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Zirconium-Based Metal–Organic Frameworks for the Removal of Protein-Bound Uremic Toxin from Human Serum Albumin
journal contribution
posted on 2019-01-31, 21:34 authored by Satoshi Kato, Ken-ichi Otake, Haoyuan Chen, Isil Akpinar, Cassandra T. Buru, Timur Islamoglu, Randall Q. Snurr, Omar K. FarhaUremic toxins often accumulate in
patients with compromised kidney
function, like those with chronic kidney disease (CKD), leading to
major clinical complications including serious illness and death.
Sufficient removal of these toxins from the blood increases the efficacy
of hemodialysis, as well as the survival rate, in CKD patients. Understanding
the interactions between an adsorbent and the uremic toxins is critical
for designing effective materials to remove these toxic compounds.
Herein, we study the adsorption behavior of the uremic toxins, p-cresyl sulfate, indoxyl sulfate, and hippuric acid, in
a series of zirconium-based metal–organic frameworks (MOFs).
The pyrene-based MOF, NU-1000, offers the highest toxin removal efficiency
of all the MOFs in this study. Other Zr-based MOFs possessing comparable
surface areas and pore sizes to NU-1000 while lacking an extended
aromatic system have much lower toxin removal efficiency. From single-crystal
X-ray diffraction analyses assisted by density functional theory calculations,
we determined that the high adsorption capacity of NU-1000 can be
attributed to the highly hydrophobic adsorption sites sandwiched by
two pyrene linkers and the hydroxyls and water molecules on the Zr6 nodes, which are capable of hydrogen bonding with polar functional
groups of guest molecules. Further, NU-1000 almost completely removes p-cresyl sulfate from human serum albumin, a protein that
these uremic toxins bind to in the body. These results offer design
principles for potential MOFs candidates for uremic toxin removal.