Competitive self and induced aggregation of Calix[4]arene ethers and their interaction with pinacyanol chloride and methylene blue in nonaqueous media

Article abstract of DOI:10.1007/s10953-009-9489-x

Long chain calix[4]arene ethers have been examined for aggregation in nonaqueous solvents by using UV-vis molecular absorbance spectroscopy. It has been observed that tetraalkylated (alkyl = hexadecyl and octadecyl, respectively) calix[4]arene ethers tend to aggregate in chloroform and tetrahydrofuran, possibly via π-π stacking interactions of the phenyl moieties, and the aggregation process appears to be facilitated by the alkyl chains. The analogous dialkylated compounds do not show any self-aggregation, plausibly due to strong hydrogen bonding between the -OH and the -O- of calix aryl ether which seems to disrupt the aggregation process. Addition of the anionic surfactant sodium dodecylsulfate (SDS) appears to hinder the aggregation process in nonpolar chloroform but the same surfactant facilitates aggregation in the polar tetrahydrofuran. The cationic surfactant (cetyltrimethyl ammonium bromide) and the nonionic surfactant (Brij-35) have no effect on this aggregation process. Unexpectedly, SDS induces aggregation of dialkylated calix[4]arene ethers in chloroform. It has been observed that the aggregated form of the tetraalkylated calix[4]arene ethers tend to increase the dimerization efficiency of cationic dyes (pinacyanol chloride and methylene blue) in chloroform.

Full text of DOI:10.1007/s10953-009-9489-x

J Solution Chem (2010) 39: 107–120
DOI 10.1007/s10953-009-9489-x
Competitive Self and Induced Aggregation
of Calix[4]arene Ethers and Their Interaction
with Pinacyanol Chloride and Methylene Blue
in Nonaqueous Media
Shubha Pandey · Jyotsna R. Kar · Amir Azam ·
Siddharth Pandey · H.M. Chawla
Received: 22 June 2009 / Accepted: 24 July 2009 / Published online: 5 January 2010
© Springer Science+Business Media, LLC 2010
Abstract Long chain calix[4]arene ethers have been examined for aggregation in nonaque-
ous solvents by using UV-vis molecular absorbance spectroscopy. It has been observed that
tetraalkylated (alkyl = hexadecyl and octadecyl, respectively) calix[4]arene ethers tend to
aggregate in chloroform and tetrahydrofuran, possibly via π–π stacking interactions of
the phenyl moieties, and the aggregation process appears to be facilitated by the alkyl
chains. The analogous dialkylated compounds do not show any self-aggregation, plausi-
bly due to strong hydrogen bonding between the –OH and the –O– of calix aryl ether which
seems to disrupt the aggregation process. Addition of the anionic surfactant sodium do-
decylsulfate (SDS) appears to hinder the aggregation process in nonpolar chloroform but
the same surfactant facilitates aggregation in the polar tetrahydrofuran. The cationic sur-
factant (cetyltrimethyl ammonium bromide) and the nonionic surfactant (Brij-35) have no
effect on this aggregation process. Unexpectedly, SDS induces aggregation of dialkylated
calix[4]arene ethers in chloroform. It has been observed that the aggregated form of the
tetraalkylated calix[4]arene ethers tend to increase the dimerization efficiency of cationic
dyes (pinacyanol chloride and methylene blue) in chloroform.
Keywords Calix[4]arene · Surfactants · Aggregation · Cationic dyes · Nonaqueous
S. Pandey · J.R. Kar · A. Azam
Department of Chemistry, Jamia Millia Islamia, New Delhi, 110028, India
A. Azam
e-mail: amir_sumbul@yahoo.co.in
S. Pandey · J.R. Kar · S. Pandey ( ) · H.M. Chawla
ꢀ
Department of Chemistry, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, 110016, India
e-mail: sipandey@chemistry.iitd.ac.in
H.M. Chawla
e-mail: hmchawla@chemistry.iitd.ac.in

