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1 s2.0 S0143720824000160 Main
PII: S0143-7208(24)00016-0
DOI: https://doi.org/10.1016/j.dyepig.2024.111951
Reference: DYPI 111951
Please cite this article as: Xu Z, Liu X, Jiang T, Ma X, Host-guest assembly triggered lower critical
solution temperature behavior with reversible photo-regulation, Dyes and Pigments (2024), doi: https://
doi.org/10.1016/j.dyepig.2024.111951.
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Laboratory for Advanced Materials and Feringa Nobel Prize Scientist Joint Research Center,
School of Chemistry and Molecular Engineering
East China University of Science and Technology
Meilong Road 130, Shanghai 200237 (P. R. China).
Abstract
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The less frequent lower critical solution temperature (LCST) phenomenon has attracted extensive
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attention due to the foresighted application in smart materials. Nevertheless, the existing LCST-type
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materials are mainly dominated by a few polymers with specific moieties due to the damped
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hydration at a higher temperature and the lack of reversible regulations of the corresponding
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was uncovered in the BSC4/Azo-4 assembly solution. Such behavior arose from the host-guest
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binding between BSC4 and Azo-4 in an aqueous solution since neither the guest nor host alone
exhibited an LCST property. Ascribing to the distinct π-π stacking between the trans- and cis-
isomers of Azo-4, a reversible regulation of LCST behavior was achieved by irradiating UV and
blue light alternately. Our study demonstrated the complexity and possibility of supramolecular self-
assembly, opening a new avenue in the fabrication and adjustment of LCST-type materials in the
future.
*Corresponding author.
E-mail address: sailing_072@163.com
Assembly; Host-Guest Assembly
Introduction
its vast potential applications in drug delivery, phase transfer catalysis, optic sensing, and bio-
medicine, and widely exists in organism activities [1-9]. The susceptibility to external stimuli, such
as light, electric fields, pH, and temperature is the key to accessing the dynamical controllability of
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dynamically controlled self-assembly [10-13]. In particular, aqueous phase temperature-sensitive
self-assembly has been a research emphasis due to the practicality and foresight in bio-materials,
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phase-transfer catalysis, and smart surface [14,15]. In this case, two opposite types of temperature-
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depended physical properties have been addressed, that is, an upper critical solution temperature
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(UCST) and a lower critical solution temperature (LCST). As a less frequent phase-separate
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behavior, LCST depicts an immiscible phenomenon in solution and blends instead when
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temperature increases. The recent LCST-type materials are mainly focused on partial ionic liquids
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[16-18] and polymers with specific moieties, such as poly N-isopropyl acrylamide (PNIPAM), oligo
ethylene glycols (OEGs), poly N-vinyl caprolactam (PVCL) [19-23]. The prevailing insight to the
LCST-type polymers is the damped hydration continuously with elevated temperature ascribing to
the break of hydrogen bonds between water molecules and the corresponding moieties on the
polymers, resulting in a stretched to the coiled transformation of polymer chains and heterogeneous
turbid solution at the macroscopic level [24,25]. Eventually, this alteration of macroscopic property
the prevailing building blocks are mainly concentrated in PNIPAM and OEGs moieties to achieve
a thermal-sensitivity, and the alternative LCST groups are rather rare so far. Besides, the adjustment
to the critical temperature of LCST commonly depends on the doping content of thermally-sensitive
building blocks or the modification of additional hydrophobic and hydrophilic groups. These
statuses have limited the molecular design of thermally-sensitive materials, especially for those
