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The surface of ZnO nanocrystal was functionalized with the amino groups using 3-aminopropyltriethoxysilane APTES and tetraethyl orthosilicate TEOS [25].. Surface modification of ZnO nano

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N A N O E X P R E S S Open Access

Effect of substrate (ZnO) morphology on enzyme immobilization and its catalytic activity

Yan Zhang1, Haixia Wu1*, Xuelei Huang2, Jingyan Zhang2and Shouwu Guo1*

Abstract

In this study, zinc oxide (ZnO) nanocrystals with different morphologies were synthesized and used as substrates for enzyme immobilization The effects of morphology of ZnO nanocrystals on enzyme immobilization and their catalytic activities were investigated The ZnO nanocrystals were prepared through a hydrothermal procedure using tetramethylammonium hydroxide as a mineralizing agent The control on the morphology of ZnO nanocrystals was achieved by varying the ratio of CH3OH to H2O, which were used as solvents in the hydrothermal reaction system The surface of as-prepared ZnO nanoparticles was functionalized with amino groups using

3-aminopropyltriethoxysilane and tetraethyl orthosilicate, and the amino groups on the surface were identified and calculated by FT-IR and the Kaiser assay Horseradish peroxidase was immobilized on as-modified ZnO

nanostructures with glutaraldehyde as a crosslinker The results showed that three-dimensional nanomultipod is more appropriate for the immobilization of enzyme used further in catalytic reaction

Introduction

The composition, size, and surface characteristics of

sub-strates have been considered as the important factors that

affect the physical/chemical properties of the immobilized

enzymes [1-3] However, for conventional bulk solid

sub-strates, such as glass slides [4], polymer monoliths [5,6],

and silica beads [3], the control on their morphologies and

functionalizing their surfaces are usually laborious

Nanos-caled materials, such as metal [7] and metal oxide

nano-spheres [8], carbon nanotubes [9,10], graphene oxide

nanosheets [11], have also been utilized as the substrates

for enzyme immobilization It has been demonstrated that

the size of nanostructured materials might play significant

roles to regulate the catalytic activity of the immobilized

enzymes [3] The preparation of nanostructured materials

with controlled chemical composition, size, morphology,

and the surface functionalization have witnessed great

pro-gressive achievements during the last two decades [12,13]

However, the systematic study of the effects of the

mor-phology of the nanoscale substrates on the enzyme

immo-bilization remains to be expanded ZnO nanocrystals have

unique physical/chemical properties and pronounced bio-compatibility, which are beneficial for many practical applications In addition, a variety of nanostructures of ZnO, such as nanospheres [14], nanowires [15], nanorods [16], nanonails [17], nanotubes [18], nanotetrapods [19], nanotablets [20], and nanoflowers [21], have been pre-pared successfully Therefore, ZnO nanocrystals are ideal materials to study the effect of the morphology of the sub-strate on the catalytic efficiency of the immobilized enzymes Horseradish peroxidase (HRP) was used as a model enzyme because it has been wildly studied and used

in many fields, such as organic syntheses [22], phenol removal [23], biosensor, and drug delivery [24]

In this study, we report the effects of the morphology

of the ZnO nanocrystals on the enzyme immobilization ZnO nanocrystals with different morphologies, including nanosphere, nanodisk, and nanomultipod, were fabri-cated simply through a hydrothermal procedure The surface of ZnO nanocrystal was functionalized with the amino groups using 3-aminopropyltriethoxysilane (APTES) and tetraethyl orthosilicate (TEOS) [25] Glutar-aldehyde was used as a crosslinker to immobilize the HRP enzyme molecules on the surface of as-modified ZnO nanocrystals Then the enzyme loading and catalytic activity were evaluated

* Correspondence: haixiawu@sjtu.edu.cn; swguo@sjtu.edu.cn

1

National Key Laboratory of Micro/Nano Fabrication Technology, Key

Laboratory for Thin Film and Microfabrication of the Ministry of Education,

Research Institute of Micro/Nano Science and Technology, Shanghai Jiao

Tong University, Shanghai 200240, PR China

Full list of author information is available at the end of the article

© 2011 Zhang et al; licensee Springer This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium,