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J Solution Chem (2010) 39: 107–120
1 Introduction
Self-assembly of amphiphilic macromolecules resulting in interesting structures has shown
great potential for applications in a variety of disciplines [1–4]. Self-assembly of am-
phiphilic macromolecules is based on the interplay of a variety of different solvophobic and
solvophilic interactions [5–7]. Macromolecules with typical solvophilic as well as solvo-
phobic segments within their infrastructure are prominent examples of such amphiphilic
molecules [8–10]. It has been observed that above a certain concentration or concentration
regime these amphiphilic macromolecules may aggregate into a variety of molecular assem-
blies, particularly when the energetic gains compensate for the entropic losses [8–10]. The
two important factors among several others that decide the nature and type of aggregation
are the macromolecular architecture and the milieu within which the aggregation is intended
to take place. While the understanding of self-assembly within aqueous systems has gained
enormous ground during the last few decades, aggregation process within non-aqueous mi-
lieu is not well understood. Complications regarding the dependence of interactions be-
tween the macromolecule and the media and macromolecular architecture apparently have
hindered the much-awaited progress in this field.
Calixarenes are macrocyclic metacyclophanes consisting of phenolic units joined to-
gether by CH2 bridges at ortho-positions to encompass a cavity in their molecular archi-
tecture with distinct hydrophobic and hydrophilic sites [11, 12]. By suitable modifications,
one can transform calixarenes into a wide variety of molecular entities with applications in
diverse areas chiefly in ionic and molecular recognition and for designing separation devices
for biological and environmental samples [11–24]. Due to their amphiphilic nature, cal-
ixarenes can be thought to behave as non-ionic surfactants, which in principle can undergo
induced or self-aggregation. Insights into their molecular organizations may provide unique
access to the understanding of molecular interactions required for molecular and ionic recog-
nition. For example, an increase in the chain length of the hydrophilic and hydrophobic
segments, as well as the introduction of a rigid segment in calixarene, is reported to in-
crease their aggregation stability [25, 26]. Analogous aggregation properties of p-tetra-kis-
2-hexadecyl thiophenyl azo calix[n]arene (where n = 4, 6) in tetrahydrofuran (THF) were
investigated earlier using dynamic laser light scattering in our group [18]. The preliminary
results have strongly suggested that calixarenes with long pendant arms tend to aggregate
extensively. The mean size of the aggregates observed earlier was found to increase with
increasing concentration above the critical aggregation concentration (cac) of around 1.6
×10−4 mol·dm−3. The aggregation behavior of their lower analogues, p-tetrakis-2-methyl
and 2-ethyl-thiophenyl-azo-calix[4]arenes, suggested a lack of aggregation by these macro-
cycles [18]. Recently, it has been observed that a homologous series of alkylated calixarene-
based surfactants form stable monolayers at the air-water interface after mercuration [27].
In light of the foregoing discussion, it can be expected that calixarene derivatives could
have the inherent capability to affect the aggregation behavior of common dyes in solu-
tion. The molecular dye aggregates play an important role in many technological applica-
tions [28]. Due to their strong light absorbing capabilities, these dye aggregates become
important for spectral sensitization of the photographic process and the understanding of
dye aggregates is critical for light harvesting systems. Such dye aggregates have demon-
strated interesting and unusual optical properties, especially as nonlinear optical materials
as well as applications in photobiological processes, photosynthesis, and charge transfer
processes. Some of the popular cationic dyes, e.g., pinacyanol chloride and methylene blue,
exhibit formation of dimers, trimers and higher-mers in solutions [29, 30]. However, their
aggregates are observed to be highly sensitive to the presence of other species or assemblies

