d -Glucose recognition based on phenylboronic acid-functionalized polyoligomeric silsesquioxane fluorescent probe

Accepted Manuscript d-Glucose recognition based on phenylboronic acidfunctionalized polyoligomeric silsesquioxane fluorescent probe

Yeon Ju Kim, Kyu Oh. Kim, Jung Jin Lee PII: DOI: Reference:

S0928-4931(18)30854-3 https://doi.org/10.1016/j.msec.2018.10.090 MSC 9016

To appear in:

Materials Science & Engineering C

Received date: Revised date: Accepted date:

22 March 2018 31 August 2018 29 October 2018

Please cite this article as: Yeon Ju Kim, Kyu Oh. Kim, Jung Jin Lee , d-Glucose recognition based on phenylboronic acid-functionalized polyoligomeric silsesquioxane fluorescent probe. Msc (2018), https://doi.org/10.1016/j.msec.2018.10.090

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. 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.

ACCEPTED MANUSCRIPT

D-glucose recognition based on phenylboronic acidfunctionalized

polyoligomeric

silsesquioxane

RI

PT

fluorescent probe

NU

Department of Fiber System Engineering, Dankook University, Republic of Korea

D

MA

a

SC

YEON JU KIM, KYU OH KIM*, JUNG JIN LEE*

PT E

Corresponding Authors: KYU OH KIM, E-mail: [email protected]/ JUNG JIN LEE, E-

AC

CE

mail: [email protected] /

ACCEPTED MANUSCRIPT

Abstract1 We report a new strategy to synthesize hybrid fluorescent nanosensors consisting of phenylboronic acid-functionalized POSS (POSS–PBA) and diol-modified 8-anilino-1naphthalenesulfonic acid (ANSA (a fluorescent dye)) for the detection of the biologically

PT

important D-glucose. The probe was characterized by FT-IR and 1H-NMR analyses, and the photoluminescence intensity was measured under various conditions to confirm its glucose

RI

sensing ability. Our POSS-APBA-dye probe could detect glucose at concentrations of 0–20

SC

mg/mL, with a good linear relationship even at low glucose concentrations of 0–1 mg/mL. The properties of the POSS-APBA-dye probe were evaluated and compared with those of an

NU

APBA-dye probe. The glucose sensing ability of our POSS-APBA-dye probe was largely

MA

unaffected by the presence of interfering substances. The probe showed high sensing ability

D

in a pH 5 environment and long-term (approximately 40 days) fluorescence stability.

PT E

Keywords: boronic acid derivative; polyhedral oligomeric silsesquioxane; glucose sensor;

AC

CE

fluorescence probe

1

phenylboronic

acid-functionalized,

POSS

(POSS–PBA);

diol-modified

8-anilino-1-

naphthalenesulfonic acid, ANSA; FT-IR, Fourier transform infrared; graphene oxide, GO; carbon nanotubes, CNTs; multiwalled carbon nanotubes, MWCNTs; photoluminescence, PL

ACCEPTED MANUSCRIPT

1. Introduction Currently, replacing traditional systems based on glucose-responsive materials used by diabetic patients with modern systems is the aim of many studies. Glucose biosensing using fluorescence techniques has advantages such as (1) higher sensitivity than that of the current

PT

method, (2) no damage to the host system, and (3) simplicity . Modern detectors based on the enzymatic oxidation of glucose are expensive and difficult to use (the enzyme can be easily

RI

denatured during the detection process). In addition, the reaction of glucose oxidase with

SC

oxygen in the air may lead to unexpected measurement errors. One method to prepare nonenzymatic glucose-responsive materials utilizes boronic acid derivatives. Boronic acid can

NU

form a stable five-member ring complex through esterification with cis-1,2 or cis-1,3 diols,

MA

including glucose. Lorand et al. conducted the first assessable study on the complexation of polyols and boronic acid, which represents the strongest single-pair reversible functional

D

group interaction in an aqueous solution among organic compounds [1]. A sensor composed

