Cynthia J. Hartzell

Rapid acquisition of NOE difference spectra. The relative merits of transient versus driven experimental protocols

Abstract The effect of substantial reduction in the preparatory waiting period employed in the collection of nuclear Overhauser effect spectra has been examined experimentally for systems near the extreme narrowing limit with particular emphasis on the truncated driven and selective inversion-recovery techniques which do not require a long evolution period. Over short evolution periods the NOE buildup rate should be directly proportional to the cross-relaxation rate by either method. The transient NOE experiment still provides accurate ratios of cross-relaxation rates even when the waiting time is less than T 1 . Comparisons of fractional enhancement data for prostaglandin F 2 α and four other prostanoids obtained by standard (long waiting time) and rapid acquisition protocols indicate that the rapid acquisition method can, with the proper choice of integration standards, be used for quantitative studies.

The single prostacyclin receptor of gel-filtered platelets provides a correlation with antiaggregatory potency of PGI2 mimics.

Gel-filtered human platelets (GFP) display only a single binding site for [3H]-PGI2: KD = 61nM, 234 fmol/10(8) platelets (1410 sites/platelet). Platelet-rich plasma (PRP) displays the same receptor density but the KD value increases to 123 nM due to protein binding of PGI2 which lowers its effective concentration. The [3H]-PGI2/GFP binding assay has been used to evaluate the molecular basis of aggregation inhibition for prostacyclin analogs and mimics, three PGE type structures, and PGD2. Antiaggregatory IC50s and radioligand binding IC50s correlate for PGE2, E1, and six PGI2 analogs. PGD2, and to a lesser extent 6-oxo-PGE1, display greater antiaggregatory potency than expected based on PGI2-binding site affinity data.

High-field 1H NMR studies of prostaglandin H2 and its decomposition pathways

Prostaglandin H2 displays at 500 MHz a detailed 1H-NMR in which all methylene groups are non-equivalent in C6D6 solution. The spectrum was assigned by analogy to isosteric structures. The dissymmetric perturbation and steric hindrance of the bicyclo [2.2.1] core caused by the side-chains provides a rationale for the selective fragmentations which PGH2 undergoes. Purified PGH2 is considerably more robust than previous literature accounts suggest. The following transformations were monitored by 1H-NMR: 1) O-O bond cleavage by Ph3P , 2) aqueous media fragmentation to PGE2 and PGD2, 3) base catalyzed fragmentation to ketoaldehydes , and 4) thermolysis attempts.

A determination of the quadrupole tensors in a single crystal of dl-serine-d2 at 4.2 K

Abstract NMR transitions are detected by electron nuclear double resonance at 4.2 K in a single crystal of doubly deuterated dl -serine. Quadrupolar splittings are measured from spectra acquired at 5° intervals in three orthogonal planes. From the angular dependence of these splittings, the quadrupole tensor and the orientation of the principal axis system with respect to the crystal axes are determined for the methylene deuterons. The relationship between the C-D bond length and the quadrupole coupling constant is discussed. In general, based on data available to date, one might expect the typical methylene bond length to lie in the range of 1.095 ± 0.010 A and the quadrupole coupling constant to lie in the range 170 ± 10 kHz.