Elsevier

Biosensors and Bioelectronics

Volume 26, Issue 6, 15 February 2011, Pages 3018-3022
Biosensors and Bioelectronics

Strategically functionalized carbon nanotubes as the ultrasensitive electrochemical probe for picomolar detection of sildenafil citrate (Viagra)

https://doi.org/10.1016/j.bios.2010.12.005Get rights and content

Abstract

The present work demonstrates the utility of the functionalized carbon nanotubes, poly(4-aminobenzene sulfonic acid) (PABS) grafted multiwalled carbon nanotubes, MWNT-g-PABS, as an electrode modifier towards achieving ultrasensitive detection of a model drug, sildenafil citrate (SC). PABS units in MWNT-g-PABS interact with SC, pre-concentrate and accumulate at the surface. The electron transduction from SC to electrode is augmented via MWNT-g-PABS. As a result, the MWNT-g-PABS modified electrode exhibited ultrasensitive (57.7 μA/nM) and selective detection of SC with a detection limit of 4.7 pM. The present work provides scope towards targeting ultrasensitivity for the detection of biomolecules/drug through rational design and incorporation of appropriate chemical components to carbon nanotubes.

Introduction

The ability to coat carbon nanotubes (CNTs) with conducting polymers (CPs) provides scope to improve the properties and application potential of CNT–CP composites or functionalized CNT. In this work, we have explored the utility of a new functionalized CNT for preferential adsorption and ultrasensitive electrochemical detection of a model drug, sildenafil citrate (SC) using the specific interactions between the drug and functional groups in the CP. Poly(4-aminobenzene sulfonic acid) (PABS) has been chosen as the functional polymer to have specific interaction with SC. The methodology adopted in the present work is as follows. SC (1-[{3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1-H-pyrazolo[4,3-d] pyrimidin-5-yl)-4-ethoxy phenyl}sulfonyl]-methyl piperazine citrate) has pyrimidine, pyrazole and piperazine rings. The nitrogen atoms in the pyrimidine and pyrazole part of SC do not favor protonation due to the resonance and steric effects. However, the nitrogen atom bonded to electron donating methyl group of piperazine ring is susceptible for protonation in acidic conditions (Liu et al., 2006). The protonated SC can have specific ion-association interactions with negatively charged sulfonic acid groups in PABS. The molecular interaction between PABS and SC can be effectively exploited for the sensitive electrochemical detection of SC.

SC is an oral drug for erectile dysfunction. The main physiological action of SC is the release or enhancement of nitric oxide (NO) by inhibiting cyclic guanosine monophosphate (cGMP), the specific monophosphodiesterase-5 (PDE-5). NO is a crucial physiological molecule and participates in blood pressure regulation, immune defense, digestion, vision and smell. NO may also participate in disease processes such as hypertension, diabetes, impotence and stroke. Thus, NO can be toxic or beneficial depending on the amount and where in the body it is released. It has been reported that excessive generation of NO may result harmful effects and cell deaths (Bosca and Hortelano, 1999). SC has a spillover effect and blocks PDE-6, an enzyme actively present in retinal photoreceptors. This eventually can increase the concentration of cGMP and can cause depolarization of rod cells to result ‘blue vision’. Also, oral administration of SC with other drugs like nitrates or nitroglycerine or isosorbide can induce headaches and low blood pressure (Tunçtan et al., 2005). Thus, the residual presence of SC even in trace (nanomolar) concentration levels, could result in adverse side effects. A sensitive method for the selective determination of SC in nanomolar level is warranted.

Analytical methods such as micellar electrokinetic chromatography (Nevado et al., 2001), flow injection analysis (Altiokka et al., 2001), extractive spectroscopy (Dinesh et al., 2002), HPLC (Abd-Elbary et al., 2004) and resonance Rayleigh-scattering (Liu et al., 2006) have been used for the detection of SC. The lowest detection limit (5 × 10−9 M) has been reported for SC at a hanging mercury drop electrode (HMDE) (Berzas et al., 2000). However, the use of HMDE is undesirable because of the high toxicity of mercury and the inherent problems associated with HMDE, such as oxygen removal, cleaning the surface of mercury drop. A new methodology based on “mercury free” electrode is desirable.

In this work, a new methodology has been developed to achieve ultrasensitive (picomolar concentration) and fast responsive electrochemical detection of SC. Our methodology involves; (i) electrografting of MWNT with a sulfonated polyaniline (PABS) to obtain MWNT-g-PABS, ii) fabrication of a modified electrode using MWNT-g-PABS as the electrode modifier, (iii) pre-concentration of SC at MWNT-g-PABS modified electrode (Scheme 1) and (iv) trace level (picomolar concentrations) electrochemical detection of SC at MWNT-g-PABS modified electrode using square wave adsorptive stripping voltammetry (SWAdSV).

Section snippets

Chemicals and reagents

MWNTs were obtained from CNT Co., Ltd., (Incheon, S. Korea). 4-aminobenzene sulfonic acid (4-ABS) and other chemicals were purchased from Aldrich (S. Korea). SC, under the brand name Viagra, was received as a gift sample from PFIZER. Inc., USA. Sodium acetate (NaAc)–HCl buffer (NHB, pH 2.0) solution was prepared using 1.0 mol L−1 NaAc and 1.0 mol L−1 HCl. Buffer solutions with different pHs were prepared through the addition of 0.01 mol L−1 HCl. A stock solution of SC was prepared in NHB and stored

Fabrication of MWNT-g-PABS modified electrode

Cyclic voltammograms (CVs) recorded during the electrochemical grafting of PABS with MWNT–NH2 are presented in Fig. 1. In the first potential scan, a steady increase in the oxidation current was witnessed for potentials beyond +1.30 V. We presume that –NH2 groups in 4-ABS and MWNT–NH2 are simultaneously electro-oxidized at potentials beyond +1.30 V (Manesh et al., 2008, Kumar and Chen, 2007). The simultaneous oxidation was ensured by performing cyclic voltammetry for GC/(pristine) MWNT–4ABS film

Conclusions

A new strategy has been evolved for the use of functionalized CNTs, PABS grafted MWNT, as the electrode modifier, towards picomolar electrochemical detection of a model drug, SC (Viagra). The PABS units in MWNT-g-PABS interact with SC molecules and accumulate them at the surface. As a result, ultrasensitive (57.7 μA/nM) and selective detection of SC was achieved with an extremely low detection limit (0.469 × 10−11 M). The present work opens the possibility of tailor designing the functionalities of

Acknowledgements

This work was supported by International Research and Development Program of the National Research Foundation of Korea (NRF) funded by the Ministry Education, Science and Technology (MEST) of Korea (F01-2009-000-10009-0) and Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0093819). The authors acknowledge Kyungpook National University Center for Scientific Instrument.

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