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Improvements to the Practical Usability of the "Crystalline Sponge" Method for Organic Structure Determination.

ABSTRACT: A microwell droplet approach provided high-quality samples in ?90% yield of the "crystalline sponge", which was exhibited previously as a revolutionary organic structure determination method. The new protocol, from crystal growth to guest soaking, was conducted in 1-7 days (depending on the guest) and was robust toward user errors, marking improvements over existing protocols. Unit cell determination was used as a practical crystal screening metric. These advances improve the practicality of the crystalline sponge technique for characterizing unknown organic molecules.

SUBMITTER: Waldhart GW

PROVIDER: S-EPMC5502779 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Improvements to the Practical Usability of the "Crystalline Sponge" Method for Organic Structure Determination.

Waldhart Greyson W GW Mankad Neal P NP Santarsiero Bernard D BD

Organic letters 20161115 23

A microwell droplet approach provided high-quality samples in ≥90% yield of the "crystalline sponge", which was exhibited previously as a revolutionary organic structure determination method. The new protocol, from crystal growth to guest soaking, was conducted in 1-7 days (depending on the guest) and was robust toward user errors, marking improvements over existing protocols. Unit cell determination was used as a practical crystal screening metric. These advances improve the practicality of the ...[more]

PMID: 27934356

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Project description:Crystalline sponges are porous metal complexes that can absorb and orient common organic molecules in their pores and make them observable by conventional X-ray structure analysis (crystalline sponge method). In this study, all of the steps in the crystalline sponge method, including sponge crystal preparation, pore-solvent exchange, guest soaking, data collection and crystallographic analysis, are carefully examined and thoroughly optimized to provide reliable and meaningful chemical information as chemical crystallography. Major improvements in the method have been made in the guest-soaking and data-collection steps. In the soaking step, obtaining a high site occupancy of the guest is particularly important, and dominant parameters for guest soaking (e.g. temperature, time, concentration, solvents) therefore have to be optimized for every sample compound. When standard conditions do not work, a high-throughput method is useful for efficiently optimizing the soaking conditions. The X-ray experiments are also carefully re-examined. Significant improvement of the guest data quality is achieved by complete data collection at high angle regions. The appropriate disorder treatment of the most flexible ZnI2 portions of the host framework and refinement of the solvents filling the remaining void are also particularly important for obtaining better data quality. A benchmark test for the crystalline sponge method toward an achiral molecule is proposed with a guaiazulene guest, in which the guest structure (with ??100% site occupancy) is refined without applying any restraints or constraints. The obtained data quality with R int = 0.0279 and R 1 = 0.0379 is comparable with that of current conventional crystallographic analysis for small molecules. Another benchmark test for this method toward a chiral molecule is also proposed with a santonin guest. The crystallographic data obtained [R int = 0.0421, R 1 = 0.0312, Flack (Parsons) = -0.0071?(11)] represents the potential ability of this method for reliable absolute structure determination.

Project description:A detailed set of synthetic and crystallographic guidelines for the crystalline sponge method based upon the analysis of expediently synthesized crystal sponges using third-generation synchrotron radiation are reported. The procedure for the synthesis of the zinc-based metal-organic framework used in initial crystal sponge reports has been modified to yield competent crystals in 3 days instead of 2 weeks. These crystal sponges were tested on some small molecules, with two being unexpectedly difficult cases for analysis with in-house diffractometers in regard to data quality and proper space-group determination. These issues were easily resolved by the use of synchrotron radiation using data-collection times of less than an hour. One of these guests induced a single-crystal-to-single-crystal transformation to create a larger unit cell with over 500 non-H atoms in the asymmetric unit. This led to a non-trivial refinement scenario that afforded the best Flack x absolute stereochemical determination parameter to date for these systems. The structures did not require the use of PLATON/SQUEEZE or other solvent-masking programs, and are the highest-quality crystalline sponge systems reported to date where the results are strongly supported by the data. A set of guidelines for the entire crystallographic process were developed through these studies. In particular, the refinement guidelines include strategies to refine the host framework, locate guests and determine occupancies, discussion of the proper use of geometric and anisotropic displacement parameter restraints and constraints, and whether to perform solvent squeezing/masking. The single-crystal-to-single-crystal transformation process for the crystal sponges is also discussed. The presented general guidelines will be invaluable for researchers interested in using the crystalline sponge method at in-house diffraction or synchrotron facilities, will facilitate the collection and analysis of reliable high-quality data, and will allow construction of chemically and physically sensible models for guest structural determination.

Dataset Information

Improvements to the Practical Usability of the "Crystalline Sponge" Method for Organic Structure Determination.

Publications

Improvements to the Practical Usability of the "Crystalline Sponge" Method for Organic Structure Determination.

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