Date of Award
2026-05-01
Degree Name
Doctor of Philosophy
Department
Chemistry
Advisor(s)
James J. Salvador
Abstract
(R)-Ibuprofen was isolated and reacted with Candida rugosa lipase (CRL) at pH 7.6, the same reaction conditions that were used to convert racemic ibuprofen methyl ester to (S)-ibuprofen by Chavez et al. The lack of conversion of (R) to (S)-ibuprofen disproves the mechanism proposed by Mortazavi et al., that ibuprofen is deracemized by being enolized while being covalently bound to CRL (Section 2.1). α‑O‑benzyl glycerol (Section 2.2) and ibuprofenol (Section 2.5) were synthesized and subjected to the same deracemization conditions as ibuprofen methyl ester with CRL. Both compounds and their derivatives did not undergo deracemization. These reactions were run to test the hypothesis that the deracemization of ibuprofen methyl ester is a manifestation of triglycerides anchored to the CRL hydrophobic tunnel deracemized by a tandem protonation/deprotonation mechanism at the active site. Six further p-substituted profen methyl esters were deracemized by the same reaction conditions as ibuprofen methyl ester with CRL. Using an inexpensive thermoelectric column cooler, all esters and profens were baseline-resolved by chiral HPLC, enabling determination of the rate constants for enantiomer interconversion and hydrolysis. Substituent-dependent trends suggest that (S)-ester inversion (k-1) and hydrolysis (k2) proceed via Serine 209-mediated deprotonation of their chiral center, first forming a negatively charged enolate, whereas (R)-ester inversion (k1) and hydrolysis (k3) proceed via Histidine 449-mediated protonation of their carbonyl first forming a positively charge oxonium. Enantiomerically pure Ibuprofenitriles were synthesized. Although they did not perform as liquid crystals, learning how to build a one-pixel liquid crystal display helped in the development of an organic chemistry teaching laboratory activity.
Language
en
Provenance
Received from ProQuest
Copyright Date
2026-05
File Size
105 p.
File Format
application/pdf
Rights Holder
Jose Antonio Rosales
Recommended Citation
Rosales, Jose Antonio, "Mechanism Of Deracemization Of Profens By Candida Rugosa Lipase" (2026). Open Access Theses & Dissertations. 4782.
https://scholarworks.utep.edu/open_etd/4782