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Thermochimica Acta 541 (2012) 62– 69

Contents lists available at SciVerse ScienceDirect

Thermochimica Acta

journa l h o me page: www.elsev ier .com/ locate / tca

thermogravimetric analysis (TGA) method developed for estimating thetoichiometric ratio of solid-state �-cyclodextrin-based inclusion complexes

uxiang Baia, Jinpeng Wanga, Mohanad Basharia, Xiuting Hua, Tao Fengb, Xueming Xua, Zhengyu Jina,∗,aoqi Tiana,∗

The State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaSchool of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai 201418, China

r t i c l e i n f o

rticle history:eceived 10 January 2012eceived in revised form 28 March 2012ccepted 23 April 2012vailable online 30 April 2012

a b s t r a c t

An approach mainly based on thermogravimetric analysis (TGA) was developed to evaluate thestoichiometric ratio (SR, guest to host) of the guest–�-cyclodextrin (Guest-�-CD) inclusion complexes (4-cresol-�-CD, benzyl alcohol-�-CD, ferrocene-�-CD and decanoic acid-�-CD). The present data obtainedfrom Fourier transform-infrared (FT-IR) spectroscopy showed that all the �-CD-based inclusion com-plexes were successfully prepared in a solid-state form. The stoichiometric ratios of �-CD to the relative

eywords:hermogravimetric analysis-CD-based inclusion complexmall guestourier transform-infrared-ray diffraction

guests (4-cresol, benzyl alcohol, ferrocene and decanoic acid) determined by the developed method were1:1, 1:2, 2:1 and 1:2, respectively. These SR data were well demonstrated by the previously reported X-raydiffraction (XRD) method and the NMR confirmatory experiments, except the SR of decanoic acid with alarger size and longer chain was not consistent. It is, therefore, suggested that the TGA-based method isapplicable to follow the stoichiometric ratio of the polycrystalline �-CD-based inclusion complexes withsmaller and shorter chain guests.

MR

. Introduction

Cyclodextrins (CDs) are macrocyclic compounds comprisingf several d-glucopyranoses linked by �-1,4-glycosidic bonds. �-

�- and �-CD are the three most common CDs [1]. They haveeen widely used as the typical hosts for the second generation

n supramolecular chemistry, since the non-covalent associationetween hosts (CD) and guests can actually improve the water sol-bility, stability and bioavailability of the guests [2,3]. Especially,he common CDs generally can be used for preparing inclusionomplexes with lower molecular weight guests, including nonpolarliphatic molecules and polar amines and acids [4]. In the commonDs, �-CD has been studied more as its comprehensive advantages,uch as a larger industry yield and a higher solubility [5]. Neverthe-ess, �-CD is often adopted to encapsulate the guests with smallerize because of its own small cavity [6–8]. Compared to the hydratesf �- and �-CDs, �-CD hydrates contain the least amount of crys-al water (CRW) and complexed water (COW) [9]. In addition, there

ave been three crystalline types of �-CD (Type I, II and III, see Fig. 1)eported previously, while most common types are Type I and II10,11]. Analysis of the common types, there are two/one water

∗ Corresponding authors. Tel.: +86 510 85913299; fax: +86 510 85913299.E-mail addresses: jinlab2008@yahoo.com (Z. Jin), yqtian@jiangnan.edu.cn

Y. Tian).

040-6031/$ – see front matter © 2012 Elsevier B.V. All rights reserved.ttp://dx.doi.org/10.1016/j.tca.2012.04.029

© 2012 Elsevier B.V. All rights reserved.

molecules forming a trimer/dimer with CD inside the cavity andthe remaining four/five water molecules distributed for building anetwork with other CD molecules [10].

Stoichiometric ratio (SR) is an important parameter when thecharacteristics of the �-CD-based inclusion complex are estimated.It can be used to calculate a precise weight ratio of guest versus �-CD to avoid waste of raw materials during the inclusion complexespreparation [12]. Furthermore, several important kinetic parame-ters (stability constant and Gibbs free energy) for the encapsulationcalculated from a series of different formulas are dependant on theSR values [13].

