Host-guest inclusion systems of tetra(alkyl)resorcin [4]arenes with choline in DMSO: Dynamic NMR studies and X-ray structural characterization of the 1:1 inclusion complex

Article abstract of DOI:10.1016/j.molstruc.2019.07.093

The host-guest complex of C-tetra(methyl)calix[4]resorcinarene (1), C-tetra(pentyl)calix[4]resorcinarene (2), and C-tetra(nonyl)calix[4]resorcinarene (3) with choline in DMSO was examined via dynamic NMR. Under these conditions, only C-tetra(methyl)calix[4]resorcinarene formed a complex with choline. In order to establish the role of DMSO during the solubilization/complexation process, titration was carried out with resorcinarenes and DMSO in CDCl₃. Our careful NMR analysis was based on the assignment of ¹H NMR signals of the resorcinarenes in CDCl₃ after the addition of variable amounts of DMSO, which showed an interesting host-guest interaction with C-tetra(pentyl)calix[4]resorcinarene. With both solvents, it is possible to define stable cone conformational arrangements based on the signals shown in the spectra of all the experiments. The results show the formation of a 1:1 inclusion complex between DMSO and C-tetra(pentyl)calix[4]resorcinarene. Suitable crystals of C-tetra(pentyl)resorcinarene in DMSO were characterized through an X-ray crystal structure determination and showed the inclusion of a molecule of DMSO in the cavity of the resorcinarene. The asymmetric unit contains one molecule of water and five molecules of DMSO, and analysis indicated that resorcinarene prefers a cone configuration (rccc conformation) in the solid state. In the crystal array, classical hydrogen bond O–H?O interactions and intermolecular contacts were observed.

Full text of DOI:10.1016/j.molstruc.2019.07.093

Accepted Manuscript
Host-guest inclusion systems of tetra(alkyl)resorcin[
4
]arenes with choline in DMSO: Dynamic NMR studies and X-ray structural
characterization of the 1:1 inclusion complex
Astrid Velásquez-Silva, Roger Sarmiento Forero, Edilma Sanabria, Adrián Pérez-Redondo,
Mauricio Maldonado
PII:
S0022-2860(19)30937-8
10.1016/j.molstruc.2019.07.093
MOLSTR 26846
DOI:
Reference:
To appear in:
Journal of Molecular Structure
Received Date:
Accepted Date:
25 May 2019
24 July 2019
Please cite this article as: Astrid Velásquez-Silva, Roger Sarmiento Forero, Edilma Sanabria,
Adrián Pérez-Redondo, Mauricio Maldonado, Host-guest inclusion systems of tetra(alkyl)resorcin[
4
]arenes with choline in DMSO: Dynamic NMR studies and X-ray structural characterization of the 1:
1
inclusion complex, Journal of Molecular Structure (2019), doi: 10.1016/j.molstruc.2019.07.093
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Graphical abstract
Host-guest inclusion systems of tetra(alkyl)resorcin[4]arenes with
choline in DMSO: Dynamic NMR studies and X-ray structural
characterization of the 1:1 inclusion complex

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Host-guest inclusion systems of tetra(alkyl)resorcin[4]arenes with
choline in DMSO: Dynamic NMR studies and X-ray structural
characterization of the 1:1 inclusion complex
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Astrid Velásquez-Silva , Roger Sarmiento Forero , Edilma Sanabria Adrián Pérez-
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Redondo and Mauricio Maldonado *
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Universidad Nacional de Colombia, Sede Bogotá, Facultad de Ciencias, Departamento
de Química, Carrera 30 No. 45-03, Bogotá, Colombia
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Grupo GICRIM, Programa de Investigación Criminal, Universidad Manuela Beltrán,
Avenida Circunvalar No. 60-00, Bogotá, Colombia
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Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28871
Alcalá de Henares-Madrid, Spain.
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Abstract
The
host-guest
complex
of
C-tetra(methyl)calix[4]resorcinarene
(1),
C-
tetra(pentyl)calix[4]resorcinarene (2), and C-tetra(nonyl)calix[4]resorcinarene (3) with
choline in DMSO was examined via dynamic NMR. Under these conditions, only C-
tetra(methyl)calix[4]resorcinarene formed a complex with choline. In order to establish the
role of DMSO during the solubilization/complexation process, titration was carried out with
resorcinarenes and DMSO in CDCl . Our careful NMR analysis was based on the
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assignment of H-NMR signals of the resorcinarenes in CDCl after the addition of variable
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amounts of DMSO, which showed an interesting host-guest interaction with C-
tetra(pentyl)calix[4]resorcinarene. With both solvents, it is possible to define stable cone
conformational arrangements based on the signals shown in the spectra of all the
experiments. The results show the formation of a 1:1 inclusion complex between DMSO
and C-tetra(pentyl)calix[4]resorcinarene. Suitable crystals of C-tetra(pentyl)resorcinarene
in DMSO were characterized through an X-ray crystal structure determination and showed
the inclusion of a molecule of DMSO in the cavity of the resorcinarene. The asymmetric
unit contains one molecule of water and five molecules of DMSO, and analysis indicated

