Separating and identifying multiple structural isomers of 3-hydroxy-3-(3′-hydroxyphenyl)propanoic acid (3,3′-HPHPA)

Abstract

3-hydroxy-3-(3′-hydroxyphenyl)propanoic acid (CID: 102959) (3,3’-HPHPA) is one of several phenolic molecules that are generated by a process involving gut microbiota and have been implicated in autism and schizophrenia. The structural isomers of 3,3′-HPHPA have been challenging to separate chromatographically. Accordingly, their distribution across brain and other compartments in humans and experimental animals remains poorly characterized. We describe a modified liquid chromatography mass spectroscopy method for the detection and separation of seven commercially available structural isomers of 3,3′-HPHPA. We used the method to screen different compartments in the mouse and demonstrate its utility in identifying multiple structural isomers and conjugates of 3,3′-HPHPA in biological matrices. Characterizing the diversity and complexity of this family of structural isomers will advance studies of their bioactivity and clinical relevance.

Graphical Abstract

Keywords:

• Brain
• β-(m-Hydroxyphenyl)hydracrylic acid
• gut microbiota
• mouse
• chromatography
• schizophrenia

Acknowledgements

We wish to thank the following: Dr. V. Prakash Reddy from the Missouri Institute of Technology for help with green tea structural chemistry. Melissa Barnes for helpful discussion and Renliang Zhang of the Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, for services from the Metabolomics Core.

Disclosure statement

George E. Jaskiw, the primary author, serves on the editorial board of the journal MDPI Metabolites.

Curtis J. Donskey, a coauthor, is an Associate Editor for the journal Pathogens and Immunity.

Curtis J. Donskey has received financial support from Clorox Inc. and Pfizer Inc.

Additional information

Funding

Clorox Inc., Pfizer Inc