Aspects of structural order in ²⁰⁹Bi-containing particles for potential MRI contrast agents based on quadrupole enhanced relaxation

Abstract

Quadrupole relaxation enhancement (QRE) has been suggested as the key mechanism for a novel class of field-selective, potentially responsive magnetic resonance imaging contrast agents. In previous publications, QRE has been confirmed for solid compounds containing 209 Bi as the quadrupolar nucleus (QN). For QRE to be effective in aqueous dispersions, several conditions must be met, i.e. high transition probability of the QN at the 1 H Larmor frequency, water exchange with the bulk and comparatively slow motion of the Bi-carrying particles. In this paper, the potential influence of structural order within the compounds ('crystallinity') on QRE was studied by nuclear quadrupole resonance (NQR) spectroscopy in one crystalline and two amorphous preparations of Triphenylbismuth (BiPh 3). The amorphous preparations comprised (1) a shock-frozen melt and (2) a granulate of polystyrene which contained homogeneously distributed BiPh 3 after common dissolution in THF and subsequent evaporation of the solvent. In contrast to the crystalline powder which exhibits strong, narrow NQR peaks the amorphous preparations did not reveal any NQR signals above the noise floor. From these findings, we conclude that the amorphous state leads to a significant spectral peak broadening and that for efficient QRE in potential contrast agents structures with a high degree of order (near crystalline) are required.

Predicting quadrupole relaxation enhancement peaks in proton R1-NMRD profiles in solid Bi-aryl compounds from NQR parameters

“…This topics are matter of ongoing work where further research is desirable. In a quite recent work, aspects of structural order of QRE-active particles based on 209 Bi are discussed with the outcome, that also in solution, particles with a highly ordered molecular structure are beneficial [29].…”

Tris(2-Methoxyphenyl)Bismuthine Polymorphism Characterized by Nuclear Quadrupole Resonance Spectroscopy

“…Some RM samples which had been prepared already before this study have been stored at room temperature for more than 1 year and do not show any change of the peak frequencies nor of the FWHM. This is in contrast to Triphenyl-Bismuth (BiPh 3 ) which, after shock-freezing in LN, shows such extreme peak broadening that no signal above the noise can be detected any more [26].…”

“…From the XRD viewpoint it is interesting to compare Tris(2-methoxy-Phenyl)Bismuthine to BiPh3 which had been characterized in terms of NQRS in a previous paper [26]. The unit cell parameters of BiPh 3 were studied crystallographically as early as 1942 [40].…”

“…485276. For investigating the behaviour of the 'RM' samples we applied a modified version of the procedure described in Reference [26]. We expected similar effects as those observed in Triphenylbismuth, that is, the at least intermediate formation of alternative crystallization states and potentially an intermediate metastable state.…”

“…For exact tuning of the compounds in this context, several representatives have been characterized comprehensively in terms of their chemical and physical properties, including extended studies of their NQR spectra and their quadrupolar relaxation behaviour. As potential polymorphisms and structural order play an important role for the exact location of the NQR transition frequencies, the respective characterizations are of high importance for the proper design of potential contrast agents and respective data have been published for Triphenyl-Bismuth [26]. It is also worth mentioning, that different polymorphic states exhibit different lattice and molecular dynamics which influence EFG fluctuations around the QN [27].…”