Sensors and Actuators B 124 (2007) 38–45 Calix[4]arene based molecules for amino-acid detection Walid Mohamed Hassen a , Claude Martelet a , Frank Davis b , S´ eamus P.J. Higson b , Adnane Abdelghani c , Saloua Helali c , Nicole Jaffrezic-Renault a,∗ a Cegely (UMR CNRS 5005) Ecole Centrale de Lyon, 69134 Ecully Cedex, France b Cranfield Health, Cranfield University, Barton Rd, Silsoe MK45 4DT, UK c Unit´ e de recherche de physique des semiconducteurs et Capteurs, IPEST, La Marsa, 2070 Tunis, Tunisia Received 15 September 2006; accepted 24 November 2006 Available online 26 December 2006 Abstract The ability of calixarene based molecules to form complexes with amino-acids has been the central topic of many studies. In this report we studied the potential complex formation between calix[4]arene based molecules and some amino-acids including arginine and lysine using faradic electrochemical impedance spectroscopy (EIS). Calix[4]arene–amino-acid complex formation was tested under two pH conditions. In this study we used cyclic voltammetry to determine the electrochemical properties of the different layers immobilized on gold electrode surfaces. The electrodes were initially functionalized using cysteamine and then used as a substrate for calix[4]arene immobilization. Impedance spectroscopy permits the study of the electrical properties of the different layers and also allows for the detection of amino-acids binding to calix[4]arene. Scanning electron microscopy (SEM) was utilised to study the topography and the organisation of calixarene on the electrode surface. Fourier transform infrared spectroscopy (FTIR) was used to study the molecular structure of the different layers on the electrode surface. Cyclic voltammetry and FTIR proved that calixarene was assembled at the thiol functionalized gold surface. SEM shows a crystalline organisation; a dendritic structure in the case of the calixarene modified by the carboxylic acid groups (calix 1) and the calixarene with sulphonated long chain (calix 3). The benzyl modified calixarene (calix 2) shows a cubic structure organisation. Faradic impedance spectroscopy allows the following of the amino-acid–calixarene interaction. Calix 1 presented the highest sensitivity to arginine and lysine and allowed 1 × 10 -3 M of arginine and 6 × 10 -3 M of lysine to be detected. © 2006 Elsevier B.V. All rights reserved. Keywords: Calix[4]arene; Amino-acid; Impedance spectroscopy; Scanning electron microscopy 1. Introduction Bimolecular recognition by synthetic receptors constitutes a topic of current interest in supramolecular and analytical chem- istry [1]. Calixarenes are synthetic substrates showing structural similarities with crown ethers and cyclodextrins compounds. They can be utilised for molecular recognition as a direct conse- quence of their vase-like structure and internal cavity [2]. They are capable of hosting both bulky organic molecules [3] and alkaline earth ions [4]. Selectivity towards guest species can be tuned by varying the shape and size of the cavity or by modifying the substituents of the upper and lower rims. The vast major- ity of studies on calixarenes are focused on the calix[4]arenes ∗ Corresponding author. Tel.: +33 472431182; fax: +33 472431206. E-mail address: Nicole.Jaffrezic@univ-lyon1.fr (N. Jaffrezic-Renault). because they possess open and rigid structures that are desirable for molecular recognition [2], however, the shape and size of the cavity is adjusted by changing the value of n, where n = 4, 6, 8, ... [5]. Calixarenes have been widely used for ionic metal recogni- tion [6]. However, the ability of calixarenes to act as artificial receptors for biomolecules like amino-acids and peptides has been long recognized [2]. Modification of calixarene structures has been studied in order to increase their specificity to some biomolecules like amino-acids. p-Sulfonatocalix[4]arene and hexasodium p-sulfonatocalix[6]arene have been used to detect amino-acids and peptides in aqueous solution [7]. Amino-acid composition analysis is important in a number of sectors ranging from the food industry to human health. It has for example, been demonstrated that the d-amino-acids level in human brain is indicator of Alzheimer disease [8]. In recent studies, non covalent inclusion complexes formed 0925-4005/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.snb.2006.11.044