Exploration of structural motifs influencing solid-state conformation and packing of unclosed cryptands sharing the same 19-membered macrocyclic core

Article abstract of DOI:10.1016/j.tet.2016.10.053

The crystal structures of a series of readily available, highly crystalline bisamide unclosed cryptands (UCs), sharing the same 19-membered macrocyclic core were thoroughly studied in order to rationalize their organization in the solid state. Despite str

Full text of DOI:10.1016/j.tet.2016.10.053

Accepted Manuscript
Exploration of structural motifs influencing solid-state conformation and packing of
unclosed cryptands sharing the same 19-membered macrocyclic core
K. Ziach, K. Dąbrowa, P. Niedbała, J. Kalisiak, J. Jurczak
PII:
S0040-4020(16)31112-7
10.1016/j.tet.2016.10.053
TET 28194
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 23 June 2016
Revised Date: 4 October 2016
Accepted Date: 20 October 2016
Please cite this article as: Ziach K, Dąbrowa K, Niedbała P, Kalisiak J, Jurczak J, Exploration of
structural motifs influencing solid-state conformation and packing of unclosed cryptands sharing the
same 19-membered macrocyclic core, Tetrahedron (2016), doi: 10.1016/j.tet.2016.10.053.
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ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Exploration of structural motifs influencing solid-state conformation and packing
of unclosed cryptands sharing the same 19-membered macrocyclic core
K. Ziach,a,b K. Dąbrowa,b P. Niedbała,b J. Kalisiakb and J. Jurczakb*
a Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
b Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
*Corresponding author. Tel: +48 22 3432330; fax: +48 22 632 66 81; e-mail address: jurczak_group@icho.edu.pl
Abstract
The crystal structures of a series of readily available, highly crystalline bisamide unclosed cryptands (UCs),
sharing the same 19-membered macrocyclic core were thoroughly studied in order to rationalize their
organization in the solid state. Despite structural variations introduced into intraannular substituents,
mode of their attachment to the macrocyclic core, and relative acidity of exterior amide protons, UCs
adopted only three well-defined geometries in all 10 analyzed crystals. This structural resemblance
between conformations of UCs, however, is not translated into similarities in terms of intermolecular
interactions and crystal packing. This contradicting intra- and intermolecular solid-state behavior is likely
connected with an ability of these macrocyclic compounds to engage in numerous interactions of
comparable energy within the crystal lattice.
Keywords
Unclosed Cryptands; Macrocyclisation; Macrocycle; Azamacrocycle; Hydrogen Bond; Solid-state Chirality;
Crystal Packing
1. Introduction
Macrocyclic compounds are the core of the supramolecular chemistry from its very beginnings.1 The
underlying principle of embedding geometrical constrains produced by the cyclic scaffold that ensure high
level of preorganization gave rise to a variety of more complex supramolecular architectures.2 For example,
macrocyclic compounds proved to be excellent hosts for cations,3 anions,4 and neutral5 guests. Recently,
we developed and investigated new class of macrocyclic host molecules, named unclosed cryptands (UCs),6
having a suitably functionalized substituent (lariat arm) installed at the intraannular position of the
macroring. The presence of a flexible lariat arm provides additional anchoring points for the selective guest
binding, similarly as in the case of structurally related cryptands.7 Bis- and tetraamide UCs of medium size,
i.e. between 19 and 26-membered macrorings, proved to efficiently complex various guests, in particular
anions6d,e and neutral molecules,6b,c using a dense network of hydrogen bonds, both in solution and in the
solid state. However, in contrast to cryptands, the synthesis of UCs is more convenient providing desired
macrocyclic compounds in considerably higher yields, and thus paves the way for a scope of relatively easy
structural modifications.6a,d
In this contribution we discuss solid state structures of several newly designed analogues of the parent UC
1a, which was previously shown to form chiral crystals.8 To allow for direct comparisons among the
compounds, we have decided to keep the 19-membered macrocycle core intact, and vary, one at a time,
the lariat arm aryl ring substituents, the macrocycle – lariat arm linker, and the relative acidity of amide
protons.
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2. Results and discussion
The synthesis of proposed bisamides, presented in Scheme 1, follows the well-established protocol with a
key step being macrocyclisation reaction involving bis-amine 2 and bis-(methyl)esters 3a-f in methanol,
mediated by sodium methoxide. This methodology typically offers high yields of macrocyclic products and
is tolerant toward variety of functional groups.6a,d,e,9 In addition, linear macrocycle precursors are easily
synthetically accessible. Accordingly, we obtained two analogues of parent compound 1a, that possess
small substituents in para position of the lariat ring (1b and 1c), and two analogues that differ in
macrocycle-lariat arm linker (1d and 1e). In addition, a set of four already published10,11 structures of
different solvates of another relevant linker-analogue 1f was included in this study. Also, to probe the
influence of acidity of amide protons, we synthesized the thioamide 1g by treating compound 1a with
Lawesson’s reagent. X-Ray suitable crystals of new compounds were obtained from methanol.