�-CD-based inclusion complexes are commonly divided intotwo types, liquid-state and solid-state. According to the differentstates, several methods have been provided to estimate the SRvalues. For instance, phase solubility curve and nuclear magneticresonance (NMR) are suitable for measuring the SR of the liquid-state inclusion complex [14,15], while X-ray diffraction (XRD) andelemental analysis (EA) can be used for the solid-state samples[16,17]. Nevertheless, the XRD and the EA methods require themonocrystal samples and generate more economic cost, althoughthey are successfully used in previous works [6–8].

In the present study, a simple and accurate method was devel-

oped to partly replace and transcend the conventional techniquesfor detecting the SR of solid-state �-CD-based inclusion complexes.Several kinds of tested inclusion complexes in a solid-state formwere prepared and identified by Fourier transform-infrared (FT-IR)

Y. Bai et al. / Thermochimica Acta 541 (2012) 62– 69 63

repre

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2

2

(a

2

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2i

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The present results showed that each guest had strong absorp-tion bands: 4-cresol at 1591.46 and 1514.50 cm−1 (Fig. 3a),

0

2

4

6

8

Mas

s o

f a-

CD

(m

g)

-0.3

-0.2

-0.1

0.0

0.1

Deriv

ative (

mg/

oC)

Fig. 1. Different crystalline types of �-CD. CRW and COW

pectroscopy and thermogravimetric analysis (TGA). The SR dataere determined by the new technique and also compared with

he results collected from the XRD and nuclear magnetic resonanceNMR) methods.

. Experimental

.1. Materials

�-CD was purchased from Sigma–Aldrich Trading Co. Ltd.Shanghai, China). Benzyl alcohol, ferrocene, 4-cresol, decanoic acidnd other reagents used were analytical grade unless other stated.

.2. Preparation of ˛-CD-based inclusion complexes

Excessive mass of �-CD was added into hot water (70 ◦C) torepare a saturated solution of �-CD. All tested guests (2–4 g),

ncluding benzyl alcohol, ferrocene, 4-cresol, decanoic acid, wereixed with the prepared �-CD solution (10 g �-CD), respectively.

he mixtures were stirred vigorously at 150 rev/min for 20 min andhen moved into Dewar flasks. The crystal could grow during tem-erature decreasing and cocrystallization process [7,18] and it wasollected for use. All the prepared complexes were more than sin-le crystals. A control sample without the guest was prepared ashe same procedure described above.

.3. Fourier transform-infrared (FT-IR) and Fourier transformnfrared attenuate total reflectance (FTIR-ATR)

FT-IR spectra of the involved samples (guests, �-CD anduests–�-CD inclusion complex) were collected using an infraredpectrophotometer (5DXC FTIR, Nicolet Co., US) [19]. The analy-is parameters were set as: wave number range, from 4000 to00 cm−1; resolution, 4 cm−1; number of scans, 64; and scan speed,.63.

Some special solid–liquid state mixtures, such as the physi-al mixture samples of cresol group and benzyl alcohol groupespectively, were measured using the FTIR-ATR method [20]. Thisechnique is non-destructive and it has a good signal to noise ratiot the origin of the spectra. The basic analysis parameters wereet as the following: wave number range, from 4000 to 600 cm−1;esolution, 2 cm−1; number of scans, 64; and scan speed, 0.63.

.4. Thermal gravimetric analysis (TGA)

The TGA curves of the prepared samples were obtained using thermogravimetric analyzer (TGA–SDTA851e, Mettler Toledo Co.

td., Switzerland) under nitrogen atmosphere with a flow rate of0 mL/min [21,22]. Around 6.0 mg of each sample was used for testnd heated from 25 to 800 ◦C with a heating rate of 10 ◦C/min toet the mass loss against heating temperature curves.

sent the crystal water and complexed water, respectively.

2.5. 1H nuclear magnetic resonance (NMR)

Spectra were recorded using a Bruker DRX Avance III 400 MHzspectrometer operating at 14.1 T. The NMR data were processedwith a SGI O2 R5000 workstation and the Bruker XWinNMRv2.1software [23]. Chemical shifts were measured from TSP used asexternal standard (to avoid TSP signal shifting upon interactionwith �-CD) with resonance set at 0 ppm. All the spectra wererecorded in 99.96% D2O at 298.0 ± 0.1 ◦C.

