Inclusion of Thymol 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.

Thymol (TML) is one of main components of essential oils from some fragrant plants, which is used as an antimicrobial additive for food preservation and a natural insecticide. TML is a monoterpene phenol and its chemical name is 2-isopropyl-5-methylphenol. Derivatives and hybrid materials of TML with carrier or capsule were prepared to decrease such side effects and increase its function.

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

Initial geometric structures of TML@CB[n] were optimized by DFTB+ in Materials Studio 2017. The resulting structures were used in DFT (B3LYP-gCP-D3/6-31G*) calculation by ORCA (Ver. 4.2), when solvent effect was treated by CPCM.

DFTB+ calculation showed that TML@CB[n=7] is more stable than other TML@CB[n=5,6,8]. By using DFT, it was found out that i2-CB[7] (doubly-inverted CB[7]) can form relatively stable inclusion compound with TML. In calculation of the interaction energy between TML and CB[n], dispersion correction played an important role. Hydrogen bonds and intermolecular non-covalent interactions between TML and i2-CB[7] played positive role in formation of TML@CB[7]. Natural bond orbital analysis showed that electron transfer from i2-CB[7] to TML makes TML@i2-CB[7] stable.

The above results were published on "Journal of Inclusion Phenomena and Macrocyclic Chemistry" under the title of "Inclusion of Thymol into Cucurbituril" (https://doi.org/10.1007/s10847-022-01135-4).