A comprehensive molecular insight into host-guest interaction of Phenanthrene with native and ionic liquid modified β-cyclodextrins: Preparation and characterization in aqueous medium and solid state

Journal Pre-proof A comprehensive molecular insight into host-guest interaction of Phenanthrene with native and ionic liquid modified β-cyclodextrins: Preparation and characterization in aqueous medium and solid state Boon Yih Hui, Nur Nadhirah Mohamad Zain, Sharifah Mohamad, Samikannu Prabu, Hasnah Osman, Muggundha Raoov PII:

S0022-2860(19)31784-3

DOI:

https://doi.org/10.1016/j.molstruc.2019.127675

Reference:

MOLSTR 127675

To appear in:

Journal of Molecular Structure

Received Date: 25 November 2019 Revised Date:

27 December 2019

Accepted Date: 31 December 2019

Please cite this article as: B.Y. Hui, N.N.M. Zain, S. Mohamad, S. Prabu, H. Osman, M. Raoov, A comprehensive molecular insight into host-guest interaction of Phenanthrene with native and ionic liquid modified β-cyclodextrins: Preparation and characterization in aqueous medium and solid state, Journal of Molecular Structure (2020), doi: https://doi.org/10.1016/j.molstruc.2019.127675. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier B.V.

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A comprehensive molecular insight into host-guest interaction of Phenanthrene

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with native and ionic liquid modified β-cyclodextrins: Preparation and

3

characterization in aqueous medium and solid state

4

Boon Yih Huia, Nur Nadhirah Mohamad Zaina, Sharifah Mohamadb,c, Samikannu

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Prabub,c, Hasnah Osmand, Muggundha Raoovb,c*

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a

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Malaysia, Pulau Pinang 13200, Malaysia

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Email: [email protected]; [email protected]

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b

Integrative Medicine Cluster, Advanced Medical & Dental Institute, Universiti Sains

Department of Chemistry, Faculty of Science,Universiti Malaya, Kuala Lumpur

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50603, Malaysia.

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c

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Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia

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Email: [email protected]; [email protected]

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d

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Malaysia

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Email: [email protected]

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*Corresponding Author. E-mail: [email protected] (M. Raoov)

Universiti Malaya Centre for Ionic Liquids (UMCiL), Department of Chemistry,

School of Chemical Sciences, Universiti Sains Malaysia, 11800, Pulau Pinang,

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Phone: +6003-79677022 (ext. 2544)

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Postal Address: Department of Chemistry, Faculty of

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Science, University of Malaya, 50603 Kuala Lumpur,

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Malaysia.

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24 1

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Abstract

26

The inclusion complexes of Phenanthrene with native βCD and ionic liquid modified

27

βCD were prepared and investigated in both solid and solution states. The formation

28

of the inclusion complexes were successfully monitored by FTIR, TGA, DSC, 1D 1H

29

NMR, 2D NOESY NMR and UV-vis spectroscopy. The results revealed that

30

Phenanthrene formed 1:1 a stoichiometry ratio for both host-guest inclusion

31

complexes with an apparent formation constant of 239.7 M-1 for native β-cyclodextrin,

32

which was higher than ionic liquid modified β-cyclodextrin (14.9 M-1). The NMR

33

studies showed that Phenanthrene penetrated into the cavity of both cyclodextrins

34

(CDs) from the more accessible wider side. For βCD, Phenanthrene displayed one

35

mode of binding, i.e., formation of an inclusion complex. Meanwhile, ionic liquid

36

modified β-cyclodextrin demonstrated two modes of binding, i.e. inclusion in the CD

37

cavities and interaction with the outer surface of the CD molecules, mainly near the

38

ionic liquid (IL) group.

39

Keywords:

40

Phenanthrene; Cyclodextrins; Ionic liquid; Host-guest inclusion complex

41

42

43

44

45

46 2

47

48

1.0

Introduction

49

Supramolecular chemistry is a branch of chemistry knowledge based on

50

molecular recognition to greater extent. It involves the selective binding orientation

51

between the host and guest. Among all the potential hosts, cyclodextrins (CDs) deem

52

to be the most promising which ideally fit various kinds of guest molecules with

53

suitable polarity and dimensions into their cavities [1,2]. CDs or cyclomaltoheptase [3]

54

are torus-shaped and macro [4], cylinder (conical cylinder) which occasionally

55

describe as doughnut or wreath-truncated cone cyclic oligosaccharides containing 6, 7

56

or 8 D-glucose units, namely α-, β-, and γ- CD respectively, linked by α-1,4-

57

glycosidic bonds [5,6]. However, β-cyclodextrins is the most largely produced CD

58

and widely employed in multiple sectors such as chemical products, food,

59

pharmaceutical and technologies [7], cosmetics, and environmental engineering [8].

60

Due to the presence of hydrophobic cavity, CDs allow the removal of organic

61

pollutants from aqueous solution when they are bound into CD cavities [9]. This

62

removal process forms a stable inclusion complexes through weak van der Waals,

63

hydrophobic, dipole–dipole, and hydrogen bonding interactions [10,11].

64

In order to widen the analytical applications, CDs are ready to be chemically

65

modified to improve both their physical and chemical properties. Herein, ionic liquids

66

(ILs) that exhibit non-flammability, non-volatility, and high thermal stability

67

properties are example of an excellent functional group that has been investigated

68

extensively. Because of their versatile nature, ILs are regarded as “designer solvents.”