3. Results and discussion

3.1. Identification of the ˛-cyclodextrin crystal type

There were two definite steps observed during the degradationof �-CD hydrates (Fig. 2). The mass loss caused by the crystallinewater (CRW) was 0.8092 mg during the first decomposition step(20–139.7 ◦C). The initial decomposition temperature of the pure�-CD observed from the derivative TGA curve was 280 ◦C. Dur-ing the second decomposition stage (280–800 ◦C), the mass lossof the pure �-CD was determined to be 6.8632 mg. These resultsindicated that the weight ratio of CRW versus pure �-CD was justmatched to the �-CD hexahydrate and the hexahydrate consistedof crystal forms I and II [10]. It also demonstrated that the crystalwater content of polycrystal �-CD was equal to the single crystalone.

3.2. Identification of the ˛-CD-based inclusion complexes

600400200

Temperature (ºC)

Fig. 2. The typical TGA and the derivative TGA curves of the control sample �-CDhydrate.

6 mica A

bfaam

FF

4 Y. Bai et al. / Thermochi

enzyl alcohol at 1453.74, 1210.32 and 694.66 cm−1 (Fig. 3b),−1

errocene at 816.37 and 998.93 cm (Fig. 3c), and decanoic

cid at 1706.76 and 1296.80 cm−1 (Fig. 3d). These peaks werettributed to the C C stretching vibration of mononuclear aro-atics in the 4-cresol, the stretching vibration of C C, C O

ig. 3. The FT-IR spectra of four groups of samples: (a) 4-cresol group, (b) benzyl alcoholT-IR curves: (I) �-CD, (II) the guest, (III) the �-CD/guest physical mixture and (IV) the �-

cta 541 (2012) 62– 69

and the rocking vibration –CH2– in benzyl alcohol, the rock-

ing vibration of –CH2– and the stretching vibration of CH2 CH2in ferrocene, and the stretching vibration of C O and C O indecanoic acid, respectively. The encapsulation, however, signifi-cantly weakened the signal of the relative peaks. This indicated

group, (c) ferrocene group, and (d) decanoic acid group. Each group consist of fourCD-based inclusion complex.

Y. Bai et al. / Thermochimica Acta 541 (2012) 62– 69 65

Fig. 3. (Continued).

tob3

hat the relevant bonds of the guests were shield by the electronsf �-CD [24]. Furthermore, the encapsulation made the absorptionand of the host (�-CD) hydroxyl group shifted from 3397.86 to381.85 cm−1 in the cresol group, from 3397.86 to 3381.85 cm−1

in the benzyl alcohol group, from 3397.86 to 3378.65 cm−1 inthe ferrocene group, and from 3397.86 to 3381.46 cm−1 in thedecanoic acid group. The wave number shift was ascribed tothe dissociation of hydrogen bonds located in tubular structure

66 Y. Bai et al. / Thermochimica A

Table 1Several common ideal types of �-CD-based complexes.

Range of ia SR (CD:guest)

(Mguest–36, Mguest) 1:1(2Mguest–36, 2Mguest) 1:2(0.5Mguest–18, 0.5Mguest) 2:1(0.33Mguest–12, 0.33Mguest) 3:1(0.67Mguest–24, 0.67Mguest) 3:2(1.5M –54, 1.5M ) 2:3

oif

3

tcC(

W

W

TP

TT

guest guest

a i represents(aWpure �-CD−k·bW ′

pure �-CD)·M�-CD

Wpure �-CDand SR is the stoichiometric ratio.

f �-CD [25]. These results suggest that the four �-CD-basednclusion complexes were successfully prepared in a solid-stateorm.

.3. Determination of stoichiometric ratio (SR)

Several decomposition steps were observed based on the deriva-ive TGA curves. Each step represented one or some certainomponent(s). The mass of each component contained in the �-D-based inclusion complex could be obtained via formulas (1) and2):

complex = WCRW + Wguest + Wpure �-CD + Wash (1)

�-CD = W ′CRW + W ′

pure �-CD + W ′ash (2)

able 2arameters, a, b, k, i and the stoichiometric ratio (SR) of the tested four �-CD-based inclu

a b

4-Cresol 0.2211 0.1179

Benzyl alcohol 0.3330 0.1179

Ferrocene 0.1788 0.1179

Decanoic acid 0.4393 0.1179

able 3he reported SR values of �-CD inclusion complexes for verifying the TGA results.

