Boronic acids for sensing and other applications - a mini-review of papers published in 2013

Boronic acids are increasingly utilised in diverse areas of research. Including the interactions of boronic acids with diols and strong Lewis bases as fluoride or cyanide anions, which leads to their utility in various sensing applications. The sensing applications can be homogeneous assays or heterogeneous detection. Detection can be at the interface of the sensing material or within the bulk sample. Furthermore, the key interaction of boronic acids with diols allows utilisation in various areas ranging from biological labelling, protein manipulation and modification, separation and the development of therapeutics. All the above uses and applications are covered by this mini-review of papers published during 2013

Optimizing the relaxivity at high fields: systematic variation of the rotational dynamics in polynuclear Gd-complexes based on the AAZTA ligand

A homogeneous series of polynuclear structures containing from 2 to 6 GdAAZTA complexes (AAZTA = 6-amino-6-methylperhydro-1, 4-diazepine tetraacetic acid) were synthesized covering a broad range of molecular weights, ca. 1200-6000 Da. A frequency and temperature dependent H-1 and O-17 NMR relaxometric study on the Gd(iii) polynuclear complexes clearly highlights a considerable gain of relaxivity (per Gd) passing from the monomer to the hexanuclear complex, with an enhancement of +370% at 1.5 T and 298 K (+470% at 310 K). In particular, the relaxivity of the hexamer reaches a remarkable value of 28.2 mM(-1) s(-1) at 1.5 T and 298 K (23.8 mM(-1) s(-1) at 310 K). The NMR study, supported by DFT calculations, allows analysis in detail of the dependence of the rotational dynamics on the size and molecular geometry of the multimers, considering both the global tumbling of the system and the local motions of the monomer units. In addition, T-1-weighted phantom MR-images at 1, 3 and 7 T on selected polynuclear complexes highlighted the effective signal enhancement of the new MRI probes at clinically relevant magnetic field strengths in comparison with the clinically approved contrast agent ProHance (R). Finally, the results obtained enable us to highlight effective strategies for relaxation enhancement, each suitable for a well-defined range of applied magnetic field strength

Contrast agents for magnetic resonance imaging: A novel route to enhanced relaxivities based on the interaction of a Gd-III chelate with poly-beta-cyclodextrins

This study proposes a novel route to improved contrast agents for magnetic resonance imaging (MRI) applications based on the formation of a non-covalent adduct between a paramagnetic complex and an exogeneous macromolecule. For this purpose a 12-membered pyridine-containing triacetate macrocyclic ligand with a p-bromo-benzyloxy substituent on the pyridine moiety was synthesized. The Gd-III complex containing this ligand shows a relaxivity of 8.25 mM(-1)s(-1) at 20 MHz and 25 degrees C The hydrophobic p-bromo-benzyloxy moiety promotes the interaction of the chelate with human serum albumin (HSA) (K-a = 4 x 10(2) M-1) and with beta-cyclodextrin (K-a = 8 x 10(2) M-1). Upon replacing beta-cyclodextrin with a poly-beta-cyclodextrin substrate (MW = ca. 6000 Da) a further relaxation enhancement is detected as a consequence of the increased molecular size of the resulting inclusion compound. In a typical experiment in blood serum, the observed relaxivity is 32 mM(-1) s(-1) (20 MHz, 25 degrees C) when the concentrations are as follows: Gd-III chelate 1 mM, poly-beta-cyclodextrin 10 mM, HSA 0.58 mM. Under these conditions the Gd-III chelate is mainly present as an inclusion compound with the poly-beta-CD. This finding suggests a potential use for such a Gd-III chelate/poly-beta-CD system in MR angiographic application

Improved route for the visualization of stem cells labeled with a Gd-/Eu-chelate as dual (MRI and fluorescence) agent

A simple labeling procedure of stem/progenitor cells based on the use of Gd-HPDO3A and Eu-HPDO3A, respectively, is described. The Gd-chelate acts as T(1)-agent for MRI visualization, whereas the corresponding Eu-chelate acts as reporter in fluorescence microscopy. Owing to their substantial chemical equivalence, the two chelates are equally internalized in EPCs (endothelial progenitor cells), thus allowing their visualization by both techniques. The lanthanide chelates are entrapped in endosomic vesicles and the labeled cells retain biological activity with preservation of viability and pro-angiogenesis capacity. Hyperintense spots in MR have been observed for Gd-labeled EPCs injected under mice kidney capsule or grafted on a subcutaneous Matrigel plug up to 14 days after transplantation

Magnetic resonance imaging of gadolinium-labeled pancreatic islets for experimental transplantation

New imaging techniques that couple anatomical resolution to sensitivity may greatly contribute to improving islet transplantation. In the present work, a report is given of the direct detection of islets by magnetic resonance imaging (MRI) after ex vivo cell labeling with the MRI T(1) contrast agent GdHPDO3A. Experiments on mouse and human islets demonstrated well-tolerated uptake of GdHPDO3A, based on morphology, viability, glucose-dependent insulin response and apoptosis/toxicity gene array profile. GdHPDO3A loading was sufficient for in vitro MRI cell detection. In vivo isotransplanted mouse islets into the kidney capsule and xenotransplanted human islets within the mouse liver were detected. Imaging specificity was supported by the absence of signal in unlabeled islet transplants, its persistence upon using fat-suppression MRI protocols and the colocalization with the transplanted islets. In conclusion, direct islet imaging with high spatial and contrast resolution after labeling with GdHPDO3A is demonstrated, allowing visualization of kidney subcapsular mouse islet grafts and intrahepatic human islet xenografts