Copper (II) Schiff Base

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Synthesis, characterization of Chlorpyrifos/Copper(II) Schiff Base Mesoporous Silica with pH-sensitivity for pesticide sustained released Huayao Chen, Yueshun Lin, Hongjun Zhou, Xinhua Zhou, Sheng Gong, and Hua Xu J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.6b03262 • Publication Date (Web): 07 Oct 2016 Downloaded from http://pubs.acs.org on October 15, 2016

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Journal of Agricultural and Food Chemistry

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Synthesis, characterization ofChlorpyrifos/Copper(II) Schiff Base Mesoporous

2

Silica with pH-sensitivity for pesticide sustained released

3

Chen Huayao, Lin Yueshun, Zhou Hongjun*, Zhou Xinhua*,Gong Sheng, Xu Hua,

4

（College of Chemistry and Chemical Engineering, Zhongkai University of Agriculture and

5

Engineering, Guangzhou 510225, Guangdong, China）

6

Abstract: The salicylaldehyde modified mesoporous silica (SA-MCM-41) was

7

prepared through a co-condensation method. Through the bridge effect from copper

8

ion which also acts as the nutrition of the plant, the

9

was supported on the copper(II)/Schiff base mesoporous silica (Cu-MCM-41) to form

10

a highly efficient sustained released system (CH-Cu-MCM-41) for pesticide delivery.

11

The experimental results showed that the larger the concentration of copper ion was,

12

the more adsorption capacity (AC) of Cu-MCM-41 for chlorpyrifos was and the

13

smaller its release rate was. The results confirmed the existence of coordination bond

14

between SA-MCM-41 and copper ions as well as the coordination bond between

15

Cu-MCM-41 and chlorpyrifos. The AC of SA-MCM-41 is 106 mg/g, while the

16

Cu-MCM-41 is 295 mg/g.

17

sensitivity. Under the condition of pH≤7, the release rate of chlorpyrifos decreased

18

with increasing pH. Whereas, its release rate in weak base condition was slightly

19

larger than in weak acid condition. Meanwhile, the drug release rate of the

20

as-synthesized system was also affected by temperature. Their sustained-release

21

curves can be described by Korsmeyer-Peppas equation.

model drug- chlorpyrifos(CH)

The as-synthesized system showed significant pH

1


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Key words: Copper(II) Schiff base; MCM-41; pH sensitive; sustained-release

23 24

INTRODUCTION

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Nowadays, porous and highly dispersed materials have attracted significant

26

attention.1 Among various types of these materials, ordered mesoporous materials are

27

much more attractive2-4

28

nm in accordance with IUPAC recommendation.5 Mesoporous silica is one of the

29

most important type and a widely studied mesoporous materials. Synthesis of

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mesoporous silica materials is usually through the aids of specific organic templates

31

(i.e., surfactant-types).6 For example, cetyltrimethylethyl ammonium bromide (CTAB)

32

is a surfactant commonly used for the synthesis of MCM-41.7 Mesoporous silica

33

materials have already been applied in many fields including sensors and separations,8

34

catalysis,9 novel functional materials,10 selective adsorption11 as well as being a host

35

to guest molecules.12

due to their uniform and adjustable pore sizes of 2 nm to 50

36

These silica materials are potential candidates for sustained release application

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for their good chemical and thermal stability, morphology control, and surface

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functionalization. Controlled delivery of pharmaceutical active agents, as well as drug

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delivery and imaging has been mentioned in the literatures.13-15 Efficiency of

40

alendronate loading and release was compared between two mesoporous silica

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matrixes of SBA-15 and MCM-41 in another research. The results showed that

42

MCM-41 loaded more drug than SBA-15, which could potentially be subscribed in 2



43

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part to the larger surface area of the former.16

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Since these pioneering investigations, the interests in using MCM-41 as drug

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delivery systems have shown significant growth.17-19 The main reason for using

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mesoporous silica materials as drug delivery systems was due to their high ordered