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Results and discussion

ZnO nanocrystals with different morphology

Figure 1 shows the SEM images of ZnO nanocrystals

with different morphologies The nanospheres, with

dia-meter of approximately 30 nm, were obtained when pure

methanol was used as the hydrothermal reaction solvent

as shown in Figure 1a When the ratio of methanol to

water was adjusted to 1:1, ZnO nanodiscs, approximately

85 nm in width and 25 nm in thickness, were acquired as

shown in Figure 1b Figure 1c shows the ZnO

nanomulti-pods composed of several rods of 100 nm in diameter

and 200 nm in length when the methanol/water ratio

reaches 1:9 This illustrates that the ratio of methanol/

water is certainly a crucial factor to control on the

mor-phology of ZnO nanocrystals Although the

morpholo-gies of aforementioned ZnO nanocrystals are different,

the XRD patterns are all well consistent with the

stan-dard wurtzite ZnO structure as shown in Figure 2 Thus,

the effect of crystal form on the surface modification and

enzyme immobilization can be neglected

Surface modification of ZnO nanocrystals

In order to immobilize enzyme, the surface of ZnO

nano-crystals were functionalized with amino groups using

APTES/TEOS Figure 3a shows a typical image of coated

ZnO nanodiscs, where a thin film with uniform thickness

of 2 nm formed on the surface Comparing the

Zeta-potentials of the bare ZnO and the as-modified ZnO

nanocrystals (Figure 3b), it can be deduced that the

sur-face electrostatic state of ZnO nanocrystals was changed

The surface groups of the modified ZnO were further

characterized by FT-IR spectra Through comparing the

FT-IR spectra before and after modification in Figure 3c,

except for a few peaks at 3430, 1630, and 433 cm-1

corre-sponding to water (moisture) and ZnO nanocrystal, the

peaks at 2936.3 and 2872 cm-1of the C-H stretching

vibration [26], and the peaks at 1330 and 1560 cm-1of the stretching vibration of C-N and bending vibration of N-H can be found In addition, the strong absorption peaks at 3428.6 and 1633.5 cm-1, assigned to N-H bend-ing vibrations, are overlapped with the bendbend-ing vibration

of the absorbed H2O [27] These results confirmed the presence of amino groups on the ZnO nanocrystals surface

The amount of amino groups and the thickness of the coating layer can be controlled by adjusting the ratio of TEOS to APTES When the ratio of TEOS to APTES was 1:1, a coating layer of approximately 2 nm can be generated on the surface of ZnO nanocrystal, but, at the same time, lots of isolated SiO2 nanocrystals were formed, as shown in Figure 4a When the ratio of TEOS

to APTES was 1:4, a layer with uniform thickness of about 2 nm was formed as shown in Figure 4b When the ratio of TEOS to APTES was decreased to 1:10, no fully covered coating layer can be generated, as shown

in Figure 4c According to the standard curve of glycine obtained by Kaiser Assay, the amount of amino groups

on the surface of ZnO nanocrystals was deduced When the ratios of TEOS to APTES were 1:1, 1:4, and 1:10 used for the surface modification, the amounts of amino groups on the surface of ZnO nanodisks were 0.03, 0.07, and 0.02 mmol/g, respectively These results show that the ratio of TEOS to APTES used for the surface modi-fication determines the uniformity of the coating layer

as well as the amount of amino groups

The aforementioned procedure was also performed on the surface modifications of ZnO nanospheres and nano-multipods with TEOS to APTES ratio of 1:4 Figure 5 depicts the TEM images of the nanosphere and nanomul-tipod after the modification Similar to the nanodisks, there are thin coating layers formed both on nanospheres and nanomultipods The amounts of amino groups on

Figure 1 SEM images of ZnO nanocryatals (a) Nanospheres, (b) nanodisks, and (c) nanomultipods prepared using mixtures of methanol and water with different volume ratios of 10:0, 1:1 and 1:9 as solvents, respectively.

