Nucleic acid-phospholipid recognition: Fourier transform infrared spectrometric characterization of ternary phospholipid-inorganic cation-DNA complex and its relevance to chemicopharmaceutical design of nanometric liposome based gene delivery formulations

Abstract

The present work is a continuation of our previous microscopic, spectroscopic and microcalorimetric measurements of liposomes and poly(ribo)nucleotides and their ternary complexes with inorganic cations as an alternative formulation employing zwitterionic phospholipids instead of cytotoxic cationic lipids. Current report describes Fourier transform infrared spectrometric study as employed to follow structural transitions of newly proposed ternary solid neutral lipid-Mg(2+)-DNA complexes as promising gene delivery formulation. Spectra of the unbound components are compared with those obtained after their complexation as binary and ternary mixtures. Results are described at the levels of carbonyl, phosphate, choline and CH groups and discussed as effects of nucleic acid and phosphatidylcholine moiety on each other in the absence and in the presence of Mg(2+). The infrared spectra of DNA-lipid phases are dominated by the lipid specific absorption bands, with a very little contribution of DNA. Data suggest that upon recognition of DNA with lipids, the DNA undergoes helical transition. Mg(2+) effects are interpreted as dehydrations of phosphates and H-bonding inducing effects on carbonyl groups. The role of residual and surface water on these associations, as well as on chain packing is also discussed followed by possible implications of the ternary complex formation for further gene transfer designs.