PT E

of fluorophore–boronic acid exhibits little or no fluorescence unless it comes into contact with diol compounds such as sugar or glucose. When a saccharide molecule competes with fluorophore and bonds to boronic acid, the fluorophore is released. The other method is to

CE

synthesize boronic acid derivatives via saccharide binding, with the changes in the electronic

AC

or steric states of the molecule leading to changes in the fluorescence emission of the fluorophore [2]. For detecting the d-glucose, the structure and distribution of our biomolecules can be probed using the phenomenon of fluorescence (or F¨or ester) resonance energy transfer (FRET) involved from a fluorescent donor molecule to an acceptor molecule in close proximity through dipole–dipole interactions [3]. The signal in FRET is a decrease in fluorescence intensity and lifetime of the donor. [4]. With the aim of preparing a sensor with high sensitivity and stability, extensive studies have been performed on fluorescence-based glucose-sensing systems derived from functionalized

ACCEPTED MANUSCRIPT

materials such as graphene oxide (GO) [5], carbon nanotubes (CNTs), and multiwalled carbon nanotubes (MWCNTs) [6]. However, when using these carbon-based materials, it is difficult to obtain a linear relationship between the glucose concentration and fluorescence intensity; furthermore, the color of the reaction system is too dark or black, which can pose

PT

problems during optical measurements. Our new approach involves the use of a hybrid biosensor that utilizes the reaction between a

RI

negatively charged fluorescent dye and a positively charged boronic acid functional quencher

SC

based on a POSS nanoprobe. Cage-like POSS molecules (R8Si8O12) feature a nanoscopic size of 1–3 nm, including vertex groups (R: hydrogen, alkyl, alkene, aryl, arylene, etc.), along

NU

with silicon-oxygen linkages with a cubic inorganic core. Unlike traditional organic

MA

compounds, POSS derivatives are colorless, nonvolatile, odorless, and environment-friendly, and show dramatically high performance. Zhou et al. prepared a polyacrylate-POSS porous

D

film that showed fluorescence quenching upon exposure to saturated vapors of nitro

PT E

compounds. The presence of POSS moieties resulted in nanoporous structures and subsequently led to a large response to explosive vapors [7]. Matsumoto et al. reported that the POSS concentration significantly affected the fluorescence intensity of dendrimers with

CE

specific fluorescence emission at 445 nm under UV irradiation [8]. The POSS should exist in

AC

a colorless or transparent form when made into a solution for glucose detection. This feature allows relatively accurate optical measurement data to be obtained, and it is advantageous for application as a substrate for the skin because of the coexistence of organic and inorganic functional groups. In addition, because the molecular size is very small (nanoscale), additional effects can be expected in the detection of a low concentration of extracted glucose [9-11]. We endeavored to design a nanoprobe based on POSS with the aim of developing a simple, cost-effective synthetic method. In this study, a POSS substrate was used to synthesize a fluorescent probe for glucose detection by measuring the photoluminescence (PL)

ACCEPTED MANUSCRIPT

intensity under various conditions, as well as to analyze the probe structure and determine the sensing performance.

2. Material and methods

PT

2.1 Materials 2-(3,4-Epoxycyclohexyl)ethyl]-heptaisobutyl substituted polyhedral oligomeric silsequioxane

RI

(POSS macromer), 3-aminophenylboronic acid (APBA), polyethylene glycol (PEG, Mw: 200),

SC

D-glucose, 8-anilino-1-naphthalenesulfonic acid (ANSA), hydrazine monohydrate, and 30%

NU

NH3 solution were purchased from Sigma-Aldrich and used without further purification.

MA

2.2 Synthesis of diol modified fluorescent material

1 mL of 0.5 M ANSA and 1 mL of 2 M PEG were dissolved in 2 mL THF. This mixture was vigorously stirred at room temperature for 1 h. Next, aqueous Na(CN)BH3 (0.1–0.2%)

PT E

D

solution was added to the mixture, 1H NMR (methanol-d4, ppm): 3.57 (a, 4H, -CH2-OH), 3.53 (c, 8H, -O CH2CH2O-, 3.44 (b, 4H, -OCH2CH2-OH).