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pore network and the high pore volume which provides more opportunity for hosting

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considerable quantities of drugs. What’s more, the ordered network with

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homogeneous size enables the fine control of the release kinetics and drug load. A

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novel utilization of MCM-41 for delivery of ibuprofen was reported in 2001.20

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Following this research, MCM-41 modified with amine groups was also studied for

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ibuprofen delivery systems and resulted in better release kinetics.21

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synthesis and surface modification of MCM-41 by aminopropyl groups on the

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immobilization and subsequent release of acetylsalicylic acid was studied in several

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papers,22-23 in which MCM-41 materials were functionalized through the

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co-condensation method, post-synthesis treatment and solvothermal processes.

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Meanwhile, the preparation of sustained released system with pH sensitivity

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coordinated with metal ion which acts as a bridge to improve its adsorption and

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sustained release performance were also frequently reported.24-27 However, the study

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in this sustained released system based on MCM-41 coordinated with metal for the

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pesticide delivery was rarely reported.

62 63

The influence of

Based on the research mentioned above, we proposed the pH responsive chlorpyrifos/copper

Schiff

base

modified mesoporous 3


silica

(Cu-MCM-41)

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sustained release system, which was prepared by the coordination of copper ions

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through impregnation method. The cetyl trimethyl ammonium bromide（CTAB）was

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adopted as template and tetraethyl orthosilicate (TEOS) as silica source respectively.

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The self-made salicylaldimine was used as organic modifying agent to prepare

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salicylaldimine modified mesoporous silica by co-condensation method. Through the

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bridge effect from copper ion which also acts as the nutrition of the plant, a model

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drug(chlorpyrifos) was supported on the Schiff base modified mesoporous silica.

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Besides, the system showed pH sensitivity which is useful for the pest control in

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agriculture.7, 28, 29 The relationship between the copper ion concentrations with its

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adsorption and sustained released performance was also investigated. Finally, the

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highly efficient sustained release system with pH-sensitivity for pesticide delivery

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was developed which would thus be expected to bring significant impact in

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agricultural fields for pest control.

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MATERIALS AND METHODS

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Chemicals

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Cetyl trimethyl ammonium bromide (CTAB), tetraethyl orthosilicate (TEOS)，

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ethanol, dichloromethane, anhydrous magnesium sulfate, ammonia, copper

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nitrate, sodium hydroxide, hydrochloride were obtained from Tianjin Damao

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Chemical Reagents. 3-aminopropyltriethyloxy silane (APTES), salicylaldehyde were

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obtained from Aladdin. And chlorpyrifos (Jiangsu Jinghong Chemical Engineering

84

Co., Ltd.) were also used in this work. All chemicals were analytical grade and used 4



85 86

as received without any further purification. Preparation of salicylaldimine

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According to the literature7, 4.42 g of APTES, 2.44 g of salicylaldehyde and 100

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mL of ethanol were added into a flask and reacted at 95 °C for 3 h. Ethanol was

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removed by rotary evaporated, and 20mL of dichloromethane was added, then the

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products washed with deionized water 3 times. The organic layer was extracted and

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standing for 12 h. Then the product was filtered to remove dichloromethane to attain

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salicylaldimine.

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Preparation of SA-MCM-41

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According to previous research,30 co-condensation method was adopted to

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prepare salicylaldehyde modified mesoporous silica (SA-MCM-41). 1.0 g of CTAB,

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100 mL deionized water and 70 mL of ammonia were added to the flask to be

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dissolved at 60 ℃ with stirring. And 5 g of TEOS was added to the solution

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dropwise. 1 hour later, 1g of as synthesized salicylaldimine was added and kept on

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reacting for 6 h before being crystalized at room temperature, filtered, washed and

100

dried. Finally, the template was removed by ethanol to attain SA-MCM-41.