X
O
a
b
X
X
Y
Ar
Ar
= O, = OCH2,
= Ph
Y
= O, = OCH2,
= p-O2N-Ph
NH2
N
O
O
O
O
H
c
d
X = O, Y = OCH2, Ar = p-Br-Ph
O
O
O
O
MeONa
X
X
X
Y
Ar
= O, = OCH2CH2,
= Ph
Y
+
Y
Ar
Ar
MeOH
rt
e
f
Y
Ar
= O, = OCO, = Ph
H
O
Y
Ar
= Ph
NH2
= O, = NHCO,
N
O
g
X = S, Y = OCH2, Ar = Ph
(from 1a, using Lawesson's reagent)
1a-g
2
3a-f
X
O
Scheme 1. Sodium methoxide mediated macrocyclisation reaction leading to unclosed cryptands 1. The synthesis of
compounds 1a, 1e, and 1f was already reported in refs 8, 10 and 11, respectively.
Compound 1a crystallizes in the space group P212121 (Fig. 1a). At the level of a single molecule, the
symmetry is broken by the existence of an internal hydrogen bond between the oxygen atom in the lariat
arm and one of the two amide protons, that corresponds to N-OBn distances of 3.06 Å (H-bonding) and 3.66
Å (non-bonding). For the purpose of uniform presentation of different conformations adopted by UCs in
crystals, hence to facilitate their direct visual comparison, in all the figures, UCs are presented in the same
way as for compound 1a, that is: the resorcine ring is located to the left and viewed perpendicular to the
plane of the picture. Further, to cross compare the geometry of molecules in crystals, we call the
conformation of 1a T-shaped.
Figure 1. X-Ray structures of: a) UC 1a, insert: intramolecular hydrogen bond; b) UC 1b, insert: superimposition of
crystallographically independent molecules in the asymmetric unit (1bA - green, 1bB - blue, 1bC – red; macroring
heteroatoms were used for RMS overlay); hydrogen atoms and solvents omitted for clarity.
Compound 1a crystallizes as monohydrate and the water molecule is localized outside the macrocyclic
cavity, close to the para position of the lariat arm ring. We concluded, that introduction into the para
position a small substituent, that could potentially occupy the position of water molecule in 1a, might
potentially not alter crystal the packing scheme. Thus, we obtained and crystallized para substituted nitro-
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and bromo- analogues 1b and 1c. In both of them water is not present in the lattice, as expected, although
the crystallinity changed as well.
In the asymmetric unit of p-nitro analogue 1b (Fig. 1b) there are three independent molecules, each
adopting a similar T-shaped conformation as in case of UC 1a. The internal NH-OBn hydrogen bonds
differentiate the “sides” of molecules although the lengths of these bonds varied significantly in each
conformation, i.e. the corresponding N-OBn distances are 3.12 Å and 3.59 Å; 3.23 Å and 3.24 Å; 3.12 Å and
3.42 Å, for 1bA, 1bB, and 1bC, respectively. Compound 1b crystallizes in low symmetry space group P-1 as
MeOH solvate, with one methanol molecule per macrocycle well localized external to the macrocyclic
cavity. Strikingly, in the crystals of UC 1a we never found methanol despite being used for crystallization.
Contrary to the UCs 1a and 1b, the bromo-derivative 1c adopts a C-shaped conformation in the crystal (Fig.
2a), in which the electron-rich catechol ring and electron-poor lariat aromatic ring π-π stack in a face-to-
face mode. Again, there is an internal hydrogen bond differentiating the “sides” of a macrocycle, that
involve one of the amide NHs and etheric OBn atoms. The corresponding N-OBn distances are 3.15 Å and
3.69 Å. Compound 1c crystallizes in the space group P21/n. Similarly, as in the crystal structures of 1a and
1b, a molecule of methanol is not present within the crystal lattice.
The first of the linker-analogues, 1d, structurally differ from 1a by the presence of additional methylene
group in the macrocycle–pendant arm linker. There are two crystallographically independent molecules of
UC 1d in the crystal (Fig. 2b), both asymmetric, that, in respect to the internal hydrogen bonds,
corresponds to N-OBn distances of 3.00 Å and 3.79 Å in conformation 1dA and 3.05 Å and 3.71 Å in
disordered conformation 1dB. In both conformations macrocycle 1d adopts C-shaped geometry. The
disorder in conformation 1dB is limited to the pendant arm that occupies two different, although well-
defined, positions in the lattice with equal probability (50:50 occupancy ratio). UC 1d crystallizes in the
space group P21/n as solvate with disordered methanol and water, both localized externally to the
macrocycles.
