Fluorescent molecules to illuminate life: simplified synthesis with formaldehyde

A research team recently achieved a breakthrough in synthesizing organic fluorophores more cost-effectively and efficiently than ever before using formaldehyde, the simplest carbon molecule. Their findings were published in Angewandte Chemie International Edition on September 18.

Organic fluorophores, known for their ability to fluoresce by absorbing specific wavelengths of light, are widely used in medical diagnostics and bioimaging, including cancer cell tracking and genetic analysis. However, the synthesis of trimethine cyanine (Cy3), a commonly used organic fluorophore, traditionally involves a complex compound of high molecular weight, leading to many byproducts and low atomic efficiency.

To solve this problem, the team used formaldehyde (HCHO), a simple molecule composed of one carbon (C), two hydrogen (H) atoms, and one oxygen (O) atom. . Although formaldehyde can become toxic by reacting with proteins and DNA in vivo, it provides a valuable tool in organic synthesis to form new carbon-carbon bonds.

By using formaldehyde instead of conventional complex compounds to add carbon into the molecular chain, a critical step in the synthesis of Cy3, the team significantly reduced the molecular size required for the process, thereby maximizing atomic efficiency. Additionally, they streamlined the traditional multistep asymmetric synthesis of Cy3 into a one-pot reaction, thereby eliminating additional steps and increasing synthesis efficiency.

The team also studied whether their technique could be applied to cells and tissues, given that some amounts of formaldehyde are naturally produced in vivo during metabolism. In their analysis of rat small intestine tissue, they observed that the inflammation-induced group had a weaker fluorescence signal than the normal group. This was attributed to relatively low levels of formaldehyde during inflammation, which limited Cy3 synthesis. These results demonstrate that the team’s method is applicable not only to in vitro synthesis but also to in vivo environments.

The team was led by Professor Young-Tae Chang from the Department of Chemistry at POSTECH and Dr. Sun Hyeok Lee from the Institute of Basic Science Research at POSTECH.

Professor Young-Tae Chang said: “This is the first successful synthesis of Cy3 molecules using formaldehyde. Our method is not only cost-effective and highly atomically efficient, but it can also be used in vivo, expanding the potential applications of organic fluorophores. in life sciences research and diagnosis.