]catenane)
has been obtained after macrocyclisation, by using a
directional alkylbenzylammonium axle (16).
The total binding constant (Ktot) for (2þ)2,4 complex,
1
determined by quantitative H NMR analysis of its 2:1
titration mixture in CDCl3 and using tetrachloroethane
(TCHE) as internal standard (28a), gave a value .107 M22
,
which was beyond the limit of reliability of the NMR
technique. Therefore, in order to have more accurate
measurements (28b) we decided to evaluate Ktot in the
presence of a polar competing solvent such as CD3CN (9).
Thus, in a mixture of CDCl3/CD3CN (99/1, v/v), we were
able to measure a value of Ktot ¼ 4.4 ^ 0.3 £ 104 M22 for
the (2þ)2,4 complex by quantitative 1H NMR analysis and
using TCHE as internal standard.
From these studies, we have deduced a sort of
‘molecular code’ which has been used to develop an
integrative self-sorting (14). This molecular code
includes the following stereochemical ‘endo-alkyl rule’
(Figure 5): ‘threading of a directional alkylbenzylammo-
nium axle (e.g. 3þ) through a p-H-hexaalkoxycalix[6]
arene (e.g. 1) occurs with an endo-alkyl preference’ (14).
On the basis of these results, we decided to verify
the validity of the endo-alkyl rule on double-calix[6]-
arene host 4. In fact, the threading of 4 with the
n-butylbenzylammonium axle 3þ could give rise to three
directional double-threaded pseudo[3]rotaxane diastereoi-
somers with endo-alkyl/endo-alkyl, endo-benzyl/endo-
2.2. Directional threading of double-calix[6]arene 4
with non-symmetrical n-butylbenzylammonium axle 31
Recently, we have shown that the threading of a non-
symmetrical directional alkylbenzylammonium cation
(e.g. 3þ, Chart 1) by a calix[6]arene (e.g. 1) leads to a
marked preference for the endo-alkyl stereoisomer 11þ
over the endo-benzyl one (Figure 5) (9). Successively,

574
R. Ciao et al.
endo-alkylrule
O
O
+
N
O
N
H
H
O
O
H
N O
O
O H
O
O
O
O
O
O
H
O
O
O
H
O
O
O N
O
H
O
O
(endo)–benzyl–11+
O
O
+
O
O
H
H
N
O
O
O
O
O
HO
H
O
H
+
N
O
H
O
O
O
H
O
O
N
O
O
ON
O
O
O
O
H
O
H
O
O
O
N
O
O
14+
(endo)–alkyl–11+
(H,H)–122+
(Preferred)
(H,T)–132+
Figure 5. (Colour online) The ‘endo-alkyl rule’ and related examples of oriented interpenetrated architectures.
1
alkyl or endo-benzyl/endo-benzyl relative orientations
(Figure 6).
rotaxane were observed in the H NMR spectrum of the
0.75:1 mixture of 3þ and 4 (Figure 7(d)). The progressive
addition of 3þ led to the disappearance of these two
singlets while a new singlet emerged at 4.96 ppm
corresponding to the doubly threaded pseudo[3]rotaxane
(3þ)2,4, as confirmed by ESI(þ)-MS and 1H NMR signal
integration.
Of course, on the basis of the above-discussed endo-
alkyl rule (Figure 5), we expected that the endo-alkyl/endo-
alkyl stereoisomer should be favoured. As in the previous
instance, the addition of butylbenzylammonium 3þ to a
solution of 4 in CDCl3 caused significant changes in its 1H
NMR spectrum. In particular, 1 equiv. of butylbenzylam-
monium 3þ led to a new species corresponding to the
singly threaded complex 3þ,4, in slow exchange with the
free host 4. The 1:1 host/guest stoichiometry was
As concerns the stereochemistry of the threading, the
1H NMR spectra of the 1:1 and 1:2 mixtures of 4 and 3þ
showed typical signatures at highfield negative values
(from 1.0 to 21.0 ppm) characteristic of an endo-alkyl
complexation (9, 13). This result and the absence of
shielded benzylic resonances in the 4–6 ppm region,
typical of an endo-benzyl complexation, were clear-cut
proofs that in both singly and doubly threaded pseudor-
otaxanes an endo-alkyl orientation of butylbenzylammo-
nium threads was present (10). This result demonstrated
the validity of the endo-alkyl rule also for double-
calixarenes and confirmed the possibility to control the
directionality of the double-threading in these systems.