Guest Method SR (CD:g

4-Cresol XRDa 1:1

Benzyl alcohol XRD 1:2

Ferrocene XRD 2:1

Decanoic acid XRD 2:1

a X-ray diffraction.b Stoichiometric ratio.c Crystalline water molecular number.

Fig. 4. The complexed water (COW) change as the guest in

cta 541 (2012) 62– 69

where Wcomplex, WCRW, Wpure �-CD, Wash and Wguest represent themass of total �-CD-based inclusion complexes, crystalline water,pure �-CD, ash and guest, in the inclusion complex system, respec-tively. W�-CD, W ′

CRW, W ′pure �-CD and W ′

ash are the mass of total�-CD, crystalline water, pure �-CD and ash in the �-CD systemwithout any guest, respectively.

The TGA curves could be divided into several clear steps fordifferent components in this experiment. Thus, the Wpure �-CD andW ′

pure �-CD were selected as primary parameters for calculating thecontent of other ingredients. The relationship of these parameterscould be described as the following formulas ((3)–(5)):

Wpure �-CD

W ′pure �-CD

= k (3)

WCRW + Wguest

Wpure �-CD= a (4)

W ′CRW

W ′pure �-CD

= b (5)

According to formulas (1)–(5), formula (6) could be deduced:

WCRW + Wguest − kW ′CRW = aWpure �-CD − k · bW ′

pure �-CD (6)

The CRW changes of each �-CD molecule in different types couldbe simulated (Fig. 4). The simulation indicated that the guests couldincorporate into the hydrophobic cavity of �-CD and replace thecomplexed water (COW).

sion complexes.

k i SR (CD:guest)

0.9263 100.36 1:10.9139 209.27 1:20.8958 59.27 2:10.8052 312.72 1:2

uest)b CRWc References

6 [6]6 [7]9 [8]

25 [26]

teracts with each �-CD molecule in different types.

imica Acta 541 (2012) 62– 69 67

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Benzyl alcohol-a-CD complex

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Y. Bai et al. / Thermoch

A series of conclusion, therefore, could be drawn according tohe deduced and simulated results.

If the relative parameters satisfied formula (7), SR (�-CD:guest)ould be defined as 1:n (n ∈ N*). This situation was applicable to theong chain and large size guests.

Mguest − 2MH2O ≤(aWpure �-CD − k · bW ′

pure �-CD) · M�-CD

Wpure �-CD≤ nMguest (7)

here Mguest, MH2O and M�-CD are the molar weight of guest, waternd �-CD, respectively.

If the relative parameters fit formula (8), SR could be defined as:q (p, q ∈ N*, p ≥ 2). This situation just could be applied to the shorthain and small size guests, since the guests with larger and longerhains could increase the space of supermolecular interstice andake the CRW number grow [9].

q

p(Mguest − 2MH2O) ≤

(aWpure �-CD − k · bW ′pure �-CD) · M�-CD

Wpure �-CD≤ q

pMguest (8)

Several common ideal types of �-CD-based inclusion complexesere listed in Table 1.

So,

If Mguest ∈ (144, +∝), there is no intersection for each type.If Mguest ∈ (108, 144), intersection occurs between the types of 3:2and 2:1; andIf Mguest ∈ (72, 108), three SR types of 3:2, 2:1 and 3:1 have colli-sion. Furthermore, very limited guests with molecular weight lessthan 72 Da have been researched before [9].