CE

2.3 Synthesis of POSS-APBA substrate

AC

POSS (10 mg) was dissolved in 8 mL of absolute THF, and 1.67 mg of APBA was added to the solution. The mixture was heated and stirred in a thermostatically controlled oil bath at 50 ℃ for 3 h. After heating, 50 μL of hydrazine monohydrate solution (N2H4, 64%-65%, Sigma) and 50 μL of ammonia solution (NH3, 28%-30%, Aldrich) were added to the solution. This solution was heated for 1 h. The epoxy group of POSS and the primary amine group of APBA reacted via reduced amination reaction to form a secondary amine with the hydroxyl group. The synthesized diol-modified solution and POSS-APBA substrate solution were

ACCEPTED MANUSCRIPT

mixed in a transparent glass vial, 1H NMR (CDCl3, ppm): 6.98-7.02 (x,y, 5H, -Ph), 3.68 (j,H, cyclohexyl ring, -CH-OH), 3.12 (i, 2H, –CH2-NH-) 1.85 (k, 7H,-Si-CH2CH(CH3)2), 1.43 (b, 14H, -Si-CH2CH(CH3)2), 0.95 (a, 42H, -Si-CH2CH(CH3)2).

PT

2.4 Apparatus and measurement The structure of the fluorescent probe was analyzed by proton nuclear magnetic resonance

RI

(1H-NMR, Ascend tm 500, Bruker) and Fourier transform infrared spectroscopy (FTIR,

SC

Spectrum Two, Perkin Elmer). Methanol-d4 and CDCl3 was used as the 1H-NMR solvents. All the samples were scanned over the range 1000–200 cm-1 with 32 scans at 8 cm-1, and a

NU

solution was prepared to conduct FTIR analysis in a KBr window. The structure of the

MA

fluorescent probe was drawn by Chem-Draw software. The PL intensity was measured on an LS 55 (Perkin Elmer). The glucose concentration was set to 0–75 mg/mL to investigate its

D

sensing performance. To investigate other factors, interfering species were added to the

PT E

fluorescent probe, and measurements were performed at different times or on different days.

3. Results and discussion

CE

Recently, fluorescence-responsive nanoprobes that are sensitive to specific glucose or

AC

external stimuli such as pH [12, 13], enzymes, temperature [14], or light [15, 16] have been designed; these probes can be show site selectivity by recognizing changes in the microenvironment.

Our strategy for designing the assembled nano-biosensor for detecting d-glucose was based on

modulation of the FRET efficiency between the PBA-conjugated POSS and ANSA-

modified diol (Scheme 1C). In the quenching state, low fluorescence was seen. On the other hand, the fluorescence was relatively high in the no-quenching state. We successfully synthesized the PBA functionalized POSS to form a –C–NH– bond using the epoxide group

ACCEPTED MANUSCRIPT

of POSS and the primary amine groups of the PBA reaction pathway in Scheme 1A. The diol-modified ANSA self-assembled into core-shell structured micelles as a result of its ability to aggregate the hydrophobic inner core between the benzene ring of ANSA and the hydrocarbon of PEG with the hydrophilic outer shell of the hydrogen of PEG (Scheme 1B).

PT

To confirm the fluorescent probe structure, each sample was subjected to FT-IR and 1H-NMR analyses, as shown in Figure 1 and Supporting Information 3. In addition, in the FT-IR

RI

spectrum, the peaks at 1000–1300 cm-1, which indicated the stretching mode of the Si-O-Si

SC

groups, were considered to be characteristic peaks of POSS. The C-N stretch peak, or the POSS peak at 1260 cm−1, was due to the C–O stretching vibration of the epoxide. The

NU

intensity of this peak decreased in the spectrum of POSS–PBA in comparison with that in the

MA

spectrum of POSS. The new peak at 1435 cm−1 in the POSS–PBA spectrum was due to the second amine (C-N-C), C-N stretching, C–C stretching (phenyl ring), and B–O stretching of APBA, but this peak was absent in the case of POSS. Furthermore, the broad peak due to O-

PT E

D

H stretching at 3300 cm−1 in the spectrum of POSS–PBA was due to epoxide ring opening.

