Theoretical Study On The Cage-like Nanostructures Formed By Amino Acids And Their Potential Applications As Drug Carriers

In this work,L-aspartic acid monomer?L-A?was used to construct the cage-like octamer?L-A?₈,decamer?L-A?₁₀ and dodecamer?L-A?₁₂,respectively.Single drug molecules with appropriate volumes were selected to explore the potential applications of the drum-shaped cages of?L-A?₈,?L-A?₁₀ and?L-A?₁₂ as drug carriers using Density functional theory?DFT?.The optimized geometries of the cage-like octamer?L-A?₈,decamer?L-A?₁₀ and dodecamer?L-A?₁₂ were obtained at the level of M06-2X/6-311G**.Analysis of the optimized structures,vibrational spectra and noncovalent interactions all indicate that there are totally 8,10,12 strong–C=O…HOOC–H-bonds and the same amounts of strong–HN…HOOC–H-bonds in the octamer,decamer and dodecamer,respectively.The existence of these strong H-bonds plays an important role in stabilizing the cage-like topologies of these oligomers.The binding energies per unit corrected by the BSSEs at the level of M06-2X/6-311+G**//M06-2X/6-311G**for the oligomers?L-A?₈,?L-A?₁₀ and?L-A?₁₂ all reach about 22 kcal mol^-1.The inner cavity volumes of the optimized cage-like octamer?L-A?₈,decamer?L-A?₁₀ and dodecamer?L-A?₁₂ reach about 166,380 and 601?³,respectively,which are large enough to accommodate small drug molecules.5-FU?5-Fluorouracil?and HU?Hydroxyurea?were inserted in the cavities of?L-A?₈,PD?Paraldehyde?and C₂₄ were respectively put in the cavities of?L-A?₁₀ and?L-A?₁₂.3,2,2 and 2 optimized conformers were obtained for the complexes5-FU-?L-A?₈,HU-?L-A?₈,PD-?L-A?₁₀ and C₂₄-?L-A?₁₂ at the level of M06-2X/6-311G**,respectively.The binding energy between a drug molecule and a drum-shaped cage was computed to be 10?53 kcal mol^-1 corrected by BSSE at the level of M06-2X/6-311+G**//M06-2X/6-311G**.Analyses of optimizated structures and noncovalent interactions both indicate that the H-bonded and vdW interactions are formed between 5-FU?or HU?and the cage of?L-A?₈,and between PD and?L-A?₁₀,while the interactions between C₂₄ and?L-A?₁₂ are mainly characteristic of vdW terms and?-facial H-bonded interactions.The noncovalent interactions between a drug molecule and a cage-like structure ensure the stable residing of a drug molecule in a cage-like structure.The results disclose that the three nanoscale cage-like oligomers all have the possibilities of being drug carriers.