Figure 2. X-Ray structures of UCs: a) 1c, insert: intermolecular hydrogen bond; b) 1d, insert: superimposition of
crystallographically independent molecules in the asymmetric unit (1dA - violet, 1dB – blue and green; macroring
heteroatoms were used for RMS overlay); hydrogen atoms and solvent molecules omitted for clarity.
The next linker analogue investigated was an ester 1e. In the crystal, the pendant arm part of the structure
is disordered, that is associated with the existence of the two forms of 1e: a free ligand - 1eA (Fig. 3a) and
an intra-cavity complex with water- 1eB (Fig. 3b), that differ by the distance of the lariat arm from the
macrocyclic core. The refined occupancy ratio of the disordered moieties is equal to 0.64:0.36. A formal
exchange of benzylic methylene (as in 1a) into a carbonyl group brings an important change to electronic
and geometry of the pendant arm, and hence can alter the conformation as well as H-bonding ability of the
whole molecule. Indeed, UC 1e adopts a different - S-shaped conformation (Fig. 3c) in both forms of a free
ligand 1eA and its water complex 1eB. The internal H-bonds engage the carbonyl oxygen atom rather than
the oxygen linking the arm to a resorcine ring (as in all described above structures lacking the carbonyl
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group in the linker). In both forms, 1eA and 1eB, the intramolecular hydrogen bonds strongly differentiate
“right” and “left” side of molecules. Interestingly, ester 1e crystallizes forming chiral crystals, in the space
group P212121, the same as UC 1a, although the packing scheme is different (see ESI). In the crystal lattice,
the characteristic interaction motif is a π-π stacking between catechol and resorcine rings of neighboring
molecules in a parallel displaced mode.
Figure 3. X-Ray structure of ester 1e:a) higher occupancy free ligand form 1eA, b) lower occupancy water complex
form 1eB, c) S-shaped geometry of 1e (1eA in a common colors, 1eB in green color); hydrogen atoms omitted for
clarity.
Hence, we invoked another analogue of UCs 1a and 1e, amide 1f (Fig. 4), of which crystals of four different
solvates have already been published (CCDC refcodes: IDADAT, IPUPUF, IPUQAM, IPUQEQ).10,11 Strikingly, in
of all four different solvates, two of which (IPUPUF, IPUQAM) contain more than one conformer in the
asymmetric unit, the geometry of amide UCs 1f highly resembles the S-shaped geometry of ester 1e.
Namely, the carbonyl oxygen is H-bonded to one of the amide NHs. Moreover, in three solvates of 1f
(IPUPUF, IPUQAM, IPUQEQ) a water molecule is bonded in a macrocycle cavity and engaged in H-bonding
in the same way as in case of ester 1e.
Figure 4. X-Ray structures of amides 1f: a) IDADAT;10 b) IPUPUF,11 insert: superimposition of two crystalographically
independent molecules in the asymmetric unit; c) IPUQEQ;11 d) IPUQAM,11 insert: superimposition of four
crystalographically independent molecules in the asymmetric unit; hydrogen atoms and solvent molecules, except for
intracavity water, omitted for clarity.
The last tested modification involved conversion of parent amide 1a into a corresponding thioamide 1g, by
reacting compound 1a with Lawesson’s reagent. In principle, this should lead to only minor alteration of
geometry and electronics of the molecule and hence the range intra- and inter-molecular interactions,
however the solid state structure of UC 1g differs significantly from amide 1a. The thioamide 1g adopts a C-
shaped conformation. The internal NH-OBn hydrogen bond discriminates the “sides” of the molecule even
more strongly than in the previous structures as the difference in the corresponding N-OBn distances
reached 1 Å (3.02 Å for the H-bonded and 4.01 Å for non-bonded).
