Deuterated Building Blocks

Pharmaceuticals lose their therapeutic activity when they are metabolized (inactivated) by enzymes in the body. To prolong drug efficacy, researchers have attempted to substitute hydrogen with fluorine, chlorine, or methyl groups at sites susceptible to metabolic degradation. However, these substitutions can significantly alter the overall properties of the molecule. Replacing hydrogen with deuterium at sites susceptible to metabolic degradation has therefore emerged as a promising approach. Deuterium-substituted pharmaceuticals are referred to as deuterated drugs (also referred to as heavy drugs).

The antidepressant venlafaxine undergoes glucuronidation or demethylation in the body, resulting in loss of activity. By replacing the hydrogen atoms at the metabolic sites with deuterium, metabolism can be suppressed, thereby prolonging the duration of therapeutic action¹⁾.

More recently, a deuterium-substituted form of tetrabenazine, a drug used to treat Huntington's disease, was developed by Teva Pharmaceuticals Ltd. This compound received FDA approval as a new drug in April 2017. Replacing hydrogen at the demethylation sites with deuterium was found not only to prolong drug efficacy but also reduced the incidence of side effects²⁾.

Organic Electroluminescence (EL) refers to the phenomenon in which organic materials emit light when a voltage is applied. Products that utilize this principle—organic light-emitting diodes (OLEDs) —are also broadly referred to as organic EL devices. When voltage is applied to an organic EL device, "holes" and "electrons" are injected from the anode and cathode, respectively. When these recombine in the emissive layer, the organic materials are activated to a high-energy "excited state." As these molecules return to the "ground state," the excess energy is released as light.

Organic EL displays consist of red, green, and blue light-emitting elements — the three primary colors of light. The compounds used in the emissive layer include fluorescent, phosphorescent, and more recently thermally activated delayed fluorescence (TADF) materials. These materials are being developed by various companies and universities. As the search for materials with stronger emission intensity and higher quantum efficiency continues, deuterated compounds have gained traction in this field. Because C–D bonds have higher bond dissociation energy than C–H bonds and are more resistant to cleavage, deuteration can enhance the durability of emissive materials.

To illustrate with one example³⁾, the fac-tris(2-phenylpyridinato)Ir(III) complex (Ir(ppy)₃) is highly emissive and electrically neutral, making it easy to fabricate vapor-deposited films. It has therefore been widely studied as a leading emissive layer material. Comparing Ir(ppy)₃-h₂₄ with deuterated Ir(ppy)₃-d₂₄, both the photoluminescence quantum yield Φ_em and the emission lifetime τ were found to increase. This is attributed to the suppression of non-radiative deactivation without affecting the radiative decay rate, resulting in improved emission efficiency.

An OLED device incorporating Ir(ppy)₃ in the emissive layer was fabricated, and the luminance half-life was compared at an initial luminance of 1,000 cd/m² and a drive current of 0.17 mA. The H-form showed a half-life of 300 hours while it was 800 hours for the D-form, an approximately 2.7-fold extension of operational lifetime.

FUJIFILM Wako offers a selection of deuterated (D-form) building blocks. Examples of H-form building block applications are provided below. These can serve as a guide for the use of D-form compounds.

Carbazole

9,9-Dimethylfluorene⁴～⁷⁾

Dibenzofuran⁵～¹¹⁾

Aromatic Compounds

Heteroaromatic Compounds

Aliphatic Compounds

1. Sato, K.: Wako Organic Square, 33, 2 (2010) (Japanese)
2. JP6138322B2
3. Kawanishi, Y.: Wako Organic Square, 36, 2 (2011) (Japanese)
4. WO2012134203A2
5. JP2008239529A
6. WO2011050888A1
7. KR20100045587A
8. WO2014034584A1
9. WO2014067614A1
10. WO2015014434A1
11. WO2014034893A1