1
confirmed by means of ESI(þ)-MS and integration of H
NMR signals. In fact, the ESI(þ)-MS of a 1:1 mixture of
3þ·TFPB2 and 4 gave a value of 1680.3 m/z as the base
peak (Figure 7(g)), corresponding to a singly threaded
pseudo[2]rotaxane ion 3þ, 4 (Scheme 3).
In analogy to the above-discussed 2þ,4 pseudorotax-
ane, also in this case, two singlets at 4.96 ppm and
4.77 ppm relative to the OCH2 protons of the m-xylylene
bridge corresponding to the singly threaded pseudo[2]
O
O
O
O
O
H
O
O
H
N
O O
O
O
O
O
O
O
O
O
H
O
O
N
H
O
N
O
O
H
HO
O
H
N
O
O
H
H
N
O
O
O
H
O
O
N
O
H
O
O
H
O
O
endo-alkyl
endo-alkyl
endo-benzyl
endo-alkyl
endo-benzyl
endo-benzyl
Figure 6. (Colour online) Possible double-threaded pseudo[3]rotaxane stereoisomers by directional threading of 4 with the n-
butylbenzylammonium axle 3þ.
4 + 3+·TFPB–
+
3+·TFPB–
O
O
O
O
H
O
H
O O
O
O
O
N
O
H
O
N
O
H
H
O
O
ON
O
O
O
O
O
O
O
O
H
CDCl3
CDCl3
Scheme 3. (Colour online) Threading equilibria of double-calix[6]arene 4 with n-butylbenzylammonium axle 3þ.

Supramolecular Chemistry
575
1
Figure 7. (Colour online) H NMR spectra (400 MHz,þ298 K,
CDCl3) of: (a) 4 (2.6 £ 1023 M); (b) 4 and 0.25 equiv. of 3 ; (c) 4
and 0.5 equiv.þof 3þ; (d) 4 and 0.75 eþquiv. of 3þ; (e) 4 and
1.0 equiv. of 3 ; (f) 4 and 2.0 equiv. of 3 ; (g) significant portion
of the ESI(þ)-MS of a mixture of 4 and 1 equiv. of 3þ.
Figure 8. (Colour online) (a) Energy-minimised structure of the
(3þ)2,4 complex (B3LYP DFT calculations using the 6-31G*
basis set). (b) Variation in the dihedral angle between OcalixZCH2
observed during the MD simulation at 500 K (time given in ps).
In analogy to the (2þ)2,4 complex above described,
DFT calculations at the B3LYP/6-31G* level of theory
(27) also in this case confirmed the presence of stabilising
NZH· · ·O hydrogen bonds (Figure 8(a)) between the
ammonium cations and the calixarene oxygens. The
optimised structure of the (3þ)2,4 complex (Figure 8(a))
was very similar to that of (2þ)2,4, showing again an
anti-conformation around OcalixZCH2xylyl bonds with
dihedral angles of 162.78 and 166.18. This conformational
preference was confirmed by MD simulation at 500 K,
which clearly evidenced that about 46% of the sampled
coconformers showed a dihedral angle in the 150–1708
range around the OcalixZCHx2ylyl bonds (Figure 8(b)).
The extension of DFT calculations to the other endo-
benzyl/endo-alkyl and endo-benzyl/endo-benzyl orienta-
tional isomers of (3þ)2,4 (Figure 9) confirmed the higher
stability of endo-alkyl/endo-alkyl orientation experimen-
tally evidenced by 1H NMR. In fact, this latter orientation
was 3.9 kcal/mol more stable than the endo-benzyl/endo-
alkyl orientation, which in turn was 4.3 kcal/mol more
stable than the endo-benzyl/endo-benzyl orientational
isomer.
