Structural Analysis of the Prostamide 15d-PMJ2 by Computational Studies

Abstract

Prostaglandins are biologically active molecules with diverse physiological functions. Derivatives such as 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) have demonstrated potent anticancer activity. Synthesis of 15d-PGJ2 typically results in a mixture of E and Z isomers. However, experiments consistently observe a strong preference for the E isomer, which has been associated with biological activity in some systems (Li et.al.,2018). This study employed Density Functional Theory (DFT) calculations using Gaussian and GaussView to investigate the origin of this stereoselectivity. Two basis sets, B3LYP/6-31G(d,p) and cc-PVTZ, were used to balance computational efficiency and accuracy. Geometry optimizations, frequency analyses, and coordinate scans were performed to evaluate stability and reaction pathways. Results showed negligible thermodynamic energy differences between the isomers. However, spontaneous conversion of the Z isomer to the E isomer during optimization highlighted kinetic control. Coordinate scans indicated shallow energy barriers and identified multiple local minima, confirming accessible isomerization pathways. The hydroxyl group positioning significantly impacted stability, emphasizing the role of internal steric effects. Future work will refine transition state location and apply experimental techniques like qNMR and Mass Spectrometry to further validate these computational findings.