Conformational restriction of flexible molecules in solution by a semirigid bis-porphyrin molecular tweezer

Article abstract of DOI:10.1016/j.tet.2013.06.013

A semirigid bis-porphyrin molecular clip with a glycoluril backbone has been synthesized. The clip provides an adaptable molecular cavity for binding of diamines. Binding constants for diamines of 10⁴-10⁷ M^-1 are orders of

Full text of DOI:10.1016/j.tet.2013.06.013

Accepted Manuscript
Conformational restriction of flexible molecules in solution by a semirigid bis-porphyrin
molecular tweezer
Sara Norrehed, Prasad Polavarapu, Wenzhi Yang, Adolf Gogoll, Helena Grennberg
PII:
S0040-4020(13)00931-9
10.1016/j.tet.2013.06.013
TET 24489
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 18 March 2013
Revised Date: 22 May 2013
Accepted Date: 3 June 2013
Please cite this article as: Norrehed S, Polavarapu P, Yang W, Gogoll A, Grennberg H, Conformational
restriction of flexible molecules in solution by a semirigid bis-porphyrin molecular tweezer, Tetrahedron
(2013), doi: 10.1016/j.tet.2013.06.013.
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Graphical Abstract
Leave this area blank for abstract info.
Conformational restriction of flexible molecules
in solution by a semirigid bis-porphyrin
molecular tweezer
Sara Norrehed, Prasad Polavarapu, Wenzhi Yang, Adolf Gogoll* and Helena Grennberg*
Department of Chemistry-BMC, Uppsala University, Uppsala, S-75123, Sweden

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1
Tetrahedron
journal homepage: www.elsevier.com
Conformational restriction of flexible molecules in solution by a semirigid
bis-porphyrin molecular tweezer
Sara Norrehed, Prasad Polavarapu, Wenzhi Yang, Adolf Gogoll and Helena Grennberg
Department of Chemistry-BMC, Uppsala University, Uppsala, S-75123, Sweden
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A semirigid bisporphyrin molecular clip with a glycoluril backbone
has been synthesized. The clip provides an adaptable molecular cavity for
binding of diamines. Binding constants for diamines of 104 – 107 M-1 are orders
of magnitude higher than those for monoamines of 103 M-1, indicating a
preference to bidentate binding. NMR studies confirmed that binding of
bidentate guests occurs inside the clip. Short- and medium-size acyclic
molecular guests are locked into a single, extended conformation, and also
guests with longer flexible chains exhibit considerably less conformational
mobility than when free in solution. The size of the cavity adapts to the guest
size, as indicated by modeling studies and self diffusion constants of the
complexes.
Available online
Keywords:
Conformational Analysis
NMR spectroscopy
Host-guest systems
Supramolecular chemistry
Porphyrinoids
2009 Elsevier Ltd. All rights reserved.
Corresponding author. Tel.: +46-018-471-3822; e-mail: adolf.gogoll@kemi.uu.se
Corresponding author. Tel.: +46-018-471-3823; e-mail: helena.grennberg@kemi.uu.se

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1. Introduction
Metallated bisporphyrins are regarded as as interesting hosts for the ditopic binding of organic guest
molecules. A variety of spacers have been used to connect two porphyrin units, providing molecular clips of varying
conformational flexibility.1 This has been exploited, e. g., for the size-selective complexation of guest molecules in
bisporphyrins with rigid spacers,2 or for the determination of absolute stereochemistry using bisporphyrins with
flexible spacers.3 Dimeric porphyrins with various topologies have been reported as model systems for enzymes4 and
the photosynthetic reaction center. The guest molecule requires the presence of preferably two Lewis-basic functional
groups to interact with the bisporphyrin metal ions, with ditopic binding providing stronger interaction as well as
conformational restriction.5,6
In this context, we found it interesting to address the effect of binding between acyclic diamines of varying
chain length and semirigid bisporphyrin clips, regarding both conformational restriction of the guest, and adaptation
of clip size (i. e., the volume of the molecular cleft) to the guest volume. For the spacer of such a semirigid
bisporphyrin clip we chose the glycoluril backbone.7,8
In this paper, we present the synthesis of a new symmetric zinc(II)porphyrin-terminated glycoluril clip 1
(Scheme1), and a survey of its host-guest interaction with a series of diamino compounds.
a
b
c
d
O
O
a
b
H
OMe
3
OMe
OMe
H
4
N
M
N
N
M
N
N
N
N
N
N
N
e
N
N
Ph
Ph
N
N
N
N
OMe
, M = Zn
, M = 2H
1
2
O
H
OMe
OMe
OMe
OMe
H
N
N
N
N
N
Ph
Ph
N
N
N
O
3
Scheme 1. Molecular structure of clips 1, 2 and previously reported clip 3.8
2. Results and Discussion
2.1 Synthesis and characterization of bis-porphyrin glycoluril clips.
Using the same strategy as for our recently reported glycoluril-based clip 3 (Scheme 1),8 Zn-porphyrin clip 1
and free-base porphyrin clip 2 were prepared from the corresponding porphyrin dione (8 or 9) and the air-sensitive
tetraamino backbone component 6 (Scheme 2). Compound 6 was synthesized in two steps from the glycoluril
derivative 4,9 prepared by condensation of urea and benzil.7c Zinc-porphyrin dione 9 was obtained by metallation of its
free-base dione 8, which was prepared in several steps starting from porphyrin 7. Alternative literature procedures
towards synthesizing the porphyrin dione, e.g., hydroxylation of β-nitroporphyrin using sodium benzaldoximate,10 or
11
dihydroxylation using OsO4 did not work in our hands. Likewise, dihydroxylation attempts of Zn(II).7 using RuO4,
produced in situ from RuCl3 and NaIO4,12 did not yield any dioxo compound.