As discussed above, also in this case, the total binding
constant (Ktot) of the (3þ)2,4 complex was determined by
quantitative 1H NMR analysis of its 2:1 titration mixture in
CDCl3/CD3CN (99/1, v/v), to give a value of 8.8 ^ 0.2
£ 104 M22. This value is only slightly higher than that
found (4.4 ^ 0.3 £ 104 M22) for dipentylammonium
complex (2þ)2,4.
3. Conclusion
In summary, we have reported on the threading abilities of
a double-calix[6]arene host with dialkylammonium axles
1
in the presence of TFPB superweak anion. H NMR and
ESI(þ)-MS spectra evidenced the stepwise formation of
singly and doubly threaded pseudorotaxane architectures
by changing the host/guest stoichiometry from 1:1 to 1:2.
The directional threading of non-symmetrical n-butylben-
zylammonium axle 3þ with double-calix[6]arene host 4
occurs with an endo-alkyl preference in accordance with
Figure 9. (Colour online) Energy-minimised structures of endo-alkyl/endo-alkyl (a), endo-benzyl/endo-alkyl (b) and endo-benzyl/endo-
benzyl (c) orientational isomers of pseudo[3]rotaxane (3þ)2,4 (B3LYP DFT calculations using the 6-31G* basis set).

576
R. Ciao et al.
the known ‘endo-alkyl rule’. DFT calculations indicated
that the lowest-energy structures of the pseudo[3]rotaxane
complexes are characterised by an anti-conformation
around the OcalixZCHx2ylyl bonds which led to a spatial
divergence of the two calix-cavities.
2.89 (s, OCH3, 12H); 13C NMR (75 MHz, CDCl3, 298 K):
d 156.7, 156.6, 156.3, 154.5, 137.9, 134.9, 134.8, 134.7,
134.6, 134.5, 130.0, 129.7, 129.3, 128.9, 128.8, 128.7,
128.2, 127.5, 127.4, 123.6, 74.9, 60.4, 60.2, 30.7, 30.4.
Anal. Calcd for C102H98O12: C, 80.82; H, 6.52. Found: C,
81.80; H, 6.43.
4. Experimental section
4.1. General comments
4.3. Preparation of singly-threaded pseudo[2]-
rotaxanes
ESI(þ)-MS measurements were performed on a Micro-
mass Bio-Q triple quadrupole mass spectrometer (Micro-
mass/Waters, Milford, MA, USA) equipped with
electrospray ion source, using CHCl3 as solvent. All
chemicals were reagent grade and were used without
further purification. When necessary, compounds were
dried in vacuo over CaCl2. Reaction temperatures were
measured externally. Derivative 2þ·TFPB2 (9),
3þ·TFPB2 (9) and 4 (22) were synthesised according to
literature procedures. NMR spectra were recorded on a
Bruker Avance-400 spectrometer (Bruker BioSpin GmbH,
Karlsruhe, DE) [400 (1H) and 100 MHz (13C)]; chemical
shifts are reported relative to the residual solvent peak
(CHCl3: d 7.26, CDCl3: d 77.23). COSY-45 spectra were
taken using a relaxation delay of 2 s with 30 scans and 170
increments of 2048 points each. HSQC spectra were
performed with gradient selection, sensitivity enhance-
ment and phase-sensitive mode using an Echo/Antiecho-
TPPI procedure. A typical experiment comprised 20 scans
with 113 increments of 2048 points each. Monte Carlo
conformational searches (10,000 steps) were performed
with the MacroModel-9.0/Maestro-4.1 program using
CHCl3 as solvent (GB/SA model). MD simulations were
performed at T ¼ 500 K, for 20,000 ps, using a time step of
1.0 fs.
Double-calixarene derivative 4 (2.0 £ 1023 g, 1.3
£ 1023 mmol) and the dialkylammonium derivative 2þ
or 3þ (1.3 £ 1023 mmol) were dissolved in 0.5 ml of
CDCl3, and the mixture was stirred for 5 min at 25 8C.
Then, the solution was transferred into an NMR tube for
1D and 2D NMR spectra acquisition.
Selected spectral data for singly threaded pseudo[2]
rotaxane ion 2þ,4. ESI(þ)-MS: m/z ¼ 1672.4 [2,4]þ.
