Céline Henoumont

How to measure the transmetallation of a gadolinium complex

The suitability of paramagnetic complexes as contrast agents depends not only on their relaxivity but also on their stability and inertness towards transmetallation processes by endogenous ions. In this work, we describe a convenient method to study the stability of paramagnetic Gd complexes through the evolution of the paramagnetic longitudinal relaxation rate of water protons at 37 °C.

How to perform accurate and reliable measurements of longitudinal and transverse relaxation times of MRI contrast media in aqueous solutions.

Knowledge of the longitudinal and transverse relaxation times (T(1) and T(2)) of water protons in an aqueous solution of an MRI contrast agent is essential for its characterization. These parameters can be measured at low field on low resolution spectrometers or at high field on high resolution spectrometers. The reliability and the accuracy of T(1) and T(2) measurements rely on several experimental settings and on the equation used to fit the data. Examples of the importance of careful adjustment of the most important parameters are illustrated through several measurements performed on a low-resolution, low-magnetic field instrument. In addition, some specificities of T(1) and T(2) measurements on high-resolution, high-magnetic field spectrometers are pointed out.

Purification and characterization of the acetone carboxylase of Cupriavidus metallidurans strain CH34

ABSTRACT Acetone carboxylase (Acx) is a key enzyme involved in the biodegradation of acetone by bacteria. Except for the Helicobacteraceae family, genome analyses revealed that bacteria that possess an Acx, such as Cupriavidus metallidurans strain CH34, are associated with soil. The Acx of CH34 forms the heterohexameric complex α2β2γ2 and can carboxylate only acetone and 2-butanone in an ATP-dependent reaction to acetoacetate and 3-keto-2-methylbutyrate, respectively.

Synthesis and physicochemical characterization of Gd-C4-thyroxin-DTPA, a potential MRI contrast agent. Evaluation of its affinity for human serum albumin by proton relaxometry, NMR diffusometry, and electrospray mass spectrometry.

Gd-C(4)-thyroxin-DTPA, a potential MRI contrast agent, was synthesized from Gd-DTPA and thyroxine, which interacts strongly with human serum albumin (HSA). It was characterized in water by its relaxometric properties and its stability versus zinc transmetalation. The affinity of the complex for HSA was studied by using three different methods: proton relaxometry, NMR diffusometry, and electrospray mass spectrometry. From the results, it appears that Gd-C(4)-thyroxin-DTPA exhibits a relatively high relaxivity (r(1) = 9.01 s(-1) mM(-1) at 1.5 T and 310 K), a good stability versus zinc transmetalation, and a strong interaction with HSA (K(a) approximately 10,000 M(-1) with two binding sites). The kinetics of the exchange between the bound and the free form of the complex was evaluated by the NMR diffusometry technique. Competition experiments have allowed the assignment of the chelates binding site on HSA.

Superparamagnetic Iron Oxide Nanoparticles

Thanks to their unique properties, inorganic nanostructures have become the center of modern material science. Among existing nanomaterials, magnetic iron oxide nanoparticles (IONP) have attracted a lot of interest. These nanoparticles are suitable for many technological applications such as contrast agent for magnetic resonance imaging. When comparing to molecular MRI probes (Gd-based organic complexes), IONP present many advantages such as a better sensitivity, a poor toxicity, and the possibility to easily modify their surface to develop some properties as multimodality, modulable half-life or specificity. However, one must stress that these properties are related to IONP’s composition, shape and stability (physical and chemical). In that paper, we will introduce some concepts related to IONP’s physico-chemical properties, the synthetic ways to obtain such structures and we will finish with some concepts governing their stability and surface modification.

HR-MAS NMR spectroscopy: an innovative tool for the characterization of iron oxide nanoparticles tracers for molecular imaging.

The development of molecular imaging by MRI requires the use of contrast agents able to recognize specifically a peculiar target at the molecular level. Iron oxide nanoparticles grafted with small organic molecules represent an interesting platform for molecular imaging. The characterization of the surface of these nanoparticles is an important step in the development of these molecular agents, and HR-MAS NMR spectroscopy appears to be a very interesting tool. The use of 1D and 2D NMR spectra is indeed very helpful to investigate the covalent grafting of organic molecules at the nanoparticle surface. DOSY spectra could also be very helpful, but we will show here that it is not possible to obtain accurate DOSY spectra on iron oxide nanoparticles.

NMR chemical shift study of the interaction of selected peptides with liposomal and micellar models of apoptotic cells

AbstractThe interaction between two peptides previously selected by phage display to target apoptotic cells and phospholipidic models of these cells (liposomes or micelles made of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and/or 1,2-dipalmitoyl-sn-glycero-3-phospho-l-serine (DPPS, phosphatidylserine analog) was studied by the simple analysis of the changes induced on the proton NMR chemical shifts of the peptides. Our approach which does not need healthy and/or apoptotic cells for assessing the affinity of different peptides is fast and efficient and requires small amounts of peptide to determine the association constant, the interacting protons, and the number of interaction sites. The micellar model gave more reliable results than the liposomal one. The preferential interaction of the peptide with DPPS was evidenced by the change of the chemical shifts of specific amino acids of the peptides. Our micellar model is thus well suited to mimic apoptotic cells.

Effect of nonenzymatic glycosylation on the magnetic resonance imaging (MRI) contrast agent binding to human serum albumin.

Enhanced nonenzymatic glycosylation (NEG) of human serum albumin (HSA) is observed in diabetic patients. This modifies some of the physiological functions of HSA, as the binding of ligands. Some gadolinium complexes, commonly used as MRI contrast agents, have a high affinity for HSA, which enhances their efficacy. The aim of this study is to evaluate the possible influence of the NEG of HSA on its affinity for some gadolinium chelates.

NMR determination of free gallium(III) ions in aqueous solutions of Ga complexes, “cold” analogs of PET/SPECT tracers†

Ga complexes are widely used as radiopharmaceuticals for PET or SPECT imaging and as therapeutic agents. At physiological pH, free gallium(III) ions can stably exist as soluble gallate [Ga(OH)(4) ](-) , a nephrotoxic compound whose presence should be avoided. Any Ga complex, therefore, should be carefully checked for the absence of gallate before use. Here we show that (71) Ga NMR is a useful tool to rapidly detect the presence of gallate in aqueous solutions of Ga complexes and to follow the purification steps of the Ga complex solutions.

Flying Cages in Traveling Wave Ion Mobility: Influence of the Instrumental Parameters on the Topology of the Host–Guest Complexes

AbstractSupramolecular mass spectrometry has emerged in the last decade as an orthogonal method to access, at the molecular level, the structures of noncovalent complexes extracted from the condensed phase to the rarefied gas phase using electrospray ionization. It is often considered that the soft nature of the ESI source confers to the method the capability to generate structural data comparable to those in the condensed phase. In the present paper, using the ammonium ion/cucurbituril combination as a model system, we investigate using ion mobility and computational chemistry the influence of the instrumental parameters on the topology, i.e., internal versus external association, of gaseous host/guest complex ions. MS and theoretical data are confronted to condensed phase data derived from nuclear magnetic resonance spectroscopy to assess whether the instrumental parameters can play an insidious role when trying to derive condensed phase data from mass spectrometry results. Graphical Abstractᅟ