J Solution Chem (2010) 39: 107–120
109
Scheme 1 Synthesis of 2a, 2b, 3a and 3b from their parent compounds. (i) A1C1 , phenol, stirring; (ii) R-Br,
3
NaH, reflux, THF/DMF; (iii) R-Br, K CO (anhydrous), acetonitrile, reflux
2
3
within the solution. Thus, the understanding of the effect of calixarene and calixarene-based
supramolecular assemblies on dye aggregates within solution can help improve our under-
standing of the basic process of molecular assemblage.
In this paper, we report our findings on the aggregation behavior of suitably-modified
calix[4]arene ethers [2a, 2b, 3a and 3b, Scheme 1] in the absence and presence of nonionic
(Brij 35), cationic (cetyltrimethylammonium bromide, CTAB), and anionic (sodium dode-
cylsulfate, SDS) surfactants within non-aqueous milieu of different polarities. The tendency
of dimer formation by the cationic dyes methylene blue and pinacyanol chloride, respec-
tively, has also been examined in the presence of 2a and 2b to understand the nature of
molecular organization of these compounds.
2 Results and Discussion
2.1 Synthesis of Calix[4]arene Ethers
The required starting materials, 5,11,17,23-tetra (p-tert-butyl)-25,26,27,28-tetra hydroxy
calix[4]arene (1a) and debutylated 25,26,27,28-tetra hydroxy calix[4]arene (1b), were syn-
thesized using published procedures in the literature [31–35]. Tetra-alkylated calix[4]arene
ethers, 25,26,27,28-tetrakis (hexadecyloxy)calix[4]arene (2a) and 25,26,27,28-tetrakis (oc-
tadecyloxy)calix[4]arene (3a), were synthesized by refluxing 1b with corresponding alkyl-
bromide in dry DMF with NaH as base [27, 36], whereas di-alkylated calix[4]arene deriv-
atives, 25,27-bis-(hexadecyloxy)-26,28-dihydroxy-calix[4]arene (2b) [37] and 25,27-bis-
(octadecyloxy)-26,28-dihydroxy-calix[4]arene (3b), were synthesized in a similar manner
by using a relatively mild base (K2CO3) in acetonitrile. The structures of the obtained

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J Solution Chem (2010) 39: 107–120
calix[4]arene ethers (2a, 2b, 3a and 3b) were established by IR, NMR (1H and 13C) and
1
mass spectrometric data analysis. The H NMR spectra of 2a, 2b, 3a and 3b showed two
sets of doublets for bridging methylene protons. The presence of a pair of doublets for
1
ArCH2Ar protons in H NMR spectra of calix[4]arene ether derivatives, and only one sig-
nal for methylene carbon in the range of 29–32 ppm in their 13C NMR spectra, suggest the
synthesized calix[4]arene ethers are in a symmetrical cone conformation in solution [38].
2.2 Self-aggregation Properties of Calixarene Ethers and Effect of Various Surfactants
Dilute solutions of 2a, 2b, 3a, and 3b in chloroform and tetrahydrofuran (THF), respec-
tively, were prepared and their self-aggregation capabilities were investigated using UV-
vis molecular absorbance spectroscopy. As expected, electronic absorption spectra of 2a in
chloroform and THF, respectively, at many different concentrations indicated the absorbance
maxima (λmax) of 2a to be at 272 1 nm. Figure 1 presents the absorbance of 2a at λmax
(···!···) as a function of concentration when dissolved in chloroform at ambient condi-
−4
−3
Fig. 1 Absorbance at λ
of 2a dissolved in chloroform in the absence and presence of 1×10 mol·dm
max
SDS. Lower inset shows cac without SDS and upper inset shows cac in the presence of SDS. M denotes the
−1
units mol·L

