Microwave synthesis and characterization of a supramolecular

βCD-based crosslinked network

Yareli Rojas-Aguirre1, Geovanni Sangabriel-Gordillo1, Israel González-Méndez1.
1Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México,
Ciudad Universitaria, C.P. 04510, México D.F., México
yarelirojas@gmail.com

Abstract
The synthesis of supramolecular networks using cyclodextrins as the crosslinking points is
gaining attention because of their potential applications in a number of fields. In this work, we
present the synthesis of a β-cyclodextrin (βCD) network with carbonyldiimidazole (CDI) as the
crosslinking agent using microwave irradiation. This approach allowed obtaining the product
in 45 minutes instead of the 8 h that takes the conventional synthesis. The physicochemical
characterization confirmed the identity of the material, which showed, in addition, an improved
host-guest complexation efficiency.

Introduction
Cyclodextrins (CDs) are cone shaped cyclic oligosaccharides formed by glucopyranose units
in which the outer surface is hydrophilic, while the cavity holds a hydrophobic
microenvironment. Hence, CDs can host molecules of different nature resulting in the
formation of inclusion complexes [1]. The synthesis of CD-based crosslinked networks is
becoming popular in current research. In these systems, the CDs can act as the crosslinking
points and interact with guest molecules simultaneously. The crosslinker, the reaction
conditions and the stoichiometry will determine the degree of crosslinking, the characteristics
of the mesh, the size and the shape of the system and, therefore, gels, polymer particles or
continuous porous structures can be obtained [2].
Trotta and co-wokers have been pioneers in the synthesis of hypercrosslinked CD systems.
Among them is the one called carbonate nanosponge, a crystalline nanometric structure,
obtained from the reaction of βCD and CDI as the crosslinking agent [3]. Inspired by the work
of Trotta and taking into account the potential applications of the βCD-based crosslinked
networks, we consider that the generation of these materials rapidly with the possibilities to
scale up their production is of great importance. In this sense, we herein present the synthesis
and characterization of a βCD network with CDI as the crosslinking agent using microwave
irradiation (βCD-CL-MW). In parallel, the crosslinked system using the conventional heating
method was also synthesized (βCD-CL-H).

Materials and methods

CDI, βCD, dimethylformamide (DMF) and ethanol were purchased from Sigma-Aldrich and
used without further purification. Milli Q water was used for all the experiments.
βCD-CL-H was synthesized following the reported methods [4]. βCD-CL-MW was performed
in an Anton-Parr Monowave 450 at 120°C and stirring rate of 500 rpm; the reaction was
monitored through the integrated camera. Both, βCD-CL-H and βCD-CL-MW were prepared
with a stoichiometric ratio βCD-CDI 1:4. The FTIR reflectance spectra were acquired in a
Perkin Elmer Spectrum 400. The powder x-ray diffraction was carried out in a Bruker D8
Advance diffractometer using Cu ƙα (λ=1.5406 Å) radiation with 30 mA current and voltage of
35 kV. The SEM micrographs of the gold sputtered samples were taken in a Jeol JSM 5900LV
in SEI mode, voltage of 20 kV, work distance of 11 mm and spot size of 22. To determine the
complexation efficiency, an amount of phenolphthalein (Phen) was added to a suspension of
the crosslinked systems, the samples were centrifuged and the free Phen was quantified in a
UV-Vis spectrophotometer at 553 nm (Genesys 10UV Thermo).

Results
Two βCD-based crosslinked structures were prepared. βCD-CL-H was obtained after 8 h,
while βCD-CL-MW was produced in only 45 min. The systems were obtained as porous
surface micrometric aggregates (Figure 1). The particle size was confirmed through their
analysis in a zetasizer instrument (Malvern) and was found to be in the range of 4-5 µm.

Figure 1. SEM micrographs of A) βCD; B) βCD-CL-H and C) βCD-CL-MW

Both, βCD-CL-MW and βCD-CL-H, were characterized in order to confirm their identity. The
IR spectra showed the characteristic band of carbonate group at 1750 cm-1 indicating the
crosslinking between CDs through carbonate moieties in both cases (Figure 2B and 2C),
whereas the IR spectrum of native βCD did not display this peak (Figure 2A). The diffraction
pattern of βCD revealed the crystallinity of the native macrocyle, which is lost in some extent
when is crosslinked. Interestingly, the degree of crystallinity in βCD-CL-MW seems to be higher
than βCD-CL-H (Figure 3).
 Figure 2. FTIR spectra of A) βCD; B) βCD-CL-H and C) βCD-CL-MW

Figure 3. X-ray diffractograms of A) βCD and B) crosslinked systems

Both, βCD-CL-MW and βCD-CL-H were incubated in the presence of Phen, a well known guest
for the macrocyle. The crosslinked systems were more efficient forming complexes than βCD.
This can be due to a cooperative effect that βCD rings have when they are close together [1]
and because the guest molecules could also be trapped in the interstitial spaces in the
crosslinked structure. It was found that the complexation ability and the impregnation volume
of βCD-CL-MW material was higher than βCD-CL-H (Table 1). The latter was performed in
order to indirectly know the porosity and the amount of water that can be taken by the material.
These results show that besides the reduction of the reaction time, the microwave irradiation
influences the crosslinking ratio and the order in which the macrocycles are packed to form the
porous structure. This, in turn, will determine the entrapment capacity of the supramolecular
materials and the further applications they could have.
 Table 1. Specific features of the BCD crosslinked systems
Reaction Yield Impregnation Complexation
System
time (%) volume (ml/g) efficiency (%)
Native βCD --- --- 0.53 68.4
βCD-CL-H 8h 49 1.61 79.2
βCD-CL-MW 45 min 57 3.16 87.3

Conclusions
Two βCD-based crosslinked systems were synthesized. As expected, the reduction in the
reaction time when working in a microwave reactor decreased dramatically from 8 h to only 45
minutes. The microwave irradiation produced structures with an enhanced capacity to form
inclusion complexes and to entrap water molecules than the same materials obtained by the
conventional synthetic methods. These outcomes open the door to a fast production of
materials with improved properties and to the possibilities for expanding their applications,
which will be part of our future work.

References
[1] Loftsson, T.; Duchêne, D. Int. J. Pharm. 2007, 329 (1-2), 1–11.
[2] Concheiro, A.; Alvarez-Lorenzo, C. Adv. Drug Deliv. Rev. 2013, 65 (9), 1188–1203.
[3] Cavalli, R.; Trotta, F.; Tumiatti, W. J. Incl. Phenom. Macrocycl. Chem. 2006, 56 (1-2), 209–213.
[4] Lembo, D.; Swaminathan, S.; Donalisio, M.; Civra, A.; Pastero, L.; Aquilano, D.; Vavia, P.; Trotta, F.;
Cavalli, R. Int. J. Pharm. 2013, 443 (1-2), 262–272.

Acknowledgment
The authors thank Prof. Francisco Hernández-Luis for the technical assistance and facility of the Anton-
Parr Microwave Reactor and Facultad de Química, UNAM for the financial support (PAIP 5000-9157).