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Preparation of Cu-MCM-41

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20 mL of copper nitrate solution with different concentration（0.3, 0.6 and 1.2

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mol/L）was added to 200mg of SA-MCM-41 at 35℃ under stirring for 24 h. Then

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Cu-MCM-41 was attained after being filtered, washed and dried. The Copper ion

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loading amount of

0.174 mmol/g, , 0.244 mmol/g and 0.286 mmol/gwas confirmed 5


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by ICP-AES.

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Preparation of CH-Cu-MCM-41

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The

supported

chlorpyrifos

was

prepared

via

impregnation.

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Cu-MCM-41(prepared in 1.2 mol/L copper nitrate solution) was activated under

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vacuum at 80 ℃ for 6 h. And 100 mg of samples was immersed in 20 mL of

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chlorpyrifos ethanol solution (10 mg/mL) at 35 ℃ under stirring for 24 h, then

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filtered, washed, and dried. The obtained products was denoted as CH-Cu-MCM-41.

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Structural Characterization of Particles

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The samples were analyzed using a Bruker AXS D8 X-ray diffractometer

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(Bruker AXS GmbH, Karlsruhe, Germany) with Cu radiation (λ=1.5418 Å) and a

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graphite monochromator at 25℃, 40 kV, and 30 mA. The measurements were scanned

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at 2°/min (angular range 2θ = 0.5~10°) in 0.02° step size. The morphology of the

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particles was analyzed by a Spectrum100 Fourier infrared spectrometer (PerkinElmer

119

Inc., USA) by using the KBr squash technique. The gold particles were sprayed on the

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surface of samples under protection of N2 and the samples were characterized by an

121

S4800 scanning electron microscope (Hitachi, Japan) to observe the surface

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topography. TEM observation was conducted on a FEI Tecnai G2 F20 transmission

123

election microscope. BET surface area of samples was determined by N2 adsorption

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isotherms at 77 K, operated on Quadrasorb SI adsorption equipment. The samples

125

were degassed at 200 oC for 12 h in vacuum before N2 adsorption experiment. A Q200

126

differential scanning calorimeter (TA Co., USA) was used to conduct differential 6



127

scanning calorimetry and detect the crystalline degree of the chlorpyrifos in the

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particles over a heating range of 20~160 ℃ and a heating rate of 20 ℃/min. An

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SDT-Q600 thermogravimetric analyzer (TA Co., USA) was used to analyze the heat

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stability of particles over the heating range of 30~800 ℃ and heating rate of 10 ℃

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/min. X-ray photoelectron spectra (XPS) were recorded on a ESCALAB250XI

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spectrometer (Thermo Fisher Scientific, Al Kα, hν = 1486.6 eV) under a vacuum of

133

~2×10-7 Pa. Charging effects were corrected by adjusting the main C 1s peak to a

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position of 284.8 eV. The loading amount of copper ion was confirmed by Inductively

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Coupled Plasma-atomic Emission Spectrometry (Agilent 725).

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Adsorption Properties Test

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A UV-2550 UV-Vis spectrophotometer from Shimadzu Co., Japan, was applied

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to measure the amount of chlopyrifos adsorbed by mesoporous silica. Linear

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regression of the solution concentration (C) and absorbance (A) of chlorpyrifos

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standard solutions of different concentrations at λ=290 nm was performed to obtain a

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standard curvilinear equation: C=61.356A-0.0613，R2=0.9997. UV spectroscopy was

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performed to measure the absorbance of this solution before and after the adsorption

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in chlopyrifos ethanol solution. Adsorption capacity (AC) and loading content (LC)

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may be calculated by the following equation:

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（C - C ) × V AC = 0 1 m

LC =

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（1）

（C0 - C1 ) × V m × 1000 +（C0 - C1 ) × V

（2）

7


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where C0 is the origin mass concentration (mg/L) of the chlorpyrifos in ethanol

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solution, C1 is the mass concentration (mg/L) of the chlorpyrifos in ethanol solution

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after adsorption, and m is the mass(g) of mesoporous silica.