All of the presented UCs differ from the reference 1a by only one structural aspect: insertion of additional
group in a lariat ring (1b and 1c) in a para position, that was otherwise occupied by water molecule in a
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crystal of 1a; extension of a linker by one methylene group (1d); replacement of a linker O-CH2 with either
O-CO (1e) or NH-CO (1f); and exchange of amide into thioamide groups (1g). However, when the
conformations adopted by USs in all the crystals are considered (including multiple crystallographically
independent molecules in crystals of 1b, 1d, 1f IPUPUF, and 1f IPUQAM, that accounts for 16 unique
geometries), they fall into three categories, arbitrarily called T-shaped, C-shaped and S-shaped. The latter is
exclusively chosen by all UCs containing carbonyl group in the linker - ester 1e and amides 1f. Figure 6
presents superimposition of S-shaped UCs 1e and 1f. All compounds exhibit remarkable similarity in terms
of conformation, with a slight exception of amide 1f IDADAT. Also for all geometries, the H-bond network
matches perfectly, including the internally bonded water molecule (except for 1f IDADAT that do not bind
water). Precisely, the variation of water position, among the structures presented in Figure 6, is lower than
0.34 Å (i.e the distance between two least matching water oxygen atoms). The remarkable stability of the
S-shaped conformation for the carbonyl-linker UCs provides indirect proof of the important role of water in
stabilizing the particular conformation,6c as water molecules occupy very well-defined positions in the
cavity, reproducible among the different crystals, despite some functional difference (ester vs amide) and
the very different way the compounds are packed in the lattice. Solvents molecules, present in different
solvates of 1f (acetone in 1f IPUPUF, toluene in 1f IPUQEQ, additional water in 1f IPUQAM), were unable to
alter the conformations either.
Figure 5. X-Ray structure of UC 1g, insert: intermolecular hydrogen bond; hydrogen atoms omitted for clarity.
Figure 6. Superimposition12 of S-shaped structures 1eA (red), 1eB (orange) and four solvates of 1f (IDADAT- grey,
IPUPUF - green, IPUQAM - violet, IPUQEQ - blue).
The same analysis was performed for T-shaped UCs 1a and 1b, for the latter, including its three solid state
conformers (Fig. 7). In this case as well, there is a very good match among all four geometries. Strikingly,
one of the conformers of 1b resembles 1a more than the other two of its own. The second geometry,
adopted by UCs that did not contain a carbonyl group in the linker, we called C-shaped. Figure 8 present
the superimposition of all the C-shaped molecules of 1c, 1d (including its three conformers) and 1g. In these
UCs the macrocyclic part overlap very well, the differences in geometries are observed only within the
flexible pendant arm.
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At this point, it is worth adding that the same conformational behavior we found even among other less
related to 1a analogues that were prepared for different projects and are not recalled here in detail.10,13
Namely, all UCs containing a carbonyl moiety in the linker (CCDC refcodes: QEKMID, QEKMOJ, IDACUM)
uniquely adopted similar to described here, S-shaped conformations, whereas O-benzyl analogues (CCDC
refocdes: QEKMUP, QEKNAW, QEKMEZ) exclusively adopted either T- or C-shaped conformation.
Figure 7. Superimposition12 of T-shaped structures of macrocycles 1a (blue) and 1b (1bA – green, 1bB - red, 1bC -
yellow).
Figure 8. Superimposition12 of C-shaped structures 1c (orange), 1d (1dA – violet, 1dB – blue and green) and 1g (red).
The similarities in the solid-state conformation of macrocycles and existence of similar intramolecular H-
bonds within macrocyclic core, does not, however, correspond to virtually any similarities in crystal packing
and intermolecular interactions within in the lattice. This solid state similarity/dissimilarity puzzle can be
conveniently analyzed by the aid of Hirshfeld surfaces (HS) that, in a visual manner, show global
intramolecular interactions in the crystals.14 For that, we use the dnorm property mapped on the Hirshfeld
surface.15 Dnorm is a van der Waals radii (vdW) normalized contact distance between the two nearest atoms
belonging to two adjacent molecules in the crystal. While presented using the common red-white-blue
coloring scheme, it especially highlights the strong contacts (the interatomic distance lower than the sum of
vdW radii of the corresponding atoms) as red spots on the HS, to be distinguished from weak contacts that
are colored blue (distances longer than vdW radii) and white (distance equal to the sum of vdW radii). As an
example we have chosen the chiral ester 1e and amide 1f IPUQAM as a reference. Crystal of 1f IPUQAM is
most closely related to 1e in terms of the structure and intra-cavity complexation of water.16 A comparison
of Hirshfeld surfaces with the dnorm property mapped for ester 1e (complex with water 1eB and a free ligand
1eA)17 and four conformers of amide 1f IPUQUAM is shown in Figure 9. One can see that the geometries
and, hence, the spatial arrangements of functional groups in all conformers are virtually the same and, so is
the potential ability for intermolecular interactions. While, in fact, as clearly represented by red spots on
the HS, the molecules are engaged in very different intramolecular interactions. Strikingly, these
differences are visible not only for 1e vs 1f IPUQAM, but also among four conformers of the latter. We find
it justified to assume that distinct maps of intermolecular contacts observed for analyzed UCs are a
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consequence of the presence of numerous H-bond acceptors and donors, as well as local interactions
between three electronically different aromatic rings (electron-rich catechol and resorcine rings in the
macrocycle and electron-rich benzyl or electron-poor benzoyl rings in the lariat arm).18 We assume that
these structural features enable multiple, energetically similar interactions among the UCs, and with the
variety of solvents, that, as a consequence, results in a differences in packing.
