Porous Silica Nanospheres with a Confined Mono(aquated) Mn(II)-Complex: A Potential T₁–T₂ Dual Contrast Agent for Magnetic Resonance Imaging

Magnetic resonance imaging has emerged as an indispensable imaging modality for the early-stage diagnosis of many diseases. The imaging in the presence of a contrast agent is always advantageous, as it mitigates the low-sensitivity issue of the measurements and provides excellent contrast in the acquired images even in a short acquisition time. However, the stability and high relaxivity of the contrast agents remained a challenge. Here, molecules of a mononuclear, mono(aquated), thermodynamically stable [log KMnL = 14.80(7) and pMn = 8.97] Mn(II)-complex (1), based on a hexadentate pyridine-picolinate unit-containing ligand (H2PyDPA), were confined within a porous silica nanosphere in a noncovalent fashion to render a stable nanosystem, complex 1@SiO2NP. The entrapped complex 1 (complex 1@SiO2) exhibited r1 = 8.46 mM-1 s-1 and r2 = 33.15 mM-1 s-1 at pH = 7.4, 25 °C, and 1.41 T in N-(2-hydroxyethyl)piperazine-N'-ethanesulfonic acid buffer. The values were about 2.9 times higher compared to the free (unentrapped)-complex 1 molecules. The synthesized complex 1@SiO2NP interacted significantly with albumin protein and consequently boosted both the relaxivity values to r1 = 24.76 mM-1 s-1 and r2 = 63.96 mM-1 s-1 at pH = 7.4, 37 °C, and 1.41 T. The kinetic inertness of the entrapped molecules was established by recognizing no appreciable change in the r1 value upon challenging complex 1@SiO2NP with 30 and 40 times excess of Zn(II) ions at pH 6 and 25 °C. The water molecule coordinated to the Mn(II) ion in complex 1@SiO2 was also impervious to the physiologically relevant anions (bicarbonate, biphosphate, and citrate) and pH of the medium. Thus, it ensured the availability of the inner-coordination site of complex 1 for the coordination of water molecules in the biological media. The concentration-dependent changes in image intensities in T1- and T2-weighted phantom images and uptake of the nanoparticles by the HeLa cell put forward the biocompatible complex 1@SiO2NP as a potential dual-mode MRI contrast agent, an alternative to Gd(III)-containing contrast agents.