J Solution Chem (2010) 39: 107–120
111
tions. A careful examination of the data clearly reveals an unexpected deviation from lin-
earity even before the concentration of 2a reaches ca. 0.5 mmol·dm−3. The deviation from
Beer-Lambert’s law at such low concentration clearly implies the possibility of aggregation
involving 2a. No such deviation from linearity was observed for a model calix[4]arene com-
pound devoid of a long alkyl chain. In order to estimate more precisely the concentration at
which the deviation from linearity occurs, i.e., the critical aggregation concentration (cac)
of 2a, a simple method proposed in the literature was used [39, 40]. Specifically, a linear
fit to the absorbance values in the lower concentration range was obtained followed by an
estimation of the deviation of all the absorbance values from that obtained from this linear
equation. A plot of the deviation of experimental absorbance values from the absorbance
values calculated from the linear relation obtained above versus [2a] obviously showed or-
dinate values close to zero in the absence of aggregation (lower inset Fig. 1). Deviation
from linearity in the Beer-Lambert plot due to aggregation of 2a was profoundly mani-
fested as the break-point at the onset of the downward slope representing cac. A cac of 4.56
( 0.10)×10−4 mol·dm−3 for 2a in chloroform indicates aggregation or possibility of some
other interaction involving 2a.
In order to further explore the nature of this aggregation, different surfactants were added
to the solution of 2a. The presence of 1.0 × 10−4 mol·dm−3 sodium dodecyl sulfate (SDS,
a popular anionic surfactant) resulted in the deviation from linearity in the absorbance spec-
trum of 2a (– –"– –) at a higher concentration of 2a in comparison to that in the absence of
SDS (Fig. 1). A cac of 5.09 ( 0.12) × 10−4 mol·dm−3 was estimated by using the method
described earlier (top inset Fig. 1). The higher observed cac in the presence of SDS could be
attributed to the possible interference of the anionic surfactant with the aggregation process
of 2a in the solution. Next, we used a common cationic surfactant cetyltrimethylammonium
bromide (CTAB) and a common nonionic surfactant Brij-35, respectively, to influence the
aggregation behavior of 2a in solution. Surprisingly, the addition of either CTAB or Brij-35
did not result in a significant change in the cac of 2a (Fig. 2), as the estimated cac values of
2a in the presence of CTAB and Brij-35, respectively, were statistically not different from
that obtained in the absence of any surfactant in the solution. It is interesting to note that no
involvement of surfactant in aggregation of 2a could be observed in the presence of these
cationic or nonionic surfactants.
The aforementioned experiments when repeated with 3a showed similar trends. Similar
to 2a, chloroform solutions of 3a also demonstrated a deviation from linearity in the Beer-
Lambert plot, again implying the aggregation (or strong interactions) involving 3a. In the
absence and presence of 1.0 × 10−4 mol·dm−3 SDS the cac of 3a was determined to be
3.87( 0.10) × 10−4 mol·dm−3 and 4.74( 0.13) × 10−4 mol·dm−3, respectively. It is perti-
nent to note that in the absence of any surfactant, the cac of 3a is significantly lower than that
of 2a. This is probably due to the fact that in 2a the alkyl chains are 16 carbon long as op-
posed to 18 carbon long chains in 3a which results in a lower cac for 3a in concurrence with
well-documented enhancement of aggregation on increase in chain length as represented by
a lower cac [25]. Further, as observed for 2a, addition of cationic CTAB or nonionic Brij-35
surfactant to 3a showed insignificant differences in the absorbance as compared to the case
when no surfactant is added.
In order to explore the effect of the presence of number of long alkyl chains on one
calix[4]arene moiety on the aggregation behavior, we synthesized dialkylated calix[4]arene
ethers 2b and 3b (Scheme 1). It is interesting to note that, contrary to what is observed for 2a
and 3a, the plot of absorbance values at λmax versus the concentration of 2b and 3b, respec-
tively, in chloroform shows no deviations from linear behavior thus hinting at the absence
of any aggregation involving these two macromolecules. This may be explained on the basis

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J Solution Chem (2010) 39: 107–120
−4
−3
Fig. 2 Absorbance at λ
CTAB and Brij-35, respectively. M denotes the units mol·L
of 2a dissolved in chloroform in the absence and presence of 1×10 mol·dm
max
−1
of hydrogen-bonding. Since 2b and 3b have only two long alkyl chains on their molecular
frameworks (Scheme 1), the hydrogen of the unsubstituted –OH group in principle can be in-
volved in hydrogen bonding with the oxygen of the ether group, which subsequently disrupts
intermolecular interactions leading to the formation of aggregates. Interestingly, when the
same experiments were repeated with 2b and 3b in the presence of 1.0 × 10−4 mol·dm−3
SDS, there was a significant change in the slope of the Beer-Lambert plot suggesting in-
teractions to be present. The estimated cac values are 4.54( 0.20) × 10−4 mol·dm−3 and
4.00( 0.19) × 10−4 mol·dm−3 for 2b and 3b, respectively, which are close to the cac ob-
served for 2a in the absence of SDS (please refer to Table 1). It appears that SDS is able to
interfere with the intramolecular hydrogen-bonding between the hydrogen of the unsubsti-
tuted –OH and the oxygen of the ether group in dialkylated calix[4]arene derivatives.
The effect of solvent, if any, on the aggregation behavior of 2a and 3a was explored
by investigating the UV-vis molecular absorbance characteristics of these compounds dis-
solved in THF, in the absence and presence of SDS, in a similar fashion. In THF, the ag-
gregation behavior was observed to be different from that in chloroform. While the effi-
ciency of aggregation of 2a in chloroform was observed to decrease in the presence of
SDS (as implied by the increased cac, Table 1, vide supra), in THF, however, addition of
SDS appears to assist the aggregation process of 2a. The observed cac value decreased
from 5.34( 0.10) × 10−4 mol·dm−3 to 4.70( 0.15) × 10−4 mol·dm−3 upon addition of
1 × 10−4 mol·dm−3 SDS. It appears that a relatively more polar solvent forces the SDS to