69

They have either been directly used or engineered to improve sensitivity, selectivity,

70

and detection limit in analytical applications [12]. As such, ILs functionalized CDs as 3

71

a supramolecular composite, do not only retain the hydrophobic cavity of CDs, but

72

the modified groups can also improve their functionality and complexity [13].

73

By considering the combination merits of CDs and ILs, their exploitation have

74

increase lately, providing a new frontier in the discipline of analytical chemistry.

75

Various analytical applications have been reported based on CD-IL, owning to their

76

excellent and remarkable properties such as high ionic conductivity, large surface area,

77

and improved supramolecular recognition. However, fundamental studies that

78

described the molecular insight, particularly the interaction and binding conformation

79

between the CD-IL and target guests in solid and liquid state are less and lack

80

reported. Thus, a study is require in order to conceptualize and understand their

81

molecular recognition and interaction.

82

Polycyclic aromatic hydrocarbons (PAHs) are large groups of organic

83

compounds that originate from incomplete combustion (by engine exhaust, industrial

84

outlet, or crude oil) or pyrolysis of organic matter [14,15], and are widespread in the

85

environment as organic pollutants [16,17]. Due to their significant toxicity and

86

potential carcinogenic properties, 16 PAHs have been included in the list of persistent

87

organic pollutants (POPs) by the US Environmental Protection Agency (US

88

EPA)[18–20]. They have been detected as contaminants in different food categories,

89

such as dairy products, vegetables, fruits, oils, rice, cereals, grilled meat, coffee, and

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tea. Their presence is mostly resulted from the processing and cooking of the food

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[21–28]. Therefore, constant monitoring of these food contaminants is of prime

92

importance.

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Numerous efforts have been devoted for the development of analytical

94

techniques capable of rapid and sensitive detection of PAHs. However, PAHs usually 4

95

exhibit low solubility and bioavailability [29], which limit their removal or extraction

96

from the contaminated samples. Among various analytical methods used to pre-

97

concentrate PAHs, supramolecular CDs appear to be a particularly promising agent

98

through host-guest interaction as reported in our previous work [24]. These well

99

applications are contributed by the merit of CDs which are able to enhance the

100

solubility of contaminations [30,31], reduce their toxicity [32], and catalyse their

101

decomposition [33,34]. Moreover, CDs prevail others due to their biocompatibility,

102

environmental friendly and non-toxic properties [35]. Yet, to the best of our

103

knowledge, no literature mentions the inclusion complexation of PAHs with CD-IL.

104

There are but some reports with native CDs [29,36–38] or other hosts [39].

105

In order to examine the effect of ionic liquid modification towards the

106

encapsulation ability of Phenanthrene (belonging to the group of polycyclic aromatic

107

hydrocarbons) into the CD cavity, the present study was conducted along with the

108

comparison with native β-cyclodextrin to form inclusion complex. The preparation (in

109

solid and liquid state) and spectroscopy studies were successfully presented to

110

elucidate the binding behaviour and molecular interaction between the host and the

111

guest. The outcomes provided clear evidence that chemical functionalization

112

influenced the binding affinity of Phenantherene towards CDs.

113

2.

Material and methods

114

2.1

Materials

115

β-cyclodextrin (purity ≥ 99%) and Phenantherene (Phe, purity ≥ 99%) were

116

purchased from Dr. Ehrenstorfer GmbH (Augsburg, Germany) and used without

117

further purification. Ionic liquid modified βCD (βCD-IL) was synthesized based on

118

our prior work [24]. Other chemicals and reagents were of analytical reagent grade. 5

119

The stock solution of Phenanthrene (0.1 M) was prepared in acetonitrile, whereas the

120

working solution was prepared by diluting to the desired concentration using

121

deionized water. Different concentrations of βCD (0.001 to 0.01 M) and βCD-IL

122

(0.01 to 0.05 mM) stock solution were prepared in deionized water. All experiments

123

were carried out in deionized water and the solutions were prepared before subjected

124

to UV analysis.

125

2.2

Preparation of solid kneaded inclusion complex

126

Kneading method was employed to prepare the solid inclusion complex of

127

βCD and modified βCD with Phenanthrene [1]. Briefly, equimolar amount ratio (1:1)

128

of βCD and Phenanthrene were admixed and kneaded together with mortar and pestle

129

for 30 min. Minimum ethanol was added during the kneading process until dried

130

constant mass was obtained. White powdery product with 68% yield percentage or

131

total recovery was attained for both βCD and βCD-IL complexes and was determined

132

using the following equation [40]. The products obtained were dried and stored in a

133

desiccator for 48 h until further analysis.

134

Total recovery (%) = 



x 100

Eq 1



135

where M0 is the weight of recovery inclusion complex; M1 and M2 are the initial

136

weight of βCD or βCD-IL and Phenanthrene.