small molecules. In this regard, throwing a sight on supramolecular self-assembly may provide an
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alternative strategy to fabricate small-molecule LCST systems [27,28]. More is different [29], it is
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a great challenge to accurately predict the emerging macroscopic properties of self-assembling
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systems which are frequently involved in multiple supramolecular interactions. On the other hand,
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the complexity of supramolecular assemblies can probably enable assembled molecules with
uncovered by a host-guest recognition between a bromonaphthol derivative and host BSC4 (Bis-p-
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sulfonatocalix[4]arene) in aqueous solution [34]. Notably, neither the free guest nor BSC4 showed
any LCST behavior before host-guest inclusion. The emerging behavior inspires us to explore other
potential LCST candidates. However, due to the unsettled mechanism of the emerging thermal
sensitivity, any minor modifications to the structure of host or guest molecules would lead to the
disappearance of the LCST phenomenon of the assemblies, let alone the corresponding adjustment
and functionalization. To this end, herein, we designed an Azo-4 guest based on azobenzene
modified with a quaternary ammonium terminal alkyl chain to assemble with BSC4. Temperature-
depended NMR, morphological analysis, and calorimetric titration showed a tiny variation of
inclusion between Azo-4 and BSC4 with temperature could remarkably affect the packing pattern
of azobenzene units and the hydration of Azo-4/BSC4 self-assembly, which was the critical
contribution to the resulting LCST behavior. Moreover, the excellent photo-isomerization ability of
Azo-4 endowed our LCST supramolecular system with a reversible light responsibility, providing
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Fig. 1. a) Schematic illustration of the LCST process of BSC4/Azo-4 complex by supramolecular interaction. b)
Temperature-dependence of transmittance of the LCST sample. c) Photographs of BSC4/Azo-4 = 1/1 solution at
different temperatures. TEM pictures of BSC4/Azo-4 = 1/1 solutions at different temperatures. d-e) 10°C; f-i) 40°C
(BSC4/Azo-4 = 2.5 mM). Scale Bar: d: 0.5 μm; f: 1 μm; h: 0.5 μm; e: 0.2 μm; g: 2 μm; i: 0.2 μm.
As a classical photo-isomeric group, the azo-unit has been widely used in various photo-
responsive assembly systems due to their excellent isomeric performance [35-37]. The synthetic
annotations are made) were shown in Scheme S1. As shown in Figure 1, the quaternary unit of the
Azo-4 can interact strongly with the poly-anion macro-cyclic of BSC4, resulting in site-specific
recognition of the encapsulation at the cavity of BSC4. As shown in Figure S1, when 1.0 eq of
BSC4 was added, the chemical shifts of all protons (f-j) in the alkyl quaternary region on Azo-4
were significantly shifted upfield due to the shielding effect of the BSC4 cavity. And the aromatic
protons (a-e) of Azo-4 also shifted upfield slightly, resulting from the π-π stacking interaction
between the azo-unit and calixarene-induced aggregation (CIA) effect [38-41]. In addition, as
shown in Figure S3, only one significant NOE signal between the protons (l) on the aromatic ring
of BSC4 and the protons (j) of the methyl group on the quaternary ammonium unit of Azo-4 is
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recorded, demonstrating that the quaternary ammonium terminal rather than Azo-unit is the
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inclusion site of Azo-4 due to the rather shallow cavity of BSC4 comparing to other typical hosts
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such as cyclodextrins. Besides, ITC measurement demonstrated that BSC4 and Azo-4 adopted a
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ratio of 1:2 inclusion pattern in an aqueous solution with a large binding constant of 3.24×104 M-2
(Figure S2), and the thermodynamic information also demonstrated that the host-guest binding
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between BSC4 and Azo-4 is an enthalpy driven process, which mainly derives from the Coulombic
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effect between poly-anion of BSC4 and the positively charged quaternary ammonium unit.