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the surfaces of ZnO nanospheres and nanomultipods

modified with TEOS to APTES ratio of 1:4 were also

measured, which are 0.127 and 0.044 mmol/g,

respec-tively The specific surface areas of ZnO nanospheres,

nanodisks, and nanomultipods are 33.59, 11.99, and

11.85 m2/g, respectively, which were measured using

Brunauer-Emmett-Teller (BET) method Thus,

consider-ing the surface areas of different morphologies, the

sur-face densities of amino groups on ZnO nanospheres,

nanodisks, and nanomultipods were calculated, which

are determined to be 3.78, 5.94, and 3.71 μmol/m2

, respectively

The effects of morphologies of ZnO nanocrystals on HRP

immobilization and their activity

The two aldehyde groups (-COH) of glutaraldehyde can

bond separately to the amino groups of HRP and

as-modi-fied ZnO [28], and thus, glutaraldehyde was used as a

crosslinker to immobilize HRP molecules on the modified

ZnO nanocrystal surfaces As shown in Figure 6, the

high-est loadings of HRP on the ZnO nanospheres, nanodisks

and nanomultipods were 0.094, 0.275, 0.240 mg/m2,

respectively From Figure 6, we find that the

immobiliza-tion of HRP on ZnO nanomultipods can reach the highest

loading at the lowest ratio of glutaraldehyde to amino

groups The maximum loading of HRP on ZnO

nanomul-tipods was higher than that on the nanospheres, but, as

high as that on the nanodisks, even if the surface density

of amino groups on ZnO nanomultipods was relatively

lower than that of the other two

The catalytic activity of the HRP immobilized on

dif-ferent ZnO nanocrystals was assayed through phenol

oxidation reaction Soluble HRP was also characterized

as a control Their kinetic parameters were obtained from the Lineweaver-Burk equation, and the data are summarized in Table 1 1/Km, which express the affinity

of phenol compounds to HRP, and the Kmof the HRP immobilized on ZnO nanospheres, nanodisks and nano-multipods were tagged as K (s), K (d), and K (m),

Figure 2 XRD patterns of ZnO nanocryatals (a) Nanospheres, (b)

nanodisks, and (c) nanomultipods.

Figure 3 The surface functionality of ZnO nanodisks before and after modification (a) The TEM images of ZnO modified by TEOS:APTES (1:4 in volume) (b) Zeta-potential curves, and (c) FT-IR spectra of ZnO nanodisks before and after modification.

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respectively Table 1 shows that Km(s) was unexpectedly

higher than that of the free HRP, while Km(d) and Km

(m) are close to that of free HRP suggesting that the

substrate affinity to the HRP was not affected by the

immobilization on these two ZnO materials Thus, we

can assume the morphology of the ZnO nanocrystals

must be an important fact that affects the affinity of

phenol compounds to HRP

The catalytic property of the immobilized HRP was

further characterized by the catalytic efficiency (Kcat/Km)

The catalytic efficiency of immobilized HRP was much

lower than that of free HRP, which coincide with the

report of the literature [29] As shown in Table 1, the

cata-lytic efficiency values of immobilized HRP on the

nanospheres, nanodisks and nanomultipods were 0.78, 1.09, 1.28 mM-1s-1, respectively Through comparing the

Kcat/Km value of the HRP immobilized on three ZnO nanocrystals with different morphologies, the nanomulti-pod ZnO nanocrystals are apparently favorable for enzyme immobilization

Those all may due to the three dimensional structural feature of nanomultipods, which could affect the enzyme interaction with the immobilized substrate and conforma-tion of the enzyme, and result in increasing the enzyme loading on the solid substrate and catalytic efficiency Because the nanomultipods have several pods, and the spaces among the pods are limited, the glutaraldehyde is difficult to self-polymerize, and the amino groups on the

Figure 4 TEM images of amino group modified ZnO nanodisks (a-c) TEM images of modified ZnO nanodisks with different TEOS:APTES ratios of 1:1, 1:4, and 1:10.

Figure 5 TEM images of amino group-functionalized ZnO nanocrystals (a) Nanospheres and (b) nanomultipods using TEOS and APTES with the ratio of 1:4 in volume.

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multipods are more efficiency to immobilize HRP While,

