University reports synthesis of methylene blue analogs
Methylene blue is a widely used dye and medication.
The Russian Science Foundation-funded project is headed by Senior Research Associate Pavel Padnya and is titled ‘New generation of electrochemically active materials for biosensors for medical diagnostics based on multifunctional macrocycles – derivatives of phenothiazine and biomolecules’. His most recent results saw light in Dyes and Pigments.
“People have learned to isolate various dyes from natural raw materials, which began to be produced on an industrial scale in the 19th century. By the end of the 20th century, the number of known synthetic dyes exceeded 6.5 thousand, and this figure is increasing every year. This is due to the fact that scientists have found additional useful properties in many dyes, such as high biological activity, the possibility of creating advanced materials and devices based on them,” comments Padnya.
One of such dyes is phenothiazine, “As a result of the chemical modification of the phenothiazine molecule, a huge number of promising drugs have been obtained that help in the fight against diseases such as bacterial infections, tuberculosis, malaria, fungal diseases, and malignant tumors. The most iconic phenothiazine derivatives include methylene blue, a well-known organic dye that is actively used in practice in photodynamic therapy, optoelectronics, and sensor technologies.”
Although the source molecule is quite cheap, derivatives of phenothiazine remain expensive.
“After analyzing many years of experience, we have identified the most promising areas for the design of new dye molecules to solve the most pressing problems of mankind – from the creation of targeted drug delivery systems to the synthesis of new materials for android robotics. The generalized data allowed us to develop the most optimal ways to obtain various aromatic analogs of methylene blue,” continues the chemist.
The team has offered three basic approaches to the synthesis of structural analogs:
- Cycle closing reaction;
- Buchwald-Hartwig reaction;
- Oxidation of phenothiazine to the phenothiazine-5 cation followed by reactions with nucleophilic agents.
“Each approach has its advantages and disadvantages; however, the third approach is the most promising in terms of the synthesis of both symmetrical and asymmetric 3,7-disubstituted phenothiazine derivatives, with molecular iodine being the most convenient oxidizing agent. It is the third approach that makes it possible to obtain various alkyl and aromatic analogs of methylene blue, as well as to vary the anions to obtain the necessary practical properties,” concludes the grantee. With such an approach, the team has already synthesized almost 30 methylene blue analogs for electrochemical sensors.