The TGA and the derivative TGA curves of the guests and theirnclusion complexes were shown in Fig. 5. The stoichiometricatio (SR) values calculated from these curves were summa-ized in Table 2. The TGA curve could be divided into two steps20–280 ◦C and 280–400 ◦C), since the final melting tempera-ure of all the tested guests was far from the initial degradationemperature of �-CD and an equivalent derivative value of eachnclusion complex at 280 ◦C was observed. In addition, the i valuesor 4-cresol–, benzyl alcohol–, ferrocene–, and decanoic acid–�-D inclusion complexes were observed between M4-cresol–3672 Da) and M4-cresol (108 Da), 2Mbenzyl alcohol–36 (180 Da) andMbenzyl alcohol (216 Da), 0.5Mferrocene–18 (56 Da) and 0.5Mferrocene74 Da), and 2Mdecanoic acid–36 (308 Da) and 2Mdecanoic acid (344 Da),espectively. According to these i values, the SR data for the testednclusion complexes were finally determined via formulas (7) and8) to be 1:1, 1:2, 2:1, and 1:2.

.4. Confirmation of the TGA results using the former results andMR method

The obtained SR values were also compared with the pre-ious data determined from the X-ray diffraction method6–8,26] (Table 3). The results showed that there was aood agreement between the developed technique andhe reported X-ray diffraction method for the tested 4-resol–, benzyl alcohol– and ferrocene–�-CD inclusionomplexes, but not for the decanoic acid–�-CD inclusionomplex.

NMR technique was also applied to check the TGA results in thistudy. The stoichiometric ratio of the inclusion complexes was cal-ulated, based on the ratio of H-proton numbers in guest moleculend host molecule. The double-overlapping peak around 5.0 ppmepresented the H(A) and H(B) of �-CD, the peaks between 6.5 and.5 ppm described the H(E) and H(F) of the cresol (in Fig. 6a) and the

eak at 7.3 ppm was the H(E) in benzyl alcohol (Fig. 6b). The tripleteak at 1.7 ppm explained the H(E) of ferrocene (Fig. 6c). H(E) ofhe –CH3 in decanoic acid was at 0.85 ppm (Fig. 6d). According tohe area of each characteristic peak, the stoichiometric ratios of

Tempera ture ( C)

Fig. 5. The TGA and the derivative TGA curves of the four groups of samples: (a)4-cresol group, (b) benzyl alcohol group, (c) ferrocene group, and (d) decanoic acidgroup. Each group contains the TGA curves of guest and �-CD-based inclusion com-plex, and the derivative TGA curves of the �-CD-based inclusion complex.

68 Y. Bai et al. / Thermochimica Acta 541 (2012) 62– 69

benzy

ttclu

Fig. 6. NMR spectra of the four complexes: (a) 4-cresol–�-CD, (b)

he complexes were 1:1, 1:2, 2:1, and 2:1, which were in line with

he previous results obtained from the developed method. Thesealculated ratios were interpreted by a fact that a longer chain andarger size guest could make the interstice space of the supramolec-lar structure increased and more CRW was merged into the cavity

l alcohol–�-CD, (c) ferrocene–�-CD and (d) decanoic acid–�-CD.

of �-CD [9]. Furthermore, �-CD was commonly used to encapsulate

smaller size and shorter chain guests. These results suggest that thedeveloped method was applicable and could be used for measur-ing SR values of the �-CD-based inclusion complexes with lowermolecular weight guests.

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. Conclusions

This work dealt with a TGA method for determining the sto-chiometric ratio (SR) of the �-CD-based inclusion complexes in

solid-state form. Four guests, 4-cresol, benzyl alcohol, ferrocenend decanoic acid, were selected to verify the possibility and accu-acy of the new method. The major results demonstrated that theeveloped method was applicable for the SR values determinations long as the guest molecule was small size and short chain one. Itas suitable for not only the single crystal but also the polycrystal

ample. Further research would be focused on the SR measurementf other CD-based inclusion complexes with larger size and longerhain guests.

cknowledgments

This study was financially supported by the Fundamentalesearch Funds for the Central Universities (No. JUSRP11225 ando. JUDCF10051), Graduate Student Innovation Project of Jiangsurovince (No. CXZZ11 0486), Project of the State Key Laboratoryf Food Science and Technology, Jiangnan University (No. SKLF-ZB-201206), and the National Key Technology R&D Program forhe 12th Five-Year Plan (Nos. 2012BAD37B01, 2012BAD37B02 and012BAD37B06).

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