0°
90°
180°
270°
1eA17
1eB17
1fA
1fB
1fC
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1fD
Figure 9. Ball and sticks representation and Hirshfeld surfaces mapped with dnorm property generated for the two
forms of 1e (A, B) and four conformers of 1f IPUQAM (A-D).
An interesting observation came from the comparison of HS for 1a and its thioamide analog 1g. Despite
large differences in conformations of macrocycles (i.e. T- and C-shaped for 1a and 1g, respectively),
contribution of S···H interactions (18%) to the HS seems to compensate a small share of O···H interactions
(7%) to such an extent that overall contribution of these interactions is comparable to that for “pure” O···H
interactions (25%) in diamide 1a (Fig. S14 and S15). In addition, slightly larger contribution of the H···H
interactions to the HS in 1g (51%) than in 1a (46%) is likely a result of the very short contacts between
protons of the ethylene linkers in the former case which is exemplified by the sharp spike for the values of
di and de close to 1.1-1.2 Å (Fig. S14).
3. Conclusions
A set of new unclosed cryptands, sharing the same 19-membered macrocyclic core, were obtained using a
convenient synthetic methodology and were analyzed in respect to their solid state conformations and
packing. Despite structural variations introduced into lariat arm substituents, in the macrocycle-arm linker
as well as upon the change in the acidity of amide NHs, in 10 analyzed crystals, which accounts for 16
crystallographically independent molecules, UCs adopt only three well-defined conformations at the
molecular level. The so-called S-shaped is uniquely adopted by UCs bearing a carbonyl group in the linker,
whereas all “non-carbonyl” compounds prefer either T-shaped or C-shaped forms. Interestingly, in none of
the solid-state conformations are the UC molecules symmetric. In the case of one compound a chiral crystal
was obtained. Despite the high predictability of their conformations and intramolecular interactions, all
UCs behave very differently in terms of intermolecular interactions and crystal packing. This contradicting
intra- and intermolecular behavior is likely connected with an ability of these macrocyclic compounds to
engage in numerous interactions of comparable energy within the crystal lattice.
4. Experimental Section
4.1. Synthesis. General Remarks
All solvents were of reagent grade quality. All reagents were purchased from Sigma-Aldrich and TCI
Chemicals and used without further purification. Column chromatography was carried out using Merck
Kieselgel 60 (63–100 μm mesh size), TLC was carried out on Merck Kieselgel F254 plates. The NMR spectra
were recorded on a Bruker Mercury 400 instrument. Chemical shifts are reported in ppm and are set to
solvent residue peak. The splitting pattern of multiplets is described by abbreviations (s – singlet, d –
doublet, t – triplet, q ¬– quartet, dd – doublet of doublets, m – multiplet, c – covered signal, b – broad
peak). J coupling constants values are reported in Hz. Mass spectral analyses were performed with the ESI-
TOF technique on a Mariner mass spectrometer from PerSeptive Biosystem.
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4.2. Synthesis. General procedure for macrocyclization of UCs
Sodium methoxide (5.0 mmol) in anhydrous methanol (20 mL) was added to a solution of 2,2'-[1,2-
phenylenebis(oxy)]diethanamine 2 (1.0 mmol) and corresponding α,ω-diester 3b-d (1.0 mmol) in methanol
(180 mL). When both substrates were consumed (~ 7 days), the solvent was evaporated off and the residue
was purified, employing column chromatography (DCM:methanol, 95:5, v/v) to obtain pure macrocycles.
The synthesis of compounds 1a, 1e and 1f was described in refs 8, 10 and 11, respectively.
UC 1b. Following General Procedure and using diester 3b (400 mg, 1.0 mmol), macrocycle 1b (220 mg, 44
1
%) was obtained. H NMR (400 MHz, DMSO) δ 7.93 (d, J = 8.7 Hz, 2H), 7.70 – 7.66 (m, 2H), 7.64 (d, J = 8.7
Hz, 2H), 7.15 – 7.07 (m, 1H), 6.94 (d, J = 8.4 Hz, 2H), 6.90 – 6.77 (m, 4H), 5.11 (s, 2H), 4.78 – 4.64 (m, 4H),
3.97 (t, J = 4.5 Hz, 4H), 3.60 – 3.39 (m, 4H). 13C NMR (101 MHz, DMSO) δ 168.44, 152.63, 147.97, 147.34,
144.56, 138.87, 128.86, 125.91, 123.73, 121.25, 113.04, 111.29, 74.95, 70.46, 67.62, 38.67. ESI-MS: 560.16
[M+Na]+. HRMS (ESI): calc 560.1645 for C27H27N3O9Na, obtained 560.1647. Elemental analysis: calc C
59.05%, H 5.49%, N 7.38% for C27H27N3O9+CH3OH, obtained C 59.35%, H 5.13%, N 7.54%.
