Optical Supramolecular Sensing of Creatinine

Calix­[4]­pyrrole
phosphonate-cavitands were used as receptors for
the design of supramolecular sensors for creatinine and its lipophilic
derivative hexylcreatinine. The sensing principle is based on indicator
displacement assays of an inherently fluorescent guest dye or a black-hole
quencher from the receptor’s cavity by means of competition
with the creatinine analytes. The systems were thermodynamically and
kinetically characterized regarding their 1:1 binding properties by
means of nuclear magnetic resonance spectroscopy (1H and 31P NMR), isothermal titration calorimetry, and optical spectroscopies
(UV/vis absorption and fluorescence). For the use of the black-hole
indicator dye, the calix[4]­pyrrole was modified with a dansyl chromophore
as a signaling unit that engages in Förster resonance energy
transfer with the indicator dye. The 1:1 binding constants of the
indicator dyes are in the range of 107 M–1, while hexylcreatinine showed values around (2–4) ×
105 M–1. The competitive displacement
of the indicators by hexylcreatinine produced supramolecular fluorescence
turn-on sensors that work at micromolar analyte concentrations that
are compatible with those observed for healthy as well as sick patients.
The limit of detection for one of the systems reached submicromolar
ranges (110 nM).