137

2.3

Preparation of liquid inclusion complex for spectroscopic study

138

The inclusion complex in aqueous solution was prepared by transferring 0.5

139

mL of 0.01 mM of Phenanthrene into 5 mL of 0.001 to 0.01 M of βCD solution or

140

into 0.01 to 0.05 mM of βCD-IL solution without pH adjustment. The mixture was

141

mixed in a vortex mixer for 30 s before subjected to UV analysis. 6

142

143

2.4

Physicochemical characterization of inclusion complex

144

Infrared analysis was conducted using Perkin Elmer Fourier Transform

145

Infrared (Spectrum 400 Perkin Elmer, Waltham, MA, USA) spectrometer with

146

transmission mode at wavenumbers ranging between 4000 and 450 cm-1. All the

147

samples were analyzed using diamond attenuated total reflection (ATR) accessory

148

with 10 scans at a resolution of ± 4 cm-1. The differential scanning calorimetry (DSC)

149

records were obtained with a differential scanning calorimeter (TA instruments, DSC

150

Q20). Approximately 4-5 mg of samples were heated at a ramp rate of 10℃ min-1

151

from 30 ℃ to 400 ℃ using an empty sealed aluminium pan as a reference. Dry

152

nitrogen was used as purge gas and the N2 flow rate was 20 mL min-1. The

153

thermostability profile of the samples was performed by using (TGA4000, Perkin

154

Elmer Waltham, MA, USA) with a temperature of 30 ℃ to 900 ℃ at a heating rate of

155

10 ℃ min-1 under nitrogen atmosphere. The formation of inclusion complex was

156

characterized by performing 1D 1H NMR and 2D 1H NMR NOESY using JEOL

157

JNM-ECX400II spectrometer with DMSO-d6 as a solvent at 25℃. Tetramethylsilane

158

(TMS) was used as internal reference and chemical shift was expressed in ppm.

159

2.5

160

complexes The stoichiometry of the βCD and βCD-IL inclusion complex was obtained

161 162

163

Determination of stoichiometry and binding constant of inclusion

from the Benesi–Hildebrand equation [41] given below:  





=  +   

Eq 2

 []

7

164

 

=

  

+



Eq 3

   [ ]

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In the above equations, A0 is the intensity of absorption of the guest without βCD or

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βCD-IL, A is the absorbance with a particular concentration of βCD or βCD-IL, A’ is

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the absorbance at the maximum concentration of βCD or βCD-IL used and K is the

168

apparent formation constant. Linearity is obtained in the plot of versus [] for







169





βCD and versus [ ] for βCD-IL. 

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On the other hand, the binding constant or apparent formation constant (K) and

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stoichiometry of the βCD and βCD-IL inclusion complex were obtained from the

172

following Benesi–Hildebrand equation:

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K= 

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The reaction between a guest (G) and a host (CD) is given below:

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mG + nCD ↔ Gm-CDn

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Where, n is the stoichiometry.



Eq 4

 !  

Eq 5

177 178

3.

Results and Discussion

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3.1

Physicochemical characterization of inclusion complex

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3.1.1

Fourier-Transom Infrared (FTIR) Analysis

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The variations of the absorption peaks such as intensity, shape, or shift in the

182

wavenumber of the guest or host, can give sufficient information for the inclusion

183

complex formation [42]. For example, the non-covalent interactions between βCD,

184

βCD-IL, and Phenanthrene, namely, van der Waals and hydrophobic interactions will 8

185

lower the energy of the included part of Phenanthrene upon inclusion complex. Thus,

186

this will reduce the absorption intensities or frequency of the corresponding bonds

187

[43,44].

188

Figure 1 (A) and Figure 1 (B) show the IR spectra of βCD, βCD-IL,

189

Phenanthrene, and their inclusion complexes. The OH group stretching vibrations at

190

3307 cm-1 and 3299 cm-1 and C-H asymmetry and symmetry stretching at 2924 cm-1

191

and 2925 cm-1 were characteristic peaks belonging to βCD and βCD-IL, respectively

192

[45,46]. The H-O-H deformation bands of water molecules present in both βCD and

193

βCD-IL were observed at 1657 and 1661 cm-1 [47]. Other intensive bands displayed

194

by βCD and βCD-IL were within the range of 1025-1153 cm-1, which were

195

contributed to the primary and secondary C-OH vibration stretching and C-O-C

196

vibration stretching (Zhang, Liu, Lumei, & Wen, 2005). Furthermore, the absorption

197

band at 1385 cm-1 signify the presence of IL (C=N) in βCD-IL [24] .

198

Meanwhile, the IR spectrum of Phenanthrene showed its characteristic band at

199

815, 728, and 711 cm-1, which were denoted to the bending vibration of Ar-H of the

200

Phenanthrene conjugate system. Another band at 1428 cm-1 was assigned to Ar C=C

201

of Phenanthrene.

202

By comparison, the frequency bands with the kneaded samples characteristic

203

of the Phenanthrene were further weakened, indicative of the inclusion process [48].

204

Evidently, the intensity of the –OH band was reduced upon the formation of inclusion

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complex [49] for βCD-Phenanthrene and βCD-IL-Phenanthrene as displayed in

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Figure 1. The characteristic stretching of H-O-H deformation bands of water

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molecules at 1657 cm-1 and 1661 cm-1 reduced and blue shifted to 1640 cm-1 and 1657

9

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cm-1 in the inclusion complex due to the encapsulation of the Phenanthrene benzene

209

ring into the hydrophobic cavity of βCD and βCD-IL [50].