UC 1c. Following General Procedure and using diester 3c (440 mg, 1.0 mmol), macrocycle 1c (178 mg, 31 %)
1
was obtained. UC 1c. H NMR (400 MHz, DMSO) δ 7.73 (t, J = 5.5 Hz, 2H), 7.33 (s, 4H), 7.09 (t, J = 8.4 Hz,
1H), 6.96 – 6.85 (m, 6H), 4.98 (s, 2H), 4.66 (dd, J = 34.5, 15.8 Hz, 4H), 3.98 (t, J = 4.6 Hz, 4H), 3.59 – 3.36 (m,
4H). 13C NMR (101 MHz, DMSO) δ 168.51, 152.79, 148.12, 138.91, 136.44, 131.59, 130.26, 125.77, 121.69,
121.39, 113.14, 111.53, 75.29, 70.69, 67.61, 38.70. ESI-MS: 595.09 [M+Na]+. HRMS (ESI): calc 593.0899 for
C27H27BrN2O7Na, obtained 593.0891. Elemental analysis: calc C 55.02%, H 4.96%, N 4.75%, Br 13.56% for
C27H27BrN2O7+H2O, obtained C 55.02%, H 5.02%, N 4.74%, Br 13.50%.
UC 1d. Following General Procedure and using diester 3d (370 mg, 1.0 mmol), macrocycle 1d (146 mg, 29
1
%) was obtained. H NMR (400 MHz, DMSO) δ 7.77 (dd, J = 6.4, 4.2 Hz, 2H), 7.19 – 7.12 (m, 3H), 7.09 – 7.04
(m, 1H), 7.02 – 6.98 (m, 2H), 6.95 – 6.87 (m, 6H), 4.68 (dAB, J = 15.8 Hz, 2H), 4.58 (dAB, J = 15.8 Hz, 2H),
4.13 (t, J = 7.5 Hz, 2H), 4.03 (t, J = 4.7 Hz, 4H), 3.67 – 3.58 (m, 2H), 3.51 – 3.41 (m, 2H), 2.88 (t, J = 7.5 Hz,
2H). 13C NMR (101 MHz, DMSO) δ 167.93, 152.29, 147.80, 138.90, 137.25, 128.46, 128.15, 126.10, 125.00,
121.10, 113.07, 111.31, 74.77, 70.34, 67.32, 38.16, 35.61. ESI-MS: 529.19 [M+Na]+. HRMS (ESI): calc
529.1951 for C28H30N2O7Na, obtained 529.1948. Elemental analysis: calc C 64.67%, H 6.36%, N 5.20% for
C28H30N2O7+CH3OH, obtained C 64.40%, H 6.11%, N 5.24%.
UC 1g. The macrocycle 1a (250 mg, 0.50 mmol) and Lawesson reagent (650 mg, 1.5 mmol) was refluxed in
toluene (30 mL) for 24 hours. Solvent was evaporated off under reduced pressure, and thus obtained
yellow residue was purified employing column chromatography (DCM:methanol, 98:2→95:5, v/v) as the
1
eluent, yielding macrocycle 1g (0.2 g, 76%) as yellow solid. H NMR (400 MHz, DMSO) δ 9.59 (t, J = 5.0 Hz,
2H), 7.41 – 7.34 (m, 2H), 7.30 – 7.22 (m, 3H), 7.07 (t, J = 8.3 Hz, 1H), 7.00 – 6.86 (m, 6H), 5.09 (dAB, J = 16.6
Hz, 2H), 5.04 (s, 2H), 4.92 (dAB, J = 16.6 Hz, 2H), 4.23 – 4.06 (m, 4H), 4.06 – 3.73 (m, 4H). 13C NMR (101
MHz, DMSO) δ 197.20, 152.30, 148.09, 138.84, 136.84, 128.80, 128.74, 128.72, 125.70, 121.69, 113.77,
112.05, 77.06, 76.55, 66.21, 44.72. ESI-MS: 547.13 [M+Na]+. HRMS (ESI): calc 547.1337 for C27H28N2O5NaS2,
obtained 547.1339. Elemental analysis: calc C 61.81%, H 5.38%, N 5.34%, S 12.22% for C27H28N2O5S2,
obtained C 61.55%, H 5.34%, N 5.21%, S 12.29%.
