Fluorine (19F) MRI to Measure Renal Oxygen Tension and Blood Volume: Experimental Protocol

Fluorinated compounds feature favorable toxicity profile and can be used as a contrast agent for magnetic resonance imaging and spectroscopy. Fluorine nucleus from fluorinated compounds exhibit well-known advantages of being a high signal nucleus with a natural abundance of its stable isotope, a convenient gyromagnetic ratio close to that of protons, and a unique spectral signature with no detectable background at clinical field strengths. Perfluorocarbon core nanoparticles (PFC NP) are a class of clinically approved emulsion agents recently applied in vivo for ligand-targeted molecular imaging. The objective of this chapter is to outline a multinuclear 1H/19F MRI protocol for functional kidney imaging in rodents for mapping of renal blood volume and oxygenation (pO2) in renal disease models.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol chapter is complemented by a separate chapter describing the basic concept of functional imaging using fluorine (19F) MR methods.

An efficient DFT method of predicting the one-, two- and three-bond indirect spin–spin coupling constants involving a fluorine nucleus in fluoroalkanes

The values of the indirect nuclear spin–spin coupling constants for a series of aliphatic fluorocompounds have been calculated using DFT-based methods and compared with the experimental values of these parameters.

A theoretical study of potentially observable chirality-sensitive NMR effects in molecules

Derivatives of fluorocyclopropene have large antisymmetric parts of the fluorine nucleus shielding tensor, thus they are promising molecules for direct determination of chirality by NMR analysis.

A Low Field Fluorine-Electron Double Resonance Study for GALV and BDPA in Some Aliphatic and Aromatic Solvents

Dynamic nuclear polarization experiments were performed to study the solutions of the stable free radicals Galvinoxyl and α,γ -Bisdiphenylene-β -phenyl allyl complex with benzene (1 : 1) in some highly fluorinated aliphatic and aromatic solvents. The measurements were performed at four different temperatures to test the dipolar and the scalar part of the coupling between the fluorine nucleus (19F) and the unpaired electron. It was found that in the samples with Galvinoxyl the dipolar interactions are more effective for the aromatic solvents, while the scalar interactions are more effective for the aliphatics. An alteration from negative to positive region for the nuclear-electron coupling parameter informing on scalar or dipole-dipole interaction was observed only for 2,2,3,4,4,4-Hexafluoro- 1-butanol solvent with increasing temperature. The nuclear-electron coupling parameter varies between −0.003 and 0.228 in all aliphatic solvents and between 0.180 and 0.318 in aromatic solvents. Overhauser enhancement was not observed in the samples prepared with Hexadecafluoroheptane, Heptafluorobutyric acid, and Nonafluoropentanoic acid for both free radicals in all temperatures. These solvents may have scavenging effects on the radicals due to their behaviour.

Six-bond 1H,1H and 1H,19F spin coupling constants as indicators of geometry in aniline and p-fluoroaniline

The long-range coupling constants between amino protons and the ring proton or fluorine nucleus in the para position of aniline and p-fluoroaniline imply that, in benzene solution, the geometry at the amino group is very similar in the two compounds. The ratio of the two coupling constants is consistent with potential functions for inversion at nitrogen derived from far infrared data, but inconsistent with microwave spectra which indicate that the angle defining the intersection of the amino and benzene planes differs by 9° in these two compounds.

Concerning the extension of the J method for internal barriers to six-bond couplings to 19F in the 4-fluorophenyl fragment

The long-range coupling constants over six bonds from the side-chain protons to the fluorine nucleus on the ring are extracted from the proton magnetic resonance spectra of p-fluorobenzyl cyanide, chloride, and bromide; of p-fluorobenzal chloride; and of p-fluoroisopropylbenzene. On the assumption that these couplings are transmitted via a σ–π mechanism, a hindered rotor treatment yields the barriers to internal rotation about the carbon–carbon bond which attaches the substituent to the benzene ring. These barriers, when compared to those derived from the analogous proton–proton coupling constants, apparently are accurate enough for the determination of ground state conformations and for a rough assessment of the energetics of conformational interconversions.

Sternheimer Antishielding of the Fluorine Ion in Octahedral (MeF6)4-Complexes of Transition Metals from Perturbed Angular-Correlation Measurements

Sternheimer antishielding factors of fluorine in octahedral transition metal complexes have been determined from nuclear quadrupole coupling data derived from differential perturbed angularcorrelation measurements taking into account ionic and covalent contributions to the electric field gradient at the fluorine nucleus. It has been found that the antishielding effect increases with increasing d-occupation in the metal ion, but is different for perovskite and rutile complexes and cannot be described by a scalar factor for the F--ions in rutile fluorides, where the fluor position is of less than axial symmetry

The para substituent dependence of the internal rotational barrier in benzenethiol

On the basis of the observed spin–spin coupling constants between the sulfhydryl and ring protons and a hindered rotor treatment of the twofold barrier to internal rotation in a series of para substituted benzenethiol derivatives, it is argued that V2 is essentially zero in p-amino-benzenethiol and is 2.5 ± 0.2 kcal/mol in p-nitrobenzenethiol; having intermediate values for the methoxy, fluoro, methyl, and bromo derivatives in solution. The results are based on an assumed relationship between the four-bond and the fictitious six-bond couplings to the sulfhydryl proton. The conclusions are consistent with the observed magnitudes of the couplings over six and seven bonds, respectively, between the sulfhydryl proton and the fluorine nucleus and the methyl protons in the appropriate derivatives; as well as with the coupling between the sulfhydryl and methyl protons in 4-bromo-3-methylbenzenethiol. The experimental barriers are compared with ab initio molecular orbital calculations of their substituent dependence.

Through-space or proximate 19F,19F and 19F,1H spin–spin coupling constants in some benzenesulfonyl fluoride derivatives

The analysis of the fluorine and proton magnetic resonance spectra of 2,4,6-trimethylbenzenesulfonyl fluoride and of 2,5-difluorobenzenesulfonyl fluoride yields the signs and magnitudes of the spin–spin coupling constants containing a through-space component. The coupling between the fluorine nucleus and the methyl protons over five bonds is +1.9 Hz, opposite in sign to the −3.1 Hz observed for the corresponding coupling in 2,6-dimethylbenzoyl fluoride. The difference of 5 Hz is possibly a consequence of the different conformational preference of the SO2F and COF substituents. The coupling over four bonds between the fluorine nucleus on the side chain and that on the ring is +11.6 Hz in 2,5-difluorobenzenesulfonyl fluoride. It is argued that this value indicates a preference of the S—F bond for a plane lying, on average, nearly perpendicular to the benzene ring. Similar indications are noted for pentafluorobenzenesulfonyl fluoride and for pentafluorobenzenesulfinyl fluoride.