Decoding information entropy of fatty acid and phospholipid vesicles via ordering combinatorial output of hydrazones

Leveraging information entropy to quantitatively measure the organizational diversity and complexity of different chemical systems is a compelling need for next-generation supramolecular and systems chemistry. It can also be a strategy for digitalizing and enabling the bottom-up development of life-like complex systems following probable origin-of-life scenarios. According to the lipid world hypothesis, lipid molecules appear first to facilitate compartmentalization, catalysis, information processing, etc. It is envisaged that fatty acid-based vesicles are more primitive than phospholipid vesicles. Herein, we decode the difference in information storage capability of a fatty acid (oleic acid, (OA)) and a phospholipid (1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)) vesicle by measuring vesicle-templated formation of nine different hydrazones through permutations and hierarchical ordering of combinatorial matrices involving three aldehydes and three hydrazines by determining Shannon entropy and the Gini coefficient at the systems level. This signifies a higher diversity and lower selectivity towards successful chemical reactions in OA vesicles, whereas DOPC vesicles are more selective and less diverse. Exploiting information theory in combinatorial supramolecular synthesis and unraveling information capacity relevant to cell membrane evolution will be important in understanding the information dynamicity of different transient and self-propagated synthetic and natural assembly processes over time.