ANSA is a commercially available biomedical dye that shows high sensitivity to changes in

CE

optical properties after interaction with PBA [8]. In the fluorescence spectrum, excitation of

AC

the POSS-APBA-dye probe causes a peak to appear at 350 nm, and emission peaks appear at approximately 500 nm (see Supporting Information 1). It was observed that the rate of change of the fluorescence intensity was related to the glucose concentration. The response rate of the POSS-APBA-dye probe, R, is arbitrarily defined as follows: [1] where I0 and Iglucose represent the fluorescence signals upon exposure to the buffer solution and glucose solution, respectively, and t is the time. In most applications, the response time

ACCEPTED MANUSCRIPT

was taken as 1 min because a constant signal could be obtained within this period. Fig. 2 (a) displays the response behavior of the POSS-APBA-dye probe toward various concentrations of glucose from 0 to 50 mg/mL. Fig. 2 (b) specifically shows the higher linear response range of the POSS-APBA-dye probe, from 0.0 to 0.9 mg/mL, at a low glucose concentration based

PT

on the linear regression equation R = 0.345 [glucose] + 0.0031 and r2 = 0.9845. The limit of detection of the POSS-APBA-dye probe was calculated to be 0-20 mg/mL from the

RI

calibration plot, which corresponded to the glucose concentration that produced an analytical

SC

signal three times the standard deviation of R at a value of zero [17].

In order to clarify the sensing performance of the POSS, we drew a parallel between the

NU

response rates of the POSS-APBA-dye and APBA-dye probes for various concentrations of

MA

glucose from 0 to 5 mg/mL. In the absence of POSS, the response was unaffected by the increasing glucose concentration, but the response of the probe containing POSS changed

D

evidently. Aromatic hydrocarbons in the APBA and ANSA form very tightly packed crystals,

PT E

as indicated by a higher packing coefficient, owing to the large surface area of intermolecular contact and van der Waals interactions [18-19]. Thus, it is difficult to add glucose or the reactant to boronic acid because of steric factors affecting the complexation and packing of

CE

benzene and naphthalene. However, the 3-D cubic structure of POSS is easily accessible near

AC

D-glucose to boronic acid. Previous research revealed that the amphiphilic POSS-PEG, PVA, or APBA telechelic aggregate flower-like micellar particles as a result of the enhanced hydrophobic interactions of POSS moieties in an aqueous environment [9-10]. Therefore, in an aqueous solution and in vivo, APBA adopts a structure that can enhance the glucose sensing performance due to a lot of boronic acid reaction site can be exposed toward glucose. APBA-POSS is easily accessible glucose. . The binding response of the glucose biosensor depended on the activity of the POSS-APBAdye probe, which in turn was related to the pH of the solution. The pH effect was investigated

ACCEPTED MANUSCRIPT

over the range pH 3.0–10.0, as shown in Fig. 5. The POSS-APBA-dye probe system also allowed for the quantitative determination of the association constants (Ka) of diol–boronic acid complexes, as listed in Table 1.

[2]

PT

In order to gain a greater understanding of the reason for the fluorescence change, the pH

RI

profile of the PBA–ARS complex was investigated (Fig. 4). The profile shows that the largest

SC

response to PBA is centered at pH 5–7. The shape of the profile is likely a result of both the stability of the glucose-POSS-APBA-dye complex and the intrinsic fluorescence of the three

NU

ionic forms of PBA (pKa = 2.2 and 9.4, as calculated from equation 2). It is well known that boronate ester complexes have decreased stability under acidic conditions [20]. This results

MA

in a high concentration of the quenched, free form of the dye at a low pH (<5). At a medium

D

pH (5–7), the boronate ester becomes stable, and therefore causes quenching.

