rapidness, sensitivity, specificity, low cost, and automated methodologies. [4][5][6] The enzyme XO is a type of liver enzyme that catalyzes the univalent and divalent reduction of ground state oxygen to generate both superoxide anion radical O 2•− and hydrogen peroxide (H 2 O 2 ) via a one-electron and a two-electron reduction, respectively, resulting in the oxidation of hypoxanthine to X and then X to uric acid. [7] To date, the determination of X through an electrochemical device is mainly focused on immobilizing XO onto different films and membranes, where the H 2 O 2 resulting from the X/XO enzymatic system is amperometrically (bio)sensed. [3] However, these XO-based amperometric biosensors have few drawbacks, such as poor stability and slow electron transfer, yielding to determine X at µm levels. More recently, (bio)sensors based on metal or metal oxide nanoparticles mixed with carbon-based nanomaterials, including graphene related nanomaterials, have shown some electrocatalytic properties toward X determination but the limit of detection (LOD) was not improved significantly. [1,3] In this regard, graphene and graphene-based materials, such as graphene oxide (GO) and reduced graphene oxide (rGO), have shown enhanced electrochemical and electrocatalytic activity over conventional carbon materials (e.g., graphite or carbon nanotubes) for (bio)sensing purposes. [8][9][10][11][12] While graphene is an electrical conductor, GO can be electrically insulating, being its reduction to rGO a simple strategy to partially restore the π electron network of graphene and hence its electrical conductivity. Among several novel applications, [13] graphene-based materials have shown to possess antioxidant activity, i.e., they can act as radical scavengers against various reactive oxygen species (ROS), especially for hydroxyl radicals or superoxides. [14,15] These studies showed that the primary active sites are associated with the pristine sp 2 -carbon network, rather than oxygen-containing functional groups.Perchlorotriphenylmethyl (PTM) radicals are persistent organic free radicals from the trityl radical family, the chemical and thermal stability of which rely on the full steric blockage of the central carbon atom by the ortho chlorine atoms. [16] Previous to our work, water soluble PTM derivative was demonstrated to react with high sensitivity and specificity with the superoxide generated from the X/XO enzymatic system. The This work is based on synergetically exploiting the activity of graphene-based materials and trityl free radicals to sense xanthine (X) by their combined scavenging properties for superoxide anion radical (O 2
•−). For this, reduced graphene oxide (rGO) and rGO covalently functionalized with a perchlorotriphenylmethyl (PTM) radical derivative (rGO@PTM) are synthesized, characterized, and casted on an electrode surface to achieve a highly sensitive electrochemical recognition platform for xanthine determination. The electrochemical analysis is based on impedimetrically monitoring a radicalinvolved react...