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O
O
OMe
OMe
OMe
OMe
H2N
O
NH2
O
, R = H
4
R
R
R
R
N
N
N
N
+
, R = NO
5
Ph
Ph
2
2
, R = NH
6
O
N
N
H
N
H
O
O
O
a
N
Zn
N
N
N
N
N
N
H
N
H
N
O
7
8
9
b
6
b
6
a
2
1
Scheme 2. Reagents and conditions: a: Zn(OAc)2·2H2O, MeOH/CHCl3, reflux, 3 h; b: THF/MeOH 1:1, reflux, 16 h.
Purification of 1 and 2 was challenging. Clip 1 was subjected to several flash chromatographic separations
with a consecutive series of eluents (CHCl3, a mixture of CH2Cl2 and MeOH at different ratios, and toluene).
Inclusion of solvent molecules contributes to purification difficulties, a common problem not only in porphyrin
synthesis but also encountered for some glycoluril compounds.13,14,15 In particular, removal of traces of toluene was
very difficult, indicating the formation of inclusion compounds. The purification of free-base clip 2 was even more
challenging as several 1H NMR signals for the porphyrin NH protons at negative chemical shifts were always
observed, indicating a mixture of porphyrin tautomers that could not be resolved even by HPLC. Considering that the
clip possesses two porphyrin units with no through-bond conjugation, the observation is not unexpected but still
potentially problematic in our intended NMR application that benefits from a high degree of symmetry in the host.
Metallation of the mixture of clip 2 tautomers with Zn(II) resulted in clean formation of clip 1 as a single compound.
Glycoluril-based clips may exist in three conformational isomers, interchanged by rotation of the single
bonds of the elbow CH2 (marked in Scheme 1), with substantial differences in the cavity opening, the closed (aa or
anti-anti) is the desired one and also the most commonly observed in this class of molecular hosts (Figure 1).13 The
conformational isomers are easily assigned by analysis of coupling constants and NOE effects in the elbow region.8 1
NMR analysis of 1 confirmed that the closed form was the only isomer present. However, the elbow region is still
conformationally dynamic: At r.t., the proton signals for the methoxy group and elbow CH2 (marked as Ha and Hb in
Scheme 1) are broad, whereas the signals for the porphyrin units and the backbone phenyls are sharp. At lower
temperatures the signals of the porphyrin units become broader. At higher temperatures, the elbow signals are
significantly sharper whereas some of the signals from the porphyrin units are broadened. These non-uniform
temperature-dependent effects are different from the quite uniform concentration-dependent aggregation effects, with
sharper signals at lower (10-5 M) and broader at higher (10-3 M) concentrations, and are most likely due to dynamics in
the elbow region that significantly influences the inter-porphyrin wall to wall distance at the rim of the clip (see
supplementary information).
H
To probe the rigidity of the molecular cleft provided by clip 1 in its closed (aa) conformation, an energy
minimization with the semiempirical PM3 method was performed, with Zn-Zn distances constrained to a series of
fixed values. The resulting potential curve of Zn-Zn distance vs. relative potential energy shows a minimum at a Zn-
Zn distance of 6.25 Å (Figure 1). The energy drop at distances below 8 Å might indicate the onset of attractive forces
due to close contacts between phenyl rings on opposite clip walls (vide infra). Overall, there appears to be a
considerable variability of wall to wall distance from 5 Å to 13.5 Å at relatively low (up to ca. 50 kJ/mol) energy cost.
Typical binding enthalpies of the axial nitrogen ligands on Zn porphyrins have been shown to be around 30 kJ/mol to
57 kJ/mol per single interaction for heteroaromatic and aliphatic diamines, respectively.16 Thus, the binding energy of

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a ditopic ligand to clip 1 should be sufficient to push apart the clip walls. It should also be noted that the open (as)
conformer has considerably higher energy than the closed (aa) conformations shown.
Figure 1. Potential energy vs. Zn-Zn distance for clip 1, and corresponding structures with closed (aa) conformation,
with the distance indicated below each structure. The energy minimized open (as) conformer is also shown (Zn-Zn
distance ca. 22.8 Å).
NMR analysis in toluene-d8 solution allowed the assignment of all protons in the porphyrin unit. Rotation of
the meso phenyl groups is hindered, yielding two pairs of signals for the eight ortho protons (a/a' and b/b', Figure 2).
The activation enthalpy was determined as ꢀG‡ = 47 kJꢀK−1ꢀmol−1, which is comparable to values reported for other
metalloporphyrins.17
e
H
(para)
H
(meta)
H
a
(ortho)
d
c
a
b
a’
a
b
b’
a’
8.7
8.6
8.5
8.4
8.3
8.2
8.1
8.0
7.9
7.8
7.7
7.6
7.5
7.4
ppm
Figure 2. Expansion from the 1H NMR spectrum of clip 1 (500 MHz, toluene-d8 solution, 25°C) with assignments of
porphyrin protons (cf. Scheme 1).
Glycoluril clips possess several potential binding sites. In addition to the Lewis-acidic Zn(II) sites, there are
Lewis-basic sites on the pyrrolic nitrogens, in the backbone glycoluril unit and at the pyrazoline imines. The clip also
possesses several potential sites for π-π or π-cation interactions that normally are considerably weaker than the Lewis
acid-base interactions. In clip 3, the pyrazoline unit dominated over all other binding sites in interactions with cations
and hydrogen-bond-donors, but the inner meso phenyls of the porphyrin units in 1 and 2 should efficiently block this
coordination site. In line with this reasoning, the very minor effects on 1H NMR shifts observed upon addition of
silver and ammonium cations was as expected,8 and the pronounced red-shift in the UV-Vis absorption spectrum upon
addition of strong acid to 1 is thus most likely caused by protonation at pyrrolic nitrogens18 that eventually may lead
to demetallation of the clip.
2.2 Complexation with organic guests with Lewis-base character
Of particular interest was to investigate if guests of varying size might be bound and if a preference to
binding inside the clip would be observed.19 This would require a not too steep energy profile of metal-metal distance
vs. potential energy (Figure 1) allowing variations in the amount of cavity opening. Guest molecules were chosen to
cover a range of sizes, and include both rigid and flexible molecules. Chelation of Lewis bases, in particular amines
and imines, to Lewis-acidic complexed metal ions is well documented both for monoporphyrin20,21 and bis-porphyrin

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systems. The extended aromatic structure would provide the desired NMR complexation-induced shifts (CISs) of the
bound guests.
The results of the UV-Vis titration studies are summarized in Table 1. As expected, 1:1 complexation with
binding constants in the range of 104 – 106 M-1 were observed for diamines, whereas Ka for monoamines and amino
alcohols were several orders of magnitude weaker. The data for clip 1 + guest, with red-shift of all bands and clear
isosbestic points suggests that only one complex is formed in each case (Figure 3).
1.8
1.6
1.4
1.2
1
A
0.8
0.6
0.4
0.2
0
400
450
500
550
600
650
Wavelength (nm)
Figure 3. A representative UV-Vis titration of clip 1 + guest (here 2,3,4-tri-O-methyl-1,5-diaminopentane 17) with
arrows indicating changes in absorbance.
Table 1. Ka measured by UV-Vis titration of clip 1 + guests.
Guest
Ka /M-1
103
Pyridinea
Octylaminea
103
2-aminoethanola
103
2-aminobutanola
103
N-methyl-2-aminoethanola
DABCO 10a
103
106
4,4’-bipyridine 11b
1,6-diaminohexane 12a
1,8- diaminooctane 13b
1,12- diaminododecane 14b
1,20- diaminoeicosane 16b
2,3,4-tri-O-methyl-1,5-diaminopentane 17b
107
106
106
106
105
104
2,3,4,5-tetra-O-methyl-1,6-diaminohexane 18b 104
aCHCl3 solution. bCH2Cl2 solution.
Diffusion studies provided further information about the complexation of various guests with clip 1 (Table
2).14e,22 As expected, clip 1 has a lower diffusion coefficient (D = 7.0ꢀ10-10 m2s-1) than the free guests (D = 9.3ꢀ10-10
- 14ꢀ10-10 m2s-1). In each of the complexes, clip 1 and the bound guest have essentially the same diffusion
coefficient, indicating the absence of any equilibrium between bound and free diamine. Furthermore, diffusion
coefficients of the complexes with smaller guests (DABCO 10, 2,3,4-tri-O-methyl-1,5-diaminopentane 1723 and
2,3,4,5-tetra-O-methyl-1,6-diaminohexane 1823) were found to be identical to the free clip (i. e., D = 7.0ꢀ10-10 m2s-1).
For the complexes with larger guests (1,12-diamine 14 and 1,20-diamine 16), diffusion was found to be slower (D =
4.7ꢀ10-10 m2s-1) than for the free clip. However, the decrease of D was substantially larger than would be expected if
it was related to the Stokes radius via the molecular weight. This indicates an alteration of clip shape, i. e., the larger
guests push the clip walls farther apart. Since diffusion coefficients depend on the hydrodynamic radius rather than the
molecular weight of molecules in solution,24 this guest-dependent variation of wall distance for clip 1 would account
for the observed diffusion behavior.22