PT E

Potential interfering substrates were chosen to evaluate the selectivity of the POSS-APBAdye probe. The response rates of the biosensor to 20 mM glucose in the absence and presence

CE

of 500 mM of each interferant were used as indicators of selectivity. In the presence of

AC

fructose, the PL intensity of glucose was low because of the competition between glucose and fructose to bind with the POSS-APBA-dye probe [21]. Similarly, sucrose interfered with the PL response of the POSS-APBA-dye probe to glucose, but to a smaller extent. The responses of the glucose-specific PL biosensor in the absence and presence of a saccharide interferent suggested that the binding affinity was not a decisive parameter for the specific PL response of the POSS-APBA-dye probe to glucose. In addition, the POSS-APBA-dye probe containing 500 mM KCl and NaCl showed a low PL intensity, but there was no clear dependence on the concentrations of KCl and NaCl (see Supporting Information 3). Sensing of materials in

ACCEPTED MANUSCRIPT

environment and biological systems is extremely important. The long-term fluorescent stability of the POSS-APBA-dye probe in THF solution was monitored for 40 days, as shown in Fig. 5. Rizvi et al. reported that the protective effect of POSS in retarding UV-induced photo-oxidation may be related to the characteristic structure of the POSS molecule [22]. The

PT

Si-O bonds in the POSS structure are more resistant to breakdown than are typical organic bonds and Si-C bonds. Under exposure to extremely oxidative environments, all the bonds

RI

except the Si-O bond may break. Therefore, the SiO2 molecule in POSS may prevent the loss

SC

of excitons, leading to the enhanced fluorescence stability of the POSS-APBA-dye probe.

NU

4. Conclusion

Our fluorescent POSS-APBA-dye probe could be used as a glucose sensor, and its detection

MA

range was 0–50 mg/mL. When a linear graph was plotted with the measured PL intensity values, an R2 value close to 1 was obtained at low glucose concentrations. Because the graph

D

was almost linear, the PL intensity value was considered to be reliable. The PL intensity

PT E

decreased slightly when an interfering substance was added. A pH test showed that pH 5 was the optimum, which corresponds to an environment similar to the human skin surface. It is

CE

believed that this sensor can be reused several times because the maximum lifetime is about 40 days, and continuous measurement is possible. This probe may find potential application

AC

to sensors for monitoring low glucose concentrations. Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government(MSIT) (No. R-2018-00235)

Author information E-mail: [email protected] (K.O. Kim) / [email protected] (J. J. Lee)

ACCEPTED MANUSCRIPT

References [1] J. P. Lorand, J. O. Edwards, Polyol complexes and structure of the benzeneboronate ion, J. Org. Chem. 24 (1959) 769−774. [2] H. Fang, G. Kaur, B. Wang, Progress in boronic acid-based fluorescent glucose sensors, J.

PT

Fluoresc. 14 (2004) 481–488.

RI

[3] Selvin, P.R., 1995. Fluorescence resonance energy transfer. Method. Enzymol.246, 300–

SC

334.

NU

[4] J.C. Pickup et al. / Biosensors and Bioelectronics 20 (2005) 2555–2565 [5] S.K. Basiruddin, S.K. Swain, Phenylboronic acid functionalized reduced graphene oxide

MA

based fluorescence nano sensor for glucose sensing, Mater. Sci. Eng. C 58 (2016) 103–109. [6] J. Wang, Carbon-nanotube based electrochemical biosensors: a review, Electroanalysis 17

PT E

D

(2005) 7−14.

[7] H. Zhou, Q. Ye, W.T. Neo, J. Song, H. Yan, Y. Zong, B.Z. Tang, T.S.A. Hor, J. Xu, Electrospun aggregation-induced emission active POSS-based porous copolymer films for

CE

detection of explosives, Chem. Commun. 50 (2014) 13785–13788.

AC

[8] A. Matsumoto, T. Ishii, J. Nishida, H. Matsumoto, K. Kataoka, Y. Miyahara, A synthetic approach toward a self-regulated insulin delivery system, Angew. Chem. 51 (2012) 2124−2128.

