Synthesis and Characterization of a Hypoxia‐Sensitive MRI Probe

Tissue hypoxia occurs in pathologic conditions, such as cancer, ischemic heart disease and stroke when oxygen demand is greater than oxygen supply. An imaging method that can differentiate hypoxic versus normoxic tissue could have an immediate impact on therapy choices. In this work, the gadolinium(III) complex of 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) with a 2‐nitroimidazole attached to one carboxyl group via an amide linkage was prepared, characterized and tested as a hypoxia‐sensitive MRI agent. A control complex, Gd(DO3A‐monobutylamide), was also prepared in order to test whether the nitroimidazole side‐chain alters either the water proton T₁ relaxivity or the thermodynamic stability of the complex. The stabilities of these complexes were lower than that of Gd(DOTA)^? as expected for mono‐amide derivatives. The water proton T₁ relaxivity (r₁), bound water residence lifetime (τ_M) and rotational correlation time (τ_R) of both complexes was determined by relaxivity measurements, variable temperature ¹⁷O NMR spectroscopy and proton nuclear magnetic relaxation dispersion (NMRD) studies. The resulting parameters (r₁=6.38 mM ^?1 s^?1 at 20 MHz , τ_M=0.71 μs, τ_R=141 ps) determined for the nitroimidazole derivative closely parallel to those of other Gd(DO3A‐monoamide) complexes of similar molecular size. In vitro MR imaging experiments with 9L rat glioma cells maintained under nitrogen (hypoxic) versus oxygen (normoxic) gas showed that both agents enter cells but only the nitroimidazole derivative was trapped in cells maintained under N₂ as evidenced by an approximately twofold decrease in T₁ measured for hypoxic cells versus normoxic cells exposed to this agent. These results suggest that the nitroimidazole derivative might serve as a molecular reporter for discriminating hypoxic versus normoxic tissues by MRI.     

Simulation of the effects of complex‐formation equilibria in electrophoresis: III. Simultaneous effects of chiral selector concentration and background electrolyte pH

This paper describes the results of the second‐level testing of the simulation program Simul 5 Complex. We compare the published experimental results with the simulated migration behavior of the enantiomers at different pH and chiral selector concentration values and use the same optimization object function, separation selectivity, as the original papers. Simul 5 Complex proved to be a suitable tool for the prediction of the effective mobilities, separation selectivities, and migration order reversals in these pH‐dependent and CD concentration dependent enantiomer separations. In addition, by performing simulations of four different separations systems (both real and model systems), Simul 5 Complex revealed the existence of unexpected and hitherto unexplained electromigration dispersion effects that were caused by the complexation process itself and could significantly impair the quality of the separations.     

Influence of different bentonites on the rare earth element concentrations of clarified Romanian wines

The rare earth element (REE) concentrations of 19 Romanian young wine samples originating from the Dealurile Moldovei viticulture area were determined by double focusing inductively coupled plasma mass spectrometry (DF-ICP-MS) after microwave-assisted digestion with nitric acid. The determination of Eu was hampered by the BaO molecular interference. Generally, the red wine samples were more concentrated for REEs than the white wine samples studied. The REE concentrations of the four bentonites (Gelbenton, Evergel, BW200, Tükrös) determined after their fusion were higher by three orders of magnitude than those of the wine samples. After a simulated wine purification process performed with these bentonite samples and a red and white pool samples, the REE concentrations of the clarified wine samples increased by 1.2–1.5 times for red, and 1.3–3 times for white wines in case of the fibrous bentonite sample (Gelbenton), by about 2–5 times in case of the bentonite containing ovalbumin, caseine and gelatine (Evergel), meanwhile this factor was about 20–25 for Na bentonite powder samples (BW200, Tükrös). On basis of the chemometric evaluation using the REE concentrations as input data, the majority of the Feteasca wines belonged to the same cluster as well as the two Cabernet Sauvignon to another subcluster. The adequate choice of the bentonite may allow the use of REEs as fingerprints for determining the wine provenance.     

Regioselective reactions of mesyloxymethylazetidinones with nucleophiles I. Cleavage of the azetidinone ring,azetidinone‐aziridine ring transformations

The reaction of 4‐mesyloxymethylazetidin‐2‐one derivatives 3 with ammonia and sodium methoxide was investigated. The two electrophilic centers of the substrate reactesuccessively, resulting in cleavage of the lactam bond and formation of a new aziridine ring. The resulting type 6 and 8 aziridinylacetic acid derivatives are related to the novel 2‐(aziridin‐2‐yl)‐3‐phenylpropionic acid type carboxypeptidase A inhibitors and, as such, potential drug candidates.     

Restricted set addition: The exceptional case of the Erd?s-Heilbronn conjecture

Let A≠B be nonempty subsets of the group of integers modulo a prime p. If p?|A|+|B|−2, then at least |A|+|B|−2 different residue classes can be represented as a+b, where a∈A, b∈B and a≠b. This result complements the solution of a problem of Erd?s and Heilbronn obtained by Alon, Nathanson, and Ruzsa.     

Heterogeneous crystal nucleation: the effect of lattice mismatch

A simple dynamical density functional theory is used to investigate freezing of an undercooled liquid in the presence of a crystalline substrate. We find that the adsorption of the crystalline phase on the substrate, the contact angle, and the height of the nucleation barrier are nonmonotonic functions of the lattice constant of the substrate. We show that the free-growth-limited model of particle-induced freezing by Greer et al. [Acta Mater. 48, 2823 (2000)] is valid for larger nanoparticles and a small anisotropy of the interface free energy. Faceting due to the small size of the foreign particle or a high anisotropy decouples free growth from the critical size of homogeneous nuclei.     

Unusual behaviour of N‐cinnamoyl‐2‐hydroxy‐2‐(trifluoromethyl)‐arylethylamines in pictet‐gams cyclization. Synthesis of 2‐styryl‐5‐aryl‐5‐trifluoromethyl‐2‐oxazolines

Cyclization of N‐acyl‐2‐hydroxy‐2‐(trifluoromethyl)arylethylamines 4 under Pictet‐Gams conditions afforded 2‐oxazolines 5 instead of the expected isoquinolines 6 . The effect of the trifluoromethyl group on the result of the reaction is discussed.     

A steroidal phenyldi­hydro‐1,3‐oxazine derivative

The structure of methyl (6R)‐6‐(3′β‐acetoxy‐5′‐androsten‐17′β‐yl)‐2‐phenyl‐5,6‐dihydro‐4H‐[1,3]oxazine, C₃₁H₄₁NO₃, synthesized from an azidopregnene derivative, is reported. The di­hydro‐1,3‐oxazine ring is connected in the β position to the sterane skeleton at C‐17′. An R configuration was found at C‐6.     

Equilibrium Swelling of an Epoxy‐Resin in Contact with Water – A Molecular Dynamics Simulation Study

Full Paper: We have studied the equilibrium swelling of an idealized model network based on a realistic epoxy‐resin in contact with water using the molecular dynamics simulation method. We use a novel method to measure the water chemical potential inside the network as function of water concentration. The equality of the water chemical potential computed in this fashion with the bulk water chemical potential under the same thermodynamic conditions determines the equilibrium water content and the swelling ratio. We study the dependence of the water content as function of temperature and as function of the size of the atomic partial charges.

Schematic representation of the simulation volume. Spheres represent epoxy units with n = 0. The dashed lines represent curing agent units with m = 5.