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that resorcinarene prefers a cone configuration (rccc conformation) in the solid state. In the
crystal array, classical hydrogen bond O-H···O interactions and intermolecular contacts
were observed.
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Keywords
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Host-guest interaction
Resorcinarene
Crown and boat conformation
Inclusion complex
1. Introduction
The development and use of selective organic cation receptors has been driven by the
important roles organic cations play in different processes. Since organic cations are
positively charged, a logical way to achieve cation binding is to employ macrocyclic
systems that generate electrostatic interactions in the cavities[1]. The host-guest system
includes various molecular interactions. Among these are cation-π interactions[2,3], and
the binding of hydrogen with guest molecules and different organic solvents[2]. Thus
resorcinarenes are known to be artificial receptors for ions and organic molecules. Many
possible structural variations lead to potential applications, such as voltammetric
sensors[4], dendrimers synthesis[5,6], dyeing of fibers[7,8], NMR solvating agents[9],
chemical receptors for molecules and ions[10,11], absorption of heavy metal ions[12], and
a stationary phase for HPLC[13], among others. An important use of host-guest systems in
C-tetra(alkyl)calix[4]resorcinarene is as a chemosensor for alkylammonium ions[1,14,15].
The activity of the resorcinarenes as chemosensors is associated with their structure in
solution, where macrocyclic compounds may exist in various isomeric states: cone, partial
cone, boat, 1,2-alternate, and 1,3-alternate[16,17]. Thondorf and co-workers[18] have
demonstrated that resorcinarene systems undergo conformations and conformational
interconversions and have established that the general stability of the four conformations
in order of stability is cone, partial cone, 1,2-alternate, and 1,3-alternate. Of these isomers,
the cone conformer (rccc) is the most thermodynamically stable compound. Alternatively,
the conformation of resorcinarenes can be rigidified into a cone by linking the hydroxyl
groups of the upper rim, which provides a greater degree of preorganization.
Resorcinarenes substituted in the lower rim can be in cone conformation in the crystal

