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

Abstract

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 (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 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@SiO2NP 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@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 T 1- and T 2-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.

Mn(ii) complex impregnated porous silica nanoparticles as Zn(ii)-responsive “Smart” MRI contrast agent for pancreas imaging

“…Note that a similar observation has already been made previously. 55 Notwithstanding, the surface functionalization of complex 1 @SiO 2 NP either with APTES or APTES-Py 2 Pic imparted no appreciable changes in the relaxivity value (Table 1 and Fig. S18, ESI†), indicating that the increase in the weight of the nanoparticles by means of the outer sphere surface functionalization did not exert any profound effect on the τ R of the incubated complex 1 molecules.…”

“…Mn-N1 Py = 2.276(2), Mn-N3 Py = 2.251(2), Mn-N2 Amide = 2.540(2), Mn-O2 acid = 2.256(2) and Mn-O4 acid = 2.261(2) Å bond distances were commensurate with previously reported Mn(II) complexes with similar ligands. 55,56 Thus, in complex 1, the Mn atom was in the +2 oxidation state. The complex core was mononegative in charge due to the presence of the coordinated chloride ion.…”

“…This minute change could be ascribed to spontaneous coagulation of the nanoparticles with time, leading to a lowered accessibility of water molecules towards the core, as previously reported for a similar nanomaterial. 55 Thus, it is expected that the contrast efficiency of the nanoparticle in vivo would not be hampered due to the presence of the cations and anions prevalent in the human body.…”

Advances in the application of manganese dioxide and its composites for theranostics

“…The conver-sion of deoxyhemoglobin (Hb) to oxygenated hemoglobin (HbO 2 ) occurs due to generated O 2 . [89][90][91][92] Hb is superparamagnetic and HbO 2 is diamagnetic. The transformation from Hb to HbO 2 leads to the reduction of the transverse relaxation rate (r 2 ) contributing to the high signal intensity of the tumor tissues present in T 2 -weighted images.…”

Probing the dynamic behaviour and magnetic identification of seven coordinated Mn(ii) complexes: a combined AIMD and multi-reference approach

“…This work has two objectives: (a) it provides an overview of the molecular and electronic structure of the four Mn( ii ) complexes in aqueous medium based on AIMD simulation. In addition, we have conducted a study to examine the effect of temperature on the coordination sphere and their comparative binding affinities of the ligands H 3 dpasam, 51 H 3 dpaaa, 50 H 3 cbda, 52 and H 2 pydpa 53 with Mn( ii ) ions in aqueous media, and (b) to explore the factors and parameters that influence the magnetic anisotropy and ZFS in high-spin PBP Mn( ii ) complexes, specifically the effect of ligand coordination environment and substituent at the ligand backbone. Also, we envisaged the factors that affect the sign of magnetic anisotropy parameter ( D ) in a mixed ligand environment.…”