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Sustained-Release Performance Test

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The performance of sustained-release chlorpyrifos particles was tested according

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to the reference. 31 Linear regression of the solution concentration (C) and absorbance

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(A) of chlorpyrifos in 40% ethanol solutions of different concentrations at λ=284 nm

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was performed to obtain a standard curvilinear equation: C=48.672A+0.0322，

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R2=0.9994. The (M1, mg) drug-loaded particles were weighed and placed in a conical

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flask filled with 50 mL of 40% ethanol. At intervals of (t), 1 mL of the sample

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solution was transferred and diluted to 25 mL. An equal volume of the original

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sustained-release solution was then added to the conical flask to replace the

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withdrawn sample. The absorbance of the 25 mL solution was obtained, and the

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cumulative release amount of chlorpyrifos was calculated as Ri. A t–Ri curve was

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drawn to study the release kinetics of chlorpyrifos. Ri was calculated as follows:

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 ρ i × 0.1  M × LC (i = 1)  1 i −1 Ri =   ρ × 0.1 ∑ ρ i × 0.002  i + i =1 (i = 2,3,4...)  M 1 × LC M 1 × LC

where ρi is the mass concentration (mg/L) of chlorpyrifos for each sampling.

164 165

（3）

RESULTS AND DISCUSSION 8



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Characterization of Mesoporous materials

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Fig. 1 shows the XRD patterns of MCM-41, Cu-MCM-41, SA-MCM-41 and

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CH-Cu-MCM-41. There are three characteristic peaks shown in MCM-41, which

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could be ascribed to (100), (110) and (200) crystal face respectively, which indicated

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that the particles had regular hexagonal pore structure.32 As modified by

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salicylaldehyde, the strength of the XRD peaks decreased, especially in (110) and

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(200) crystal face, which proved that APTES was introduced to the system and

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decreased its degree of orderliness.33 And the loading of copper ion and chlorpyrifos

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didn’t change its structure indicating that the regular hexagonal pore structure

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remained in Cu-MCM-41.

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Figure 2 depicts the SEM and TEM image of MCM-41 (a&b) and

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SA-MCM-41(c&d). As shown, the regular hexagonal pore structure was well-

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maintained without agglomeration after salicylaldehyde modification which was in

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consistent with the XRD results.

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As shown in Figure 3, the N2 adsorption/desorption isotherms of MCM-41,

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SA-MCM-41, Cu-MCM-41and CH-Cu-MCM-41 belong to Langmuir Ⅳ(the slope of

182

it was decreasing) with H4 hysteresis loop (hysteresis loop was closed at P/Po-=0.4)

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which confirmed their mesoporous structure according to the previous report34.

184

What’s more, the salicylaldehyde modification, coordination with copper ion and

185

loading of chlorpyrifos would significantly decrease its BET surface and pore volume,

186

but draw slight effect on the pore size as shown in Table 1.

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FTIR was carried out to compare the different composition of MCM-41,

188

SA-MCM-41, Cu-MCM-41 and CH-Cu-MCM-41. As shown in figure 4, two bands 9


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appeared in 3420 cm-1 and 960 cm-1 for MCM-41 ascribed to stretching and bending

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vibration of Si-OH respectively.35 1083 cm-1 and 810 cm-1 were attributed to the

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characteristic peaks of Si-O-Si on the SiO2 framework. Comparing to MCM-41, two

192

new bands appeared at 2981 cm-1 and 2936 cm-1 belonging to the symmetric and

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nonsymmetric C-H stretching vibration bands from aminopropyl group for

194

SA-MCM-41. And stretching band of C=N and the vibration band of benzene ring in

195

the salicylaldehyde located at 1628 cm-1 and 780 cm-1 respectively. The blue shift of

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C=N from 1628 cm-1 to 1635cm-1 happened after the coordination with copper ion.

