Tetrahedron Lett.2017 Sep;58(37):3623-3627

A novel anthracene-based fluorescent colorimetric sensor for the simple naked-eye diagnosis of methylmalonic aciduria.

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Abstract

A novel molecular sensor using anthracene bearing two amidopyridines emits blue fluorescence in the presence of succinic acid and green fluorescence in the presence of malonic acid, and its fluorescence intensity increased upon binding. Using this molecular sensor, we succeeded in detecting the difference of one carbon atom between succinic acid and malonic acid with the naked-eye. Furthermore, when methylmalonic acid was dissolved in urine to provide a model system for methylmalonic aciduria, the fluorescence changed from blue to green, and methylmalonic acid was successfully detected with the naked-eye.

 

Additional text

This research aims not only to study academic molecular recognition but also to use molecular recognition for diagnosis of intractable diseases. There are many children suffering from organic metabolic disorders such as methylmalonic aciduria in the world. Especially, mass screening for newborn infants is important, but there are many children in developing countries who cannot receive diagnosis at high cost. Because of our desire to save such children, we have worked on the development of a fluorescent molecular sensor that can detect the malonic acid skeleton with the naked-eye. Since the newly developed fluorescent molecular sensor can be used for the diagnosis of methylmalonic aciduria easily and inexpensively, it is expected to be used in developing countries from now on. Considering that it is widely used in the world, we decided to publish our findings to the international magazine, Tetrahedron Letters. See: H. Miyaji, J. Fujimoto, R. Mabuchi, M. Okumura, S. Goto, Y. Honda, Tetrahedron Letters, 58, 3623-3627 (2017).

In this study, we used the anthracene for the fluorescent colorimetric molecular sensor. Two amidopyridines were attached at the 1- and 3-positions of anthracene. In this stage, the anthracene emitted blue fluorescence. But once recognized malonic acid, the fluorescence found to change from blue to intense green (Fig.1).

This result was applied to the model system for methylmalonic aciduria. One drop of methylmalonic acid dissolved in urine was added to an acetonitrile solution of the anthracene and the color of the fluorescence changed from blue to intense green. The controls (only urine, and succinic acid in urine) provided no color change in fluorescence (Fig.2).

Furthermore, to the best of our knowledge, this is the first report of a compound that can distinguish the difference in length between malonic acid (C3) and succinic acid (C4) by a fluorescent color change. We believe this is a very significant finding, especially since succinic acid (C4) is involved in the citric acid cycle and malonic acid (C3) causes metabolic disorders. Therefore, we believe this article is worthwhile for all readers interested in chemistry and biomedical science.

 

 

Figure 1  The anthracene molecular sensor and the hydrogen bonding with a compound of a malonic acid skeleton.

 

 

Figure 2  Detection of methylmalonic acid (200 equiv.) dissolved in urine by fluorescence color changes of the anthracene molecular sensor (0.1 mM in CH3CN).