Tridocosahexaenoin (also known as glyceryl tridocosahexaenoate or tri-DHA TAG) is an ultra-polyunsaturated triacylglycerol (TAG) composed of three docosahexaenoic acid (DHA, C22:6 n-3, all-cis-4,7,10,13,16,19) chains esterified to a glycerol backbone. Abundant in fish oils, algal lipids, and neural tissues, this advanced omega-3 TAG provides major neuroprotective potential despite its high oxidative vulnerability.
Chemical Structure
Tridocosahexaenoin has the molecular formula C69H98O6 and a molecular weight of 1023.5 g/mol. Each docosahexaenoyl chain contains six cis double bonds, resulting in a total of 18 unsaturations. This extensive unsaturation confers maximal lipid fluidity, conical molecular packing, and increased susceptibility to peroxidation, making it a valuable compound for LC-MS analytical standards.
Physical Properties
This compound is typically a pale yellow, low-viscosity oil with a melting point below -30°C and an approximate density of 0.92 g/cm³. It is miscible in chloroform and requires inert storage at -80°C due to extreme oxidation sensitivity. Tridocosahexaenoin is water-insoluble, with a TPSA of 78.9 Ų and a heavy atom count of 75, reflecting its highly flexible lipid structure.
Biological Functions
Upon lipase-mediated hydrolysis, tridocosahexaenoin releases DHA, the predominant neuronal polyunsaturated fatty acid (PUFA), accounting for nearly 50% of retinal and neuronal phospholipids. It contributes to synaptogenesis, neuroprotectin D1 synthesis, and anti-inflammatory signaling via GPR120 activation. Compared with EPA-derived TAGs, tri-DHA TAG demonstrates enhanced brain delivery and stronger inhibition of ferroptosis, supporting its relevance in neurodegenerative research.

