Colorimetric method for detecting palladium that is quicker, more convenient, and less expensive than competing methods.
Rigorous and iterative purification and analytical processes are necessary to ensure the absence of toxic metals such as palladium in active pharmaceutical ingredients to comply with federal regulations. Palladium catalysis is also used to synthesize organic polymers, including photovoltaic materials, which causes metal contamination that can negatively impact the materials’ performance. Traditionally, trace palladium is quantified using either inductively coupled-plasma mass spectrometry (ICP-MS) or inductively coupled-plasma optical emission spectroscopy (ICP-OES), which are sensitive and robust but expensive, slow, and usually unavailable at production sites. A significant drawback of these methods is a multi-week delay, including sample shipping times, to quantify trace metals. Presented is a method of measuring metals on-site with simple procedures and instruments using a colorimetric method that makes use of a chemosensor that rapidly, reversibly, and autonomously stalls, allowing the user to stop, start, and reverse the reaction, with the ability to detect palladium in concentrations as low as 0.1 ppb.
Technology Description
The colorimetric method for palladium detection employs resorufin allyl ether (RAE) that cleaves to release resorufin in the presence of palladium, shifting the solution color from yellow to purple. Sequential additions of sodium borohydride (NaBH4 ) can quantify palladium concentrations ranging over five orders of magnitude (0.1 ppb-10 ppm), a range rivaling spectroscopic and spectrometric methods. Unlike other methods that continue to deallylate over time, preventing the user from leaving the reaction unattended, the conversion of RAE to resorufin halts autonomously after a period of time dependent on the initial concentration of NaBH4. The reaction can be restarted, allowing users to leave the reaction unattended and collect the same data at any time. While providing similar precision and dynamic range compared to spectroscopic and spectrometric methods, this colorimetric method is comparatively low-cost and can be performed quickly and on-site.Advantages
Less costly than ICP-MS or ICP-OES
Easy to perform on-site
Reduces sample shipping and processing time
Does not require constant monitoring
Autonomously halts in 10-30s, allowing users to inspect the sample at any time, and can be reversed and restarted
Similar sensitivity compared to other leading methodsApplications
Quantifying trace palladium in pharmaceuticals, ores, and organic polymers
Compliance with federal regulations to minimize toxic metals in active pharmaceutical ingredients
Other catalysis-based assaysStage of Development
PrototypeIP Status
National, PCT application filedNotable Mentions
Merck Technology Collaboration Award (2014)Relevant Publications
Nieberding, M.; Tracey, M.P.; Koide, K. Non-effervescent method for catalysis-based palladium detection with color or fluorescence. ACS Sens. 2017, 2, 1737-1743
Tracey, M. P.; Pham, D.; Koide, K. Fluorometric imaging methods for palladium and platinum and the use of palladium for imaging biomolecules. Chem. Soc. Rev. 2015, 44, 4769–4791
Lukomski, L., Pohorilets, I., & Koide. Third-Generation Method for High-Throughput Quantification of Trace Palladium by Color or Fluorescence. K Org. Process Res. Dev 2020, 24, 85–95
Koide, K.; Tracey, M. P.; Bu, X.; Jo, J.; Williams, M. J.; Welch, C. J. A competitive and reversible deactivation approach to catalysis-based quantitative assays. Nat. Commun. 2016, 7, Article Number 10691External links
Koide LabInnovators
Kazunori Koide, PhD
Professor, Department of Chemistry, University of Pittsburgh
Dr. Koide’s research focuses on the organic synthesis of natural products, new synthetic methods, and organic fluorescent sensors. He is the recipient of several awards, including the University of Pittsburgh Innovator Award in 2019, the University of Pittsburgh Chancellor’s Distinguished Research Award in 2009, the 2008 University of Pittsburgh Innovator Award, and the Thieme Chemistry Journals Award in 2007. He was the Merck Fellow of the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation from 1998-2000 and was awarded the Naito Foundation Fellowship in 1991-1992.Recent Publications
Gambino, A., Burnett, J. C., & Koide, K. Methyl Scanning and Revised Binding Mode of 2-Pralidoxime, an Antidote for Nerve Agent Poisoning. ACS Med. Chem. Lett 2020, 11, Published Online
Pohorilets, I., Tracey, M. P., LeClaire, M. J., Moore, E. M., Lu, G., Liu, P., & Koide. Kinetic and Inverse Temperature Dependence of a Tsuji-Trost Reaction in Aqueous Buffer. K ACS Catal 2019, 9, 11720
Bressin, R. K., Driscoll, J. L., Wang, Y., & Koide, K. Scalable Preparations of Methylated Ando-Type Horner-Wadsworth-Emmons Reagent. Org. Process Res. Dev 2019, 23, 274-277
Chan, W. C. & Koide, K. Total Synthesis of the Reported Structure of Stresgenin B Enabled by the Diastereoselective Cyanation of an Oxocarbenium. Org. Lett 2018, 20, 7798-7802
Ando, S.; Burrows, J.; Koide, K. Synthesis of violaceic acid and related compounds through aryl triazene. Org. Lett. 2017, 19, 1116-1119
Bu, X. D.; Williams, M.; Jo, J.; Koide, K.; Welch, C. J. Online sensing of palladium in flowing streams. Chem. Commun. 2017, 53, 720-723
Pham, D.; Koide, K. Discoveries, target identifications, and biological applications of natural products that inhibit splicing factor 3B subunit 1. Nat. Prod. Rep. 2016