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state[19,20]. In solution, the isomer (rccc) may adopt cone and boat conformations[21,22],
which interconvert rapidly at room temperature.[23] studies of the conformational
properties of resorcinarenes modified on the lower rim show that the most stable
conformer in solution is the cone, and this trend is favored by bulky substituents in the
macrocyclic ring[24]. Cone and boat conformations are the most common conformations in
the host-guest processes in solution. In addition, the solvent can have an influence on the
capacity of the chemosensor, since it can compete with the analyte, as shown in some
papers[2,25,26].
Continuing our studies of the structure and properties of the resorcinarene
derivatives[25,27,28] in solution, we report the host-guest interaction of representative
calix[4]resorcinarenes with choline, as well as the solvent effect (DMSO) and the incidence
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of the substituents in the process. These interactions were followed by H-NMR titration
and XRD analysis of a suitable solvate of C-tetra(pentyl)calix[4]resorcinarene isolated from
the reaction mixture, and the interaction of the DMSO with the macrocyclic system was
confirmed.
2. Experimental section
2.1.
Materials
All the reagents and solvents used in the synthesis of C-tetra(alkyl)calix[4]resorcinarenes
were of analytical grade and used without further purification. Resorcinol (99%),
hexanaldehyde (99%), acetaldehyde (99%), decanaldehyde (99%) and hydrochloric acid
(37%) were purchased from Merck. A Thermo Fisher Scientific Nicolet iS10 FT-IR
spectrometer was employed for recording IR spectra, using KBr pellets. A BRUKER
Avance 400 (400.131 MHz for H and 100.263 MHz for 13C) was used for recording
nuclear magnetic resonance spectra in dimethyl sulfoxide ((CD ) SO) and for NMR titration
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in CDCl using tetramethylsilane (TMS) as the internal reference. The chemical shifts are
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given in δ units (ppm). The melting point was determined with Bibby Scientific Limited
Stone, Staffordshire, ST15 0SA, UK equipment and is uncorrected.
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2.2.
General Synthesis of calix[4]resorcinarenes
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The macrocycles were produced according to the procedure used by the research
group[23,29,30]. Hydrochloric acid (10 mL) was carefully added to a solution of
resorcinol (5.2 mmol) and the respective aldehyde (acetaldehyde, hexanaldehyde,
and decanaldehyde, 5.2 mmol) dissolved in a water/ethanol (1:1) mixture. Then the
reaction mixture was refluxed and stirred for various periods, depending of the
starting aldehyde: 1 h (acetaldehyde), 12 h (hexanaldehyde) and 24 h
(decanaldehyde). The precipitate was separated, washed with water/ethanol (1:1)
mixture and allowed to dry.
C-tetra(methyl)calix[4]resorcinarene (1):
-1
Yield: 41,12%; Mp: > 250°C (decomposition). IR(KBr) (cm ) = 3418 (OH), 2969
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(ArCH), 2932-2874 (aliphatic CH), 1612 (C=C). H-NMR ((CD ) SO), δ, ppm): 1.26
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(d, 12H, CH ), 4.42 (c, 4H, CH), 6.11 (s, 4H, H ortho to OH), 6.73 (s, 4H, H meta to
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OH), 8.53 (s, 8H, OH). 13C-NMR ((CD ) SO), δ, ppm): 20.3, 29.1, 104.0, 124.8,
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126.4, 152.7.
C-tetra(pentyl)calix[4]resorcinarene (2):
-1
Yield: 75%; Mp: > 250°C (decomposition). IR(KBr) (cm ) = 3415 (OH), 2928-2857
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(aliphatic CH), 1620 (C=C). H-NMR ((CD ) SO), δ, ppm): 0.85 (t, 12H, CH ), 1.19
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(m, 8H, CH ), 1.28 (m, 16H, CH ), 2.03 (m, 8H, CH ), 4.24 (t, 4H, CH), 6.17 (s, 4H,
2
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H ortho to OH), 7.16 (s, 4H, H meta to OH), 8.76 (s, 8H, OH). C-NMR ((CD ) SO),
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δ, ppm): 14.1, 22.4, 27.6, 31.6, 33.1, 34.1, 102.5, 123.2, 124.4, 151.8
C-tetra(nonyl)calix[4]resorcinarene (3):
-1
Yield: 60%; Mp: > 250°C (decomposition). IR(KBr) (cm ) = 3258 (OH), 2925
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(ArCH), 2853 (aliphatic CH), 1619 (C=C). H-NMR ((CD ) SO), δ, ppm): 0.83 (t,
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12H, CH ), 1.20 (m, 54H, CH ), 1.96 (br. s, 8H, CH ), 4.21 (t, 4H, CH), 6.15 (s, 4H,
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H ortho to OH), 7.07 (s, 4H, H meta to OH), 8.88 (br. s, 8H, OH). 13C-NMR
((CD ) SO), δ, ppm): 13.8, 22.1, 27.8, 28.8, 28.9, 29.2, 29.2, 29.3, 31.4, 34.2,
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102.4, 123.0, 124.3, 151.7.
2.3. X-Ray Structure Determination of 2
Colorless crystals of 2·5(DMSO)·H O were obtained from a dimethylsulfoxide-
2
water(1:1) solution of 2 by slow evaporation at room temperature. The crystals were

