Rational Design of a Fluorescence-Turn-On Sensor Array for Phosphates in Blood Serum

Phosphate anions, both inorganic and organic, hold a unique position in nature, as they take part in almost all metabolic processes. Nucleotide phosphates such as AMP or ATP are important for their role in bioenergetics, metabolism, and transfer of genetic information. Phosphates in biological liquids are often present in high concentrations and may be utilized in the diagnosis of certain diseases. Human serum contains 0.80– 1.45 mm phosphate; higher phosphate levels are directly connected to cardiovascular disease and acute renal failure. Similarly, ATP is present in resting muscle at a concentration of 4 mm, and in erythrocytes at a concentration of just under 2 mm. Numerous materials have been developed to sense phosphate ions in water at biological pH values. The sensors based on anion-induced enhancement of intrinsic fluorescence (turn-on) are attractive as they offer the potential for high sensitivity 7] and, unlike the displacement assays, are instantly reversible. Alas, few fluorescence-turn-on sensors exist for phosphate that function in electrolyte solutions. To the best of our knowledge, fluorescence-turn-on sensors capable of sensing phosphate ions in complex biological milieu, such as blood serum, have not yet been developed. Recently, we demonstrated that simple anion sensors based on hydrogen-bonding interactions can bind and sense anions in hydrophilic polymer matrices, despite their inability to bind anions in water. 11] This method combined with the sensitivity of the fluorescence-turn-on signaling could allow for the sensing of phosphate ions in aqueous environments, including biological milieu such as blood serum. Here, we present tripodal sensor molecules S1–S8 (Scheme 1) based on 1,3,5-triaminomethyl-2,4,6-triethylbenzene which can form arrays of six hydrogen-bond donors.