nanospheres and nanodisks have opened spaces,

glutaral-dehyde tends to polymerize Thus, HRP loadings on

nano-spheres and nanodisks need more glutaraldehyde to reach

the maximum loadings Due to the opened structure and

lower surface density of amino groups, the loading of HRP

on nanospheres is lowest Thus, HRP loadings on

nano-spheres and nanodisks need more glutaraldehyde to reach

the maximum loadings Compared with nanodisks and

nanospheres, the HRP loading on ZnO nanomultipods

reached the highest when its glutaraldehyde to amino

groups ratio was lower, which indicates that every HRP

molecule needs less glutaraldehyde to immobilize HRP on

the surface of ZnO nanocrystal and less conformation

happened Therefore, the 3D structure of nanomultipods

and the lowest ratio of Nglutaraldehyde/N-NH2may result in

the stabilization of HRP immobilized on nanomultipods,

which indicates that the 3D nanomultipod is more

appro-priate for the immobilization of enzyme and its catalytic

efficiency

Conclusions

ZnO nanocrystals with different morphologies, including

nanosphere, nanodisk, and nanomultipod, were prepared

via hydrothermal reactions using the mixtures of

metha-nol/water with different volume ratios The surfaces of

ZnO nanocrystals were modified with amino groups using TEOS and APTES to study the effect of the mor-phology of the materials to the enzyme immobilization The surface density of the amino groups and the thick-ness of coating were controlled by tuning the ratio of TEOS to APTES It was demonstrated when the ratio of TEOS to APTES was 1:4, a layer of uniform thickness of approximately 2 nm can be generated on surface of the ZnO nanocrystals

HRP molecules were immobilized on the modified ZnO nanocrystal surfaces using glutaraldehyde as a crosslinker

It was illustrated that the enzyme loading on the ZnO nanostructure was in the order of nanospheres < nano-multipod < nanodisks, while the nanonano-multipod reached the highest loading when its glutaraldehyde to amino groups ratio was lower than the other two, causing less conformation change of HRP on the ZnO surface, leading

to a higher catalytic efficiency In brief, the 3D nanomulti-pod is more appropriate for the immobilization of enzyme and for being used in catalytic reaction than the other two, which has great implications for the many ongoing studies

of enzyme immobilization and applications of the immobi-lized enzymes

Methods

Materials

Zn(Ac)2·2H2O, (CH3)4NOH (25%), Glutaraldehyde (25%), phenol (99%), 4-aminoantipyrine (4-AAP), methanol, and

H2O2(30%) were purchased from Sinopharm Chemical Reagent Company, Shanghai, China APTES (≥98.0%) was bought from Sigma-Aldrich, USA TEOS was obtained from Linfeng Chemical Reagent Company, Shanghai, China HRP was purchased from Majorbio Biotech Com-pany, USA All reagents were used as-received

Synthesis of ZnO nanocrystals

The ZnO nanocrystals were prepared through a thermal procedure using tetramethylammonium hydro-xide as a mineralizing agent The control on the morphology of ZnO nanocrystals was achieved by vary-ing the ratio of CH3OH to H2O, which were used as solvents in the hydrothermal reaction system In a typi-cal experiment, Zn(Ac)2·2H2O (5 mmol) was dissolved

in 15 mL of the mixture of methanol and water with different volume ratios in a flask under vigorous stirring Then, 15 mL of (CH3)4NOH was dropped into the flask

Figure 6 The enzyme loadings on different morphologies of

ZnO nanocrystals The loadings of HRP with different ratios of

glutaraldehyde and amine groups on the surface of the modified

ZnO nanocrystals.

Table 1 The loadings and kinetic properties of the HRP immobilized on ZnO nanocrystals

sample Enzyme loading (mg/m 2 ) K m (mM) K cat / K m (mM -1 s -1 )

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as mineralizing agent The as-obtained turbid

suspen-sion was transferred into a Teflon inner reactor of

stain-less-steel autoclave The autoclave was heated at 200°C

for 24 h for the hydrothermal reaction The reaction

solution was then cooled down to room temperature

and the solid product was separated from the reaction

mixture by centrifugation (4000 rpm), and was washed

with ethanol and water alternately, each for three times

Characterization of the ZnO nanocrystals

The size, morphology, BET surface area, and crystallinity

of the ZnO nanocrystals before and after the surface

modification were characterized using scanning electron

microscope (Zeiss ultra 55, Germany), transmission

elec-tron microscopy (TEM) (JEM-2100, Japan), accelerated

surface area, porosimetry system (Micromeritics ASAP

2010 M+C, USA), and X-ray powder diffraction (XRD)

(BRUKER-AXS, Germany) The surface functionalities of

the ZnO nanocrystals after the modification were

stu-died using FT-IR with a Nicolet 5700 Fourier transform

infrared spectrometer (Thermo Electron, USA), and

Zeta potentials obtained on Nicomp 380/ZLS (America)