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removed from the vial and covered with a layer of a viscous perfluoropolyether. A
suitable crystal was selected with the aid of a microscope, mounted on a cryoloop,
and placed in the low-temperature nitrogen stream of the diffractometer. The
intensity data sets were collected at 200 K on a Bruker-Nonius KappaCCD
diffractometer equipped with an Oxford Cryostream 700 unit. The molybdenum
radiation used was graphite monochromated and enhanced with a MIRACOL
collimator. The crystallographic data are presented in Table 1.
The structure was determined using the WINGX package[31] by direct methods (SHELXS-
2013)[32] and refined by least-squares against F2 (SHELXL-2014/7). Compound 2
crystallized with a molecule of water and five molecules of dimethylsulfoxide. Two DMSO
molecules exhibited disorder (atoms S(4), O(4), C(4)a and C(4)b, and atoms S(5), O(5),
C(5)a and C(5)b), which were treated conventionally by using the PART tool, allowing free
refinement of the occupancy factors with the FVAR command. The final values for the
occupancy factors were 69.0 and 31.0% for one molecule and 51.0 and 49.0% for the
other one. All non-hydrogen atoms were anisotropically refined. Methyl, methylene,
methane, and aromatic hydrogen atoms were positioned geometrically and refined by
using a riding model, whereas hydrogen atoms of the water molecule and the hydroxyl
groups were isotropically refined. Moreover, SADI and DELU restraints were employed for
both disordered molecules of DMSO. Additionally, the water molecule was treated with
DFIX instructions.
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2.4.
For the NMR titration, 18.46 µL DMSO (analytical grade) was added to 800 μL
CDCl3 and
1H-NMR was performed. Increasing amounts of C-
NMR Titration
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tetra(pentyl)calix[4]resorcinarene were added to the solvent mixture, and after each
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addition the H-NMR spectrum was taken. 25 mg was initially added to 175 mg of
resorcinarene.
1H-NMR titrations were done by subsequently adding increasing amounts of the C-
tetra(pentyl)calix[4]resorcinarene (from 0 to 200 mg) in a mixture of DMSO (0.26
mmol) with CDCl (800 μL) and recording the spectra after each addition at room
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In the NMR titration with choline, a mixture of 600 μL of DMSO-d6 with 10 mg of C-
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tetra(pentyl)calix[4]resorcinarene was added to 2 mg of choline and the H-NMR spectrum
was taken.
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3. Results and Discussion
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To study the effect of the alkyl substituent in the lower rim and its influence on the binding
ability and complexation preferences, we used resorcinarenes with different substituents:
C-tetra(methyl)calix[4]resorcinarene (1), C-tetra(pentyl)calix[4]resorcinarene (2) and C-
tetra(nonyl)calix[4]resorcinarene (3). These compounds were obtained through the acid-
catalyzed cyclocondensation of resorcinol with aldehyde (ethanal, hexanal, and decanal,
respectively) in a 1:1 mixture of ethanol:water to reflux in a manner similar to that
described in the literature[10,33] (Scheme 1). The products were purified by
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recrystallization and were characterized using spectroscopic techniques such as FT-IR, H-
13
NMR, and C-NMR (see the Experimental Section).
Being calixarenes[34], resorcinarenes can assume different conformations, which depend
on the rotational disposition of their single bonds[35], the solvents, and the substituents in
the lower rim. If the calix[4]resorcinarene is small and non-bulky, such as the methyl group,
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the observed H-NMR spectra show characteristic signals for two conformations: cone and
boat[24]. However, if the substituent in the lower rim is bulky, such as the nonyl group, the
possibility of forming the boat conformer is very low[16]. Calix[4]resorcinarene systems can
be dynamic with respect to solvent interactions, but the cone conformation is retained in
solution with aprotic solvents such as DMSO or CHCl [2]
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H-NMR spectra of synthesized resorcinarenes in DMSO- were consistent with the
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presence of one conformer. In the H-NMR spectra of all the compounds, three
signals that confirmed the cone conformation could be seen: a signal between 4.00
and 4.50 ppm for the bridge proton and another two in the aromatic zone for H ortho
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and meta to OH. These signals are coherent with other analogue macrocycles. H-
NMR signals in DMSO- exhibit a great tendency to retain the cone conformation in
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solution, which is desirable for molecular recognition processes.

