Executive Summary : | The gadolinium(III) complexes (Gd) are used as MRI contrast agents (CA) and tens of millions of contrast-enhanced MRI scans are performed each year worldwide. Recent studies indicate that the patients suffering from severe renal impairment cannot be utilized Gd CAs and the long-term effects of retained Gd are also limiting its usefulness in MRI scans. Thus, it demands Gd-free MRI contrast agents and drives a new direction of bioinorganic chemistry innovation. The MRI contrast agents based on manganese (Mn) are reported as a promising alternative in this area. Among these, the CAs activated by analytes via redox changes are known as smart MRI CAs and it operates via reduction of paramagnetic center. It shows different r1 relaxivity with metabolite molecules (analytes) of tumor cells, only a few such smart CAs are reported and none of them are approved for clinical trials. Thus, it is proposed to synthesize mononuclear Mn(II/III) complexes of multidentate ligands that contain redox responsive groups, which triggers the Mn-center to function via redox and spin crossover as mechanisms. These redox-responsive CAs are designed to respond to the redox imbalance environment of tumor cells, such as overexpressed L-cysteine (Cys) and glutathione (GSH) or reactive oxygen species (ROS). The in-vitro and in-vivo capabilities of the Mn CAs will be studied using various cancer lines and by obtaining MRI phantom images. All the Mn(II/III) complexes are designed to have high kinetic stability and biocompatibility. Our proposed Mn(II/III) complexes have technical as well as safety advantages. |