These spectral changes suggest that LPEI and BPEI bind DNA and package it into polyplexes through distinct mechanisms that involve interactions with both the phosphate backbone and nucleobases. For example, the frequency shift and intensity changes in the 1222 cm -1 band indicate that LPEI primarily binds DNA through strong electrostatic interactions with the phosphate backbone. The downshift of this band to 1215 cm -1 at high N/P ratios further suggests that LPEI binding to the phosphate backbone induces a conformational transition in DNA from B-form to Z-form .