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And the weak band at 669 cm-1 for Cu-MCM-41 was the vibration caused by the

198

coordination between copper and nitrogen which further convinced the coordination

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between copper ion and Schiff base. For CH-Cu-MCM-41,

200

of chlopyrifos located at 1547, 1412, 1339, 678 cm-1 which proved that the

201

chlopyrifos was successfully adsorbed by Cu-MCM-41.

the characteristic peaks

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The XPS analysis was carried out to identify the surface elements chemical states,

203

as shown in Figure 5. The binding energy (BE) positive shift of N 1s was observed

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after the coordination of copper ion, with a BE value of 399.20 eV for Cu-MCM-41 in

205

comparison with the BE of 399.59 eV for SA-MCM-41. The electron transfer from

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nitrogen to copper was proposed to be responsible for this positive shift. What’s more,

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a new peak appeared at 406.5eV for the nitrate residue during the preparation. And the

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binding energy (BE) of copper ion decreased from 934.48 eV to 933.35 eV after

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loading chlorpyrifos due to the electron transfer from chlorpyrifos to copper which

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confirm the coordination interaction between copper ion and chlopyrifos.36, 37

10



211

Thermogravimetric analysis (TG) was used to investigate the thermal stability.

212

As shown in figure 6a, the loss in mass for Cu-MCM-41 and CH-Cu-MCM-41 was

213

slight below 100 ℃ due to the evaporation of water. The significant loss in mass

214

occurred within the temperature range 155～800 ℃ caused by the carbonization and

215

decomposition of the organic compounds on the mesoporous silica for Cu-MCM-41.

216

For CH-Cu-MCM-41, the loss percentage in mass was apparently bigger than copper

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Schiff base modified mesoporous silica for the decomposition and evaporation of

218

chlorpyrifos. And the DSC thermograms of chlopyrifos, SA-MCM, Cu-MCM-41 and

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CH-Cu-MCM-41 were shown in figure 6b. The fusion peak of salicylaldehy modified

220

mesoporous silica had a significant shift from 78 ℃ to 98 ℃ after the coordination

221

with copper ion which convinced the interaction between copper ion and Schiff base

222

in the salicylaldehy modified mesoporous silica in accordance with the XPS results. A

223

further shift of the fusion peak happened after loading the chlopyrifos indicating the

224

coordination between Cu-MCM-41 and chlopyrifos. But the fusion peak of

225

chlopyrifos disappeared for CH-Cu-MCM-41 comparing with the DSC thermograms

226

of chlopyrifos, proving that the chlopyrifos is distributed in amorphous state in the

227

pore of Cu-MCM-41.

228

Adsorption Performance

229

Table 2 listed the AC of various mesoporous silica. The copper-Schiff complex

230

increased in higher copper ion concentration, which led to larger active area and

11


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231

improved the interaction between chlorpyrifos and mesoporous silica support.26 The

232

Ac of the synthesis samples increased while the copper ion concentration of copper

233

nitrate solution increased during the preparation. When the copper ion concentration

234

of copper nitrate solution is 1.2 mol/L with an actual copper ion loading amount of

235

0.286 mmol/L, the AC of the samples increased up to 295 mg/g, 178% more than the

236

sample without copper ion.

237

Sustained released test

238

Figure 7a shows the sustained released performance of Cu-MCM-41 prepared in

239

different concentration of copper ion solution at pH 7. The larger the concentration of

240

copper ion was, the more AC of Cu-MCM-41 for chlorpyrifos was and the samller its

241

release rate with a high sustained release performance was. The sustained release

242

performance in different temperature at pH 7 was illustrated in Figure 7b. As the

243

temperature increasing, in one side, the thermodynamic movement of the chlorpyrifos

244

molecules was intensified; in the other side, the coordination between Schiff base and

245

copper ion was weakened. As a result, the diffusion of chlorpyrifos from Cu-MCM-41

246

to the solution was accelerated and the release rate became faster.

