BMS-747158-02 exhibited high and sustained cardiac uptake that was proportional to blood flow, and it represents a new class of PET myocardial perfusion imaging agent.

No abstract

13C NMR spectra of labeled [1-13C]- and [2-13C]ascorbic acid were seen to contain resonances arising from the intra- and extracellular populations in suspensions of human erythrocytes; i.e., they displayed the "split-peak" phenomenon. This new observation enabled the ready determination of the location, whether inside or outside cells, of the redox reactions in which the vitamin C was involved and to monitor the transport of the compounds into and out of the cells. Thus, the membrane permeability of ascorbic acid and the apparent Vmax and KM for the reduction of dehydroascorbic acid were determined in a noninvasive manner. In contrast to other work, evidence was found of a transporter of dehydroascorbic acid which is different from the glucose transporter. This transport system also appeared to be involved in the simultaneous reduction of dehydroascorbic acid on its passage into the cells. A second reduction process appeared to occur extracellularly, by the passage of reducing equivalents through the plasma membrane, as occurs with the reduction of ferricyanide. Evidence is presented that the processes of vitamin C recycling rely on different cellular sources of reducing equivalents. Whereas the transport and reduction via the membrane appeared to be dependent on glycolysis (NADH), the reduction of intracellular dehydroascorbic acid, formed in the process of transmembrane electron transfer or by transport from the outside of the cell, is currently thought to depend on NADPH.

The effect of ring-oxygen protonation on the structure and conformational properties of a model deoxyaldofuranose, 2-deoxy-β-d-glycero-tetrofuranose 2, has been examined with the use of NMR spectroscopy and ab initio molecular orbital calculations conducted at the HF/6-31G* level of theory. The computational method was validated by comparing the conformational behavior of 2 derived from PSEUROT treatment of 3 J HH values measured in 2 (2H2O solvent) with that predicted from the theoretical calculations. Coupling data indicate that 2 favors S forms in solution (∼89% 4T3, ∼11% E2), while MO data indicated more comparable populations of the same or very similar N and S forms. Protonation of 2 at the ring oxygen (O4), yielding 1, gave two distinct protonated forms which differed in the orientation of the proton about O4. Both forms showed substantial changes in ring structure and conformation compared to 2. Protonated forms almost exclusively prefer S forms (E3), and energy barriers for N/S interconversion were found to be considerably higher than those for 2, leading to the conclusion that 1 is more conformationally constrained than 2. Bond lengths in the vicinity of O4 changed significantly upon conversion of 2 to 1; for example, the C1−O4 bond length increases by ∼14%, the C1−H1 and C1−O1 bond lengths decrease by 1−5%, and the C4−O4 bond length increases by ∼5%. These results indicate that O4 protonation predisposes 2 toward ring opening by inducing specific structural and conformational modifications, thus providing a more concise explanation of the role of acid catalysis in furanose anomerization (i.e., 1 resembles the transition state of the acid-catalyzed anomerization reaction more than 2). The molecular orbital data obtained in this investigation also provide evidence for a new structural factor (a 1,3-effect involving oxygen lone-pair orbitals) that influences bond lengths in carbohydrates.