Automated Nanocrystalline Sponge Workflow Enabled by 3D Electron Diffraction

TL;DR

A new automated workflow using nanocrystalline sponges and 3D electron diffraction enables high-throughput structural analysis of organic molecules.

Contribution

An automated workflow combining nanocrystalline sponges and 3D electron diffraction for high-throughput structural analysis of organic molecules.

Findings

A nanocrystalline bismuth-based MOF (SU-100) was successfully used as a crystalline sponge for 10 organic molecules.

3D electron diffraction data enabled automated identification and refinement of guest molecules under low electron fluence and cryogenic conditions.

Guest molecules in SU-100 pores are arranged periodically through coordination, hydrogen, and π–π stacking interactions.

Abstract

The crystalline sponge
(CS) method utilizes a crystalline porous
material to arrange target molecules within its periodic pores. This
enables the determination of the 3D atomic structures of organic molecules
without the need for crystallization. However, its applicability is
currently limited by the availability of suitable porous single crystals
that can grow to a sufficient size for X-ray diffraction analysis.
Although three-dimensional electron diffraction (3D ED) allows structure
determination from nanosized crystals, ab initio structural analysis
of organic molecules hosted in nanocrystalline sponges remains challenging
and largely manual. Here, we present a 3D ED-based nanocrystalline
sponge (NanoCS) workflow that integrates guest soaking, low-dose cryogenic
data collection, and automated structure solution and refinement.
A key advance is a newly developed automated approach for guest identification
and structural analysis implemented in the AutoSolveX pipeline. Using
the nanocrystalline bismuth-based metal–organic framework (MOF)
SU-100 as a prototype crystalline sponge, we demonstrated the general
applicability of this NanoCS strategy. 10 organic molecules, introduced
as pure liquids, solutions, or vapors, are investigated. For all systems,
3D ED data collected under low electron fluence and cryogenic conditions
enabled fully automated identification and refinement of the guest
molecules using AutoSolveX. The results confirm the periodic arrangement
of the guest molecules within the pores of SU-100, mediated by coordination
bonding, hydrogen bonding, offset π–π stacking,
and van der Waals interactions. This work establishes NanoCS combined
with automated structural analysis as a practical and high-throughput
platform for routine ab initio structural determination of organic
molecules from nanocrystalline hosts.

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