A series of fluorinated macrocyclic complexes, M-DOTAm-F12, where M is La, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Fe, was synthesized, and their potential as fluorine magnetic resonance imaging (MRI) contrast agents was evaluated. The high water solubility of these complexes and the presence of a single fluorine NMR signal, two necessary parameters for in vivo MRI, are substantial advantages over currently used organic polyfluorocarbons and other reported paramagnetic F probes. Importantly, the sensitivity of the paramagnetic probes on a per fluorine basis is at least 1 order of magnitude higher than that of diamagnetic organic probes. This increased sensitivity is due to a substantial-up to 100-fold-decrease in the longitudinal relaxation time (T) of the fluorine nuclei. The shorter T allows for a greater number of scans to be obtained in an equivalent time frame. The sensitivity of the fluorine probes is proportional to the T/T ratio. In water, the optimal metal complexes for imaging applications are those containing Ho and Fe, and to a lesser extent Tm and Yb. Whereas T of the lanthanide complexes are little affected by blood, the T are notably shorter in blood than in water. The sensitivity of Ln-DOTAm-F12 complexes is lower in blood than in water, such that the most sensitive complex in water, Ho-DOTAm-F12, could not be detected in blood. Tm yielded the most sensitive lanthanide fluorine probe in blood. Notably, the relaxation times of the fluorine nuclei of Fe-DOTAm-F12 are similar in water and in blood. That complex has the highest T/T ratio (0.57) and the lowest limit of detection (300 μM) in blood. The combination of high water solubility, single fluorine signal, and high T/T of M-DOTAm-F12 facilitates the acquisition of three-dimensional magnetic resonance images.

A molecular probe for the luminescent detection of adenosine nucleotides is presented. The probe, Tb-DOTAm-Phen, readily distinguishes among the three adenosine nucleotides in buffered aqueous conditions at neutral pH, a requirement for the direct monitoring of enzymatic reactions converting adenosine triphosphate (ATP) to adenosine diphosphate or adenosine monophosphate. The probe is most efficient under millimolar concentrations of ATP which are relevant to intracellular conditions. Moreover, the long luminescence lifetime of the probe readily enables time-gating experiments.

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The synthesis and properties of two responsive magnetoluminescent iron oxide nanoparticles for dual detection of DNA by MRI and luminescence spectroscopy are presented. These magnetoluminescent agents consist of iron oxide nanoparticles conjugated with metallointercalators via a polyethylene glycol linker. Two metallointercalators were investigated: Ru(bpy′)(phen)(dppz), which turns on upon DNA intercalation, and Eu-DOTAm-Phen, which turns off. The characteristic light-switch responses of the metallointercalators are not affected by the iron oxide nanoparticles; upon binding to DNA the luminescence of the ruthenium complexes increases by ca. 20 fold, whereas that of the europium complex is > 95 % quenched. Additionally, the 17–20 nm magnetite cores, having permeable PEG coatings and stable dopamide anchors, render the two constructs efficient responsive contrast agents for MRI with unbound longitudinal and transverse relaxivities of 12.4 – 9.2 mM−1Fes−1 and 135 – 128 mM−1Fes−1, respectively. Intercalation of the metal complexes in DNA results in the formation of large clusters of nanoparticles with a resultant decrease of both r1 and r2 by 32 – 63 % and 24 – 38 %, respectively. The potential application of these responsive magnetoluminescent assemblies and their reversible catch-and-release properties for the purification of DNA is presented.