Correlation of Drug and Carbon Nanotube Size in Encapsulation and Free Energy Calculation: A Molecular Insight

Spontaneous encapsulation of drugs into carbon nanotubes (CNTs) has attracted great interest because of their importance in biological and biomedical devices. In this work, the diameter dependence of 20 drugs on the carbon nanotube size was explored via molecular dynamics (MD) simulation. Negative free energy of interaction, reduced potential of mean force, reduced CNT-drug distance, and reduced number of water molecules after encapsulation confirm the encapsulation of the drug into the smallest possible size of CNT. The variations of the radius of gyration of the CNTs and drugs were compared to explore the correlation trend. One of the factors influencing the encapsulation and insertion of drug is the size of the nanotube. In addition, the linear correlation between the drug and the nanotube size was confirmed by quantitative structure-property relationship (QSPR) analysis, and the multiple linear regression (MLR) method was applied to develop the correlation model. The regression parameter provided by the MLR method was R-2 = 0.99 for prediction of the drug gyration radius. The MLR prediction confirms that the larger drug molecule prefers to locate inside a larger CNT, which agrees with MD data. It was found that there is pi-pi interaction between the oxygen atoms and the aromatic ring of some of the drugs and the aromatic rings of CNTs are conjugated; this helps the drug molecule to locate inside the CNT. These theoretical methods provide a simple, detailed, and alternative method to obtain optimal tube size for encapsulation.