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UV-Vis absorption spectra further verified the host-guest interaction between Azo-4 and BSC4
and the self-assembly of supra-amphiphilic BSC4/Azo-4 (Figure S4). When the equivalent of BSC4
was less than 0.5 eq, the absorption at 345 nm kept decreasing, but with further addition of BSC4,
the absorbance at 345 nm showed a certain degree of increase instead. This unusual phenomenon is
due to the combined effect of the host-guest encapsulation and CIA of BSC4. With the subsequent
addition of BSC4, the assembly mode turns to 1:1 rather than the original 1:2, thus weakening the
aggregation of BSC4/Azo-4 assemblies due to the large hydrophily and charge repulsion of BSC4.
conducted to reveal the microscopic morphological changes (Figure S6-7). The aqueous solution of
Azo-4 showed a planar structure in TEM; when 0.5 eq of BSC4 was added, the morphology was
transformed into a cross-linking of sphere/membrane hybrid (Figure S6b-c); for the case of
BSC4/Azo-4 =1/1, the large cross-linked structures were further converted into spherical
nanoparticles with a size below 200 nm (Figure S6d). This morphological variation illustrates that
the over-equivalent BSC4 can effectively prohibit the formation of large self-assembled
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nanostructures.
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Both Azo-4 and BSC4 exhibited profound solubility in water especially at high temperatures.
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However, the Azo-4 /BSC4 =1/1 assembly solution showed significant turbidity at 35°C, and turned
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to the clarified state perversely with decreasing temperature below 10°C (Figure 1a,1c). As shown
in Figure 1c, the yellow limpid solution gradually evolved into a heterogeneous system when
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temperature was increased. Accordingly, the word “LCST” on the background plate turned out to
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be invisible. Instead, such turbid solution could be clear again when the temperature turned back to
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10°C. Meanwhile, the transmittance curve also showed a remarkable change in the range of 18°C-
30°C and the Tcloud was approximately at 24°C (Figure 1b). To reveal the microscopic changes d,
low temperature (10°C), the system exhibited spherical nanoparticles with diameters less than 200
nm (Figure 1d-e); when the temperature raised to 40°C, extensive cross-linking nanostructures were
formed between the original spherical nanoparticles resulting in forming irregular structures with
the hydrodynamic size during this process, and the results are consistent with TEM (Figure S8, S9).
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Fig. 2. a) Schematic diagram of photo-isomerization of Azo-4. b) The photographs of the LCST sample under
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continuous irradiation by 365/430 nm light in sequence. c) Alteration of transmittance of the LCST sample under
periodic irradiation by 365 nm and 430 nm light in sequence. All measurement processes were carried out at 30°C.
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The above results showed that slight changes in molecular structure would result in a dramatic
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hindrance, molecular planarity, and dipole change significantly upon irradiation (Figure 2a, S10).
Therefore, the isomerization may exert a considerable impact on the LCST behavior. As shown in
Figure 2, the turbid BSC4/Azo-4 (1/1) solution gradually evolved to a clarified one under
continuous irradiation of 365 nm light at 30°C and stayed transparent even at a higher temperature.
Conversely, the clarified solution would eventually return to the initial turbid state upon 430 nm
light irradiation and maintain the switch thoroughly after 25 cycles of irradiation owing to the
configuration. As shown in Figure S12, the morphologies of the Azo-4 monomer and BSC4/Azo-4
assemblies underwent significant dissociation after 365 nm light irradiation compared with those in
Figure S6-7. We deduce that the inter-aromatic π-π stacking is severely inhibited when trans-Azo-
4 transforms into cis-configuration and the increased dipole moment of cis-Azo-4 favors the
hydration. Due to the two factors, the aggregation of BSC4/Azo-4 = 1:1 is impaired as the result of
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As shown in Figure S10, the upfield shift of protons (a’-e’) on the Azo-unit changes a little
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after host-guest inclusion, indicating that the π-π stacking between trans-Azo-4 is larger than cis-
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Azo-4 after being included by BSC4. In comparison, the chemical shifts of protons on the alkyl
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chain of cis-Azo-4 (f’-j’) present a remarkable upfield shift. This difference may result from the
aggregation of trans-Azo-4. For the case of cis-Azo-4, the less planarity limited the π-π stacking
