The structural properties of the polyethylenimine (PEI)
polymer
are generally tuned and selectively modified to reinforce its potential
in a broad spectrum of applied domains of medicine, healthcare, material
design, sensing, and electronic optimization. The selective modification
of the polymer brings about changes in its interfacial characteristics
and behavior. The current work involves the synthesis of naphthalimide
conjugated polyethylenimine organic nanoparticles (NPEI-ONPs). The
interfacial molecular structure of NPEI-ONPs is explored in an aqueous
medium at pH 7.4 using surface tensiometry and sum-frequency generation
vibrational spectroscopy (SFG-VS). The hydrophobic functionalization
rendered a concentration-dependent surface coverage of NPEI-ONPs,
where the SFG-VS analysis exhibited the molecular rearrangement of
its hydrophobic groups at the interface. The interaction of NPEI-ONPs
with double-stranded DNA (dsDNA) is carried out to observe the relevance
of the synthesized nanocomposites in the biomedical domain. The bulk-specific
studies (i.e., thermal denaturation, viscometry, zeta (ζ) potential,
and ATR-FTIR) reveal the condensation of dsDNA in the presence of
NPEI-ONPs, making its structure more compact. The interface-sensitive
SFG-VS showcased the impact of the dsDNA and NPEI-ONP interaction
on the interfacial molecular behavior of NPEI-ONPs at the air–aqueous
interface. Our results exhibit the potential of such hydrophobically
functionalized ONPs as promising candidates for developing biomedical
sealants, substrate coatings, and other biomedical domains.