1H-NMRD and17O-NMR assessment of water exchange and rotational dynamics of two potential MRI agents: MP-1177 (an extracellular agent) and MP-2269 (a blood pool agent)

The parameters that govern water proton magnetic relaxation (e.g. water exchange rates, and rotational and electronic correlation times) of representatives of two classes of Gd(III) complexes have been estimated, using two different approaches and the results compared with those derived for known analogs. The complexes studied are: (i) the non-ionic GdDTPA-bis(methoxyethyl-amide) [Gd(DTPA-BMEA)], a typical small-molecule extracellular MR agent, and (ii) the ionic Gd(III) complex of 4-pentylbicyclo[2.2.2]octane-1-carboxyl-di-l-aspartyl-lysine-derived-DTPA [GdL]⁴⁻, a prototype MR blood pool agent, which binds to serum albumin in vivo through non-covalent hydrophobic interactions. An¹⁷O-NMR study of [Gd(DTPA-BMEA)] gives a water exchange rate constant ofk _ex ²⁹⁸ =(0.39±0.02)×10⁶ s⁻¹, identical to that for the bismethylamide analog [Gd(DTPA-BMA)]. Both approaches yield longer rotational correlation times for [Gd(DTPA-BMEA)], consistent with its higher molecular weight. An¹⁷O-NMR study of [GdL]⁴⁻ gives a water exchange rate constant ofk _ex ²⁹⁸ =(4.2±0.1)×10⁶ s⁻¹, identical to that for [Gd(DTPA)]²⁻. The water exchange rate on [GdL]⁴⁻ did not decrease considerably when bound to albumin, the lowest limit isk _ex,GdL-BSA=k _ex,GdL/2. Both approaches yield identical rotational correlation times for [GdL]⁴⁻, however, it was difficult to derive a consistent rotational constant for the albumin-bound [GdL]⁴⁻ using the different approaches (values ranged between 1.0 and 23.0 ns).     

UV–Vis observation of different F0 → D0 transitions for both isomeric species in Eu(III) DOTA-like complexes

The presence of the two isomeric species (M and m) of Eu(III) (DOTA-like) complexes has been detected in aqueous solution by UV–Vis absorbance spectrophotometry. It shows that the ⁷F₀ → ⁵D₀ transition in Eu(III) complexes does not only depend on the coordinating atoms present in the first coordination sphere but that it may also be influenced by small differences in the coordination geometry. The absorbance spectra could be well fitted with the K=M/m equilibrium constants measured by NMR. The wavelength variation between the two isomers is found to be 0.20 nm (DTMA), 0.14 nm (DOTA) and about 0.25 nm (DOTAM) (DTMA=1,4,7,10-tetrakis-(methylcarbamoylmethyl)-1,4,7,10-tetraazacyclo-dodecane; DOTA=1,4,7,10-tetraaza-1,4,7,10-tetrakis(carboxymethyl)-cyclododecane; DOTAM=1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane). This is small enough not to affect the quantitative determination of water coordination equilibria in solution as hydration equilibria produce differences of about 0.5 nm.     

Gadonanotubes as ultrasensitive pH-smart probes for magnetic resonance imaging

With their nanoscalar, superparamagnetic Gd(3+)-ion clusters (1 x 5 nm) confined within ultrashort (20-80 nm) single-walled carbon nanotube capsules, gadonanotubes are high-performance T1-weighted contrast agents for magnetic resonance imaging (MRI). At 1.5 T, 37 degrees C, and pH 6.5, the r1 relaxivity (ca. 180 mM(-1) s(-1) per Gd(3+) ion) of gadonanotubes is 40 times greater than any current Gd(3+) ion-based clinical agent. Herein, we report that gadonanotubes are also ultrasensitive pH-smart probes with their r1/pH response from pH 7.0-7.4 being an order of magnitude greater than for any other MR contrast agent. This result suggests that gadonanotubes might be excellent candidates for the development of clinical agents for the early detection of cancer where the extracellular pH of tumors can drop to pH=7 or below. In the present study, gadonanotubes have also been shown to maintain their integrity when challenged ex vivo by phosphate-buffered saline solution, serum, heat, and pH cycling.     

High-pressure stopped-flow spectrometer for kinetic studies of fast reactions by absorbance and fluorescence detection

The development of a stopped-flow instrument that operates over a temperature range of -40 to +100 °C and up to 200 MPa is described. The system has been designed so that measurements can be performed in absorbance and fluorescence modes simultaneously, without dismantling the unit. It can easily be combined with an optical system of a conventional ambient pressure setup by using light guides. Optimum optical performance and a wide operating wavelength range (220-850 nm) are achieved as the light is not passing through the pressurizing fluid. A special design for the pistons has been developed; thus, the apparatus has proven to be leak-free, even under extreme conditions (high pressure, low temperature, various solvents). The dead time of the system is found to be less than 2 ms at 298 K and is pressure independent up to 200 MPa. We examined the kinetics for the formation of the Mg(2+)-8-hydroxyquinoline chelate in aqueous solutions at pH 8.0 in order to develop a convenient alternative test method for high-pressure stopped-flow spectrometers with absorption and fluorescence detection.