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Binding studies
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As mentioned above, the macrocyclic cone conformation produced by lower rim
substituents and solvents is an important factor in the process of complexation. For this
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reason, the H-NMR titrations described here were performed in DMSO-d . Other factors
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were the good solubility of resorcinarenes 1-3 and the subsequently formed complexes
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with choline. For all the compounds studied, the H-NMR spectra contained signals
corresponding to the resorcinarene backbone (depending on the substitution pattern) and
a signal between 4.00 and 4.50 ppm which was ascribed to the CH bridge. Hydroxyl
protons are sometimes prone to proton exchange with the residual water molecules in
DMSO, and they can widen or disappear completely, making them unsuitable for
monitoring the binding. During the titrations, the change in chemical shift values was
observed not only for the CH bridge signals but also for the choline signal (methyl groups).
1H-NMR spectra of mixtures of choline and 1 were investigated, as depicted in Figure 1.
The signals for the aromatic ring protons of 1 shifted slightly downfield (protons in the ortho
position to the hydroxyl, 0.02 ppm and the meta protons to the hydroxyl, 0.06 ppm). This
behavior may be due to the greater interaction of the meta protons of 1 (lower rim) with the
methyl groups of choline. This interaction of choline with the bottom of the cavity can be
confirmed by the downfield shift of the methylene protons of choline.
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After performing the titration experiments, association constants of resorcinarenes
with choline were estimated using the HypNMR2008 (v.4.071).20. computer
program [36], and the results are shown in Table 2. As can be seen from the
calculated association constant values, the binding of choline by 1 showed a
constant log β 2.96, which indicates a high degree of affinity with a 1:1
stoichiometric ratio. This is not surprising, since the only structural feature
responsible for binding is the structural arrangement of resorcinarene. Thus the
cation coordination is possibly dictated by hydrogen bonds and π interactions in the
resorcinarene cavity. According to this observation, similar behavior was expected
in the coordination process with the other resorcinarenes; however, no effect was
observed during the NMR titration.

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To understand these results, we evaluated the effect that DMSO can have on the
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complexation process, so H-NMR titration was done between 1-3 and DMSO in CDCl as
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a solvent. The results shown in Table 1 indicate a high affinity of 2 with DMSO and for 1
and 3 the formation of a complex was not found. During the titration of receptor 2 with
DMSO, we noticed that a signal at 2.55 ppm was shifted to the upper field (0.55 ppm). This
signal corresponds to the protons of DMSO (Figure 2) and shows the interaction of 2 with
DMSO. The chemical shift variation for protons of methyl groups of DMSO as a function of
their concentration is shown in Figure 3. The observed downfield shifts of the guest under
conditions of fixed guest and varying host concentrations were carried out using the
HypNMR2008 (v.4.071).20. computer program [36] (Figure 2).
Also, macrocyclic ring 2 exhibits a signal shift of its aromatic protons and CH bridge,
which allows concluding that the strongest interaction is observed at the bottom of
the cavity. After performing the titration experiments, the association constants of 2
with DMSO were estimated using the HypNMR2008 (v.4.071).20. computer
program [36], and the results are shown in Table 2 with 1:1 stoichiometry and
stability constant log β = 4.88. Analysis of the inclusion complex between 2 and
DMSO (Scheme 2) provided the most accurate and detailed information to date on
the molecular binding interactions.
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Single-Cristal X-Ray Diffraction Analysis
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Our attempts to grow single crystals for compounds 1 and 3 were unsuccessful. However,
a crystalline sample of 2 was obtained from a dimethylsulfoxide-water (1:1) solution by
slow evaporation at room temperature. An X-Ray diffraction determination revealed the
structure of the inclusion complex 2-DMSO (Figure 4), which crystallized with four
additional molecules of DMSO and a water molecule. The crystallographic data are shown
in Table 2.
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The C···C diagonal distances for the resorcinarene skeleton are C(16)···C(56)
5.264(4) Å, C(13)···C(53) 9.416(5) Å, C(36)···C(76) 5.174(5) Å, and C(33)···C(73)
7.453 Å (see Figure 4 and Table 3), giving centroid-to-centroid distances of 6.30
and 7.34 Å, respectively. If the quotient of the shortest centroid-to-centroid distance
divided by the longest one is considered, the resultant cone-boat conformation