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Table 2. Diffusion coefficients for free species and ≈1:1 complexes.
Species
D (m2 s-1) rH (Å) MW
2.1ꢀ10-9
1.4ꢀ10-9
1.4ꢀ10-9
1.4ꢀ10-9
9.3ꢀ10-10
7.0ꢀ10-10
7.0ꢀ10-10
7.0ꢀ10-10
7.0ꢀ10-10
4.7ꢀ10-10
4.7ꢀ10-10
1.9
2.9
2.9
2.9
4.3
5.8
5.8
5.8
5.8
8.6
8.6
DABCO 10
112.0
2,3,4-tri-O-methyl-1,5-diaminopentane 17
193.2
2,3,4,5-tetra-O-methyl-1,6-diaminohexane 18
237.2
1,12-diaminododecane 14
1,20-diaminoeicosane 16
Clip 1
200.4
312.6
2018.0
2130.0
2211.2
2255.2
2218.4
2523.8
Clip 1:10
Clip 1: 17
Clip 1: 18
Clip 1:14
Clip 1:16
Diffusion coefficients were measured by NMR LEDPGSE experiments, 500 MHz, in CDCl3 solutions at 25°C with
residual CHCl3 as reference (2.33ꢀ10-9 m2s-1).
1H NMR analysis of 1 with diamines provided clear evidence that the guests are bound inside the clip. The number of
signals for the bound guests corresponds to symmetrical 1:1 complexes, the structures of which are shown in Scheme
3. For the C12 and C20 diamines, only one of multiple conformations is shown.

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.
.
1 10 (dZn-Zn = 7.02 Å)
1 11(dZn-Zn = 11.16 Å)
.
a
.
b
1 12 (dZn-Zn = 12.24 Å)
1 13 (dZn-Zn = 12.37 Å)
.
c
.
d
1 14 (dZn-Zn = 12.52 Å)
1 16 (dZn-Zn = 11.18 Å)
Scheme 3. Structures of inclusion compounds of clip 1 with various guests, from semi empirical calculations (PM3).
a Extended conformation (i. e., aaaaa). b aagagaa conformer. c gggggagaggg conformer. d gggaaggaaggagaggagg
conformer.
2.3 Binding of guests with fixed N-N distance
Clip flexibility for the binding of guests of varying size was investigated by adding aliquots of
1,4-diazabicyclo[2.2.2.]octane (DABCO) (10, dN,N = 2.60 Å), and 4,4'-bipyridyl (11, dN,N = 7.15 Å) to clip 1 in CDCl3
solution. The 1H NMR signals of CH3O and elbow protons became sharper, indicating reduced conformational
mobility in this region upon complexation, and an alteration of the overall shape of the complex compared to that of
pure 1 in accordance with the calculated structures. Addition of 4,4'-bipyridyl 11 resulted in moderate chemical shift
changes for the porphyrin signals and negative CIS values for the guest, i. e., ꢀδ = -2.67 (H-3) and ꢀδ = -6.35 (H-2).
Only two bipyridyl proton signals were observed for mixtures where the clip was in excess proving a symmetric
binding in the cleft. When the guest was present in excess, separate broad peaks for both bound and free bipyridyl
protons were observed, the broadening being due to ligand exchange. On addition of DABCO 10, the signal for the
guest protons exhibited a pronounced CIS (ꢀδ ≈ -7.20). Only one signal was observed for the bound guest, indicating
ditopic binding in the clip cavity. NOEs between bound 10 and the porphyrin phenyl protons of 1 provide further
proof for binding.
The negative CIS for all porphyrin pyrrolic protons and positive CIS for the elbow Ha protons are
attributable to a closer equilibrium wall to wall distance in the complex than in the free clip, as has previously been

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observed for clip 3.8 When an excess of clip was present, two distinct sharp signals for bound and free clip,
respectively, were observed. Thus, although the binding constants for the two guests are in the same range, the
exchange between free and (internally) bound guest on the NMR timescale is moderate for 11 and very slow for 10.
The differences could be due to electronic differences between the aliphatic amine 10 and the aromatic imine 11 but,
more likely to the favorable close porphyrin-porphyrin interaction which is more pronounced in the complex with 10
than in the free clip or in the complex with 11.
2.4 Flexible diamine ligands: Conformational restriction.
The absence of exchange broadening of the ligand signals was observed for mixtures of clip 1 and
1,6-diaminohexane 12 (dN,N = 8.83 Å for extended conformer). The observation of only four ligand signals, with
pronounced negative CIS values, proves binding in the clip cavity. NOEs between 1,6-diaminohexane protons
(NOE(i, i+2) but not NOE(i, i+3) or NOE(i, i+4)) indicate an extended, i. e., all-trans, conformation of 12 in the complex
(Figure 4, Figure 5).1 In contrast to its complex with Zn(II)TPP,25 the stronger binding to clip 1, indicated by absence
of exchange broadening, also illustrates the importance of cooperative binding to two sites, i. e., the two metal centers.
NOE
(i, i+2)
a
b
NOE
(i, i+1)
NOE
(i, i+4)
d
c
NOE
(i,i+3)
Figure 4. Expected NOEs for two conformers of 1,6-diaminohexane (12) protons. For anti bonds: a = NOE(i, i+2), b =
NOE(i, i+1); for gauche bonds: c = NOE(i, i+3), d = NOE(i, i+4)
.
3,3’
1,1’
NH2
2,2’
F2
(ppm)
-5.0
-4.5
-4.0
-3.5
-3.0
-2.5
-2.0
-1.5
NOE
(i, i+2)
3
a
1
2’
NH2
H2N
2
3’
1’
b
NOE
(i, i+2)
a
b
b
a
-1.5 -2.0 -2.5 -3.0 -3.5 -4.0 -4.5 -5.0
F1 (ppm)
Figure 5. Expansion from ROESY spectrum of clip 1 with 1,6-diaminohexane 12 (500 MHz, CDCl3 solution, 25°C),
guest/clip ≈1, mixing time = 0.5s.
As the binding of 1,6-diaminohexane 12 is ditopic, resulting in stretching of the alkyl chain, it is interesting
to study longer diamines. Thus, 1,8-diaminooctane 13 (dN,N = 11.34 Å for all-trans conformer) binds to clip 1, with
similar effects on signal widths and chemical shifts as for 1,6-diaminohexane 12 (Figure 6, Figure 7). However, in
contrast to the latter, a larger variety of NOEs between protons of 1,8-diaminooctane 13 (i. e., NOE(i, i+1), NOE(i, i+2)
,

