Article
Detection and quantification of hydrogen peroxide in aqueous solutions using chemical exchange saturation transfer (CEST) David Ryoo, Xiang Xu, Yuguo Li, Joel Tang, Jia Zhang, Peter C.M. van Zijl, and Guanshu Liu Anal. Chem., Just Accepted Manuscript • Publication Date (Web): 19 Jun 2017 Downloaded from http://pubs.acs.org on June 20, 2017
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Analytical Chemistry
Detection and quantification of hydrogen peroxide in aqueous solutions using chemical exchange saturation transfer (CEST) David Ryoo,†,#,‡ Xiang Xu,†,# Yuguo Li,†,# Joel A. Tang,§ Jia Zhang,†,# Peter C.M. van Zijl,†,# and Guanshu Liu†,#,* †
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F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland; De‡ § partment of Radiology; Department of Chemical & Biomolecular Engineering, Department of Chemistry; Johns Hopkins University, Baltimore, Maryland. ABSTRACT: The development of new analytical methods to accurately quantify hydrogen peroxide is of great interest. In the current study, we developed a new magnetic resonance (MR) method for noninvasively quantifying hydrogen peroxide (H2O2) in aqueous solutions based on chemical exchange saturation transfer (CEST), an emerging MRI contrast mechanism. Our method can detect H2O2 by its specific CEST signal at ~6.2 ppm downfield from water resonance, with more than 1000 times signal amplification compared to the direct NMR detection. To improve the accuracy of quantification, we comprehensively investigated the effects of sample properties on CEST detection, including pH, temperature, and relaxation times. To accelerate the NMR measurement, we implemented an ultrafast Z-spectroscopic (UFZ) CEST method to boost the acquisition speed to two seconds per CEST spectrum. To accurately quantify H2O2 in unknown samples, we also implemented a standard addition method, which eliminated the need for predetermined calibration curves. Our results clearly demonstrate that the presented CEST-based technique is a simple, non-invasive, quick, and accurate method for quantifying H2O2 in aqueous solutions.
Hydrogen peroxide (H2O2) is widely used in a variety of industrial applications1. It is the most versatile agent for pulp- and paper-bleaching2, treating pollutants and eliminating organic and inorganic contaminants in wastewater3. It is also an important biological molecule involved in redox processes, for instance as a key component in cell signaling pathways, and highly relevant to oxidative stress and inflammation4,5. In tissue engineering, H2O2 is utilized as a highly efficient and clean oxygen generating agent that has been demonstrated to supply oxygen to transplanted stem cells6,7. In the latter application, H2O2-encapsulated polymeric carriers are incorporated into stem cell supporting scaffolds that contain catalase, and after being released from the carriers, H2O2 is hydrolyzed by catalase into H2O and O2 8-11. Due to the importance of H2O2, numerous analytical methods have been developed to detect and quantify it, including potassium permanganate titration12, infrared, Raman spectrophotometry13,14, and fluorescence spectroscopy15. Most of these methods however are destructive as they require the addition of reagents to the original samples. As a versatile non-invasive analytical tool, 1H NMR spectroscopy has also been exploited for the quantification of H2O216-19. For example, Stephenson and Bell quantified H2O2 using its unique 1H NMR signal at around 10–11 ppm in both aqueous and non-aqueous solutions17. Relaxometric NMR can also report the detection of H2O2 due to its transverse relaxation time (T2) enhancing ability18. Unlike the method reported by Stephenson, NMR relaxometry has been applied to monitor heterogeneous catalysis systems dynamically, despite its detectability being only around
0.1%. Recently, another ultra-sensitive 1H NMR method was reported with a 20 µM detection limit19. However, this method requires the combined use of DMSO-d6, cryoprotective and low temperature measurements (260 K or -13 oC) which required a total acquisition time of approximately 10 minutes. In this study, we aimed to develop a new H2O2 detecting MR method using chemical exchange saturation transfer (CEST), a recently emerged MR contrast-generating technology20-23. The CEST technology has been demonstrated in many studies for specifically detecting a wide array of labile protons of exchange rate (kex) in the slow to intermediate regime (i.e., kex
