Strategically functionalized carbon nanotubes as the ultrasensitive electrochemical probe for picomolar detection of sildenafil citrate (Viagra)
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.
References (15)
- et al.
J. Pharm. Biomed. Anal.
(2001) - et al.
Anal. Chim. Acta
(2000) - et al.
Cell. Signal.
(1999) - et al.
Talanta
(2002) - et al.
Talanta
(2008) - et al.
Sens. Actuators B
(2007) - et al.
Anal. Chim. Acta
(2008)
Cited by (8)
Functionalized conjugated polymers for sensing and molecular imprinting applications
2019, Progress in Polymer ScienceCitation Excerpt :The sensitivity and selectivity of the PANI-g-MWNT ME towards CEL were superior to those of the MWNT/PANI (bilayer) electrode. Poly(4-aminobenzene sulfonic acid) (PABS) chains were grafted onto MWNTs (MWNT-g-PABS) were fabricated and utilized for the electrochemical detection of sildenafil citrate (SC; Viagra) [264]. The fabrication of this electrode involved the following steps: (i) preparation of MWNT-NH2 and (ii) electrografting of PABS onto MWNT-NH2 ME to obtain MWNT-g-PABS.
The use of nano-carbon as an alternative to multi-walled carbon nanotubes in modified electrodes for adsorptive stripping voltammetry
2012, Sensors and Actuators, B: ChemicalCitation Excerpt :Adsorption can take place on the CNTs, resulting in a much enhanced stripping signal due to the very large surface area of the CNTs in comparison with the planar substrate electrode. Table 1 highlights the diversity and extent of the AdsSV systems studied to date in this manner [2–40]. It can be seen that in many cases the targets are relatively planar molecules, which likely facilitate strong adsorption onto carbon and other electrode surfaces.
Amperometric dot-sensors based on zinc porphyrins for sildenafil citrate determination
2011, Electrochimica ActaCitation Excerpt :The study of electrochemical oxidation of sildenafil citrate on carbon-based electrodes led to the development of amperometric sensors with even better characteristics [13,14]. The modification of a glassy carbon electrode with carbon nanotubes gave a performance of picomolar detection of the analyte [15]. Several studies proved that diamond could be used reliably as electrode material in the determination of sidenafil citrate [16], due to its unique electrochemical proprieties such as low background current, lack of adsorption and wide potential range.
Differential Pulse Voltammetric Determination of Sildenafil Using Nano-Iron Oxides Modified Electrode
2022, Journal of Nanoparticle ResearchA Comprehensive Review on Analytical Techniques for Determination of Sex Stimulants, PDE5 Inhibitors in Different Matrices with Special Focus on the Electroanalytical Methods
2022, Critical Reviews in Analytical ChemistryElectrochemical behaviour of sildenafil citrate at gold and cystein modified gold electrode in acid solution
2018, Journal of Electrochemical Science and Engineering