[9] K.O. Kim, Y.A. Seo, B.S. Kim, K.J. Yoon, M.S. Khil, H.Y. Kim, I.S. Kim, Transition behaviors and hybrid nanofibers of poly(vinyl alcohol) and polyethylene glycol–POSS telechelic blends, Colloid Polym. Sci. 289 (2011) 863– 870. [10] K.O. Kim, B.S. Kim, I.S. Kim, Self-assembled core-shell poly(ethylene glycol)-POSS

ACCEPTED MANUSCRIPT

nanocarriers for drug delivery, J. Biomat. Nanobiotech. 2 (2011) 201−206. [11] K.O. Kim, I.S. Kim, cytocompatibility and osteogenesis of adipose tissue-derived stem cells on POSS-PEG coated collagen, J. Nanosci. Nanotech. 18 (2018) 4439–4444. [12] S. Li, K. Hu, W. Cao, Y. Sun, W. Sheng, F. Li, Y. Wu, X. J. Liang, pH-responsive

PT

biocompatible fluorescent polymer nanoparticles based on phenylboronic acid for

RI

intracellular imaging and drug delivery, Nanoscale 6 (2014) 13701−13709.

SC

[13] Y. Chen, K. Ai, J. Liu, G. Sun, Q. Yin, L. Lu, Multifunctional envelope-type mesoporous silica nanoparticles for pH-responsive drug delivery and magnetic resonance imaging,

NU

Biomaterials 60 (2015) 111−120.

MA

[14] Z. Zhang, D. Zhang, L. Wei, X. Wang, Y. Xu, H. W. Li, M. Ma, B. Chen, L. Xiao, Temperature responsive fluorescent polymer nanoparticles (TRFNPs) for cellular imaging

D

and controlled releasing of drug to living cells, Colloid. Surface. B, 159 (2017) 905−912.

PT E

[15] L. Zhu, P. Kate, V.P. Torchilin, Matrix metalloprotease 2-responsive multifunctional liposomal nanocarrier for enhanced tumor targeting, ACS Nano, 6 (2012) 3491−3498.

CE

[16] J. L. Viveroescoto, I.I. Slowing, C.W. Wu, V.S.Y. Lin, Photoinduced intracellular

AC

controlled release drug delivery in human cells by gold-capped mesoporous silica nanosphere, J. Am. Chem. Soc. 131 (2009) 3462−3463. [17] I. Apostol, K.J. Miller, J. Ratto, D.N. Kelner, Comparison of different approaches for evaluation of the detection and quantitation limits of a purity method: A case study using a capillary isoelectrofocusing method for a monoclonal antibody, Anal. Biochem. 385 (2009) 101–106. [18] C.A. Hunter, K.R. Lawson, J. Perkins, C.J. Urch, Aromatic interactions, J. Chem. Soc.

ACCEPTED MANUSCRIPT

Perkin Trans. 2 (2001) 651–669. [19] R.L. Avoyan, Y. T. Struchkov, V. G. Dashevskii, Steric hindrance and conformation in aromatic molecules, . tru t. hem. 7 (1967) 283−320. [20] X.C. Liu, W.H. Scouten, New ligands for boronate affinity chromatography, J.

PT

Chromatogr. A 687 (1994) 61−69.

RI

[21] Y. Liu, C. Deng, L. Tang, A. Qin, R. Hu, J.Z. Sun, B.Z. Tang, Specific detection of D-

SC

glucose by a tetraphenylethene-based fluorescent sensor, J. Am. Chem. Soc. 133 (2011) 660–

NU

663.

[22] S.B. Rizvi, L. Yildirimer, S. Ghadiri, B. Ramesh, A.M. Seifalian, M. Keshtgar, A novel

MA

POSS-coated quantum dot for biological application, Int. J. Nanomedicine. 7 (2012) 3915–

AC

CE

PT E

D

3927.

