Porous Silica Nanospheres with a Confined Mono(aquated) Mn(II)-Complex: A Potential T 1 - T 2 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 K MnL = 14.80(7) and pMn = 8.97] Mn(II)-complex ( 1 ), based on a hexadentate pyridine-picolinate unit-containing ligand (H 2 PyDPA), were confined within a porous silica nanosphere in a noncovalent fashion to render a stable nanosystem, complex 1 @SiO 2 NP. The entrapped complex 1 (complex 1 @SiO 2 ) exhibited r 1 = 8.46 mM -1 s -1 and r 2 = 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 @SiO 2 NP interacted significantly with albumin protein and consequently boosted both the relaxivity values to r 1 = 24.76 mM -1 s -1 and r 2 = 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 r 1 value upon challenging complex 1 @SiO 2 NP 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 @SiO 2 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 T 1 - and T 2 -weighted phantom images and uptake of the nanoparticles by the HeLa cell put forward the biocompatible complex 1 @SiO 2 NP as a potential dual-mode MRI contrast agent, an alternative to Gd(III)-containing contrast agents.