Triazoles as T2-Exchange Magnetic Resonance Imaging Contrast Agents for the Detection of Nitrilase Activity

Jia Zhang, Zheng Han, Jiaqi Lu, Yuguo Li, Xuhe Liao, Peter C. van Zijl, Xing Yang, Guanshu Liu

Research output: Contribution to journalArticlepeer-review

Abstract

We characterized the T2-exchange (T2ex) magnetic resonance imaging (MRI) contrast of azole protons that have large chemical shifts from the water proton resonance as a function of pH, temperature, and chemical modification. Our results showed that 1,2,4-triazoles could be tuned into excellent diamagnetic T2ex contrast agents, with an optimal exchange-based relaxivity r2ex of 0.10 s−1 mm−1 at physiological pH and B0=9.4 T. A fit of r2ex data to the Swift–Connick equation indicated that imino proton exchange of triazoles is dominated by a base-catalyzed process at higher pH values and an acid-catalyzed process at lower pH. The magnitude of r2ex was also found to be heavily dependent on chemical modifications, that is, enhanced by electron-donating groups, such as amines and methyls, or by intramolecular hydrogen bonding between the imino proton and the carboxyl, and weakened by electron-withdrawing groups like bromo, cyano, and nitro. In light of these findings, we applied T2ex MRI to assess the activity of nitrilase, an enzyme catalyzing the hydrolysis of 1,2,4-triazole-3-carbonitrile to 1,2,4-triazole-3-carboxylic acid, resulting in the enhancement of R2ex. Our findings suggest that 1,2,4-triazoles have potential to provide sensitive and tunable diagnostic probes for MRI.

Original languageEnglish (US)
Pages (from-to)15013-15018
Number of pages6
JournalChemistry - A European Journal
Volume24
Issue number56
DOIs
StatePublished - Oct 9 2018

Keywords

  • T-exchange MRI
  • nitrilase
  • swift–connick equation
  • triazoles

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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