1H NMR (CDCl3, 400 MHz, 298 K): d 21.07 [broad,
(CH2)b, 2H], 20.17 [broad, (CH2)g, 2H], 20.02 [broad,
(CH2)a, 2H], 0.37 [broad, (CH2)d þ (CH3)1, 5H], 3.53 and
4.29 (broad overlapped, ArCH2Ar, 24H), 2.87, 2.99, 3.23
(br s, OCH3, 6H, 3H, 6H), 3.78, 3.84, 3.90 (br s, OCH3,
3H, 6H, 6H), 4.79 (br s, OCH2, 2H), 4.98 (br s, OCH2, 2H),
6.63–6.99 (overlapped, ArH, 40H).
Selected spectral data for singly threaded pseudo[2]
rotaxane ion 3þ,4. ESI(þ)-MS: m/z ¼ 1680.3 [3,4]þ.
1H NMR (CDCl3, 400 MHz, 298 K): d 21.02 [broad,
(CH2)b, 2H], 0.04 [broad, (CH2)g þ (CH3)d, 5H], 0.22
[broad, (CH2)a, 2H], 2.30 [broad, (H2NþCH2aPh), 2H],
2.87–3.93 (broad overlapped OCH3 þ ArCH2Ar, 42H),
4.31–4.41 (broad overlapped, ArCH2Ar, 12H), 4.78 (br s,
OCH2, 2H), 4.98 (br s, OCH2, 2H), 5.37 (br s, þNH2, 2H),
6.76–7.40 (overlapped, ArH, 45H).
4.2. Synthesis and characterisation of double-
calixarene 4 (23)
4.4. Preparation of pseudo[3]rotaxanes
NaH (1.30 g, 54.2 mmol) was added at 0 8C, under stirring,
to a solution of derivative 9 (1.47 g, 2.07 mmol) in dry
THF/DMF (75 ml, 7/3 v/v). The mixture was kept at 25 8C
under stirring, and after 1 h, 1,3-bis(bromomethyl)benzene
(0.26 g, 0.98 mmol) was added. The reaction was stirred at
reflux for 12 h under a nitrogen atmosphere, then the
solvent was removed under reduced pressure and
the mixture was partitioned between CH2Cl2 and
H2O. The organic layer was washed with 1 N HCl
(50 ml), brine (50 ml) and dried over Na2SO4. The crude
product was purified by column chromatography (SiO2;
Et2O/CH2Cl2 3/97) to give derivative 4 as a white solid
(1.04 g, 0.69 mmol, 33%). ESI(þ)-MS: m/z ¼ 1516
(MHþ); 1H NMR (400 MHz, CDCl3, 298 K): d 7.06–
6.78 (overlapped ArH, 40H), 4.80 (s, OCH2Ar, 4H), 3.96
(s, ArCH2Ar, 8H), 3.92 (s, ArCH2Ar, 8H), 3.90 (s,
ArCH2Ar, 8H), 3.16 (s, OCH3, 12H), 3.11 (s, OMe, 6H),
Double-calixarene derivative 4 (2.0 £ 1023 g, 1.3
£ 1023 mmol) and the dialkylammonium derivative 2þ
or 3þ(2.6 £ 1023 mmol) were dissolved in 0.5 ml of
CDCl3, and the mixture was stirred for 5 min at 25 8C.
Then, the solution was transferred into an NMR tube for
1D and 2D NMR spectra acquisition.
Selected spectral data for doubly threaded pseudo[3]
rotaxane ion (2þ)2,4. ESI(þ)-MS: m/z ¼ 915.5
[(2)2,4]2þ 1H NMR (CDCl3, 400 MHz, 298 K): d
.
21.07 [broad, (CH2)b, 4H], 20.18 [broad, (CH2)g, 4H],
20.01 [broad, (CH2)a, 4H], 0.39 [broad,
(CH2)d þ (CH3)1, 10H], 3.52 and 4.33 (broad, ArCH2Ar,
24H), 3.79, 3.84, 3.91 (br s, OCH3, 6H, 12H, 12H), 4.98
(br s, OCH2, 4H), 6.66–7.61 (overlapped, ArH, 40H).
Selected spectral data for doubly threaded pseudo
[3]rotaxane ion (3þ)2,4. ESI(þ)-MS: m/z ¼ 921.5
[(3)2,4]2þ
.