210

In addition, the intensity of the absorption band at 1428 cm-1 and 1385 cm-1

211

was reduced or disappeared (Table S1) as the complex inclusion was formed,

212

suggesting that some molecular interactions might exist [46] between Phenanthrene,

213

βCD and βCD-IL . This was attributed to the changes in the microenvironment that

214

led to the possible formation of van der Waals force and hydrophobic interaction

215

during the inclusion process [1,51,52]. Restriction of the stretching vibration after the

216

formation of inclusion complex could also weaken and reduce the peak intensity [42].

217

The IR spectra of the inclusion complexes were similar to that of βCD and

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βCD-IL due to the low quantity of Phenanthrene in the system [42,53]. Several

219

variations were noticeable in the spectra. For example, the absorption bands at 815

220

cm-1 and 729 cm-1 were red shifted in the complex, whereas 711 cm-1 was blue shifted

221

as tabulated in Table S1 and S2, confirming the guest had been encapsulated into the

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cavity of βCD. The same observation was obtained for βCD-IL. These changes are

223

good indicators of an inclusion complex formation.

224

From the above discussion, it is confirmed that Phenanthrene was

225

encapsulated into the hydrophobic cavity of βCD and βCD-IL. It is speculated that

226

Phenanthrene probably interacted with the IL part of βCD-IL that was located at the

227

outer surface of the CD molecules mainly near the benzyl group, accounting to the

228

disappearance of band at 1385 cm-1 displayed in the βCD-IL inclusion complex

229

spectra. Nevertheless, greater wavenumber changes were observed in βCD-

230

Phenanthrene, suggesting stronger host-guest interaction as compared to βCD-IL-

231

Phenanthrene. 10

Figure 1

232

233

234

235 236

3.1.2

Thermogravemetric Analysis (TGA) The thermal properties of Phenanthrene, βCD, βCD-IL, and their inclusion

complexes were investigated by TG methods shown in Figure 2.

237

Phenantherene presented a single weight loss in the temperature of 260 ℃,

238

while, βCD and βCD-IL displayed weight loss at two different temperatures. The first

239

weight loss at 109 ℃ and 72 ℃ was due to the loss of water molecules from the

240

cavity, whereas the subsequent weight loss at 380 ℃ and 260 ℃ was due to the

241

decomposition of the macrocycles [54]. It is interesting to point out that the

242

modification of βCD shifted the decomposition temperature of βCD-IL to a lower

243

temperature region, which confirmed the presence of IL.

244

However, the single weight loss of Phenantherene in both βCD and βCD-IL

245

inclusion complexes was decreased to 200 ℃, with significantly lower intensity might

246

be ascribed to the dilution of Phenantherene with β-cyclodextrin [46] and

247

displacement of water molecules in cavity by Phenantherene [48], strongly suggesting

248

the occurrence of inclusion complex.

249

Apparently, the inclusion complex reduced the thermal stability of

250

Phenantherene, but there was no effect towards βCD and βCD-IL. This phenomenon

251

was in agreement with the previous reported works that observed reduction in peak

252

intensity and shifting of the temperature of guests and hosts or disappearance of the

253

guest peak after the inclusion complex [1,46,55,56]

254

Figure 2 11

255

256

257

3.1.3

Differential Scanning Calorimetry (DSC) Analysis

258

The physical properties of guest molecules such as boiling, melting or

259

sublimation points may differ from their natural behaviour as they were included into

260

the cavities of CD. Variations such as shifting or disappearance of the peaks are

261

general characteristics for the formation of inclusion complex [57,58]. The DSC

262

curves of βCD, βCD-IL, Phenanthrene, and their inclusion complexes are presented in

263

Figure 3.

264

The DSC curve of Phenanthrene exhibited a strong and sharp endothermic

265

peak at 102 ℃ indicating the melting point of Phenanthrene. The typical endothermic

266

peaks of βCD at first were shown at 139 ℃, corresponding to the dehydration process,

267

followed by an irreversible solid–solid phase transition [59,60] and finally,

268

degradation process, which took place at around 311 ℃ [61]. However, in the DSC

269

curve of the inclusion complex, the strong endothermic peaks corresponding to the

270

free Phenanthrene disappeared, and the endothermic peak, attributing to the free CD

271

shifted to 146 ℃ and 315 ℃ with reduced intensity, respectively. The shifting

272

occurred most probably due to the changes of water molecules energy when

273

Phenanthrene entered the cavity [4]. Whereas, the reduction of intensities indicated

274

the amorphous character of both samples after the encapsulation of Phenanthrene

275

within the cavity of the βCD molecule, consequence of the formation of true inclusion

276

complex [62,63]

12

277

For βCD-IL, the loss of crystallized water from the cavity exhibited a broad

278

endothermic peak at around 165 ℃ and a sharp melting peak at 228 ℃ , which

279

ascribed to the presence of IL substituent in the βCD-IL complex. By analyzing the

280

DSC curve of the inclusion complex, it can be observed that bands of endothermic

281

peaks were shifted to 151 ℃ and 229 ℃, respectively. Meanwhile, shifting in melting

282

peak positions of Phenanthrene was observed from 102 ℃ to 99℃ with a significant

283

reduce peak intensity [64]. This may contribute to the dilution effect of βCD-IL that

284

caused a sharp decrease in the intensity of the melting peak and shifted towards a

285

lower temperature [65].

