TY - JOUR
T1 - Zirconium-Based Metal-Organic Frameworks for the Removal of Protein-Bound Uremic Toxin from Human Serum Albumin
AU - Kato, Satoshi
AU - Otake, Ken Ichi
AU - Chen, Haoyuan
AU - Akpinar, Isil
AU - Buru, Cassandra T.
AU - Islamoglu, Timur
AU - Snurr, Randall Q.
AU - Farha, Omar K.
PY - 2019/2/13
Y1 - 2019/2/13
N2 - Uremic 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 Zr 6 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.
AB - Uremic 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 Zr 6 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.
UR - http://www.scopus.com/inward/record.url?scp=85061235093&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061235093&partnerID=8YFLogxK
U2 - 10.1021/jacs.8b12525
DO - 10.1021/jacs.8b12525
M3 - Article
C2 - 30707010
AN - SCOPUS:85061235093
VL - 141
SP - 2568
EP - 2576
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 6
ER -