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and impeded the aggregation of BSC4/cis-Azo-4; on the other hand, BSC4/trans-Azo-4 presented
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apparent aggregation at a high concentration due to the well-stacking behaviour and hydrophobicity
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of trans-Azo-4. However, the π-π stacking of trans-Azo-4 contradicted the steric hindrance of
BSC4 upon host-guest recognition, resulting in a shallower inclusion between the chain terminal of
trans-Azo-4 and the cavity of BSC4. Notably, the compromise of the two factors is crucial to the
shown in Figure S13 and S14, when the temperature was increased up to 50°C, the chemical shift
of the aromatic ring and the nearby protons (a-f) on BSC4/trans-Azo-4 significantly shifted
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downfield; instead, the signals of terminal protons (g-j) on the alkyl chain shifted upfield. Especially,
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a split and upfield-shifted NMR signal of the terminal proton j was observed evidently, indicating
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a deeper encapsulation between BSC4 and Azo-4. In comparison, the signals of BSC4/cis-Azo-4
protons (red letter) merely changed a little. Considering the remarkable aggregation distinction
between trans- and cis-Azo-4, it is reasonable to deduce that the efficient π-π stacking of Azo-4
limits the encapsulation of BSC4 resulting in a superficial binding; in turn, the large steric hindrance
and coulomb repulsion of BSC4 impedes the slide face-to-face stacking between azo-units, thus
leading to a V-shape stacking motif. There are two shreds of evidence to support this speculation: i)
the curved super-amphiphilic stacking favors to form spherical nanoparticles as addressed by TEM
and ii) the chemical shift of protons a and b shifts more upfield than that of the others on the azo-
unit since the closer distance between the head of Azo-4. The increased temperature induces a
disruption of the V-shape stacking to promote a deeper encapsulation and a parallel style for
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Fig. 4. Dilution enthalpy traces of BSC4/Azo-4 (=1/1) solution titrated into pure water examined by ITC at 298 K
a) before and b) after 365 nm light irradiation.
Besides, the dilution enthalpy of concentrated BSC4/Azo-4 solution before and after
irradiation was examined by an ITC study. As shown in Figure 4, both isomeric BSC4/Azo-4
assemblies exhibit an exothermic effect when diluted in water, demonstrating the existence of
compared with the cis-counterpart, indicating a considerable aggregation when the concentration
approximately exceeds 0.3 mM. This exothermic effect also suggests that the hydration of
BSC4/Azo-4 self-assembly at high concentrations will probably be suppressed if the temperature
rises. As a result, a turbid solution can be obtained from a clear one when heated up to a certain
temperature.
stimulation response to temperature and light through a host-guest assembly process between an
alkyl quaternary ammonium-modified azobenzene guest molecule and the host BSC4. Notably, at
a BSC4/Azo-4 = 1:1 mixing ratio, the assembled solution (2.5 mM) exhibits an unexpected LCST
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behavior at the Tcould of 24°C, which was unsuspected in both the Azo-4 solution and the BSC4
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solution. A series of systematic characterizations suggest that this unanticipated LCST behavior
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arises from the delicate compromise of the different intermolecular interactions, and the exothermic
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hydration effect. This assembly equilibrium is highly susceptible to perturbation by subtle changes
in external temperature and intermolecular stacking, thus exhibiting the LCST phenomenon in
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response to photo-stimulation. This work aims to demonstrate the potential and value of supra-
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amphiphilic assemblies in functional materials. It is expected that this strategy will play an essential
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Acknowledgments
This work was supported by the National Key Research and Development Program of China
(2022YFB3203500), the National Natural Science Foundation of China (22125803, 22108078, and
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Supplementary Material
Supplementary material that may be helpful in the review process should be prepared and
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Research Highlights of this work are including:
3. The distinct π-π stacking between the trans- and cis- isomers of Azo-4 gave
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rising to a reversible regulation of the LCST behavior by irradiating UV and blue
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light alternately.
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Conflicts of interest
All authors disclosed no relevant relationships.
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