Silver-modified titanium-based MXene as a promising SERS substrate for the characterization of cytotoxic agent cyclophosphamide: Experimental and DFT study

The emergence of new generations of two-dimensional (2D) nanostructured materials with unique electronic features and efficient charge transfer properties can significantly impact the performance of surface-enhanced Raman scattering (SERS) substrates leading to a fast and reliable spectroanalytical ultra-low concentration detection of bioactive molecules. Due to its short-range charge transfer and superior plasmonic effects, the titanium carbide (Ti₃C₂T_x) family of MXenes has been proven to be a promising candidate for a wide range of optics and sensing-related applications. In this work, the synthesis and characterization of 2D Ti₃C₂T_x MXene layered sheets were carried out. A charge transfer bridging between Ti₃C₂T_x and cyclophosphamide (CPA) drug molecules was successfully established by incorporating silver nanoparticles (AgNPs), resulting in a significantly enhanced Raman response and achieving up to 1 × 10⁻¹⁰ M detection limit of CPA in aqueous media. Spectroscopic and DFT results indicate that the oxazaphosphorine ring, with its heterocyclic nature and multiple electron-rich sites, plays a major role in facilitating the charge transfer mechanism, resulting in a strong analyte-substrate interaction. Given their impressive performance and cost-efficient synthesis protocols, silver-modified metal-based MXene nanocomposites hold great potential for developing a new class of stable SERS substrates, enabling reliable detection in biomedical samples.