Computationally Guided Design of Isostructural Formamide Hydrogen-Bonded Organic Frameworks

The rational design of novel hydrogen-bonded motifs for constructing robust molecular hydrogen-bonded organic frameworks (HOFs) is challenging, particularly for mesoporous solids. Here, we demonstrate that the integration of chemical insights and crystal structure prediction (CSP) enables the rational design of novel HOFs based on trigonal formamide-terminated linkers. The well-defined spikes of low-energy, isostructural HOFs on the predicted lattice-energy landscapes reveal a family of crystal packings with diverse hydrogen-bonded motifs that nonetheless all result in similar predicted pore topologies. These CSP results enabled the experimental discovery of isostructural HOFs with predetermined pore channel sizes and functionalities to be identified. For a linker with extended arms (TTBF), a hydrogen-bonded dimeric structure with cis -configured formamide groups was identified as a higher-energy ‘spike’ in a CSP landscape, corresponding to a mesoporous HOF with unprecedentedly large pores. This material was successfully synthesized and shown to be permanently mesoporous with the largest pore size exhibited by a HOF to date (4.2 nm). Our methodology illustrates the potential of a simple and scalable formylation reaction between formic acid and abundant amine precursors to generate porous HOFs, redefining the limit of pore sizes that can be achieved in molecular solids.