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index (CBConf index) could be informative about the conformation of the
macrocycle. The CBConf index ranges from 1.00 for a perfect cone conformation (if
both centroid-to-centroid distances are equal) to a value close to 0.50 for a boat
conformation (if the longest centroid-to-centroid length is approximately twice that of
the shortest). The value of the CBConf index for the crystal structure of complex
2·DMSO was 0.86, so the geometry of the resorcinarene skeleton could be
described as intermediate between cone and boat, although it is closer to a cone
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conformation. The structures of complexes 2· BuOH and 2·MeOH have previously
been determined. The resorcinarene skeletons in these inclusion compounds are
held in the cone conformation, with CBConf index values of 0.99 (with centroid-to-
centroid distances of 6.82 and 6.87 Å) and 0.98 (with distances of 6.76 and 6.93 Å).
The intermediate geometry in 2·DMSO is the result of three O-H···O hydrogen
bonds in the macrocycle with O···O bond distances of O(12)···O(74) 2.752(4) Å,
O(14)···O(32) 2.684(4) Å, and O(72)···O(54) 2.792(4) Å (average value 2.74 Å)
(see Table 4 for the rest of the hydrogen bond parameters). The longer fourth O···O
distance, O(34)···O(52) of 3.074(4) Å, denotes the lack of hydrogen bonding
interaction. However, the geometry of the analogous alcohol complexes is set by
four hydrogen bonds, with shorter O···O distances of 2.651(3)-2.677(3) Å (average
t
2.67 Å) for 2· BuOH and 2.689(3)-2.712(2) Å (average 2.70 Å) for 2·MeOH[37].
The structure of complex 2·DMSO shows a dimethylsulfoxide molecule (S(1), O(1), C(1a)
and C(1b)) nestled in the resorcinarene cavity (Figure 4) through CH··· π interactions with
C(methyl)-centroid distances ranging from 3.43 to 3.55 Å (Table 5). The macrocycle is also
connected to other molecules of DMSO by O-H···O hydrogen bonds (Figure 5), with O···O
distances between hydroxyl groups and the oxygen atoms of dimethylsulfoxide molecules
ranging from 2.52(2) to 2.80(2) Å (Table 4). Additionally, these DMSO molecules
participate in weak C-H···O hydrogen bonding interactions with C···O separations from
3.31(2) to 3.647(5) Å (Table 4). Finally, the water molecule is bound to the resorcinarene
skeleton by hydrogen bonds with O···O distances of 2.844(6) and 2.924(5) Å (Figure 5).
The analysis of the crystal packing reveals that molecules of complex 2·DMSO are
connected by the water molecules, constructing an infinite chain (Figure 6).
Simultaneously, the dimethylsulfoxide molecules of the inclusion complex are involved in a
zigzag pattern of the resorcinarene skeletons (Figure 7). These two arrangements produce

