  Although carbon nanotubes are potential candidates for DNA encapsulation and
subsequent delivery of biological payloads to living cells, the thermodynamical
spontaneity of DNA encapsulation under physiological conditions is still a
matter of debate. Using enhanced sampling techniques, we show for the first
time that, given a sufficiently large carbon nanotube, the confinement of a
double-stranded DNA segment, 5'-D(*CP*GP*CP*GP*AP*AP*TP*TP*CP*GP*CP*G)-3', is
thermodynamically favourable under physiological environments (134 mM, 310 K, 1
bar), leading to DNA-nanotube hybrids with lower free energy than the
unconfined biomolecule. A diameter threshold of 3 nm is established below which
encapsulation is inhibited. The confined DNA segment maintains its
translational mobility and exhibits the main geometrical features of the
canonical B form. To accommodate itself within the nanopore, the DNA end-to-end
length increases from 3.85 nm up to approximately 4.1 nm, due to a 0.3 nm
elastic expansion of the strand termini. The canonical Watson-Crick H-bond
network is essentially conserved throughout encapsulation, showing that the
contact between the DNA segment and the hydrophobic carbon walls results in
minor rearrangements of the nucleotides H-bonding. The results obtained here
are paramount to the usage of carbon nanotubes as encapsulation media for next
generation drug delivery technologies.