J Solution Chem (2010) 39: 107–120
113
Table 1 Critical aggregation concentration (cac) of 2a, 3a, 2b and 3b at ambient conditions
−4
−3
−3
Compound
Solvent
Surfactant/10 mol·dm
cac/mol·dm
−4
2a
CHCl
3
None
SDS
4.56( 0.10) × 10
5.09( 0.12) × 10
4.56( 0.13) × 10
4.56( 0.12) × 10
5.34( 0.10) × 10
4.70( 0.15) × 10
3.87( 0.10) × 10
4.74( 0.13) × 10
3.87( 0.14) × 10
3.87( 0.12) × 10
–
−4
−4
−4
−4
−4
−4
−4
−4
−4
CHCl
3
CHCl
3
CTAB
Brij-35
None
SDS
CHCl
3
THF
THF
3a
CHCl
3
None
SDS
CHCl
3
CHCl
3
CTAB
Brij-35
–
CHCl
3
a
THF
2b
3b
CHCl
CHCl
CHCl
CHCl
None
SDS
No aggregation
4.54( 0.20) × 10
No aggregation
4.00( 0.19) × 10
3
3
3
3
−4
−4
None
SDS
a
Represents poor solubility of 3a in THF
assist the aggregation process of 2a. Unfortunately, the poor solubility of 3a in THF forbids
us to investigate the aggregation behavior of this compound in THF.
It is important to remark on the mode of aggregation of our long alkyl chain containing
calix[4]arene ethers in the two nonaqueous solvents, chloroform and THF. Specifically, it
can be proposed that the aggregation prominently occurs either due to the entanglement of
long alkyl chains of the calixarene molecular framework or the π–π stacking of the phenyl
rings. In order to get further insight into the aggregation mechanism, the two-dimensional
1
(2-D) H–1H COSY NMR spectrum of 2a was recorded in CDCl3 at ambient conditions
(Fig. 3). The COSY spectrum of 2a exhibited 3 cross correlation peaks. The first one was
obtained due to the coupling of doublets at 3.39 ppm and 4.33 ppm that correspond to
ArCH2Ar protons of 2a; the second correlation peak shows the coupling of a quintet at
2.06 ppm (OCH2CH2) and triplet at 3.99 ppm (OCH2); and the third correlation peak was
obtained due to the coupling of a broad multiplet at 1.26 ppm (CH2CH3) and quintet at 2.06
ppm (OCH2CH2). The possibility of interaction among the long alkyl chains may be ruled
out on the basis of COSY cross-correlation data as all the peaks obtained were very sharp
and no broadening of peaks was observed. Correlation peaks were obtained only for the
protons that were just near to each other within one alkyl chain. If the interaction among
the long alkyl chains was the reason for the aggregation in our case there would have been
more correlation peaks due to the coupling of distant protons, i.e., the protons of other alkyl
chains. Thus, in our opinion, the mode of aggregation is primarily due to the π–π stacking
of the phenyl rings of the calixarene though this stacking appears to be facilitated by the
presence of long alkyl chains (Fig. 4). It is supplemented by the fact that the aggregation is
exhibited via the deviation of the electronic absorbance of the phenyl rings on the calixarene
from the Beer-Lambert behavior, strongly suggesting the involvement of phenyl rings in the
aggregation process. Further support to this claim is provided by the investigation of Raston
and coworkers [36] who showed the stacking of the phenyl rings in the crystal structure of
similar long chain containing calixarenes.

