C-a16 |ionizable lipid

Cas No.:
Chemical Name:	C-a16
Synonyms:	Ca16， C a16
SMILES:	CCCCCCCCC1=CC=C(O)C(CN(CC2=C(O)C=CC(CCCCCCCC)=C2)CCCCC2NC(=O)C(CCCCN(CC3=CC(CCCCCCCC)=CC=C3O)CC3=C(O)C=CC(CCCCCCCC)=C3)NC2=O)=C1
Formula:	C₇₂H₁₁₂O₆N₄
M.Wt:	1129.71
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
Publication:	Mannich reaction-based combinatorial libraries identify antioxidant ionizable lipids for mRNA delivery with reduced immunogenicity-N Gong, D Kim, MG Alameh, R El-Mayta, EL Han- Nature Biomedical …, 2025

Description:

C-a16 is an ionizable lipid engineered through Mannich reaction chemistry, designed to revolutionize mRNA delivery by synergizing high efficiency with minimized immune activation. Synthesized by reacting a phenolic tail derivative, formaldehyde, and a branched tertiary amine core under optimized ethanol conditions, this lipid integrates antioxidant phenol groups directly into its structure. These phenol moieties serve as intrinsic radical scavengers, effectively neutralizing intracellular reactive oxygen species that typically degrade mRNA and trigger inflammation.In lipid nanoparticle formulations, C-a16 constitutes the functional backbone, enabling superior mRNA encapsulation efficiency while maintaining a stable nanoparticle size of approximately 80–100 nm. Critically, it outperforms conventional lipids like DLin-MC3-DMA by achieving significantly higher target-protein expression in vivo alongside markedly reduced pro-inflammatory cytokine secretion. The antioxidant capability is not incidental but fundamental—quenching the phenol groups drastically diminishes both ROS suppression and delivery efficacy, confirming the design's mechanistic elegance.C-a16 represents a paradigm shift: its biomimetic antioxidant architecture addresses the chronic trade-off between delivery potency and immunogenicity, unlocking safer therapeutic applications for vaccines and gene therapies.

References:

Mannich reaction-based combinatorial libraries identify antioxidant ionizable lipids for mRNA delivery with reduced immunogenicity-N Gong, D Kim, MG Alameh, R El-Mayta, EL Han- Nature Biomedical …, 2025

Cat. No.	Product name	Field of application
DC60941	Antioxidant lipid AO12	AO12 is a novel antioxidant ionizable lipid derived from SM-102 skeleton with para-hydroxyphenyl propionic acid side chains. Integrated into LNPs, it efficiently scavenges diverse reactive oxygen species including ·OH and ONOO⁻, shielding encapsulated mRNA from oxidative degradation. It retains fine LNP formulation features and cellular uptake capacity of conventional lipids, boosting in vivo mRNA translation. Applied for regenerative mRNA therapy and CRISPR gene editing against fibrosis and inflammatory disorders.
DC67564	C-a16	C-a16 is an ionizable lipid engineered through Mannich reaction chemistry, designed to revolutionize mRNA delivery by synergizing high efficiency with minimized immune activation. Synthesized by reacting a phenolic tail derivative, formaldehyde, and a branched tertiary amine core under optimized ethanol conditions, this lipid integrates antioxidant phenol groups directly into its structure. These phenol moieties serve as intrinsic radical scavengers, effectively neutralizing intracellular reactive oxygen species that typically degrade mRNA and trigger inflammation.In lipid nanoparticle formulations, C-a16 constitutes the functional backbone, enabling superior mRNA encapsulation efficiency while maintaining a stable nanoparticle size of approximately 80–100 nm. Critically, it outperforms conventional lipids like DLin-MC3-DMA by achieving significantly higher target-protein expression in vivo alongside markedly reduced pro-inflammatory cytokine secretion. The antioxidant capability is not incidental but fundamental—quenching the phenol groups drastically diminishes both ROS suppression and delivery efficacy, confirming the design's mechanistic elegance.C-a16 represents a paradigm shift: its biomimetic antioxidant architecture addresses the chronic trade-off between delivery potency and immunogenicity, unlocking safer therapeutic applications for vaccines and gene therapies.