Encapsulation, isomer discrimination, and selective capture of substituted pyrazines by an adaptable cofacial zinc porphyrin dimer.

Positional isomers of substituted pyrazines-important aroma compounds and pharmacophores-are notoriously difficult to distinguish because of their nearly identical physical properties, and hosts that could discriminate them through molecular recognition face a further obstacle: substituents adjacent to the coordinating nitrogen atoms severely impede metal coordination, and the binuclear receptors so far reported for dimethylpyrazines bind them with association constants below 1 M-1. Here we show that a rigid cofacial zinc porphyrin dimer, in which two macrocycles are held face-to-face by covalent linkers, encapsulates a range of substituted pyrazines with binding constants of 105-108 M-1 in solution. The host discriminates between positional isomers of identical molecular formula: 2,5-dimethylpyrazine is bound about tenfold more strongly than its 2,3-isomer, and whereas the 2,5-isomer is encapsulated with both nitrogen atoms coordinated to the two zinc centers, the 2,6-isomer is excluded from the cavity and instead coordinates only from outside. Exploiting this affinity difference, a single capture-and-release operation enriches the 2,5-isomer from an equimolar mixture with its 2,3-isomer. The host also encapsulates benzopyrazine (quinoxaline), which a previously reported self-assembled cofacial dimer cannot accommodate. Single-crystal X-ray structures and quantum-chemical calculations reveal that the isomer discrimination arises not from the energetic cost of host deformation, but from how the substituent pattern weakens the axial coordination at the two metal centers. Combining a fixed metal-metal distance with deformable macrocycles thus provides a design principle for receptors that recognize and distinguish sterically demanding guests.