4.3. X-Ray Crystallography
The measurements of 1b, 1d and 1e crystals were performed on a KM4CCD κ-axis diffractometer with
graphite-monochromated MoKα radiation. The data were corrected for Lorentz and polarization effects.
Data collection, reduction and analysis were carried out with the Oxford Diffraction programs.19 Particular
absorption correction method that was applied is mention in the ‘Crystal data and structure refinement
9

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details’ section in ESI. The structures were solved by direct methods20 and refined using SHELXL.21
Scattering factors were taken from International Tables.22
The measurements of 1c and 1d crystals were performed at on a Bruker D8 Venture Photon100
diffractometer equipped with a TRIUMPH monochromator and a MoKα fine focus sealed tube. Data
collection, reduction and analysis were carried out with Bruker programs.23a,b Data were corrected for
absorption effects using the multi-scan method (SADABS).23c The structures were solved and refined using
SHELXTL Software Package.20,21 Unless states otherwise (see: ESI), the non-hydrogen atoms were refined
anisotropically and hydrogen atoms were placed in calculated positions and refined within the riding
model. The temperature factors of these hydrogen atoms were not refined and were set to be equal to
either 1.2 or 1.5 times larger than Ueq of the corresponding heavy atom. The atomic scattering factors were
taken from the International Tables.22
Selected crystal data and structure refinement parameters for UCSs 1b-1e and 1g are summarized in Table
1. More details regarding the above can be found in ESI. Crystallographic data (excluding structure factors)
for the structures in this paper have been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication nos. CCDC. Copies of the data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, (fax: +44-(0)1223-336033 or e-mail:
deposit@ccdc.cam.ac.Uk).
Table 1. Selected crystal data and structure refinement parameters for UCs 1b-1e and 1g.
1b
1c
1d
1e
247076
1g
CCDC no.
1472817
C28H31N3O10
569.56
1472818
C27H27BrN2O7
571.41
1472819
1472816
C27H28N2O5S2
524.63
Empirical formula
C225H249N16O63
4185.39
C27H26.73N2O8.36
513.03
Formula weight
[g/mol]
Temperature [K]
100(2)
0.71073
Triclinic
P-1
100(2)
0.71073
Monoclinic
P21/n
100(2)
0.71073
Monoclinic
P21/n
150(2)
0.71073
293(2)
0.71073
Monoclinic
P21/n
Wavelength [Å]
Crystal system
Orthorombic
P212121
Space group
Unit cell params:
a [Å]
16.2762(15)
17.7332(15)
17.951(3)
16.366(11)
96.698(12)
112.632(8)
4017.4(8)
6
8.5223(10)
19.562(2)
15.4538(19)
90
14.5271(13)
15.4368(13)
23.233(2)
90
7.9512(16)
8.7607(18)
35.018(7)
90
10.4421(11)
15.4416(14)
15.7716(16)
90
b [Å]
c [Å]
α [°]
103.827(3)
90
91.970(2)
90
90
98.940(9)
90
β [°]
90
γ [°]
Volume [Å3]
2501.7(5)
4
5207.0(8)
1
2439.3(9)
4
2512.2(4)
4
Z
Calc. density [g/cm3]
1.413
1.517
1.335
1.397
0.105
1.387
Absorption
coefficient [mm-1]
F(000)
0.108
1.694
0.098
0.254
1800
1176
2215
1079
1104
Theta range for data
collection [°]
2.58 to 25.00
2.49 to 25.05
2.94 to 25.05
3.91 to 25.05
2.93 to 28.81
Limiting indices
-19<=h<=19,
-21<=k<=21,
-21<=l<=21
-10<=h<=10,
-23<=k<=23,
-18<=l<=18
-17<=h<=17,
-18<=k<=18,
-27<=l<=27
-9<=h<=9,
-10<=k<=8,
-41<=l<=41
18570 / 4317
-14<=h<=14,
-20<=k<=20,
-21<=l<=21
Reflections 59775 / 14124
42658 / 4429
85764 / 9212
46179 / 6264
collected/unique [R(int) = 0.0877] [R(int) = 0.0611] [R(int) = 0.0306] [R(int) = 0.0462] [R(int) = 0.0305]
Data / restraints / 14124 / 0 / 1481 4429 / 0 / 342
parameters
9212 / 2 / 793
4317 / 25 / 451
6264 / 0 / 437
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Goodness-of-fit on F2
0.880
1.078
1.040
1.091
1.115
Final R indices
[I>2sigma(I)]
R indices (all data)
R1 = 0.0481,
wR2 = 0.0881
R1 = 0.1173,
wR2 = 0.1104
R1 = 0.0232,
wR2 = 0.0608
R1 = 0.0255,
wR2 = 0.0620
R1 = 0.0334,
wR2 = 0.0782
R1 = 0.0414,
wR2 = 0.0840
R1 = 0.0345,
wR2= 0.0842
R1 = 0.0400,
wR2= 0.0885
R1 = 0.0378,
wR2 = 0.1010
R1 = 0.0518,
wR2 = 0.1079
Largest diff. peak and 0.259 and -0.309 0.325 and -0.336 0.271 and -0.214 0.183 and -0.190 0.365 and -0.439
hole [e Å-3]
Flack parameter
-
-
-
-0.4(4)
-
Acknowledgements
We would like to acknowledge the Polish National Science Centre (project 2011/02/A/ST5/00439) for
financial support.