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9
NOE(i, i+3) and NOE(i, i+4)) indicates the presence of gauche bonds, i. e., its longer chain is no longer stretched out into
the all-trans conformation (Figure ).
For the even longer alkyl chains of 1,12-diaminododecane 14 (dN,N = 16.53 Å for all-trans conformer) and
1,20-diaminoeicosane 16 (dN,N = 26.61 Å for all-trans conformer), 7 and 11 ligand signals are observed, respectively.
This proves location inside the cavity also for guests that are without possibility of adopting an all-trans conformation
upon ditopic binding. NOE patterns for 14 and 16 are also more complex as for 1,8-diaminooctane i.e., NOE(i, i+1)
,
NOE(i, i+2), NOE(i, i+3) and NOE(i, i+4) are observed.
In alkyl chains, transforming an anti conformer to a gauche conformer increases the conformational energy
by only 3 – 4 kJ/mol,26 which is lower than typical binding energies between Zn(II)TPP and amines, i. e., 57 kJ/mol
per single interaction for aliphatic diamines.16
Thus, for the interaction between clip 1 and guests 12, 13, 14 and 16 with Ka of 105-107 M-1, only a small
energy penalty, including the opening of the clip, has to be paid.
b
a
Figure 6. Expansion from 1H NMR spectra of clip 1 with 1,8-diaminooctane 13 (500 MHz, CDCl3 solution, 25°C). a:
only guest 13; b: guest/clip: ≈1.
4,4’
1,1’
2,2’
3,3’
F2
(ppm)
a
-2.2
-2.0
-1.8
b
c
NOE
(i, i+2)
3
-1.6
-1.4
-1.2
-1.0
-0.8
-0.6
-0.4
NOE
(i, i+3)
NH2
a
d
1
4’
2’
H2N
c
1’
2
4
b
3’
NOE
(i, i+1)
NOE
(i, i+2)
c
a
d
b
-0.4
-0.8
-1.2
-1.6
-2.0
-2.4
F1 (ppm)
Figure 7. Expansion from ROESY spectrum (mixing time 0.5 s) of clip 1 with 1,8-diaminooctane 13 (500 MHz,
CDCl3 solution, 25°C), guest/clip ≈1.
The ditopic binding of diamines to clip 1 is only possible in a “head-on” fashion with the porphyrin units in opposite
positions, in contrast to a recently reported bisporphyrin system where, due to its flexible link, a distinction between
this and an alternative “side-on” mode with sideways dislocation of the porphyrin units, accommodating all-trans
conformations of the guests, was not possible.27

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3. Conclusion
The semirigid bisporphyrin clip 1 binds diamine guests of varying size ditopically inside of its molecular cleft. Shorter
acyclic guests (carbon chain ≤ C6) bind in an all-anti, i. e., zig-zag conformation, whereas longer acyclic guests
(carbon chain ≥ C8) bind in a conformation including gauche kinks. The adaptation of the clip to increasing guest size
is indicated by diffusion data. Conformational restriction of acyclic guest molecules with several stereogenic centers
should be a useful method to determine their relative stereochemistry, as we have shown in a parallel study.23
4. Experimental
UV-Vis titrations were carried out on a Varian Cary 3 Bio spectrophotometer using 10 mm or 5 mm quartz
cuvettes at r.t. with CH2Cl2 or CHCl3, filtered over basic aluminium oxide, as solvent. Ka for diamines was determined
utilizing the iterative fitting program (in Matlab R2012b) recently published by P. Thordarsson.28 A 1:1 complexation
model and global fitting to several datasets was applied, Ka is calculated by (eqn. 1). The standard error (SEy) is
estimated by (eqn. 2). For monoamines line fitting using Origin software was utilized to calculate Ka. 1H and 13C NMR
spectra were recorded on a Varian Unity Inova (1H at 499.94 MHz, 13C at 125.7 MHz) spectrometer. Chemical shifts
are reported in ppm referenced to tetramethylsilane via the residual solvent signal (CDCl3, 1H at 7.26 and 13C at 77
ppm; toluene-d8, 1H at 2.36 and 13C at 21.5 ppm; CH3COOH-d4, 1H at 2.09 and 13C at 20.4 ppm). Signal assignments
were derived from P.E.COSY,29 gHSQC,30 gHMBC,31 gNOESY,32 ROESY,33 and TOCSY34 spectra. For NMR
titrations, aliquots of a guest solution were added to a solution of clip 1 in an NMR tube using an Eppendorf pipette.
Diffusion coefficients were determined from LED-PGSE experiments,35 using z-gradients, acquiring a series of 10-20
spectra for an array of gradient pulse strengths (0 to 20 gauss/cm). Typically, a relaxation delay of 1 s, 9 ms gradient
pulse duration, 100 ms diffusion delay, and 5 ms storage delay were used. The LED-PGSE spectra were evaluated by
plotting the square of the gradient strength against the natural logarithm of the signal amplitude, resulting in a straight
line with a slope proportional to –D (diffusion coefficient). The actual value for D was obtained by relating this slope
to that of a compound with known diffusion coefficient, measured under the same conditions. In the present
investigation, we have used the residual CHCl3 signal in CDCl3 (D = 2.33×10-9 m2 s-1).36 Diffusion coefficients (D)
were calculated by (eqn. 3) and the hydrodynamic radius (rH) by (eqn. 4). The activation energy for phenyl rotation
was determined by full lineshape fitting using gNMR 5.0.6.37 MALDI-TOF spectra were recorded using a Bruker
Daltonics Ultraflex II MALDI-TOF mass spectrometer using an α-cyano-4-hydroxycinnamic acid matrix. HRMS was
acquired using a Thermo Scientific LTQ Orbitrap Velos apparatus in infusion mode. Analytical TLC was performed
using Merck precoated silica gel 60 F254 plates. For column chromatography Matrex silica gel (60 Å, 35-70 ꢁm) was
used. Melting points were determined using a Stuart Scientific melting point apparatus SMP10 and are uncorrected.
Computations of clip energies were performed with Titan 1.0.5 (Wavefunction, Inc.) using semi-empirical PM3.
Elemental analysis was performed by Eurofins Mikrokemi AB, Uppsala, Sweden. Commercially available compounds
were used without purification. meso-Tetraphenylporphyrin (TPPH2) 7 was purchased from Porphyrin Systems GbR,
Germany, or prepared according to literature procedures38 and transformed into beta-nitroTPPH2 as previously
reported.10a Dry solvents were obtained by distillation from sodium and benzophenone (diethyl ether, THF) or CaH2
(CH2Cl2).
4.1. 5,7,12,13b,13c,14-Hexahydro-1,4,8,11-tetramethoxy-13b,13c-diphenyl-6H,13H-5a,6a,12a,13a-tetraazabenz-
[5,6] azuleno[2,1,8-ija]benz[f]azulene-6,13-dione (4) was prepared following literature procedures.7c

