Solvent Mediated Optimization of DNA-Nanoparticle Crystal Growth and Structure Analysis for SERS Activity

Abstract This study investigated the structure−property relationship of DNA-functionalized gold nanoparticle (DNA-AuNP) colloidal single crystals composed of ordered superlattices using small-angle X-ray scattering (SAXS) and rotational crystallographic analysis. We obtained colloidal single crystals suitable for single-crystal SAXS measurements using heavy water (D2O) as an alternative growth medium. The crystal enlargement is discussed in terms of suppressed early-stage nucleation, reduced nanoparticle diffusion, and possible isotope effects on DNA duplex stability. The increase in crystal dimensions enabled the detailed structural characterization of the internal lattice arrangement and three-dimensional order of the DNA-AuNP superlattice. The diffraction profiles exhibited well-defined Bragg reflections, which allowed the quantitative assessment of lattice broadening and internal lattice coherence under different growth conditions. The D2O-grown DNA-AuNP superlattice crystals exhibited measurable surface-enhanced Raman scattering (SERS) activity using rhodamine B as a probe molecule. Boundary element method simulations showed that the average integrated |E|4 enhancement remained comparable over the investigated range of lattice disorder, whereas the spatial distribution and variability of the electromagnetic hotspots changed with the gSC-factor. These results demonstrate the SERS functionality of the DNA-AuNP superlattice crystals and suggest that moderate structural disorder mainly affects hotspot uniformity rather than the average electromagnetic enhancement. These findings clarify the relationship between the structural characteristics of DNA-AuNP superlattices and their optical functionality, and provide insights into the development of DNA-programmed plasmonic superlattices with tunable structural and optical properties.