Fig. 3: Process of virtual amine–carboxylic acid reaction enumeration and analysis of results.
From: Exploring the combinatorial explosion of amine–acid reaction space via graph editing
a Schematic of enumeration from amine 1 and acid 2 to yield ~56 million unique transformation matrices, which are filtered first to 222,740 unique products assuming carbon and oxygen atoms are degenerate, and further to 80,941 unique products after eliminating highly improbable structures. b Two-dimensional histogram showing distribution of ring count and bond edit distance of the initial 222,740 products. c Kernel density estimate (KDE) plots of various physiochemical properties of the expanded amine-acid coupling system, along with selected products. The respective property of the classic amide is shown by the vertical gray line. HBD hydrogen bond donor, PSA polar surface area, FSP3 fraction sp3-atoms, MW molecular weight, HBA hydrogen bond acceptors, QED quantitative estimate of drug-likedness, LogP partition coefficient, ROTB number of rotatable bonds, Rings number of rings. d Principal Moment of Inertia (PMI) ratio distributions of all products from the expanded enumeration.