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4.2. 5,7,12,13b,13c,14-Hexahydro-1,4,8,11-tetramethoxy-2,3,9,10-tetranitro-13b,13c-diphenyl-6H,13H-
5a,6a,12a,13a-tetraazabenz[5,6]azuleno[2,1,8-ija]benz[f]azulene-6,13-dione (5) was prepared as previously
reported.9
4.3. 5,7,12,13b,13c,14-Hexahydro-1,4,8,11-tetramethoxy-2,3,9,10-tetraamino-13b,13c-diphenyl-6H,13H-
5a,6a,12a,13a tetraazabenz[5,6]azuleno[2,1,8-ija]benz[f]azulene-6,13-dione (6)was prepared via a slightly modified
procedure as previously reported.9
4.4. 2,3-Dioxo-5,10,15,20-tetrakisphenylchlorine (8)40
TPPNO2 (prepared from TPP 7, using a literature procedure)10a (367 mg, 0.56 mmol) was dissolved in dry
CH2Cl2 (30 mL), and to this tin(II)chloride dihydrate (1.26 g, 5.6 mmol) and conc. HCl (3.5 mL) were added. The
reaction mixture was stirred under argon atmosphere for 3.5 days in the dark, upon which CH2Cl2 (100 mL) and water
(100 mL) were added. The organic layer was separated and washed with water (100 mL), sodium bicarbonate solution
(5%, 100 mL), and water, dried over anhydrous sodium sulfate, filtered and the solvent completely removed. Crude
TPPNH2 was obtained as a dark purple-green solid and used without further purification. UV-Vis: (CH2Cl2) λmax: 423,
523, 556, 594, 651, 667, 681 nm, in accordance with literature.39 To the crude TPPNH2 was added dry CH2Cl2 (30
mL), followed by Dess-Martin periodinane (DMP) (156 mg, 0.42 mmol). After stirring for 2.5 h in the dark, excess
DMP (70 mg, 0.16 mmol) was added, and stirring in the dark was continued. After 12 h, 80 mL of 1 M HCl was
added and stirring continued for one hour. The organic layer was separated and washed with water (2×100 mL), dried
over Na2SO4, and filtered. The filtrate was evaporated to dryness and the residue was flash chromatographed through
a column of silica gel using CH2Cl2:pentane (2:3) yielding porphyrin dione 8 as a dark blue solid (114 mg, 0.18 mmol,
32%). Rf = 0.47 (silica-CH2Cl2) 1H NMR (500 MHz, 25 oC, CDCl3): δ 8.75 (dm, J = 4.8 Hz, 2H), 8.60 (dm, J = 4.8
Hz, 2H), 8.56 (s, 2H), 8.14 -8.11(m, 4H), 7.91-7.89 (m, 4H), 7.80-7.67 (m, 12H), -2.01 (br s, 2H). UV-Vis: (CH2Cl2)
λmax: 403, 475 nm. Spectroscopic data were in accordance with the literature.40b
4.5. (2,3-Dioxo-5,10,15,20-tetrakisphenylchlorinato)zinc(II) (9)41
The porphyrin dione 8 was metallated quantitatively with Zn(II)acetate dihydrate following a literature
procedure, and 9 was obtained as a green-bluish solid. UV-Vis: (CH2Cl2) λmax: 416, 497 nm. 1H NMR (500 MHz,
25 oC, CDCl3): δ 8.54 (d, J = 4.7 Hz, 2H), 8.46 (s, 2H), 8.31 (d, J = 4.7 Hz, 2H), 8.04-8.02 (m, 4H), 7.80-7.88 (m,
4H), 7.62-7.81 (m, 12H). Spectroscopic data were in accordance with the literature.40b
4.6. Free-base porphyrin-terminated diphenylglycoluril clip (2)
With care to maintain an argon atmosphere, molecular sieves, degassed THF/methanol/CH2Cl2 (1:1:1, 24
mL) and porphyrin dione 8 (114 mg, 0.18 mmol) were added to freshly prepared 6 (from 89 mg, 0.11 mmol of the
tetranitro compound 5). The solution was heated to reflux for 36 h, after which time it was cooled to r.t., filtered, and
the precipitate was washed with CH2Cl2 (5×20 mL). The combined filtrate was washed with 1N NaOH solution, water
and brine and dried over anhydrous Na2SO4, then filtered. The filtrate was evaporated to dryness and purified by
column chromatography using 1:1 pentane:CH2Cl2 as eluent, followed by CH2Cl2, gradually adding ethyl acetate up to
CH2Cl2:ethylacetate (8:2). Clip 2 was obtained as a dark purple solid (160 mg, mixture of tautomers). UV-Vis:
+
(CH2Cl2) λmax: 432, 527, 599, 652, 682. MS (MALDI-TOF), [M+H] , m/z = 1895. Calculated for C124H86N16O6: m/z =
1894 (nominal MW), 1895 (100% peak). Clip 2 was directly metallated according to a literature procedure,42
producing clip 1 as a dark purple solid (39 mg, 0.019 mmol, 23%). For characterization, see 4.7. Zinc(II)porphyrin-
terminated diphenylglycoluril clip (1).
4.7. Zinc(II)porphyrin-terminated diphenylglycoluril clip (1)
With care to maintain an argon atmosphere, molecular sieves, degassed THF/methanol/CH2Cl2 (1:1:1, 24
mL) and zinc-porphyrin dione 9 (360 mg, 0.51 mmol) were added to freshly prepared 6 (from 254 mg, 0.32 mmol of
5). The solution was heated at reflux for 36 h, after which time it was cooled to r.t., filtered, and the precipitate
washed with CH2Cl2 (5×20 mL). The combined filtrate was washed with 1M NaOH solution, water, brine, dried over
anhydrous Na2SO4 and then filtered. The filtrate was evaporated to dryness and purified by sequential column
chromatographies using CHCl3:MeOH (100:1), 2% MeOH in toluene and 5% MeOH in toluene, followed by
precipitation upon addition of n-pentane to a methanol solution. The precipitate was isolated by centrifugation, then
dried under vacuum to obtain clip 1 as a dark purple solid (105 mg, 0.052 mmol, 20 %). UV-Vis: (CH2Cl2) λmax: 271,
326, 436 (broad), 575, 619, 794. HRMS (CI): m/z calculated for C124H82N16O6Zn2 [M+]: 2018.5164, [M+H2O]+2:
1027.2688 found: 1027.2689. 1H NMR (500 MHz, 25 oC, toluene-d8): δ 8.73 (d, J = 4.8 Hz, 4H, H-e), 8.70 (s, 4H, H-
d), 8.47 (d, J = 4.8 Hz, 4H, H-c), 8.17 (dm, J = 6.9 Hz, 4H, H-ortho-a), 8.09 (dm, J = 6.9 Hz, 4H, H-ortho-b), 8.02
(dm, J = 6.9 Hz, 4H, H-ortho-b), 7.85-7.57 (m, 44H), 7.32-7.13 (m, 10H) 5.92 (d, J = 16.1 Hz, 4H, CH2), 3.90 (d, J =
16.1 Hz, 4H, CH2), 3.79 (s, 12H, OCH3) 13C NMR (100.58 MHz, 40oC, CDCl3): δ 157.4 (CO), 153.0 (-COCH3),