1H NMR (CDCl3, 400 MHz, 298 K):

Supramolecular Chemistry
577
2003, 42, 5706–5711; (d) Collier, C.P.; Mattersteig, G.;
Wong, E.W.; Luo, Y.; Beverly, K.; Sampaio, J.; Raymo, F.
M.; Stoddart, J.F.; Heath, J.R. Science 2000, 289, 1172–
1175.
d 2 1.01 [broad, (CH2)b, 4H], 0.03 [broad, (CH2)g þ
(CH3)d, 10H], 0.23 [broad, (CH2)a, 4H], 2.27 [broad,
(H2NCHa2 Ph), 4H], 3.28, 3.59, 3.70 (s, OCH3, 6H,
12H, 12H), 3.50 and 4.44 (broad, ArCH2Ar, 8H), 3.52
and 4.32 (broad, ArCH2Ar, 8H), 3.58 and 4.43 (broad,
ArCH2Ar, 8H), 4.97 (br s, OCH2, 4H), 5.35 (br s,
þNH2, 4H), 6.64–7.59 (overlapped, ArH, 50H).
(4) Lewandowski, B.; De Bo, G.; Ward, J.W.; Papmeyer, M.;
Kuschel, S.; Aldegunde, M.J.; Gramlich, P.M.E.; Heck-
mann, D.; Goldup, S.M.; D’Souza, D.M.; Fernandes, A.E.;
Leigh, D.A. Science 2013, 339, 189–193.
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in Supramolecular Chemistry; The Royal Society of
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(10) For comprehensive reviews on calixarene macrocycles, see:
(a) Gutsche, C.D. Calixarenes, An Introduction; Royal
Society of Chemistry: Cambridge, UK, 2008, Chapter 5, pp
4.5. Determination of Kass values of (21)2,4 and
(31)2,4 complexes by quantitative 1H NMR analysis
(28a)
The samples were prepared by dissolving 4 (1.24
£ 023 mmol) and the appropriate alkylammonium guest
2þ or 3þ(2.48 £ 1023 mmol) in CDCl3 (0.4 ml) containing
1 ml of 1,1,2,2-TCHE (d ¼ 1.59 g/ml) as internal standard.
The complex concentration [complex] was evaluated by
1
integration of the H NMR signal of CHCl2CHCl2 versus
¨
116–128; (b) Bohmer, V. Angew. Chem. Int. Ed. Engl.
the shielded signals at negative values of the guest
molecule. The following equation (28a) was used to obtain
the moles of the complex:
1995, 34, 713–745; (c) Gutsche, C.D. Calixarenes
Revisited; Royal Society of Chemistry: Cambridge, UK,
¨
1998; (d) Asfari, Z., Bohmer, V., Harrowfield, J., Vicens J.,
Eds.; Calixarenes 2001. Kluwer: Dordrecht, 2001.
¨
(e) Bohmer, V. In The Chemistry of Phenols; Rappoport,
Ga Fa Nb Ma
¼
£
£
;
Z., Ed.; Wiley: Chichester, UK, 2003; Chapter 19, pp
1369–1453; (f) Vicens J.; Harrowfield, J., Eds.; Calixarenes
in the Nanoworld. Springer: Dordrecht, 2007.
Gb Fb Na Mb
where Ga are the grams of 1,1,2,2-TCHE; Gb are the grams
of complex; Fa and Fb are the areas of the signals of
1,1,2,2-TCHE and the shielded signal of the guest,
respectively; Na and Nb are the numbers of nuclei which
cause the signals (Na for 1,1,2,2-TCHE; Nb for guest); and
Ma and Mb are the molecular masses of 1,1,2,2-TCHE (a)
and complex (b), respectively.
(11) (a) Strauss, S.H. Chem Rev. 1993, 93, 927–942; (b)
Nishida, H.; Takada, N.; Yoshimura, M.; Sonoda, T.;
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Arduini, A.; Ferdani, R.; Pochini, A.; Secchi, A.; Ugozzoli,
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Acknowledgement
We thank the Italian MIUR (PRIN 20109Z2XRJ_006) for
financial support.
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