286

Nonetheless, DSC results revealed that Phenanthrene displayed a stronger

287

host-guest interaction with native βCD as compared to IL modified βCD since both of

288

the endothermic peaks in Figure 3 (A)c shifted to a higher temperature than the host

289

in Figure 3(A)a after the formation of inclusion complex. Figure 3

290

291

3.1.4

1D 1H NMR measurements

292

To further investigate the mechanism of guest encapsulation [51], such as

293

inclusion within the host cavity or external surface and to identify and characterize the

294

interacting groups involved during the inclusion complexation, 1H NMR study was

295

carried out.

296

The screening constant of the βCD protons inside the cavity (H3 and H5)

297

should be sensitive to the changed environment if a guest molecule was incorporated

298

into the CD cavity. Whereas, the chemical shifts of the hydrogen atoms on the outer

299

surface (H1, H2, H4, and H6) would be unaffected or experience only a minimum 13

300

shift [42]. In other words, chemical shift in the upfield and downfield values (#)

301

resulting from the chemical and electronic environment alternation of innate protons,

302

was a good indicator of inclusion complexation [47].

303

The present study compared the 1H NMR spectra of βCD, and βCD-IL and in

304

the presence and absence of Phenanthrene in order to elucidate the possible inclusion

305

mode of complexes. The chemical shifts are listed in Table 1 and Table 2, whereas

306

Figure 4 and Figure 5 illustrate the NMR spectra of free βCD, Phenanthrene, βCD-IL

307

and their complexes in support of the discussion. 1H NMR spectra of both inclusion

308

complexes depicted the proton peaks of βCD, βCD-IL, and Phenanthrene.

309

The protons located inside the βCD and βCD-IL cavities (H3 and H5) clearly

310

underwent significant guest-induced chemical shift changes as compared to those that

311

were exterior of the torus. Both H3 and H5 displayed downfield shift due to the

312

deshielding zone of the Phenanthrene benzene ring which was possibly generated by

313

hydrophobic interaction [66] and van der Waals force [42]. This was consistent with

314

the chemical structure of the hydrophobic Phenanthrene, where hydrogen bonding

315

was less likely to occur due to the absence of lone pair electrons on Phenanthrene.

316

On the other hand, the chemical shift values for H1, H2, H4, and H6 were only

317

slightly affected by Phenanthrene [50][67], which confirmed that Phenanthrene

318

mostly interacted with the inner side of the cavity as expected upon the inclusion

319

complex formation.

320

Furthermore, for βCD, the downfield shift of the H3 and H5 protons located in

321

the inner surface of the cavity was the most prominent as compared to the chemical

322

shifts displayed by βCD-IL. The higher deshielding effect was consistent with the

323

spectroscopic study, whereby the apparent formation constant for βCD proton was 14

324

higher than that of βCD-IL. This indicated that more Phenanthrene penetrated the

325

cavity of free βCD than βCD-IL. Nevertheless, the clear downfield shift (deshielding

326

effect) of the signals of H3 and H5 protons in both βCD and βCD-IL was attributed to

327

the magnetic anisotropy effects in the CD cavity due to the inclusion of a π-electron-

328

rich group of the Phenanthrene benzene ring into the host cavity [68]. Concurrently,

329

when Phenanthrene entered into the hydrophobic cavity of βCD and βCD-IL, the

330

change of the micro-environment of Phenanthrene led to the significant aromatic ring

331

upfield shift for βCD and downfield shift for βCD-IL.

332

The outer proton of IL substituents also experienced significant downfield

333

changes of chemical shift, suggesting some partial interactions of the Phenanthrene

334

molecules with the outer surface of βCD-IL. The results suggested that the outside

335

interactions particularly occurred near Ha, Hb, Hc and Hd of the vinyl group at the C-

336

6 position, mainly through $-$ interaction between benzene ring and double bond of

337

the IL group.

338

Thus, from the above discussion, it is interesting to propose that for βCD,

339

Phenanthrene only formed an inclusion complex. In contrast, for βCD-IL, two types

340

of binding modes including inclusion complex, and surface binding near the IL

341

substituents vinyl group. These findings are well corroborated with the results

342

obtained by the UV-Vis spectrophotometry.

343

Table 1

344

Table 2

345

Figure 4

346

Figure 5 15

347

3.1.5

2D NOESY NMR measurement

348

In order to confirm which part of aromatic guest penetrated into the CD cavity,

349

2D NOESY spectral study was carried out. Figure S1 and Figure S2 depicted the

350

expansion of 2D NOESY spectral data that showing 1H–1H cross connection peaks

351

between host βCD, βCD-IL and guest Phenanthrene.

352

NOESY data showed that all aromatic protons of Phenanthrene were close in

353

space to cavity proton (H3, H5), particularly a strong cross correlation peak between

354

H5’ and H6’ of Phenanthrene. This suggests that a molecular interaction existed,

355

whereby the benzene rings of Phenanthrene were included into the cavity of βCD.

356

Therefore, the spectra of NOESY were conclusive to present the encapsulation of

357

guest Phenanthrene into the hydrophobic cavity of βCD.

