Hafnium-Based Contrast Agents for X-ray Computed Tomography.

Heavy-metal-based contrast agents (CAs) offer enhanced X-ray absorption for X-ray computed tomography (CT) compared to the currently used iodinated CAs. We report the discovery of new lanthanide and hafnium azainositol complexes and their optimization with respect to high water solubility and stability. Our efforts culminated in the synthesis of BAY-576, an uncharged hafnium complex with 3:2 stoichiometry and broken complex symmetry. The superior properties of this asymmetrically substituted hafnium CA were demonstrated by a CT angiography study in rabbits that revealed excellent signal contrast enhancement.

Fab MOR03268 triggers absorption shift of a diagnostic dye via packaging in a solvent-shielded Fab dimer interface.

Molecular interactions between near-IR fluorescent probes and specific antibodies may be exploited to generate novel smart probes for diagnostic imaging. Using a new phage display technology, we developed such antibody Fab fragments with subnanomolar binding affinity for tetrasulfocyanine, a near-IR in vivo imaging agent. Unexpectedly, some Fabs induced redshifts of the dye absorption peak of up to 44 nm. This is the largest shift reported for a biological system so far. Crystal structure determination and absorption spectroscopy in the crystal in combination with microcalorimetry and small-angle X-ray scattering in solution revealed that the redshift is triggered by formation of a Fab dimer, with tetrasulfocyanine being buried in a fully closed protein cavity within the dimer interface. The derived principle of shifting the absorption peak of a symmetric dye via packaging within a Fab dimer interface may be transferred to other diagnostic fluorophores, opening the way towards smart imaging probes that change their wavelength upon interaction with an antibody.

Accurate solubility prediction with error bars for electrolytes: a machine learning approach.

Accurate in silico models for predicting aqueous solubility are needed in drug design and discovery and many other areas of chemical research. We present a statistical modeling of aqueous solubility based on measured data, using a Gaussian Process nonlinear regression model (GPsol). We compare our results with those of 14 scientific studies and 6 commercial tools. This shows that the developed model achieves much higher accuracy than available commercial tools for the prediction of solubility of electrolytes. On top of the high accuracy, the proposed machine learning model also provides error bars for each individual prediction.

Fluorinated dihydroquinolines as potent n-NOS inhibitors.

Fluorinated dihydroquinolines showed reduced basicity of the amidine function. Their syntheses and potencies as neuronal nitric oxide synthase (n-NOS) inhibitors are reported.

NMR and chiroptical examination of the diastereoisomers of (S)-Eu-EOB-DTPA.

The solution structure of the diastereoisomers of (S)-Eu--EOB--DTPA has been analysed by (1)H NMR, CD and CPL spectroscopy. Two major species exist which possess very similar (1)H NMR paramagnetic shifts and emission spectra, consistent with a 9-coordinate structure involving one bound water. Circularly polarised luminescence data are consistent with a common Lambda-helicity for each isomer; the isomers differ only in the absolute configuration of the central nitrogen atom.

Dihydroquinolines with amine-containing side chains as potent n-NOS inhibitors.

Dihydroquinolines with aminoalkyl side chains have been synthesized and have been shown to be potent n-NOS inhibitors. A marked selectivity versus e-NOS of up to approximately 300-fold was observed, whereas i-NOS was moderately inhibited.

Dihydroquinolines as novel n-NOS inhibitors.

Dihydroquinolines have been synthesized and have been shown to be potent n-NOS inhibitors. Selectivity versus e-NOS was increased to approximately 100-fold through appropriate substitution at the benzene ring.