Constructing, deconstructing, and reconstructing ternary supermolecules

Abstract

A hypothesis-driven protocol comprising precise and predictable molecular recognition events based upon an electrostatic view of competing hydrogen-bond interactions is proposed and subsequently employed in the construction of ternary co-crystals.

Competing hydrogen-bond donors: phenols vs. cyanooximes

“…It could have been argued that the cyanooxime group has 10 an inherent geometric preference for a pyridyl moiety as this type of hydrogen is formed in the first four crystal structures. However, as a cyanooximeimidazole O-HN hydrogen bond is present in the crystal structure of PhOx:6, there is nothing to suggest that a geometric bias is responsible for the consistent 15 structural patterns that were found. Furthermore, acceptor 6, which is the only compound that produces a 1:2 co-crystal, carries a charge on its A1 site of -301 kJ/mol which is greater than that found on the corresponding site in any of the other acceptors.…”

“…It has previously been shown that both cyanooxime moieties 15 and phenolic -OH groups 16 are more effective hydrogen-bond donors than carboxylic acids. The 40 question is, can we establish a reliable ranking of the hydrogenbond efficiency of these two moieties based upon systematic cocrystallizations of a single molecule that contains both moieties on the same molecular backbone?…”

“…Scheme 3 Eight ditopic acceptors (5-7 were synthesized according to previously published methods. 15,18 ) In each case, A 1 indicates the stronger acceptor and A 2 the weaker hydrogen-bond acceptor site based on calculated MEP values. The charges bear the units of potential as they are calculated based on the 5 maxima and minima of a calculated molecular electrostatic potential surface which represents the points of highest and lowest charge on the molecule.…”

“…All molecules were geometry optimized using AM1, with the maxima and minima in the electrostatic potential surface (0.002 e au -1 isosurface) determined using a positive point charge in vacuum as a probe. 15 Ditopic acceptors 1-8 were co-crystallized with PhOx by combining the relevant reactants in methanol in a 1:1 ratio, followed by slow evaporation. Five co-crystals suitable for single crystal X-ray diffraction were obtained.…”

Competing hydrogen-bond and halogen-bond donors in crystal engineering

“…Recently, halogen bonds 6 which can play important roles in areas such as biochemistry 7 , medicinal chemistry 8 , and material science, 9 have found uses in crystal engineering because these interactions have properties that parallel those of hydrogen 25 bonds in terms of directionality and strength. 10,11 Typical hydrogen-bond strength ranges from approximately 4-60 kJ/mol 12 while halogen bonds range from 5-180 kJ/mol (the strong interaction I 2 I -in I 3 -is the extreme). 13 Consequently, iodine/bromine suitably 'activated' through a fluorinated 30 backbone should be capable of competing with hydrogen bonds in a supramolecular reaction.…”