Application of Room Temperature Ionic Liquid As Sensing Modality for Selective Detection of Important Phenylpyperidine Analogue.
Authors: Paul Anirban , Muthukumar Sriram , Prasad Shalini 
Published: May 2020

Room temperature ionic liquid (RTIL) is a unique chemical which possesses exceptional physical and chemical properties. It is viscous in nature and the general architecture consists of a long chain cation and a long/short chain anion seated side by side, in a zwitter ion format. The cation and anion are equi-charged species makes the compound electrically neutral in nature (Hallett and Welton 2011).The density of RTIL is higher than water and it possesses negligible vapor pressure, which enables it for many important applications. One of the most important properties of RTIL is its low volatility and high thermal stability (up to 400K) compared to other organic solvents, attracts the scientific community and hence RTIL is extensively used in various applications like energy, catalysis, chemo and bio sensing, gas sensing etc (Marsh et al. 2004). Most of the RTIL is non-conducting in nature due to its high viscosity (>50cP), and restrains the charge distribution. While few RTIL possess low viscosity and very high conductivity. This complex relation between viscosity and ionic conductance is easy understood by Walden’s rule which suggests that mostly long alkyl chain hydrocarbon cation based RTIL possesses lower conductivity (Schreiner et al. 2010). The electrochemical stability of cation generally follows this order (Fig.1):

Whereas the anion follows this order (Fig.2):

Any one combination of above cation and anion may not have desired chemical, electrical or electrochemical property (Liang et al. 2002). RTIL consists of one Common cation with two different anions that can show separate electrical and electrochemical property. For example, 1-ethyl-3-methyl imidazolium (EMIM+) based cation when constituted with thiocyanate (SCN-) has an ionic conductivity >20mS/cm but the electrochemical stability is 2.9 V, whereas the same cation when coupled with has an ionic conductivity of 12 mS/cm whereas the electrochemical stability is 4.3 V which is much higher compared to thiocyanate (Fro et al. 2008). It is found that EMIM+ based RTIL with these two different anions: and are suitable for electrochemical application.

Phenylpiperidines are a chemical class of drugs with a phenyl moiety directly attached to piperidine. (Fig3)

Fig.3: Chemical structure of 1-phenyl-pipyridine

These agents have an important role in many aspects of medicine including anesthesia and pain medicine. Pharmacological effects associated with phenylpiperidines are vastly different, yet similar; they include morphine-like activity in some derivatives, while in others they exert potent central nervous system effects. One of the famous subclass of Phenylpiperidines are fentanyl analogs, which is currently one of the most worrying factor for scientific community.

In this paper, we have tried to explore an electrochemical sensor for detection of different compounds based on 1-phenyl-pipyridine using a specific RTIL [EMIM] [BF4]. A commercially available screen printed electrode was functionalized with RTIL and a DC based electroanalytical technique was implemented to obtain sensor performance to detect N-phenyl-N-(piperidin-4-yl) propionamide used as a 1-phenyl-pipyridine analogue with high specificity. The LOD of this system has been calculated to be 0.5 ppm.

Fig 4: (a) Experimental protocol (b) Square wave voltammetry result shows distinct peak for the Norfentanyl analog.

References:

Fro AP, Kremer H, Leipertz A (2008) Density , Refractive Index , Interfacial Tension , and Viscosity of Ionic Liquids [ EMIM ][ EtSO 4 ], [ EMIM ][ NTf 2 ], [ EMIM ][ N ( CN ) 2 ], and [ OMA ][ NTf 2 ] in Dependence on Temperature at Atmospheric Pressure. J Phys Chem B 112:12420–12430

Hallett JP, Welton T (2011) Room-Temperature Ionic Liquids: Solvents for Synthesis and Catalysis. 2. Chem Rev 111:3508–3576. https://doi.org/10.1021/cr1003248

Liang C, Yuan C-Y, Warmack RJ, et al (2002) Ionic Liquids: A New Class of Sensing Materials for Detection of Organic Vapors Based on the Use of a Quartz Crystal Microbalance. Anal Chem 74:2172–2176. https://doi.org/10.1021/ac011007h

Marsh K., Boxall J., Lichtenthaler R (2004) Room temperature ionic liquids and their mixtures—a review. Fluid Phase Equilib 219:93–98. https://doi.org/10.1016/j.fluid.2004.02.003

Schreiner C, Zugmann S, Hartl R, Gores HJ (2010) Fractional Walden Rule for Ionic Liquids: Examples from Recent Measurements and a Critique of the So-Called Ideal KCl Line for the Walden Plot †. J Chem Eng Data 55:1784–1788. https://doi.org/10.1021/je900878j

Figure 1