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a layered array, which is sustained by hydrophobic interactions between the n-pentyl
groups. The DMSO crystallization molecules contribute to the formation of the packing in
layers through the C-H···O hydrogen bonding interactions.
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Analysis of the crystal structure and the association constants of the inclusion complex of
2 with DMSO and the association constants provided the most accurate and detailed
information to date on the molecular interactions that bind choline and DMSO with
resorcinarenes. According to these results, the binding of DMSO and 2 is stronger than for
choline. The solvent effect in the interactions of choline with 2 consists of the binding of
DMSO in the bottom of the cavity and showed an interesting effect on the alkyl chain size
in the lower rim of the resorcinarene moiety. An increase in the alkyl chain size (methyl,
pentyl, and nonyl) results in a decrease in the affinity of choline with the resorcinarene
cavity. So taking into account hydrophobic interactions in the lower rim of resorcinarenes,
in 1 these interactions were less than for 2 and 3, and the cavity was selective for choline.
For 2, these interactions were larger than for 1, and the cavity was stretched and selective
for DMSO, while the alkyl substituents in 3 exhibited the greatest hydrophobic interactions
and non-selectivity for choline and DMSO.
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15
Conclusions
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A detailed study of the interaction of C-tetra(methyl)calix[4] resorcinarene (1), C-
tetra(pentyl)calix[4]resorcinarene (2), and C-tetra(nonyl)calix[4]resorcinarene (3) with
1
1
choline and DMSO was performed with the help of H-NMR titrations. According to the H-
NMR titration, in DMSO-d choline binds C-tetra(methyl)calix[4] resorcinarene (1) with 1:1
6
stoichiometry and a stability constant log β = 2.2, while for resorcinarene 2 and 3, no
1
complex formation was found. With H-NMR titration between resorcinarenes and DMSO
in CDCl , the formation of an inclusion complex was observed with resorcinarene 2, with
3
1:1 stoichiometry and stability constant log β = 3.2. Analysis of the inclusion complex
between 2 and DMSO provided the most accurate and detailed information to date on the
molecular binding interactions. Finally, an analysis of the crystal structures of the inclusion
complex C-tetra(pentyl)calix[4]resorcinarene·DMSO provided the most accurate and
detailed information about the solvate that was formed, confirming the great affinity of this
resorcinarene with the solvent.
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Acknowledgments
This research was conducted with the financial support of the División de
Investigación y Extensión sede Bogotá (DIEB) Universidad Nacional de Colombia-
Sede Bogotá (project code 37676) and Universidad de Alcalá (CCGP2017-
EXP/021). Astrid Velasquez-Silva thanks the program Colciencias Doctorado
Nacional No. 647 for financing his Ph.D studies.
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Table 1- Crystallographic data for 2·5(DMSO)·H O
2
Crystal parameters
Data / Values
a
CCDC deposition number
1841816
Empirical formula
Formula weight
Temperature
C H O S
5
58
96 14
1177.64
200(2) K
0.71073 Å
Wavelength
Crystal system
Space group
Monoclinic
P2 /c
1
a = 14.6491(2) Å
b = 37.725(3) Å, β= 101.371(1)°
c = 11.723(1) Å
6351(1) Å3
Unit cell dimensions
Volume
Z
Dcal
4
1.232 g.cm-3
Absorption coefficient
F(000)
0.242 mm-1
2544
Crystal size
0.40 x 0.28 x 0.12 mm3
3.04 to 27.00°
Theta range for data collection
-18 to 18
Index ranges
-48 to 47
-14 to 14
Reflections collected
Unique data
94595
13826 [R(int) = 0.112]
7243
Observed data (I > 2σ(I)]
Goodness-of-fit on F2
1.044
b
Final R indices [I>2σ(I)]
R1 = 0.073, wR2 = 0.136
R1 = 0.166, wR2 = 0.175
0.500 and -0.493 e·Å-3
b
R indices (all data)
Largest diffraction peak and hole
a
b
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4
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Cambridge Crystallographic Data Centre. R1 = Ʃ||F |–|F ||/[Ʃ|F |], wR2 =
o c o
2
2 2
2 2 1/2
{[Ʃw(F –F ) ]/[Ʃw(F ) ]}
o
c
o

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1
Fig. 1. H-NMR spectra (DMSO-d , 400 MHz, 298 K) of (A) 1; (B) Choline; (C) Choline and
6
1 (0.1:1); (D) Choline and 1 (1:1)
4
4
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79
80
OH
HO
HO
HO
HO
OH
OH
HO
HO
OH
O
EtOH:H O, HCl
2
Reflux
H
R
R
R
R
R
4
4
81
82
Scheme 1. Synthetic route to C-tetra(alkyl)calix[4]resorcinarene.
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Table 2: Constants of 1, 2 and 3 with DMSO and choline
Resorcinarenes
Guest
(1)
(2)
(3)
DMSO
-------
2.96
4.88
-------
-------
-------
Log β
Choline
4
92
4
93
1
4
4
4
94
95
96
Fig. 2. H-NMR titration spectra for DMSO with 2 in CDCl as solvent. (A) DMSO-CDCl ,
3
3
adding quantities successive of 2 in molar ratio of (B) 0.12, (C) 0.25, (D) 0.37, (E) 0.50, (F)
0.62, (G) 0.75, (H) 0.87, (I) 1.0
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5
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Scheme 2: Interaction 2 (Host) with DMSO (Guest)
0
0
0
0
0
0
0
0
.7
.6
.5
.4
.3
.2
.1
.0
0
.0
0.2
0.4
0.6
0.8
1.0
M 2 / M DMSO
5
5
07
08
1
Fig 2. Plot of Δδ DMSO (ppm) for DMSO with 2 in CDCl as solvent from H-NMR titration
3
5
09

