Deuterated Molecular Probes for Metal Sensing

Abstract

Deuterium is generating a lot of interest due to its relevance in, e.g., drug discovery. It is also arising as a new tool to design molecular probes for nuclear magnetic resonance (NMR), offering advantages as it can be quantified and referenced with respect to natural abundant deuterium in water. Herein, we introduce the concept of using deuterium as a readout for metal sensing. Metals play an important role in biology and new sensing capabilities pave the pathways to a better understanding of their role in health and diseases. In particular, we developed a Zn2+ sensor based on selectively deuterated tris (2-pyridylmethyl)amine (TPA) for which we introduce isotopic labeling strategies. The probe selectively detected Zn2+ over other physiologically relevant ions, which include copper, iron, calcium, potassium, and sodium, and was sensitive down to 100 μM. T1 measurements for bound (36.6 ms for pyridine and 41.0 ms for aliphatic deuterons) and unbound TPA-d9 showed a 10-fold difference with water (366.6 ms), making it suitable for fast averaging sequences in potential MRI applications.