The ubiquity of inorganic anions such as fluoride, chloride and phosphate in Nature, their importance as food additives, agricultural fertilizers, herbicides, pesticides, and industrial raw materials, commands considerable attention of the scientific community. The industrial and agricultural utilization of anions raises a number of environmental concerns. These issues necessitate the development of highly sensitive sensor materials. Also, biologically important anions such as nucleotide phosphates (think ATP, but also others) are of significant interest. The sensors based on anion-induced changes in fluorescence appear particularly attractive because they offer the potential for high sensitivity at low analyte concentration. Unfortunately, binding of anions (for example for environmental remediation) or sensing (environmental and health-related applications) is difficult.
There are several reasons why reliable sensing of anions is a particularly challenging area of research. Anions are larger than isoelectric cations and therefore have lower charge-to-radius (surface) ratio, a feature that makes the electrostatic binding of anions to the receptors less effective. Anions have a wide range of geometries and are often present in delocalized forms, which results in higher design complexity of receptors and sensors required for successful recognition and binding. These and other factors make sensing of anions difficult task. Perhaps most importantly, anions are strongly solvated, which is particularly important in water. of hydration (delta Ghyd, kJ/mol) of -473, -1089, and -2753 kJ/mol for H2PO4-, HPO42-, and PO43-, respectively. As a result, even simple anions such as orthophosphate form hydrates with up to 40 water molecules (~11 for H2PO4-, ~20 HPO42-, and ~39 PO43-).
In our research we focus on the development new compounds and materials that can easily be used to achieve signal amplification in the simple fluorescent anion sensor. This is very important point, because the signal amplification in sensors is expected to yield more sensitive sensors.
An example of one of our new receptors-sensors is shown below (Chem 2022, 8, 2228-2244). It is a flexible macrocycle endowed with a combination of hydrogen bond donors and acceptors (A). In the resting state, the macrocycle is folded onto itself (we know the conformation from 2D NMR and DFT calculations) and the fluorescent labels are self-quenched (B). Upon addition of anion, in this case ADP, the macrocycle forms a complex, opens up, and the fluorescence labels are now separated and are fluorescent (C).
The degree of fluorescence amplification and the anion-specific shift in the spectra then allow for this one molecule to monitor biochemical reactions such as the hydrolysis of ATP to AMP and pyrophosphate (PPi) or conversion of ATP to ADP and phosphate (Pi). Here, the high-throughput (HTS) fluorescence measurements in combination with the use of artificial intelligence allows to monitor these biologically important reactions.
This work was published last year (Chem 2022, 8, 2228-2244) and another similar study in ChemSci 2023, 14, 7545-7552 as well as Chem. Eur. J. 2024,e202401872.