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12
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15
Fig. 4. ORTEP diagram of the complex 2·DMSO (thermal ellipsoids at the 50% probability
level). All hydrogen atoms linked to carbon are omitted for clarity, except those in the
DMSO molecule
5
5
16
17
Table 3. Selected distances for 2·5(DMSO)·H O
2
Atoms
Atoms
Length (Å)
5.264(4)
Length (Å)
9.416(5)
7.453(5)
C(16)···C(56)
C(36)···C(76)
C(13)···C(53)
C(33)···C(73)
5.174 (5)
5
5
18
19

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5
20
Table 1. Relevant hydrogen bonds for 2·5(DMSO)·H O.
2
D-H···A
D···A/Å
2.752(4)
2.684(4)
H···A/Å
1.99(4)
1.97(4)
2.00(4)
1.88(5)
1.77(4)
2.05(4)
1.72(4)
1.91(4)
1.85(5)
1.89(4)
2.05(8)
2.18(9)
D-H···A/°
162(4)
158(5)
165(4)
166(5)
177(5)
171(4)
175(4)
170(4)
176(4)
170(5)
161(7)
149(6)
O(12)-H(12)···O(74)
O(14)-H(14)···O(32)
O(72)-H(72)···O(54)
O(52)-H(52)···O(3)
O(54)-H(54)···O(5)
O(54)-H(54)···O(5)’
O(32)-H(32)···O(1)i
O(34)-H(34)···O(4)i
O(34)-H(34)···O(4)’i
O(74)-H(74)···O(2)ii
O(1)w-H(1)w···O(52)
O(1)w-H(2)w···O(12)ii
C(3b)-H(3b)1···O(4)
C(3b)-H(3b)1···O(4)’
C(4a)-H(4a)2···O(72)
C(5a)-H(5a)1···O(3)
C(2a)-H(2a)2···O(1)ii
C(2a)-H(2a)1···O(32)iv
C(2b)-H(2b)3···O(14)v
2
.792(4)
.696(4)
2
2.52(2)
2.80(2)
2.587(3)
2.68(2)
2.62(3)
2.636(4)
2.844(6)
2.924(5)
3
.55(2)
.55(4)
.31(2)
.44(2)
3
3
3
3.486(6)
3.647(5)
3.515(5)
5
5
5
21
22
23
aData for the two positions of disordered DMSO molecules are included. Symmetry code:
(i) x, –y + 1/2, z + 1/2; (ii) x – 1, y, z; (iv) x – 1, y, z – 1; (v) x – 1, –y + 1/2, z – 1/2. A =
acceptor; D = donor
5
5
24
25
Table 2. Selected C(methyl)-centroid distances for the complex 2·DMSO.
Atoms
Length (Å)
C(1a)···Ct(5)
C(1b)···Ct(1)
C(1b)···Ct(3)
C(1b)···Ct(7)
3.43
3.45
3.45
3.55
5
5
26
27
Ct(1): centroid for the ring C(11)-C(16). Ct(3): centroid for the ring C(31)-C(36). Ct(5):
centroid for the ring C(51)-C(56). Ct(7): centroid for the ring C(71)-C(76).
5
28

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Fig. 3. DMSO and water molecules connected to the resorcinarene skeleton by hydrogen
bonding interactions. Symmetry code: (i) x, –y + 1/2, z + 1/2; (ii) x – 1, y, z; (iii) 1 + x, y, z.
5
32
5
5
33
34
Fig 4. Complexes 2·DMSO connected by water molecules through hydrogen bonding
interactions
5
5
5
5
5
35
36
37
38
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Fig 5. Zigzag pattern of the resorcinarene skeletons in the crystal packing of complex
2·DMSO
5
5
5
5
5
5
5
5
5
5
43
44
45
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Alkyl chain affect the complex.
Crown conformer complex choline
DMSO affects complexation