The solution conformation of prostacyclin as determined by high field proton magnetic resonance techniques

Abstract

The proton magnetic resonance (1H nmr) spectrum at 400 MHz of prostacyclin at pH 10.4 in glycine buffer has been completely analyzed utilizing homonuclear double resonance, inversion recovery, and difference nOe experiments. The spectral analysis shows that the two protons at C-4 are non-equivalent even though they are removed from the asymmetric centres at C-8 and C-9 by five bonds. The difference nOe measurements verify the configuration at C-5.Proton longitudinal relaxation times (T1) were measured at 400 and 200 MHz. From the T1 frequency dependence, effective rotational correlation times ranging from 2.3 × 10−10 to 3.0 × 10−10 s were calculated for H-5, H-9, H-11, and H-15. This indicates that the portion of the molecule encompassed by these protons has a longer correlation time than is observed for the C-2 and the C-17 to C-19 protons, for which the average correlation time is 1.2 × 10−10 s. Hence the aliphatic side chains have more segmental motion.

A nuclear Overhauser effect difference study of the solution conformation of (6R)-prostaglandin I1

“…This was previously observed for PGI, (20), and prostaglandin E, (21). This conclusion is in agreement with the torsion angle dependency of chemical shifts for fivemembered prostanoid precursors (22).…”

“…These results confirm the assignment of H-1 1 . In fact, the chemical shifts of H-9, H-15, and H-11 from low to high field, respectively, fall in the same order as was observed for PGI, previously (20). The chemical shift for H-100 is obtained from both of these experiments.…”

“…The C-11 OH group will be further away from the (C-8HC-9) bond in buffer solution than in CDC1, due to solvation of this OH group by the water. Finally, a comparison of the chemical shift data in phosphate buffer (Table 2) with the data obtained for PGI, (20) shows that the highest change is for H-7a (1.36 ppm) and for H-7P (2.23 ppm) since for PGI, these chemical shifts are 2.38ppm and 2.65 ppm, respectively. These high-field shifts, in addition to that for H-5, must be due to the saturation of the (C-5HC-6) double bond.…”

A nuclear Overhauser effect difference study and a two-dimensional J proton magnetic resonance study of (6S)-prostaglandin I1

“…The structure contains a surements have proved to be invaluable in the nmr between C5 and C61 the studies of PGI, (18) and (6R)-PGI, (19). In the atom at C5 has the 5Z but the rest present study, these measurements, together with the molecule is identical to PGI,.…”

Homonuclear one- and two-dimensional nuclear Overhauser effect experiments and spin-echo correlated spectroscopy. Application to prostaglandin E1 and 6-keto-prostaglandin E1

“…The selective proton-proton one-dimensional (ID) nOe experiments have been extensively applied in the study of molecular structure and conformation (6)(7)(8)(9). This experiment requires the measurement of the intensity change of a proton resonance upon saturating another proton.…”