PT E

D

MA

NU

SC

RI

PT

ACCEPTED MANUSCRIPT

CE

Scheme 1 Proposed design and synthesis of POSS-APBA-dye fluorescent probe: (A) a – synthetic route to POSS-APBA macromers, (B) ANSA micelle formation, (C) formation of

AC

fluorescent probe, and (D) quenching mechanism of glucose specific sensing by POSSAPBA-ANSA.

PT E

D

MA

NU

SC

RI

PT

ACCEPTED MANUSCRIPT

CE

Figure 1. FT-IR spectra of (A) POSS, PEG-ANSA, APBA, and PEG-ANSA-POSS substrate at 450–4000 cm-1, (B) POSS, PEG-ANSA, APBA, and PEG-ANSA-POSS substrate at 450–

AC

1600 cm-1, (C) PEG-ANSA, PEG-ANSA-POSS substrate, and PEG-ANSA-POSS substrateglucose at 450–4000 cm-1, (D) PEG-ANSA, PEG-ANSA-POSS substrate, and PEG-ANSAPOSS substrate-glucose at 450–1600 cm-1.

AC

CE

PT E

D

MA

NU

SC

RI

PT

ACCEPTED MANUSCRIPT

Figure 2 (a) Emission spectra of POSS-APBA-dye probe at increasing concentrations of glucose from 0 to 20 mg/mL in DMF solution. (b) Typical calibration curves of the glucose biosensor at increasing concentrations of glucose, 0–0.9 mg/mL. Error bars correspond to the 95% confidence interval calculated from three replicate measurements.

AC

CE

PT E

D

MA

NU

SC

RI

PT

ACCEPTED MANUSCRIPT

Figure 3. Comparison of response rates of non-POSS substrate and POSS substrate.

ACCEPTED MANUSCRIPT

Table 1 Effect of interfering species in 5 mg/mL, in the presence of 0.02 M glucose.

Solution

Response time

Interferent

(M)

(min-1)

Fructose

0.5

0.774

Sucrose

0.5

0.861

0.5

KCl

glucose

0.5

0.66

RI

0.02 M

SC

Citric acid

PT

Concentration

0.18

0.5

0.24

-

0.5

1

AC

CE

PT E

D

MA

NU

NaCl

SC

RI

PT

ACCEPTED MANUSCRIPT

Figure 4. (a) Relative response of fluorescence intensity of POSS-PBA according to pH

NU

titration Em: λ = 500 nm, Ex ., λ = 350 nm, and (b) association constants (Ka) of POSS-

AC

CE

PT E

D

MA

APBA-dye probe.

ACCEPTED MANUSCRIPT

6 1 day 30 days 33 days 40 days

4

PT

3 2

RI

PL intensity (a.u.)

5

0 400

NU

SC

1

500

600

700

800

MA

wavelength (nm)

AC

CE

PT E

D

Figure 5. Long-term fluorescence stability of POSS-APBA-dye probe in THF solution.

MA

NU

SC

RI

PT

ACCEPTED MANUSCRIPT

AC

CE

PT E

D

Graphical abstract

ACCEPTED MANUSCRIPT

Highlights: 

we report a new stategy to synthesize hybrid fluorescent based nano-sensor consist of phenylboronic acid functionalized POSS (POSS–PBA) with di-ol modified 8-anilino1-naphthalenesulfonic acid (ANSA) fluorescent dye for detection of biologically

PT

important d-glucose.  Previous studies have been performed on fluorescence-based glucose-sensing

RI

systems derived graphene, CNT, and MWCN. However, there was difficult to obtain

SC

a linear relationship between the glucose concentration and fluorescence intensity;

NU

furthermore, the color of the reaction system is too dark or black, which can be a problem in optical measurement. The synthesized POSS-APBA-dye probe was able

MA

to detect glucose at 0-20 mg/mL concentration and good linear relationship at the low glucose concentration of 0-1 mg/mL.

D

 Properties of the POSS-APBA-dye probe have been studied and results were

PT E

compared with APBA-dye probe.  The POSS-APBA-dye probe have high sensing ability at pH 5 environment among

AC

CE

various pH conditions and long-term fluorescent stability for approximately 40 days.