Tuning Nuclear Quadrupole Resonance: A Novel Approach for the Design of Frequency-Selective MRI Contrast Agents

The interaction between water protons and suitable quadrupolar nuclei (QN) can lead to quadrupole relaxation enhancement (QRE) of proton spins, provided the resonance condition between both spin transitions is fulfilled. This effect could be utilized as a frequency selective mechanism in novel, responsive T1 shortening contrast agents (CAs) for magnetic resonance imaging (MRI). In particular, the proposed contrast mechanism depends on the applied external flux density—a property that can be exploited by special field-cycling MRI scanners. For the design of efficient CA molecules, exhibiting narrow and pronounced peaks in the proton T1 relaxation dispersion, the nuclear quadrupole resonance (NQR) properties, as well as the spin dynamics of the system QN−1H, have to be well understood and characterized for the compounds in question. In particular, the energy-level structure of the QN is a central determinant for the static flux densities at which the contrast enhancement appears. The energy levels depend both on the QN and the electronic environment, i.e., the chemical bonding structure in the CA molecule. In this work, the NQR properties of a family of promising organometallic compounds containing 209Bi as QN have been characterized. Important factors like temperature, chemical structure, and chemical environment have been considered by NQR spectroscopy and abinitio quantum chemistry calculations. The investigated Bi-aryl compounds turned out to fulfill several crucial requirements: NQR transition frequency range applicable to clinical 1.5- and 3T MRI systems, low temperature dependency, low toxicity, and tunability in frequency by chemical modification.