358

Apart from that, the cross peaks of βCD-IL (H3, H5) and Phenanthrene (H1’,

359

H3’, H8’, and H10’) demonstrated strong intensity. This strong correlation observed

360

suggested that the Phenanthrene benzene ring also exhibited a strong interaction with

361

βCD-IL. Furthermore, Ha, Hb, Hc and Hd of IL substituent group showed a cross

362

correlation peak with Phenanthrene but no peak was observed with He and Hf,

363

suggesting lower or no binding of Phenanthrene to that region. On the basis of the

364

aforementioned spectral data from 1D and 2D NMR, it is confirmed that βCD-IL

365

displayed two types of binding modes including inclusion complex and surface

366

binding near the ionic liquid group.

367

Overall, it can be affirmed that Phenanthrene formed 1:1 inclusion complex

368

from the wider side of the cavity in aqueous solution for βCD and βCD-IL,

369

respectively. The structure of the inclusion complexes were elucidated based on their

370

chemical shifts in ascending order (a, b, c) as shown in Figure 6 and Figure 7. 16

371

Figure 6

372

Figure 7

373

374

375

3.2

Absorption spectral characteristics of the inclusion complex

376

The maximum absorbance, shape of UV spectra and molar coefficient of the

377

studied compound strongly depend on the CD microcavity environments [69].

378

Therefore, absorbance spectroscopy was used to qualitatively assess the molecular

379

encapsulation behaviour of Phenanthrene into βCD and βCD-IL in aqueous solution.

380

The

381

Phenanthrene, βCD and βCD-IL were recorded, respectively according to the

382

procedures mentioned in Section 2.3.

absorption

spectra

of

βCD-Phenanthrene

and

βCD-IL-Phenanthrene,

383

No absorption was observed in the range of 220–280 nm for βCD as shown in

384

Figure S3, thus, its absorbance can be neglected [55,70]. Nevertheless, βCD-IL

385

(Figure S4) had slight absorption at about 260-270 nm.

386

The absorption spectrum shape of Phenanthrene (at λmax 250 nm) was similar

387

to that of βCD-Phenanthrene and βCD-IL-Phenanthrene inclusion complexes.

388

However, higher absorbance of the inclusion complexes was obtained at every

389

wavelength than that of Phenanthrene. Eventually, these data were conclusive and

390

rationalized to reflect the successful preparation of the inclusion complex [1,44].

391

In addition, the concentration effects of βCD and βCD-IL on Phenanthrene

392

were also examined and the outcomes are presented in Figure 8A and Figure 8B.

17

393

Since Phenanthrene exists at neutral pH, its absorption spectra were observed at 250

394

nm, with the addition of βCD and βCD-IL.

395

It is interesting to point out that the absorption intensity was observable as the

396

concentration of βCD and βCD-IL increased. After the inclusion of βCD and βCD-

397

IL into the cavity, the absorbance of the Phenanthrene molecule underwent

398

hyperchromic effect (increase in absorbance). This is due to the shielding of the

399

excited species from non-radiative processes that occur in the bulk solution, together

400

with an increase in the molar absorption coefficient of the inclusion complex [4]. The

401

transfer of Phenanthrene from more protic environments (bulk aqueous phases) to less

402

protic CD nano-cavity environments caused the spectral bands of Phenanthrene to

403

greater absorbance intensity, thus creating the hyperchromic shift [11]. This is a good

404

indicative of host guest interaction between βCD-Phenanthrene and βCD-IL-

405

Phenanthrene and the outcomes were in accordance to the previous literature that

406

absorbance of guest will increase upon the formation of inclusion complexes [71,72].

407

Nevertheless, the spectra of inclusion complex were slightly red shifted with a gradual

408

increase in absorbance upon increasing the concentration of βCD, but no shifting was

409

observed upon increasing the concentration of βCD-IL.

410

Figure 8

411

The binding constant and stoichiometry of the βCD and βCD-IL inclusion

412

complex were obtained from the Benesi–Hildebrand equations. The values obtained

413

in absorption were used in Benesi–Hildebrand equations for the 1:1 complex since the

414

changes in absorbance with the addition of βCD and βCD-IL were very small.

415

An apparent formation constant value for the inclusion complex can be

416

determined through the changes in the absorbance. The result is shown in Figure S5 18

417

and Figure S6, and the good linear relationship obtained (R2 = 0.9973 for βCD-

418

Phenanthrene and 0.9976 for βCD-IL-Phenanthrene) proved that the stoichiometric

419

ratio of both inclusion complexes was 1:1. The apparent formation constant was

420

determined to be 239.7 M-1 for βCD-Phenanthrene and 14.9 M-1 for βCD-IL-

421

Phenanthrene at pH 7 and 298 K. Native β-CD registered a greater formation constant

422

value thereby supporting the fact that Phenanthrene has a stronger binding affinity

423

towards β-CD as compared to βCD-IL. Table 3 summarizes the outcomes of the

424

binding parameters for both inclusion complexes.