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J Solution Chem (2010) 39: 107–120
1
1
Fig. 3 H– H COSY spectrum of 2a in CDCl at 25 °C
3
2.3 Effect of Calixarene Ethers on the Dimerization of Cationic Dyes
Many common dyes are known to aggregate in solution [29] depending on external condi-
tions such as type of solvent, temperature, and presence of additives [30]. In most cases such
aggregation is observed to depend on the concentration of the dye. Formation of aggregates
has been observed to be well manifested through the UV-vis molecular absorbance spectra
of the dye; a change in absorbance and/or a shift in absorbance band or band maxima fol-
lowed on many occasions by the appearance of a new band implying an aggregation process
involving a dye. Dimerization of certain cationic dyes in solution, for example, has been
well-studied. In cases where dimer formation is the primary aggregation process, an increase
in the concentration of the dye leads to a decrease in the ratio of monomer to dimerized dye
concentrations. The formation of dimer has been proposed to be a result of strong disper-
sion forces associated with the high polarizability of the chromophoric units of the dye. The
interactions of monomeric versus dimeric forms of a dye with an external additive could
provide information on the nature and extent of interactions in an efficient manner. Two
common dyes that are known to highlight such behavior are pinacyanol chloride (PYCN)
and methylene blue (MB) (structures shown in Scheme 2). We have investigated the effect
of the presence of 2a and 2b on the dimerization efficiency of these two dyes in solution.
For this purpose, we have chosen concentrations of 2a greater than its cac to determine the
effect of the aggregated form of 2a on the efficiency of dimerization of PYCN and MB.
Absorption bands corresponding to the monomer and the dimer forms of PYCN in chlo-
roform appear at ∼610 nm and ∼567 nm, respectively [41]. Figure 5 presents monomer-
to-dimer absorbance ratio as a function of the PYCN concentration in the absence and
presence of 2a. A careful examination of Fig. 5 reveals several interesting features. As ex-

J Solution Chem (2010) 39: 107–120
115
Fig. 4 Proposed simplified
mode of aggregation of 2a via
π–π stacking
Scheme 2 Structures of pinacyanol chloride (PYCN) and methylene blue (MB)
pected, increasing the [PYCN] facilitates the formation of dimers as clearly depicted by the
decrease in the monomer-to-dimer absorbance ratio. A more interesting observation, how-
ever, is that the dimerization process appears to become more efficient in the presence of
8 × 10−4 mol·dm−3 2a. It is also noteworthy that it happens at a concentration of PYCN
above ca. 6.0 × 10−5 mol·dm−3. When the concentration of 2a is varied in the solution by
keeping [PYCN] constant at 4.0 × 10−5 mol·dm−3 (lower [PYCN], where the monomer-to-
dimer absorbance ratio in the absence and presence of 2a are statistically not different, see
Fig. 5), the efficiency of dimer formation is observed to increase only after the concentra-
tion of 2a has reached ca. 6 × 10−4 mol·dm−3 (data presented in the inset of Fig. 5). The
efficiency of the dimer formation can be represented by the association constant (Ka) for the
equilibrium
2M ꢀ D
(1)

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J Solution Chem (2010) 39: 107–120
Fig. 5 Monomer-to-dimer absorbance ratio of PYCN dissolved in chloroform in the absence and presence
−4
−3
−4
−3
of 8 × 10 mol·dm 2a. Inset shows monomer-to-dimer absorbance ratio of 4 × 10 mol·dm PYCN
−1
as a function of [2a]. M denotes the units mol·L
here M and D are the monomer and the dimer, respectively, of PYCN, and
Ka = CD/CM2
(2)
where CM and CD are the equilibrium concentrations of the monomer and the dimer form
of the dye, respectively. By suitable manipulation, Ka can be expressed as
Ka = (CPYCN − CM)/2CM2
(3)
where CPYCN is the analytical concentration of PYCN in the solution. At extremely low
dye concentrations, the dimer concentration can be considered negligible and CM may be
approximated from the Beer’s law plot of absorbance versus CPYCN, allowing calculations
for Ka. The Ka thus obtained is 9.5( 1.7) × 103 dm3·mol−1 in the absence of 2a and a
significantly higher Ka = 1.7( 0.3) × 104 dm3·mol−1 value is obtained in the presence
of 8 × 10−4 mol·dm−3 2a. Contrary to our observation with 2a, the dimer formation effi-
ciency of PYCN does not change significantly in the presence of 2b. This can tentatively
be attributed to the fact that while 2a exists in the aggregated form within the solution, the
intramolecular hydrogen-bonding in 2b forbids it to aggregate in solution (vide supra). It
may be concluded that only the aggregated form of the long-chain containing calix[4]arene
ethers appears to facilitate the dimerization of PYCN.