Supplementary data
Supplementary data associated with this article can be found in the online version, at
http://dx.doi.org/xxxxxxxxxxxx
References and notes
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R. B. P.; Jolliffe, K. A. Chem. Commun. 2015, 51, 4951-4968; (g) Havel, V.; Svec, J.; Wimmerova, M.; Dusek,
M.; Pojarova, M.; Sindelar, V. Org. Lett. 2011, 13, 4000-4003.
5 For selected examples, see: (a) Li, C.; Han, K.; Li, J.; Zhang, H.; Ma, J.; Shu, X.; Chen, Z.; Weng, L.; Jia, X. Org.
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(a) Dąbrowa, K.; Niedbała, P.; Majdecki, M.; Duszewski, P.; Jurczak, J. Org. Lett. 2015, 17, 4774-4777; (b)
Dąbrowa, K.; Ceborska, M.; Jurczak, J. Cryst. Growth Des. 2014, 14, 4906-4910; (c) Paluch, P.; Kaźmierski, S.;
Jeziorna, A.; Sniechowska, J.; Dabrowa, K.; Panek, J. J.; Jezierska-Mazzarello, A.; Jurczak, J.; Potrzebowski,
M. J. J. Phys. Chem. B 2013, 117, 14420-14431; (d) Dąbrowa, K.; Pawlak, M.; Duszewski, P.; Jurczak, J. Org.
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11
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12 In Figures 6-8 the macroring O and N heteroatoms were chosen for RMS overlay, as they are common for
all the structures and are distributed uniformly over the molecules. Hence, we assume this provides a way
of ‘global fitting’, resistant to bias from structural modifications and conformational distortions at the
peripheries.
13 Kalisiak, J.; Skowronek, P.; Gawroński, J.; Jurczak, J. Chem. Eur. J. 2006, 12, 4397-4406.
14
(a) Hirshfeld surfaces were calculated and visualized using CrystalExplorer software (Version 3.1,
downloaded from: http://www.hirshfeldsurface.net), by: Wolff, S. K.; Grimwood, D. G.; McKinnon, J. J.;
Turner, M. J.; Jayatilaka, D.; Spackman, M. A. University of Western Australia, 2012; (b) for general aspects
of HS analysis see: Spackman, M. A.; Jayatilaka, D. CrystEngComm 2009, 11, 19-32.
15 McKinnon, J. J.; Jayatilaka, D.; Spackman, M. A. Chem. Commun. 2007, 3814-3816.
16 Among the solvates of 1f, only IPUQAM contains no other solvents than water.
17
Due to the disorder in 1e crystal, attributed to the existence of two forms - 1eA and 1eB, calculation of
HS is unreliable for the original data. Hence, HS surfaces were generated, independently, for 1eA and 1eB
using prepared CIF files of artificial crystals composed of only one respective form.
18 Wheeler, S. E. Acc. Chem. Res. 2012, 46, 1029-1038.
19 (a) CrysAlis CCD, Oxford Diffraction Ltd., Version 1.171.28cycle2 beta; (b) CrysAlis RED, Oxford Diffraction
Ltd., Version 1.171.28cycle2 beta.
20 Sheldrick, G. M. Acta Cryst. 1990, A46, 467-473.
21 Sheldrick, G. M. Acta Cryst. 2008, A64, 112-122.
22 Wilson, A. J. C. International Tables for Crystallography, Kluwer, Dordrecht, 1992, Vol. C.
23
(a) APEX2, Bruker AXS Inc., Madison, Wisconsin, USA, 2013; (b) SAINT, Bruker AXS Inc., Madison,
Wisconsin, USA, 2013; (c) SADABS, Bruker AXS Inc., Madison, Wisconsin, USA, 2012.
12