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149.8, 148.9, 142.8, 142.4, 140.8, 136.0 (CH-d), 134.1 (CH-ortho-a+b), 133.8 (CH-ortho-b’), 133.6 (CH-ortho-a’),
132.2 (CH-c), 131.5 (CH-e + -CCNNPh), 129.8, 129.0, 128.9, 128.8, 128.4, 128.2, 127.6, 127.4, 126.9, 126.6, 123.4,
117.3 (-CH2CCCOCH3), 63.8 (-OCH3), 38.1 (CH2).
4.8. 1,20-Diaminoeicosane dihydrochloride (15)
1,20-Eicosanedicarboxylic acid (4 g, 11.7 mmol) was dissolved in SOCl2 (40 mL) and heated to reflux for
2.5 h until gas evolution had ceased completely. The solvent was evaporated and the solid residue redissolved in
dioxane (20 mL). A NH3-solution (conc., in H2O, 25 mL) was added upon which a white precipitate was formed
(violent reaction, heat). The mixture was stirred for 1 h, filtered off and left to dry in air over night. The obtained
white solid (3.75 g) was used as is, dissolved in hot dry THF and added to a suspension of LiAlH4 (1 g, 30 mmol) in
dry THF (30 mL) at r.t. The mixture was heated to reflux over night and then quenched with H2O and filtered over a
Büchner funnel. The product was obtained as a waxy white solid (3.67 g, 82 %). For storage the diamine was
dissolved in hot EtOH and bubbled with HCl (g) to precipitate the dihydrochloric salt as a white solid (quant.), m.p.
200 oC (dec.) Calc. for C20H46Cl2N2: C, 62.4; H, 12.0; N, 7.3%. Found: C, 62.7; H, 12.0; N, 7.0%. 1H NMR (500
MHz, 100 oC, CH3COOH-d4): δ 3.18 (dm, J = 7.7 Hz, 4H, H-1+H-20), 1.87-1.81 (m, 4H, H-2+H-19), 1.53-1.36 (m,
32H, H-3 – H-18). 13C NMR (100.58 MHz, 100 oC, CH3COOH-d4): 42.4 (C-1+C20), 31.4 (C-7 - C-14), 31.3 (C-6+C-
15), 31.2 (C-5+C-16), 30.9 (C-4+C-17), 29.1 (C-2+C19), 28.2 (C-3+C-18).
4.9. 1,20-Diaminoeicosane (16)44
Amberlite IRA-400 resin (chloride form, Sigma-Aldrich, 0.5 cm3) was rinsed with H2O (5 mL), NaOH (1M,
10 mL) and again with H2O (5 mL) upon which a AgNO3-test for chloride was performed to verify complete
conversion of the resin to the OH- form. The converted resin was rinsed with MeOH (5 mL) and transferred into a 1
mL vial. 1,20-Diaminoeicosane dihydrochloride 15 (18 mg, 0.047 mmol) was dissolved in 0.5 mL MeOH and poured
over the resin. The mixture was left to stir gently under argon atmosphere over night and then filtered through a glass
wool plug. Evaporation of the solvent afforded the product as a pale yellow solid (14 mg, 0.044 mmol, 95 %). m.p.
84-85 oC (lit. 85 oC). 1H NMR (500 MHz, 25 oC, CDCl3): δ 2.67 (dm, J = 6.9 Hz, 4H, H-1+H-20), 1.46-1.39 (m, 4H,
H-2+H-19), 1.33-1.20 (m, 32H, H-3 – H-18).
Acknowledgments
We are grateful to Helena Melander for her initial contribution to the synthesis of glycoluril clips, and Bo Ek
for HRMS spectra. This work was supported by grants from The Swedish Research Council and The Göran
Gustavsson Foundation.
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(a) Brückner, C.; Rettig, S. J.; Dolphin, D. J. Org. Chem. 1998, 63, 2094. (b) Daniell, H. W.; Williams, S. C.;
Jenkins, H. A.; Brückner, C. Terahedron. Lett. 2003, 44, 4045.
41.
42.
Monti, D.; Venanzi, M.; Mancini, G.; Marotti, F.; Monica, L. L.; Boschi, T. Eur. J. Org. Chem. 1999, 1901.
(a) Munro, O. Q.; Shabalala, S. C.; Brown, N. J. Inorg. Chem. 2001, 40, 3303; (b) Rovira, C.; Kunc, K.;
Hutter, J.; Parrinello, M. Inorg. Chem. 2001, 40, 11.
43.
44.
Power, N. P.; Dalgarno, S. J.; Atwood, J. L. New J. Chem. 2007, 31, 17.
Plateau, J.; Brouillet, G. Patent DE2133650 (A1), 1972. Chem.Abstr. 1972, 76, # 72000.

ACCEPTED MANUSCRIPT
Table 1. Ka measured by UV-Vis titration of clip 1 + guests.
Guest
Ka /M-1
103
Pyridinea
Octylaminea
103
2-aminoethanola
2-aminobutanola
N-methylaminoethanola
DABCO 10a
103
103
103
106
4,4’-bipyridine 11b
1,6-diamine 12a
1,8-diamine 13b
1,12-diamine 14b
1,20-diamine 16b
2,3,4-tri-o-methyl-1,5-diaminopentane 17b
107
106
106
106
105
104
2,3,4,5-tetra-o-methyl-1,6-diaminohexane 18b 104
aCHCl3 solution. bCH2Cl2 solution.

ACCEPTED MANUSCRIPT
Table 1. Diffusion coefficients for free species and ≈1:1 complexes.
Species
D (m2 s-1) rH (Å) MW
2.1ꢀ10-9
1.4ꢀ10-9
1.4ꢀ10-9
1.4ꢀ10-9
9.3ꢀ10-10
7.0ꢀ10-10
7.0ꢀ10-10
7.0ꢀ10-10
7.0ꢀ10-10
4.7ꢀ10-10
4.7ꢀ10-10
1.9
2.9
2.9
2.9
4.3
5.8
5.8
5.8
5.8
8.6
8.6
DABCO 10
112.0
2,3,4-tri-O-methyl-1,5-diaminopentane 17
193.2
2,3,4,5-tetra-O-methyl-1,6-diaminohexane 18
237.2
1,12-diaminododecane 14
1,20-diaminoeicosane 16
Clip 1
200.4
312.6
2018.0
2130.0
2211.2
2255.2
2218.4
2523.8
Clip 1:10
Clip 1: 17
Clip 1: 18
Clip 1:14
Clip 1:16
Diffusion coefficients were measured by NMR LEDPGSE experiments, 500 MHz, in CDCl3 solutions at 25°C with
residual CHCl3 as reference (2.33ꢀ10-9 m2s-1).

ACCEPTED MANUSCRIPT

1
ACCEPTED MANUSCRIPT
Supplementary material
Conformational restriction of flexible molecules in solution by a semirigid
bis-porphyrin molecular tweezer
*
*
Sara Norrehed, Prasad Polavarapu, Wenzhi Yang, Adolf Gogoll and Helena Grennberg
Dept. of Chemistry - BMC, Uppsala University, Box 576, S-751 23 Uppsala, Sweden
adolf.gogoll@kemi.uu.se
Clip 1.......................................................................................................................................... 4
Clip 1 with 4,4'-bipyridyl ......................................................................................................... 11
Clip 1 with DABCO................................................................................................................. 13
Clip 1 with 1,6-Diaminohexane ............................................................................................... 17
Clip 1 with 1,8-Diaminooctane ................................................................................................ 21
Clip 1 with 1,12-diaminododecane .......................................................................................... 23
Clip 1 with 1,20-diaminoeicosane............................................................................................ 25
1,20-diaminoeicosane............................................................................................................... 28
UV-Vis data for various guests ................................................................................................ 29
Diffusion data for various guests and complexes..................................................................... 30
Table S1: CIS for mixtures of clip 1 and 4,4'-bipyridyl 11 (500 MHz, 1H NMR, CDCl3
solution, 25°C). ........................................................................................................................ 11
Table S2: CIS for mixtures of clip 1 and DABCO 10 (500 MHz, 1H NMR, CDCl3 solution,
25°C). ....................................................................................................................................... 13
Table S3: CIS for mixtures of clip 1 and 1,6-Diaminohexane 12 (500 MHz, 1H NMR, CDCl3
solution, 25°C). ........................................................................................................................ 17
Table S4: CIS for mixtures of clip 1 and 1,8-Diaminooctane 13 (500 MHz, 1H NMR, CDCl3
solution, 25°C). ........................................................................................................................ 21
Table S5: CIS for mixtures of clip 1 and 1,12-diaminododecane 14 (500 MHz, 1H NMR,
CDCl3 solution, 25°C).............................................................................................................. 23
Table S6: CIS for mixtures of clip 1 and 1,20-Diaminoeicosane 16 (500 MHz, 1H NMR,
CDCl3 solution, 25°C).............................................................................................................. 25
Table S7: Maximum wavelength shift Δ (nm) of clip 1 upon addition of excess guest........... 29
Table S8: Diffusion coefficients for free species and ≈1:1 complexes.................................... 30
Figure S1: 1H NMR spectrum of clip 1 at various concentrations (500 MHz, CDCl solution,
3
-3
-1
-4
.
-1
-4
.
-1
-4
.
25°C). c(clip 1) = (a) 1.4×10 mol L , (b) 8.2×10 mol L , (c) 4.1×10 mol L , (d) 1.4×10
mol.L-1, (e) 8.2×10-5 mol.L-1....................................................................................................... 4
Figure S2: Expansion from ROESY spectrum of clip 1 (500 MHz, 25°C, toluene-d8 solution).
.................................................................................................................................................... 5
Figure S3: TOCSY spectrum of clip 1 (500 MHz, 25°C, toluene-d8 solution).......................... 6
Figure S4: Expansion from TOCSY spectrum of clip 1 (500 MHz, 25°C, toluene-d8 solution).
.................................................................................................................................................... 6