J Solution Chem (2010) 39: 107–120
117
Fig. 6 Monomer-to-dimer absorbance ratio of MB dissolved in chloroform in the absence and presence of
−4
−3
−4
−3
8 × 10 mol·dm 2a (panel A) and in the absence and presence of 8 × 10 mol·dm 3a (panel B). The
−3
MB concentration, M, is expressed in mol·dm
The aggregation behavior of methylene blue (MB) was also investigated in a similar
fashion in the absence and presence of 2a and 3a, respectively. The presence of 2a and 3a,
respectively, also resulted in the increase of MB dimer formation efficiency in chloroform
(Fig. 6). Further, it is important to note that the decrease in monomer-to-dimer absorbance
ratio in the presence of 2a is not as dramatic for MB as it was for PYCN. Further, the
concentration of MB at which deviation in the monomer-to-dimer absorbance ratio, in the
absence and presence of 2a, begins is significantly higher (i.e., ca. 1 × 10−4 mol·dm−3 for
MB versus ca. 6 × 10−5 mol·dm−3 for PYCN in the presence of 8 × 10−4 mol·dm−3 2a).
Overall, our results strongly indicate the presence of significant dye-aggregated macrocycle
interactions. It may be concluded that the aggregation of calixarene macrocycles is able to
help the dimerization of common cationic dyes within the solution.
3 Conclusions
Self-aggregation of long-chain appended calix[4]arene ethers (i.e., 2a and 3a) in chloro-
form and THF has been demonstrated. The aggregation seems to involve the chromophoric

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J Solution Chem (2010) 39: 107–120
moieties of the calix[4]arene ethers while the presence of long alkyl chains appears to help
the aggregation process. Addition of the anionic surfactant SDS has been found to alter the
aggregation behavior in chloroform but not in a more polar solvent, THF. This is probably
because SDS is more prone to self-aggregation in polar solvents. The mode of aggrega-
tion in this case is π–π stacking of the phenyl rings. The dimer formation efficiency of
common cationic dyes PYCN and MB has been found to increase in the presence of ag-
gregated long-chain containing calix[4]arene ethers. Aggregation and interactions involving
such long chain appended macrocycles appear to be fairly complex in nature. The observa-
tions reported here may have significant potential applications in the near future in the field
of supramolecular chemistry, among others.
4 Experimental
4.1 Materials and Methods
All the reagents used in the study were purchased from Sigma-Aldrich or Merck and were
chemically pure. The solvents used were of spectrophotometric grade and were dried and
distilled additionally. Column chromatography was performed on silica gel (60–120 mesh)
obtained from Merck. 1H and 13C NMR spectra were recorded on a 300 MHz Bruker DPX
300 instrument at room temperature using tetramethylsilane (TMS) at 0.00 as an internal
standard. IR spectra were recorded on a Nicolet Protégé 460 spectrometer using KBr pel-
lets. Elemental analyses were taken on a Perkin-Elmer 240C Elemental analyzer. The FAB
mass spectra were recorded on a JEOL SX102/DA-6000 Mass Spectrometer/Data System
using argon/xenon (6 kV, 10 mA) as the FAB gas. Melting points were determined on an
electrothermal melting point apparatus obtained from M/S Toshniwal (Mumbai) and were
uncorrected. UV-visible electronic absorption spectra have been recorded on a Perkin Elmer
Lambda 35 spectrophotometer in the wavelength range of 200–800 nm using a 1 cm3 quartz
cuvette at ambient conditions. Blank spectra were subtracted in all cases. All the measure-
ments were taken in triplicate, starting from the sample preparation, and averaged. Dilution
corrections were also carried out wherever necessary. All data analysis was performed using
Microsoft Excel or SigmaPlot 8.0 softwares. The working stock solutions of compounds 2a,
2b, 3a and 3b, dyes and surfactants were prepared in chloroform or THF and stored in amber
glass vials. The appropriate amount of the solution was directly transferred to the cuvette
containing a pre-calculated amount of solvent for data acquisition.
4.2 Synthesis of Starting Material
5,11,17,23-tetra-(p-tert-butyl)-25,26,27,28-tetra hydroxy calix[4]arene (1a), and its debuty-
lated analog 25,26,27,28-tetra hydroxy calix[4]arene (1b), were synthesized according to
the method described by Gutsche et al. [11, 12, 31, 32]. The analytical data for compounds
1a and 1b were found to be the same as reported earlier [31–35].
4.3 General Procedure for the Synthesis of Tetra-alkylated and Di-alkylated Calix[4]arene
Ethers (Synthesis of 2a, 2b, 3a, and 3b)
Tetra and di substituted calix[4]arene ethers (2a, 3a and 2b) were prepared by employing
a procedure similar to that previously described in the literature [Scheme 1] [27, 36, 37].
The synthesized compounds were purified by column chromatography and characterized

