Mechanisms of Action of (Meth)acrylates in Hemolytic Activity, in Vivo Toxicity and Dipalmitoylphosphatidylcholine (DPPC) Liposomes Determined Using NMR Spectroscopy

International Journal of Molecular Sciences

Seiichiro Fujisawa¹ 

[1] Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan; E-Mail:

关键词: (meth)acrylates;    QSA(P)R;    biological activity;    NMR;    chemical shift;    β-carbon;    theoretical parameters;    DSC;    liposomes;   

DOI  :  10.3390/ijms13010758

来源: mdpi

【 摘 要 】

We investigated the quantitative structure-activity relationships between hemolytic activity (log 1/H₅₀) or in vivo mouse intraperitoneal (ip) LD₅₀ using reported data for α,β-unsaturated carbonyl compounds such as (meth)acrylate monomers and their ¹³C-NMR β-carbon chemical shift (δ). The log 1/H₅₀ value for methacrylates was linearly correlated with the δC_β value. That for (meth)acrylates was linearly correlated with log P, an index of lipophilicity. The ipLD₅₀ for (meth)acrylates was linearly correlated with δC_β but not with log P. For (meth)acrylates, the δC_β value, which is dependent on the π-electron density on the β-carbon, was linearly correlated with PM3-based theoretical parameters (chemical hardness, η; electronegativity, χ; electrophilicity, ω), whereas log P was linearly correlated with heat of formation (HF). Also, the interaction between (meth)acrylates and DPPC liposomes in cell membrane molecular models was investigated using ¹H-NMR spectroscopy and differential scanning calorimetry (DSC). The log 1/H₅₀ value was related to the difference in chemical shift (ΔδHa) (Ha: H (trans) attached to the β-carbon) between the free monomer and the DPPC liposome-bound monomer. Monomer-induced DSC phase transition properties were related to HF for monomers. NMR chemical shifts may represent a valuable parameter for investigating the biological mechanisms of action of (meth)acrylates.

【 授权许可】

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© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.