247

Figure 7c depicts the sustained release curves at various pH with a sequence of

248

pH=3 > pH=9 > pH=5 > pH=7 in release rate. Under acid conditions, the lower the

249

pH was, the faster the release rate was. Because the Schiff base was unstable in acid,

250

C=N tended to decompose. As a result, the coordination bond between copper ion and

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251

C=N broke down, and the nitrogen on Schiff base was protonated. So the interaction

252

between chlorpyrifos and Cu-MCM-41 was weakened and the release rate was

253

accelerated. Under basic conditions, the coordination between hydroxide ion and

254

copper ion was stronger than that between Schiff base and copper ion which

255

apparently weakened the interaction between C=N and copper ion. So the release rate

256

was slightly faster than in acid (pH=5). Apparently different from the performance at

257

pH=7, obvious “sudden release” activity was observed about 23 h into drug release at

258

pH=3, at which point the release rate reached 49.8%. The results proved that the

259

system was pH sensitive with various sustained released performance according to the

260

different pH value.

261

Kinetics Study

262

To further understand the sustained release mechanism, the data of sustained

263

release of chlorpyrifos from Cu-MCM-41 in various pH values were fitted to

264

zero-order model, first order model, Higuchi model,38 and Korsmeryer-Pappas

265

model39 respectively. As shown in Table 3, the drug release behavior of

266

sustained-release

267

Korsmeryer-Pappas kinetic equation. When pH= 5, 7 and 9, the diffusion coefficient

268

nth power for time(t) are 0.3233, 0.3108 and 0.4087 calculated from the kinetic

269

equation , while all of them were below 0.45. And the values obtained indicate that

270

the sustained release of chlorpyrifos from the particles was controlled by a Fickian

271

diffusion mechanism40, 41 which proved that the difference of the concentration is the

272

main impact on the release process. When pH=3，the diffusion coefficient n is 0.6485

273

which is larger than 0.45 and the mechanism become non-Fickian，namely synergic

274

effect of diffusion and coordination bond breaking between the Schiff base and the

chlorpyrifos/PA

particles

was

most

13


consistent

with

the

Page 15 of 35


275

copper ion as well as between the copper ion and chlorpyrifos. As a result, obvious

276

“sudden release” activity was observed at pH=3 as mentioned above.

277

By now, the complete drug release of CH-Cu-MCM-41 was generally illustrated

278

in consideration of kinetic mechanism and the data in this work, as shown in Figure 8.

279

Copper ion act as a bridge to coordinate with Schiff base modified mesoporous silica

280

and chlorpyrifos. Under acid or basic conditions, the C=N bond in Schiff base would

281

decompose leading to the broken of coordination between copper ion and C=N bond,

282

and the chlorpyrifos would be released. What’s more, under basic conditions,

283

hydroxide ion would compete with Schiff base to coordinate with copper ion while

284

further weaken the interaction between copper ion and C=N bond. As a result, the

285

released rate of CH-Cu-MCM-41 would accelerate under basic or acid conditions.

286 287

CONCLUSION

288

In conclusion, the salicylaldehyde modified mesoporous silica (SA-MCM-41)

289

was prepared by co-condensation method. PH-Responsive sustained release System of

290

Chlorpyrifos/Copper(II) Schiff Base Mesoporous Silica was prepared through

291

coordination between copper ion and Schiff base. The characterization confirmed the

292

existence of coordination bond between SA-MCM-41 and copper ions and between

293

Cu-MCM-41 and chlorpyrifos. The AC of SA-MCM-41 was 106 mg/g, while the

294

Cu-MCM-41 was 295 mg/g which increased 178% after the introduction of copper

295

ion. The larger the concentration of copper ion was, the more AC of Cu-MCM-41 for

14



Page 16 of 35

296

chlorpyrifos was and its release rate was smaller. The as-synthesized system showed

297

significant pH sensitivity. When pH≤7, the release rate of chlorpyrifos decreases

298

with pH increasing. And in weak base condition, its release rate is slightly larger than

299

the weak acid condition. Meanwhile, the drug release rate of the as-synthesized

300

system was also affected by temperature. Their sustained-release curves could be

301

described by Korsmeyer-Peppas equation in consistence with Fickian diffusion

302

mechanism at 5

Copper (II) Schiff Base

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