J Solution Chem (2010) 39: 107–120
119
by NMR, IR, Mass and UV-Vis spectrometry which conformed to the data available in the
literature [27, 36, 37].
Starting material 1b (1g, 2.36 mmol) was taken in dry DMF; after 10 minutes of refluxing
with NaH, cetyl bromide/steoryl bromide was added. The reaction of compound 1b with an
equimolar amount per hydroxyl group of the reagents (1: 4 : 4 :: OH : cetyl/steroyl bromide :
NaH) after two days of refluxing yielded 2a and 3a in crude form. The solvent was removed
under reduced pressure and the crude product was extracted by chloroform followed by
exhaustive washing with water. The chloroform fraction was dried over Na2SO4; solvent
was evaporated to dryness to yield an off white semi-solid that solidified after 1 day. The
crude product obtained was purified by column chromatography (hexane : chloroform) to
give pure white compounds 2a and 3a.
Di-alkylated calixarene derivatives 2b and 3b were obtained in similar manner by the
reaction of 1b in dry acetonitrile with cetyl/steroyl bromide and anhydrous K2CO3 as base
(1 : 2 : 2 :: OH : cetyl/steroyl bromide : anhydrous K2CO3) [37].
Compound 3b. White solid, yield: 55%; m.p. 55–57 °C; IR (KBr, υmax/ cm−1): 3308, 2922,
1633, 1589, 1466; 1H NMR (300 MHz, CDCl3, δ in ppm): 0.86 (t, 6H, CH3), 1.26 (bs, 56H,
CH2), 1.69 (q, 4H, OCH2CH2CH2), 2.06 (q, 4H, OCH2CH2), 3.39(d, 4H, ArCH2Ar), 3.99
(t, 4H, OCH2), 4.33 (d, 4H, ArCH2Ar), 6.63 and 6.71 (t, 4H, ArH), 6.90 and 7.03 (d, 8H,
ArH), 8.24 (s, 2H, OH, D2O exchangeable); 13C NMR (75 MHz, CDCl3, δ in ppm): 158.2,
157.7, 151.0, 139.6, 133.7, 129.4, 128.6, 128.2, 121.3, 115.4, 85.3, 68.5, 61.1, 52.0, 45.8,
37.2, 31.8, 22.6, 14.1; UV (λmax, chloroform): 272 1 nm; Anal. calculated for C64H96O4:
C 82.7, H 10.41; found: C 82.9, H 10.2; FAB-MS: m/z 929 (M+).
Acknowledgements We thank the CSIR, India for a Senior Research Fellowship to Shubha Pandey and
DST, Government of India for financial assistance. We also thank the Sophisticated Analytical Instrumenta-
tion Facility (SAIF), Central Drug Research Institute (CDRI), Lucknow, India for the mass spectra reported
in this paper. Financial assistance from Ministry of Rural Development is also acknowledged.
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