When does a supramolecular synthon fail? Comparison of bridgehead-functionalized adamantanes: the tri- and tetra- amides and amine hydrochlorides

1,3,5-Trisubstituted adamantane carboxamide and amine hydrochloride, Ad(CONH2)(3)center dot 2.5H(2)O and [Ad(NH3)(3)]Cl-3 center dot H2O (Ad = adamant-n-yl) respectively, crystallized from aqueous solutions, possess crystal structures with predictable H-bonded assembly, consistent with the C-3v symmetry of the building blocks. The triamide structure consists of interpenetrated hexagonal networks, sustained by the well-known cyclic H-bonded bis-amide synthon, R-2(2)(8), which ensures linear connectivity. The structure of the triamine hydrochloride, assembled through the tetrahedral {RN+H3 center dot center dot center dot(Cl-)(3)} synthon, features a remarkably symmetric assembly with narrow trigonal pore channels, hosting water molecules. The structures of the tetrahedral 1,3,5,7-tetrasubstituted Ad(CONH2)(4) and [Ad(NH3)(4)]Cl-4, obtained similarly, demonstrate a formal prediction failure of synthon-based approach. Instead of the anticipated bis-amide synthon-based diamond network (1.485 g cm(-3)) analogous to the 5-fold interpenetrated paradigmatic structure of Ad(COOH)(4), a non-interpenetrated assembly, sustained by a dense network of H-bonds, is realized (1.433 g cm(-3)). Lessened geometric regularity was also found in the tetrahydrochloride salt assembled via 5-connected nodes, {RN+H3 center dot center dot center dot(Cl-)(4)}, which involve a bifurcated H-bond. The failures of the supramolecular synthons in these simple cases could be interpreted in terms of either symmetry and/or limitations associated with the "synthon density". A potential machine-learning approach oriented on heuristic retro-supramolecular synthesis relies on such selected high-weight conceptual cases.