2
ACCEPTED MANUSCRIPT
Figure S5: Top: Expansion from 1D TOCSY spectrum of “a”-Ph protons in clip 1, bottom:
corresponding region from 1H NMR spectrum, indicating the 1D TOCSY target signal (500
MHz, 25°C, toluene-d8 solution)................................................................................................ 7
Figure S6: Top: Expansion from 1D TOCSY spectrum of “b”-Ph protons in clip 1, bottom:
corresponding region from 1H NMR spectrum, indicating the 1D TOCSY target signal (500
MHz, 25°C, toluene-d8 solution)................................................................................................ 7
Figure S7: Saturation transfer experiments of clip 1 ortho protons, * denotes saturated signal
(500 MHz, toluene-d8 solution).................................................................................................. 8
Figure S8: Expansion of variable temperature 1H NMR spectrum of clip 1 (CH2 protons) at a)
100 oC, b) 75 oC, c) 50 oC d) 25 oC (500 MHz, toluene-d8 solution)......................................... 9
Figure S9: Expansion of variable temperature 1H NMR of clip 1 (CH2 protons) a) 25 oC, b)
0 oC, c) -25 oC d) -50 oC (500 MHz, toluene-d8 solution)........................................................ 10
Figure S10: Expansion of variable temperature 1H NMR of clip 1 (Aromatic region) a)
100 oC, b) 75 oC, c) 50 oC d) 25 oC (500 MHz, toluene-d8 solution)....................................... 10
Figure S11: Expansions from 1H NMR spectra of clip 1 with 4,4'-bipyridyl 11 (500 MHz,
CDCl3 solution, 25 °C). a: Clip 1, b: guest/clip:<1, c: guest/clip ≈1, d: 11. ........................... 11
Figure S12: Expansions from 1H NMR spectra of clip 1 with 4,4'-bipyridyl 11 (500 MHz,
CDCl3 solution, 25°C). a: Clip 1, b: guest/clip:<1, c: guest/clip ≈1, d: 11.............................. 12
Figure S13: 1H NMR spectra of clip 1 with DABCO 10 (500 MHz, CDCl3 solution, 25°C). a:
Clip 1, b: guest/clip:<1, c: guest/clip ≈1. ................................................................................. 13
Figure S14: Expansion from ROESY spectrum of clip 1 with DABCO 10 (500 MHz, CDCl3
solution, 25°C), guest/clip ≈1................................................................................................... 14
Figure S15: Expansion from ROESY spectrum of clip 1 with DABCO 10 (500 MHz, CDCl3
solution, 25°C), guest/clip ≈1................................................................................................... 14
Figure S16: Expansion from ROESY spectrum of clip 1 with DABCO 10 (500 MHz, CDCl3
solution, 25°C), guest/clip ≈1................................................................................................... 15
Figure S17: Expansion from ROESY spectrum of clip 1 with DABCO 10 (500 MHz, CDCl3
solution, 25°C), guest/clip ≈1................................................................................................... 15
Figure S18: 1H NMR spectra of clip 1 with DABCO 10 (500 MHz, CDCl3 solution, 25°C). a:
Clip 1, b: guest/clip:<1, c: guest/clip ≈1. ................................................................................ 16
Figure S19: 1H NMR spectra of clip 1 with 1,6-diaminohexane 12 (500 MHz, CDCl3 solution,
25°C). a: Clip 1, b: guest/clip:<1, c: guest/clip ≈1, c: 12........................................................ 17
Figure S20: Expansion from 1H NMR spectra of clip 1 with 1,6-diaminohexane 12 (500 MHz,
CDCl3 solution, 25°C). a: Clip 1, b: guest/clip:<1, c: guest/clip ≈1. ...................................... 18
Figure S21: Expansion from 1H NMR spectra of clip 1 with 1,6-diaminohexane 12 (500 MHz,
CDCl3 solution, 25°C). a: Clip 1, b: guest/clip:<1, c: guest/clip ≈1. ...................................... 18
Figure S22: Expansion from ROESY spectrum of clip 1 with 1,6-diaminohexane 12 (500
MHz, CDCl3 solution, 25°C), guest/clip ≈1, mixing time = 0.5s. ........................................... 19
Figure S23: P.E.COSY spectrum of clip 1 with 1,6-diaminohexane 12 (500 MHz, CDCl3
solution, 25°C), guest/clip ≈1................................................................................................... 20
Figure S24: 1H NMR spectra of clip 1 with 1,8-diaminooctane 13 (500 MHz, CDCl3 solution,
25°C). a: Clip 1, b: guest/clip ≈1, c: 13.................................................................................... 21
Figure S25: Expansion from 1H NMR spectra of clip 1 with 1,8-diaminooctane 13 (500 MHz,
CDCl3 solution, 25°C). a: Clip 1, b: guest/clip < 1, c: guest/clip ≈1. ...................................... 22
Figure S26: P.E.COSY spectrum of clip 1 with 1,8-diaminooctane 13 (500 MHz, CDCl3
solution, 25°C), guest/clip ≈1................................................................................................... 23
Figure S27: Expansion of 1H NMR spectrum of clip 1 with 1,12-diaminododecane 14 (500
MHz, CDCl3, -40 oC) guest/clip ≈1.......................................................................................... 24

