Electronic structure of inclusion compounds of 5-fluorouracil and cucurbiturils


The respected Comrade Kim Jong Un said:

"New areas of medical science and technology where there is urgent practical need should be explored. Koryo medicine should be put on a scientific basis and the latest developments in medical science and technology introduced proactively."

We carried out quantum chemical study on structure and stability of supramolecular inclusion compounds, where low molecular weight organic compounds (anticancer drugs or fragrant) are inserted into the inner space of cucurbiturils.

Cucurbiturils are cage-like organic compounds (CB[n]) synthesized by condensation of glycoluril and formic aldehyde, where n of glycolurils are linked by methylene bridge. CB[n] can include small molecule in its inner space to make supramolecular inclusion compounds for catalyst, molecular device, sensor, drug delivery system and biomimetics.

5-fluorouracil (5FU) was synthesized as pyrimidine antagonist in 1950s and has been used as anticancer drug. But it causes some side effects such as vomit, diarrhea and acomia. To decrease such side effects and increase its medical function, previous researches were carried out to make its derivatives and hybrid materials with carrier or capsule.

Researchers at Institute of Physical Chemistry studied electronic structure and stability of inclusion compounds (5FU@CB[n]) of 5FU and CB[n] (n=5~8) by DFT.

Initial geometric structures of 5FU@CB[n] were optimized by PM6-D3H4 in MOPAC 2016 (version 20.119W) with COSMO for solvent effect. The resulting structures were used in DFT (B3LYP-gCP-D3/6-31G*) calculation by ORCA (version 4.2), when solvent effect was treated by CPCM.

PM6-D3H4 calculation showed that 5FU@CB[y=6,7] is more stable than 5FU@CB[x=5,8]. By using DFT, it was found out that i2-CB[6] with two inverted glycoluril units can form more stable inclusion compound than i-CB[6] and i-CB[7] with one inverted glycoluril unit. Electron transfer from i2-CB[y] to 5FU can stabilize 5FU@i2-CB[6]. HOMO of 5FU@i2-CB[6] is mainly localized at i2-CB[6] and its LUMO is at 5FU.

The above results were published on "Monatshefte für Chemie-Chemical Monthly" (2020, 151, 721–727) with the title of "Quantum chemical investigation on interaction of 5-fluorouracil with cucurbiturils". (https://doi.org/10.1007/s00706-020-02599-1)