425

Based on the findings, Phenanthrene showed higher binding affinity with βCD,

426

but relatively weaker binding with βCD-IL. It is inferred that the presence of IL

427

substituent groups on βCD-IL have participated during the complexation by forming

428

$ to $ interactions with Phenanthrene, creating a competition between the CD cavities

429

and IL substituents. In addition, Phenanthrene had higher surface contact with the IL

430

substituents since it was located externally. At the same time, steric hindrance

431

resulting from the chemical modification of IL could prevent the guests from

432

approaching the host cavities to form inclusion complexes, which led to a smaller

433

apparent formation constant obtained for βCD-IL. In other words, the existence of the

434

IL groups limited and restricted the insertion of the Phenanthrene molecules. This

435

supposition is confirmed by the low formation constant, 14.9 M-1, in which the results

436

were in good agreement with the NMR measurement. It is interesting to point out that

437

Phenanthrene is a non-polar compound which is favour to be bounded into the

438

hydrophobic cavity of native β-cyclodextrin as compared to IL modified β-

439

cyclodextrin. In short, the ionic liquid functionalization and the nature of guests do

440

influence the molecular orientation of the β-CD during the inclusion process.

19

Table 3

441 442 443

4.0

Conclusion

444

In the present work, Phenanthrene formed inclusion complexes with both

445

native β-cyclodextrin and ionic liquid modified β-cyclodextrin, with a 1:1

446

stoichiometry, prepared by kneading method. The formation of solid complexes were

447

successfully investigated by 1D and 2D 1H NMR, FTIR, TGA and DSC analysis,

448

which suggested Phenanthrene molecules were included completely into both cavities.

449

It is proposed that for βCD, Phenanthrene showed one mode of binding, i.e. formation

450

of an inclusion complex. Meanwhile, for modified βcyclodextrin, it showed two

451

modes of binding, i.e. inclusion in the CD cavities and interaction with the outer

452

surface of the CD molecules mainly near the IL group. The spectroscopic study

453

demonstrated that Phenanthrene molecules exhibited a higher binding constant (239.7

454

M-1) towards native β-cyclodextrin as compared to modified β-cyclodextrin (14.9 M-1).

455

The outcomes from characterization studies also suggested that βCD-Phenanthrene

456

displayed stronger supramolecular host-guest interaction than that of βCD-IL-

457

Phenanthrene. This study concluded that host-guest complexation is a dependent

458

process. Functionalization of ionic liquid affect the molecular orientation of β-

459

cyclodextrin and Phenanthrene during the binding process.

460

Conflict of interest

461

The authors declare no conflict of interest.

462

Acknowledgement

463

This work was supported by the University Malaya Faculty Research Grant,

464

(GPF058B-2018), Fundamental Research Grant Scheme, Ministry of Higher 20

465

Education (MOHE), Malaysia (FRGS, FP071-2018A), and Malaysian Pharmaceutical

466

Industries (MPI) Sdn. Bhd.

467

468

469

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27

1

A comprehensive molecular insight into host-guest interaction of Phenanthrene

2

with native and ionic liquid modified β-cyclodextrins: Preparation and

3

characterization in aqueous medium and solid state

4 5

Boon Yih Huia, Nur Nadhirah Mohamad Zaina, Sharifah Mohamadb,c, Samikannu

6

Prabub,c, Hasnah Osmand, Muggundha Raoovb,c*

7

a

8

Malaysia, Pulau Pinang 13200, Malaysia

9

Email: [email protected]; [email protected]

Integrative Medicine Cluster, Advanced Medical & Dental Institute, Universiti Sains

10

b

11

50603, Malaysia.

12

c

13

Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia

14

Email: [email protected]; [email protected]

15

d

16

Malaysia

17

Email: [email protected]

18

*Corresponding Author. E-mail: [email protected] (M. Raoov)

Department of Chemistry, Faculty of Science,Universiti Malaya, Kuala Lumpur

Universiti Malaya Centre for Ionic Liquids (UMCiL), Department of Chemistry,

School of Chemical Sciences, Universiti Sains Malaysia, 11800, Pulau Pinang,

19

Phone: +6003-79677022 (ext. 2544)

20

Postal Address: Department of Chemistry, Faculty of

21

Science, University of Malaya, 50603 Kuala Lumpur,

22

Malaysia.

23

24

1

25 26

Table 1. 1H chemical shifts values corresponding to the βCD, Phenanthrene and inclusion complex of βCD and Phenanthrene. Proton

βCD (ppm)

H1 H2 H3 H4 H5 H6 H1’ H2’ H3’ H4’ H5’ H6’ H7’ H8’ H9’ H10’

4.789 3.330 3.570 3.330 3.505 3.617

Phenanthrene (ppm)

8.829 7.676 7.646 7.996 7.843 7.843 7.997 7.628 7.695 8.809

27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42

2

Inclusion Complex (ppm) 4.832 3.332 3.619 3.332 3.563 3.637 8.832 7.704 7.668 7.998 7.487 7.487 7.980 7.695 7.684 8.813

∆ (ppm) +0.043 +0.002 +0.049 +0.002 +0.058 +0.020 +0.003 +0.028 +0.022 +0.022 -0.356 -0.356 +0.003 +0.022 -0.011 +0.004

43 44

Table 2. 1H chemical shifts values corresponding to the βCD-IL, Phenanthrene and inclusion complex of βCD-IL and Phenanthrene. Proton H1 H2 H3 H4 H5 H6 H8 H9 H11 Ha Hb Hc Hd He Hf H1’ H2’ H3’ H4’ H5’ H6’ H7’ H8’ H9’ H10’

βCD-IL (ppm)

Phenanthrene (ppm)

