FTIR spectral study of intramolecular hydrogen bonding in E-type of 15-keto-prostaglandins in dilute CCl 4 solution: Structure-activity relationships

Abstract

FTIR spectra of 15-keto-prostaglandin (PG)E 1 (1), 15-keto-PGE 1 (2), 13,14-dihydro-15-keto-PGE 2 (3), 13,14-dihydro-15-keto-PGE 1 (4), and their related compounds were measured in dilute tetrachloromethane solution in order to examine the structure-activity relationships for the 5,6- cis-double bond of the α-side chain and the 13,14- trans-double bond and the 15-hydroxyl group of the ω-side chain in PGE 2, PGD 2, and PGF 2α. The spectra were subjected to curve analysis to separate overlapping absorption bands. For compounds 1–4, an intramolecular hydrogen bond involving a 15-membered ring similar to that observed for PGE 2, PGD 2, and PGF 2α was found between the carboxyl and 15-carbonyl groups. The percentages (p) of the intramolecular hydrogen-bonded molecules with the 15-membered rings in 1–4 and PGE 2 were compared with the known binding activities of PGs for various PG receptors, and we found that these activities decrease as the p values decrease. These results strongly supported our hypothesis that, in PGs, the conformation with the 15-membered ring formed by the intramolecular hydrogen bonds between the carboxyl group of the α-side chain and the 15-hydroxyl group of the ω-side chain is a precursory conformation of the active one.