Copper Capture in a Thioether-Functionalized Porous Polymer Applied to the Detection of Wilson's Disease.
Copper is an essential nutrient for life, but at the same time, hyperaccumulation of this redox-active metal in biological fluids and tissues is a hallmark of pathologies such as Wilson's and Menkes diseases, various neurodegenerative diseases, and toxic environmental exposure. Diseases characterized by copper hyperaccumulation are currently challenging to identify due to costly diagnostic tools that involve extensive technical workup. Motivated to create simple yet highly selective and sensitive diagnostic tools, we have initiated a program to develop new materials that can enable monitoring of copper levels in biological fluid samples without complex and expensive instrumentation. Herein, we report the design, synthesis, and properties of PAF-1-SMe, a robust three-dimensional porous aromatic framework (PAF) densely functionalized with thioether groups for selective capture and concentration of copper from biofluids as well as aqueous samples. PAF-1-SMe exhibits a high selectivity for copper over other biologically relevant metals, with a saturation capacity reaching over 600 mg/g. Moreover, the combination of PAF-1-SMe as a material for capture and concentration of copper from biological samples with 8-hydroxyquinoline as a colorimetric indicator affords a method for identifying aberrant elevations of copper in urine samples from mice with Wilson's disease and also tracing exogenously added copper in serum. This divide-and-conquer sensing strategy, where functional and robust porous materials serve as molecular recognition elements that can be used to capture and concentrate analytes in conjunction with molecular indicators for signal readouts, establishes a valuable starting point for the use of porous polymeric materials in noninvasive diagnostic applications.
Sumin
S
Lee
Gokhan
G
Barin
Cheri M
CM
Ackerman
Department of Physiology, Johns Hopkins University, School of Medicine , Baltimore, Maryland 21205, United States.
Abigael
A
Muchenditsi
Jun
J
Xu
Jeffrey A
JA
Reimer
Department of Physiology, Johns Hopkins University, School of Medicine , Baltimore, Maryland 21205, United States.
Svetlana
S
Lutsenko
Jeffrey R
JR
Long
Christopher J
CJ
Chang
D000818:Animals; D003300:Copper / Q000652:urine*; D004195:Disease Models, Animal; D006527:Hepatolenticular Degeneration / Q000175:diagnosis* / Q000652:urine; D051379:Mice; D015394:Molecular Structure; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D016062:Porosity; D012680:Sensitivity and Specificity; D013440:Sulfides / Q000138:chemical synthesis / Q000737:chemistry
D011108:Polymers; D013440:Sulfides; D003300:Copper