An Integrated Experimental and Computational Approach for Characterizing the Kinetics and Mechanism of Triadimefon Racemization. Issue 9 (1st August 2016)

• Record Type: Journal Article
• Authors: Cheng, Qianyi; Teng, Quincy; Marchitti, Satori A.; Dillingham, Caleb M.; Kenneke, John F.
• Is Part Of: Chirality. Volume 28:Issue 9(2016)
• Page Start: 633
• Page End: 641
• Publication Date: 2016-08-01
• Subjects: chirality -- conazoles -- enantiomerization -- environmental chemicals -- pesticides -- risk assessment -- stereochemistry; Chirality -- Periodicals; Pharmaceutical chemistry -- Periodicals; 541.22
• DOI: 10.1002/chir.22622
• Languages: English
• ISSNs: 0899-0042

Abstract

Abstract: Enantiomers of chiral molecules commonly exhibit differing pharmacokinetics and toxicities, which can introduce significant uncertainty when evaluating biological and environmental fates and potential risks to humans and the environment. However, racemization (the irreversible transformation of one enantiomer into the racemic mixture) and enantiomerization (the reversible conversion of one enantiomer into the other) are poorly understood. To better understand these processes, we investigated the chiral fungicide, triadimefon, which undergoesracemization in soils, water, and organic solvents.Nuclear magnetic resonance (NMR) andgas chromatography /mass spectrometry (GC/MS) techniques were used to measure the rates of enantiomerization andracemization, deuterium isotope effects, and activation energies for triadimefon in H2 O and D2 O. From these results we were able to determine that: 1) the alpha‐carbonyl carbon of triadimefon is the reaction site; 2) cleavage of the C‐H (C‐D) bond is the rate‐determining step; 3) the reaction is base‐catalyzed; and 4) the reaction likely involves a symmetricalintermediate . The B3LYP/6–311 + G** level of theory was used to compute optimized geometries, harmonic vibrational frequencies, nature population analysis, and intrinsic reaction coordinates for triadimefon in water and threeracemization pathways were hypothesized. This work provides an initial step in developing predictive, structure‐based models that are needed to identify compounds of concern that may undergoracemization . Chirality 28:633–641, 2016 . © 2016 Wiley Periodicals, Inc. Abstract :