Surface functionalization of ZnO nanocrystals

A typical surface functionalization process was as

follows

In general, 100 mg of ZnO nanocrystals was suspended

into 20 mL of ethanol (pH = 10.8) under sonication

Then, 15μL of TEOS and 60 μL of APTES were added

into the ethanol solution, and the mixture was stirred for

5 h The solid product was filtered and washed with

etha-nol, and then dried at room temperature The amounts of

amino groups on the surface of ZnO nanocrystals were

measured by Kaiser Assay At first, the standard curve of

glycine obtained by Kaiser Assay Glycine were mixed

with 2 mL of acetate buffer (0.6 M, pH = 4.5) and 2 mL

of 10 mg/mL ninhydrin ethanol solution The mixture

was treated at 90°C for 20 min After centrifugation at

10,000 rpm for 3 min, the amino groups’ concentration

in the supernatant was monitored spectrophotometrically

565 nm, and then, 10 mg of modified ZnO was utilized

to monitor spectrophotometrically as glycine Then, the

amount of amino groups was calculated based on the

standard curve of glycine

100 mg modified ZnO was suspended into 20 mL pH

7.0 0.1 M phosphate buffers, and then 750 μL of 25%

glutaraldehyde solution was added to the mixture The

mixture was incubated at room temperature, 200 rpm

for 2 h After filtration and washing with the phosphate

buffer, the samples were utilized to immobilize HRP

HRP immobilization

For HRP immobilization, 100 mg of functionalized ZnO

nanocrystals was added into 1 mL, 0.1 M, and pH 7.0 of

potassium phosphate buffer containing 100 μg of HRP The mixture was incubated at 4°C for 2 h with 240 rpm shaking, and then centrifuged at 10,000 rpm for 3 min The supernatant was collected The sediments were cen-trifuged and rinsed alternately three times with 0.1 M,

pH 7.0 phosphate buffer solution to remove non-specifi-cally adsorbed enzymes The solid was stored at 4°C for further measurements The supernatants were employed

to determine the enzyme loading on modified ZnO

Characterization of the immobilized HRP

The enzyme loading is obtained by subtracting the amount of the left HRP in the supernatant from the total HRP added Free HRP and the immobilized HRP activity was assayed by colorimetric method using 4-AAP as pre-viously described [2] In brief, the immobilized enzyme was added into 1 mL of 0.1 M, pH 7.0, phosphate buffer which contained 60 mM of phenol, 14.38 mM of 4-AAP, and 1.21 mM of hydrogen peroxide, and then reacted at 30°C for 3 min The initial catalytic reaction rates of the enzyme in the supernatant and the immobilized enzyme were determined by measuring the UV absorbance of the reaction mixture at 510 nm The double reciprocal plots

of the rates and substrate concentrations were plotted to obtain Kmand Kcat according to the Lineweaver-Burk equation

Abbreviations 4-AAP: 4-aminoantipyrine; APTES: aminopropyltriethoxysilane; BET: Brunauer-Emmett-Teller; HRP: horseradish peroxidase; TEM: transmission electron microscopy; TEOS: tetraethyl orthosilicate; XRD: X-ray powder diffraction; ZnO: zinc oxide.

Acknowledgements This study was financially supported by the National “973” Program (Nos 2007CB936000 and 2010CB933900), the NSFC (No 20774029 and

No 20906055) of China, the State key laboratory of bioreactor engineering (No 2060204), and China postdoctoral science foundation

(No 20100470131).

Author details 1

National Key Laboratory of Micro/Nano Fabrication Technology, Key Laboratory for Thin Film and Microfabrication of the Ministry of Education, Research Institute of Micro/Nano Science and Technology, Shanghai Jiao Tong University, Shanghai 200240, PR China 2 State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, PR China

Authors ’ contributions

YZ conducted the experiments and performed data analysis XH helped in designing the immobilized enzyme test JZ participated in the design and helped in compiling the data of immobilization enzyme interpretation HW helped during the most of operation and data interpretation of analytic equipments used SG conceived basic idea of this technique and supported the organization of this article.

Competing interests The authors declare that they have no competing interests.

Received: 24 March 2011 Accepted: 13 July 2011 Published: 13 July 2011

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doi:10.1186/1556-276X-6-450 Cite this article as: Zhang et al.: Effect of substrate (ZnO) morphology

on enzyme immobilization and its catalytic activity Nanoscale Research Letters 2011 6:450.

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