Computer-assisted design and synthesis of a highly selective smart adsorbent for extraction of clonazepam from human serum Heydar Aqababa a , Mehrdad Tabandeh a, ⁎, Meisam Tabatabaei b , Meisam Hasheminejad c , Masoomeh Emadi d a Department of Biology, Arsanjan Branch, Islamic Azad University, Arsanjan, Iran b Membrane Separation Technology (MST), Biofuel Research Team (BRT), Agricultural Biotechnology Research Institute of Iran (ABRII), Karaj, Iran c Young Researchers Club, Science and Research Branch, Islamic Azad University, Tehran, Iran d Department of Chemistry, University of Isfahan, Isfahan, Iran abstract article info Article history: Received 25 October 2011 Received in revised form 25 July 2012 Accepted 11 August 2012 Available online 19 August 2012 Keywords: Molecular imprinted polymer Clonazepam Smart adsorbent Counterpoise correction Basis set superposition error A computational approach was applied to screen functional monomers and polymerization solvents for rational design of molecular imprinted polymers (MIPs) as smart adsorbents for solid-phase extraction of clonazepam (CLO) form human serum. The comparison of the computed binding energies of the complexes formed between the template and functional monomers was conducted. The primary computational results were corrected by taking into calculation both the basis set superposition error (BSSE) and the effect of the polymerization solvent using the counterpoise (CP) correction and the polarizable continuum model, respectively. Based on the theoret- ical calculations, trifluoromethyl acrylic acid (TFMAA) and acrylonitrile (ACN) were found as the best and the worst functional monomers, correspondingly. To test the accuracy of the computational results, three MIPs were synthesized by different functional monomers and their Langmuir–Freundlich (LF) isotherms were studied. The experimental results obtained confirmed the computational results and indicated that the MIP synthesized using TFMAA had the highest affinity for CLO in human serum despite the presence of a vast spectrum of ions. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Clonazepam, 5-(2-chlorphenyl)-1,3-dihydro-7-nitro-2H-1,4- benzodiazepin-2-one (CLO) is an anti-anxiety medication in the benzo- diazepine family widely used in treatment of myoclonus, akinetic sei- zures and epilepsy [1,2]. The drug acts by enhancing the effects of gamma-aminobutyric acid (GABA) in the brain that inhibits brain activ- ity. Due to the fact that the drug presents within a slender therapeutic range from 10 to 50 ng/mL [3], therefore, fast and accurate monitoring of serum concentrations of CLO in patients is strongly recommended [4]. As a result, several analytical methods have been developed, involving gas chromatography with or without mass spectrometry [5,6] as well as liquid chromatography [7–13]. These methods suffer from some draw- backs such as long-time sample preparation, extractions [7], prolix analy- sis [8,9] and expensive equipments [10,11]. An analytical tool which could be used to simplify the analytical determinations is solid-phase extraction (SPE). Separation by the tra- ditional SPE materials is commonly done based on physiochemical retention on the functionalized surface. However, typical SPE adsor- bents lack selectivity especially when a highly selective separation has to be performed. Therefore, a considerable number of studies have been conducted on constructing more selective SPE adsorbents. An enhancement of the adsorbents` molecular selectivity has been achieved by the invention of molecular imprinted polymers (MIPs) [14]. These polymers are a novel group of smart materials with notable recognition properties for their template molecule [15,16]. Basically, MIPs are prepared by polymerizing a mixture consisting of functional monomer, cross-linker, template, solvent and initiator. After polymeri- zation, the template is removed from the polymeric matrix and the cavities complementary in size and shape to the template molecules are formed, enabling the resulted MIP to rebind to the same molecules. Given this unique feature, when a certain degree of selectivity is re- quired, MIPs are proposed as a reasonable option. Recently, MIPs have been employed in various fields such as catalysis [17], solid-phase ex- traction [18], sensors [19] and chromatography methods [20,21]. Despite the above-mentioned advantages of MIPs, the long time consumed in seeking suitable functional monomers and solvents is an obstacle in MIPs preparation. Therefore, the combinatorial and computa- tional methods have been used to overcome this shortcoming [22–25]. In these approaches, the binding energy (ΔE) is used as the criterion to quantitatively evaluate the interaction between the template molecules and the monomers [26,27]. The data obtained is used to select the proper components of the polymerization mixture resulting in the most stable complex. In the present study, a rational computational approach i.e. the den- sity functional theory (DFT) method was applied to develop a novel and selective adsorbent (CLO-MIP) in order to improve the selectivity and Materials Science and Engineering C 33 (2013) 189–195 ⁎ Corresponding author. Tel./fax: +98 7284662955. E-mail addresses: tabandeh_m@iaua.ac.ir, tabandeh.g@gmail.com (M. Tabandeh). 0928-4931/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.msec.2012.08.029 Contents lists available at SciVerse ScienceDirect Materials Science and Engineering C journal homepage: www.elsevier.com/locate/msec