3
ACCEPTED MANUSCRIPT
Figure S28: ROESY spectrum of clip 1 with 1,12-diaminododecane 14 (500 MHz, CDCl3, -40
oC) guest/clip ≈1....................................................................................................................... 24
Figure S29: Expansion of 1H NMR spectrum of clip 1 with 1,20-diaminoeicosane 16 (500
MHz, CDCl3, 25 oC) guest/clip ≈1........................................................................................... 25
Figure S30: Expansion of variable temperature 1H NMR spectrum of clip 1 with
1,20-diaminoeicosane 16 (500 MHz, toluene-d8) guest/clip ≈1. From top to
bottom: -20 oC, -40 oC, -70 oC, 90 oC. ..................................................................................... 26
Figure S31: TOCSY spectrum of ≈1:1 clip 1:1,20-diaminoeicosane 16 (500 MHz, -20 oC,
toluene-d8 solution). ................................................................................................................. 27
Figure S32: 1H NMR spectrum of 1,20-diaminoeicosane dihydrochloride 15 (500 MHz,
D2O/MeOD solution, 25 o C).................................................................................................... 28
Figure S33: 1H NMR spectrum of 1,20-diaminoeicosane 16 (500 MHz, CDCl3 solution, 25
o C)............................................................................................................................................ 28

4
ACCEPTED MANUSCRIPT
Clip 1
e
9.0
8.5
8.5
8.5
8.5
8.5
8.0
8.0
8.0
8.0
8.0
7.5
7.5
7.5
7.5
7.5
7.0
7.0
7.0
7.0
7.0
6.5
6.5
6.5
6.5
6.5
6.0
6.0
6.0
6.0
6.0
5.5
5.5
5.5
5.5
5.5
5.0
5.0
5.0
5.0
5.0
4.5
4.5
4.5
4.5
4.5
4.0
4.0
4.0
4.0
4.0
3.5
3.5
3.5
3.5
3.5
ppm
ppm
ppm
ppm
ppm
d
9.0
c
9.0
b
9.0
a
9.0
Figure S1: 1H NMR spectrum of clip 1 at various concentrations (500 MHz, CDCl3 solution,
25°C). c(clip 1) = (a) 1.4×10-3 mol.L-1, (b) 8.2×10-4 mol.L-1, (c) 4.1×10-4 mol.L-1, (d) 1.4×10-4
mol.L-1, (e) 8.2×10-5 mol.L-1.

5
ACCEPTED MANUSCRIPT
Figure S2: Expansion from ROESY spectrum of clip 1 (500 MHz, 25°C, toluene-d8 solution).

6
ACCEPTED MANUSCRIPT
F2
(ppm)
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
8.0
8.5
9.0
9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5
F1 (ppm)
Figure S3: TOCSY spectrum of clip 1 (500 MHz, 25°C, toluene-d8 solution).
F2
(ppm)
7.4
7.5
7.6
7.7
7.8
7.9
8.0
8.1
8.2
8.3
8.4
8.5
8.6
8.7
8.8
8.8
8.6
8.4
8.2
8.0
7.8
7.6
7.4
F1 (ppm)
Figure S4: Expansion from TOCSY spectrum of clip 1 (500 MHz, 25°C, toluene-d8 solution).

7
ACCEPTED MANUSCRIPT
8.7
8.6
8.5
8.4
8.3
8.2
8.1
8.0
7.9
7.8
7.7
7.6
7.5
ppm
*
8.7
8.6
8.5
8.4
8.3
8.2
8.1
8.0
7.9
7.8
7.7
7.6
7.5
ppm
Figure S5: Top: Expansion from 1D TOCSY spectrum of “a”-Ph protons in clip 1, bottom:
corresponding region from 1H NMR spectrum, indicating the 1D TOCSY target signal (500
MHz, 25°C, toluene-d8 solution).
8.7
8.6
8.5
8.4
8.3
8.2
8.1
8.0
7.9
7.8
7.7
7.6
7.5
ppm
*
8.7
8.6
8.5
8.4
8.3
8.2
8.1
8.0
7.9
7.8
7.7
7.6
7.5
ppm
Figure S6: Top: Expansion from 1D TOCSY spectrum of “b”-Ph protons in clip 1, bottom:
corresponding region from 1H NMR spectrum, indicating the 1D TOCSY target signal (500
MHz, 25°C, toluene-d8 solution).

8
ACCEPTED MANUSCRIPT
e
*
d
*
c
*
b
*
a
8.7
8.6
8.5
8.4
8.3
8.2
8.1
8.0
7.9
7.8
7.7
7.6
7.5
7.4
ppm
Figure S7: Saturation transfer experiments of clip 1 ortho protons, * denotes saturated signal
(500 MHz, toluene-d8 solution).

9
ACCEPTED MANUSCRIPT
d
6.2
6.2
6.2
6.2
6.0
6.0
6.0
6.0
5.8
5.8
5.8
5.8
5.6
5.6
5.6
5.6
5.4
5.4
5.4
5.4
5.2
5.2
5.2
5.2
5.0
5.0
5.0
5.0
4.8
4.8
4.8
4.8
4.6
4.6
4.6
4.6
4.4
4.4
4.4
4.4
4.2
4.2
4.2
4.2
4.0
4.0
4.0
4.0
3.8
3.8
3.8
3.8
3.6
3.6
3.6
3.6
ppm
ppm
ppm
ppm
c
b
a
Figure S8: Expansion of variable temperature 1H NMR spectrum of clip 1 (CH2 protons) at a)
100 oC, b) 75 oC, c) 50 oC d) 25 oC (500 MHz, toluene-d8 solution).

10
ACCEPTED MANUSCRIPT
d
6.2
6.2
6.2
6.2
6.0
6.0
6.0
6.0
5.8
5.8
5.8
5.8
5.6
5.6
5.6
5.6
5.4
5.4
5.4
5.4
5.2
5.2
5.2
5.2
5.0
5.0
5.0
5.0
4.8
4.8
4.8
4.8
4.6
4.6
4.6
4.6
4.4
4.4
4.4
4.4
4.2
4.2
4.2
4.2
4.0
4.0
4.0
4.0
3.8
3.8
3.8
3.8
3.6
3.6
3.6
3.6
ppm
ppm
ppm
ppm
c
b
a
Figure S9: Expansion of variable temperature 1H NMR of clip 1 (CH2 protons) a) 25 oC, b)
0 oC, c) -25 oC d) -50 oC (500 MHz, toluene-d8 solution).
d
8.2
8.2
8.2
8.2
8.1
8.1
8.1
8.1
8.0
8.0
8.0
8.0
7.9
7.9
7.9
7.9
7.8
7.8
7.8
7.8
7.7
7.7
7.7
7.7
7.6
7.6
7.6
7.6
7.5
7.5
7.5
7.5
ppm
ppm
ppm
ppm
c
b
a
Figure S10: Expansion of variable temperature 1H NMR of clip 1 (Aromatic region) a)
100 oC, b) 75 oC, c) 50 oC d) 25 oC (500 MHz, toluene-d8 solution).

11
ACCEPTED MANUSCRIPT
Clip 1 with 4,4'-bipyridyl
N
N
Table S1: CIS for mixtures of clip 1 and 4,4'-bipyridyl 11 (500 MHz, 1H NMR, CDCl3
solution, 25°C).
Clip:guest 0:1 δ ≈1:1 δ Δδ
8.75 2.40
7.54 4.87
-6.35
-2.67
d
c
b
a
8
8
8
8
7
7
7
7
6
6
6
6
5
5
5
5
4
4
4
4
3
3
3
3
ppm
ppm
ppm
ppm
Figure S11: Expansions from 1H NMR spectra of clip 1 with 4,4'-bipyridyl 11 (500 MHz,
CDCl3 solution, 25 °C). a: Clip 1, b: guest/clip:<1, c: guest/clip ≈1, d: 11.