Corking and Uncorking Carbon Nanotubes by Metal Nanoparticles Bearing pH-Cleavable Hydrazone Linkers. Theoretical Analysis Based on Molecular Dynamics Simulations

In this work we determine and discuss free-energy barriers associated with the detachment of metal (gold) nanoparticles covered by an organic shell from carbon nanotubes functionalized by hydrazide segments. At neutral pH, both compounds can form hydrazone bonds which in turn lead to the chemically corked form of the nanotube. At slightly acidic pH, the hydrazone bonds undergo hydrolysis, leading to chemically unbonded nanotube and gold nanoparticles. We found that at this state the dispersion interactions between the nanotube and gold nanoparticles are still very strong and spontaneous detachment of gold nanoparticles does not occur. Therefore, the uncorked state of the nanotube cannot be realized at normal conditions. The presence of guest molecules (cisplatin) in the inner cavity of the nanotube affects the energetic balance of the system, and spontaneous uncorking can occur with some small activation barrier. However, the uncorking is in this case related to the shift of the nanoparticle from the nanotube tip to its sidewall. That model system can thus realize the mechanism of pH-controlled drug release from the inner cavities of carbon nanotubes. Determination of the free-energy barriers in the considered systems architectures required a special treatment. Standard application of the weighted histogram analysis of biased probability distributions turned out to be totally ineffective. Therefore, we developed a special version of that method which tolerates weak overlapping of the probability histograms. This method may be useful for fast survey of free-energy barriers in any other system architectures.