4.790 3.309 3.529 3.346 3.504 3.529 7.443 7.081 2.246 5.520 5.488 4.495 7.907 7.829 7.270 8.829 7.676 7.646 7.996 7.843 7.843 7.997 7.628 7.695 8.809

Inclusion Complex (ppm) 4.793 3.310 3.571 3.351 3.547 3.541 7.467 7.103 2.244 5.654 5.686 4.530 7.948 8.844 7.686 7.672 8.002 7.851 7.851 7.983 7.654 7.686 8.823

∆ (ppm) +0.003 +0.001 +0.042 +0.005 +0.043 +0.012 +0.024 +0.022 -0.002 +0.134 +0.198 +0.035 +0.041 +0.015 +0.010 +0.026 +0.006 +0.008 +0.008 +0.006 +0.026 -0.009 +0.014

45 46

Table 3. Binding parameters of both inclusion complexes

βCD-Phenanthrene

Apparent formation constant (M-1) 239.7

βCDIL-Phenanthrene

14.9

Inclusion Complex

47

48 49 50 3

Correlation of determination

Stoichiometry ratio

0.9973

1:1

0.9976

1:1

1

A comprehensive molecular insight into host-guest interaction of Phenanthrene

2

with native and ionic liquid modified β-cyclodextrins: Preparation and

3

characterization in aqueous medium and solid state

4

Boon Yih Huia, Nur Nadhirah Mohamad Zaina, Sharifah Mohamadb,c, Samikannu

5

Prabub,c, Hasnah Osmand, Muggundha Raoovb,c*

6

a

7

Malaysia, Pulau Pinang 13200, Malaysia

8

Email: [email protected]; [email protected]

9

b

Integrative Medicine Cluster, Advanced Medical & Dental Institute, Universiti Sains

Department of Chemistry, Faculty of Science,Universiti Malaya, Kuala Lumpur

10

50603, Malaysia.

11

c

12

Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia

13

Email: [email protected]; [email protected]

14

d

15

Malaysia

16

Email: [email protected]

17

*Corresponding Author. E-mail: [email protected] (M. Raoov)

Universiti Malaya Centre for Ionic Liquids (UMCiL), Department of Chemistry,

School of Chemical Sciences, Universiti Sains Malaysia, 11800, Pulau Pinang,

18

Phone: +6003-79677022 (ext. 2544)

19

Postal Address: Department of Chemistry, Faculty of

20

Science, University of Malaya, 50603 Kuala Lumpur,

21

Malaysia.

1

(A)

22 23

(B)

24 25 26

Fig. 1 FTIR spectra of (A) (a) βCD; (b) Phenanthrene; and (c) their solid inclusion complex; (B) (a) βCD-IL; (b) Phenanthrene; and (c) their solid inclusion complex

27

28 2

29

(A)

(B)

30

31

32

33

34

(C)

35

36

37

38

39

(D)

(E)

40

41

42

43

44

45 46 47

Fig. 2 (a) TGA and (b) DTG thermogram of (A) βCD; (B) Phenanthrene; (C) inclusion complex of βCD-Phenanthrene; (D) βCD-IL; and (E) inclusion complex of βCD-IL-Phenanthrene

48

3

(A)

49

(B)

50 51 52 53

Fig. 3 The DSC curves of (A) (a) βCD; (b) Phenanthrene; and (c) inclusion complex of βCD with Phenanthrene; (B) (a) βCD-IL; (b) Phenanthrene; and (c) inclusion complex of βCD-IL with Phenanthrene

4

Fig. 4 1H NMR spectra of (a) βCD; (b) Phenanthrene; and (c) inclusion complex of βCD and Phenanthrene in DMSO-d6

5

Fig. 5 1H NMR spectra of (a) βCD-IL; (b) Phenanthrene; and (c) inclusion complex of βCD-IL and Phenanthrene in DMSO-d6

6

(a)

(b)

(c)

Fig. 6 The proposed structures of inclusion complex between βCD and Phenanthrene

Fig. 7 The proposed structures of inclusion complex between βCD-IL and Phenanthrene

7

(A)

(B)

Fig. 8 (A) Absorption spectra of Phenanthrene with various concentration of βCD. From lines (a) to (g): 0 M; 0.001 M; 0.003 M; 0.005 M; 0.006 M; 0.008 and 0.010 M; (B) Absorption spectra of Phenanthrene with various concentration of βCD-IL. From lines (a) to (e): 0 M; 0.01 mM; 0.03 mM; 0.04 mM and 0.05mM , both complex at pH 7, T = 298 K

8

Research Highlights •

Inclusion complex of Phenanthrene with native and βCD-IL were analyzed in aqueous medium and solid state

•

FT-IR, TGA/DSC, 1D 1H and 2D NOESY NMR analysis confirmed the complexes formation

•

UV-vis spectroscopy suggested Phenanthrene formed 1:1 stoichiometry complexes

•

Complexes of Phenanthrene with native βCD showed higher binding constant than βCD-IL

Author contributions Boon Yih Hui: Writing - Original Draft, Investigation, Formal analysis. Nur Nadhirah Mohamad Zain: Supervision. Sharifah Mohamad: Writing-Review & Editing, Supervision. Samikannu Prabu: Software. Hasnah Osman: Supervision. Muggundha Raoov: Supervision, Funding acquisition, Writing - Review & Editing

Declaration of interests ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: