Synthesis and Characterization of a Copper‐Based Macrocyclic Chelate for Quantitation and Sequestration of Oxalate: the Major Component of Kidney Stones

• Published in: The FASEB journal Vol. 32; no. S1; p. lb631
• Main Authors: VanWert, Adam L, Hensley, Jayden L, Hontz, David S, Torsiello, Maria L, Venditto, Michael L, Luchetta, Jared L, Lucent, Del L, Terzaghi, William L
• Format: Journal Article
• Language: English
• Published: The Federation of American Societies for Experimental Biology 01-04-2018
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.2018.32.1_supplement.lb631

Background
Roughly eighty percent of kidney stones are calcium oxalate‐based. Oxalate is found both in diet and synthesized in the liver. Furthermore, blood‐borne oxalate likely undergoes enteroenteric recirculation via transporters in the small intestine (SLC26A6, secretory) and colon (SLC26A3, absorptive). There is a great need for pharmacotherapeutic options to prevent and treat calcium‐oxalate kidney stones. Furthermore, methods for quantifying oxalate in biological matrices are costly and time consuming.
Objective
We aimed to synthesize and further characterize a small‐molecule oxalate binder, with two ultimate goals in mind: (1st) to be employed in a quantitative fluorescence‐based oxalate assay, and (2nd) to prevent colonic oxalate absorption.
Methods & Results
We optimized the synthesis of a copper‐based chelate (~70% yield) and expanded characterization beyond literature reports: (1) for the first time we crystallized the chelate and determined its lattice unit cell as triclinic via X‐ray crystallography; (2) for the first time we obtained NMR spectra of the chelate; (3) we obtained mass spectra of the two intermediates, showing excellent purity; (4) we confirmed the ability of the chelate to quench eosin Y fluorescence, and to release eosin Y upon oxalate binding; and (5) we have, for the first time, determined that citrate can also give a positive fluorescence response, unlike other acids.
Conclusions
The macrocyclic chelate can be produced readily with high yield and purity. Its crystal structure helps to predict the binding orientation of oxalate, which may lead to more specific oxalate binders. We have found, for the first time, that although the compound is selective for oxalate, contrary to previous reports, it is not specific. These findings indicate that the chelate may serve as a useful tool for quantifying oxalate provided that a strategy for mitigating citrate binding is developed. Furthermore, armed with more thorough knowledge on its specificity for oxalate and other biological chemicals, developing the chelate as prophylaxis for oxalate kidney stones is becoming a promising goal.
Support or Funding Information
All work was funded by Wilkes University
This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal.