Inclusion of Capecitabine into 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."

Institute of Applied Chemistry, Faculty of Chemistry, Kim Il Sung University, has carried out quantum chemical study on structure and stability of supramolecular inclusion compounds, where low molecular weight organic compounds (anticancer drugs or fragrants) are inserted into the inner space of cucurbiturils.

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

Capecitabine (CAP) as a prodrug of 5-fluorouracil (5-FU) is used in treatment of breast, collateral, pancreatic and other types of cancer. CAP is a fluoropyrimidine carbamate and its chemical name is 5′-deoxy-5-fluoro-N-[(pentyloxy)carbonyl]cytidine. Derivatives and hybrid materials of CAP with carrier or capsule were prepared to decrease such side effects and increase its medical function.

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

Initial geometric structures of CAP@CB[n] were optimized by PM6-D3H4 in MOPAC 2016 (version 20.119W) and solvent effect was treated with COSMO approach. 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 CAP@CB[y=6,7] is more stable than CAP@CB[x=5,8]. By using DFT, it was found out that CB[7] can form relatively stable inclusion compound with CAP. In calculation of the interaction energy between CAP and CB[n], dispersion correction played an important role. The intermolecular non-covalent interaction between CAP and CB[7] played positive role in formation of CAP@CB[7]. Natural bond orbital analysis showed that electron transfer from CB[7] to CAP makes CAP@CB[7] stable, when two hydrogen bonds (N–H…O and O–H…O) between CAP and CB[7] are important.

The above results were published under the title of "Inclusion of Capecitabine into Cucurbiturils" ( on "Monatshefte für Chemie-Chemical Monthly" (2021, 152, 209–216).