Amino acid quasiracemates – generated from the assembly of pairs of chemically distinct amino acids of opposite handedness – continue to provide important opportunities to understand how self-assembly can be promoted despite using components with drastically different sizes and molecular shapes. Previous studies by Görbitz et al. and others cataloged 32 crystal structures of amino acid quasiracemates, with each showing the building blocks aligned with near inversion symmetry similar to their racemic counterparts. This investigation examined the impact of using a secondary coformer molecule, hydrogen oxalate, on the cocrystalline landscape of amino acid quasiracemates with hydrocarbon side chains. Eight racemic (4) and quasiracemic (4) hydrogen oxalate structures were generated. Crystal structures of these systems show the hydrogen oxalate moieties assembled into C(5) molecular columns by the construction of robust O–H⋯O − hydrogen bonds with the amino acid enantiomers and quasienantiomers linked to these column motifs using a complex blend of N + –H⋯O − , O–H⋯O − , and N + –H⋯OC contacts. The racemates and quasiracemates form similar packing motifs; however, due to the chemically non-identical nature of the quasiracemic components, the outcome is that the amino acids organize with near inversion symmetry. Both the conformational similarity ( χ RMS ) and degree of inversion symmetry ( C i ) of related pairs of quasienantiomeric components have been systematically assessed using readily available structural tools. This study shows how coformer molecules such as hydrogen oxalate can provide new and critical insight into the molecular recognition process of quasiracemic materials.
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Accessing Centnerszwer's quasiracemate – molecular shape controlled molecular recognition
M. Centnerszwer's seminal 1899 report investigated the stereochemical relationship between optical antipodes of different substances using melting-point behavior. One intriguing melting-point phase diagram produced from this early investigation combined (+)-2-chlorosuccinic acid [(+)- 1 ] and (−)-2-bromosuccinic acid [(−)- 2 ]. While Centnerszwer's data clearly indicates the formation of a quasiracemic phase – i.e. , materials constructed from pairs of isosteric molecules of opposite handedness – at the 1 : 1 component ratio, this material is energetically less favorable than the chiral counterparts. The consequence of this crystal instability is significant as evident by the absence of literature sited crystal structures for the quasiracemic phase (+)- 1 /(−)- 2 and racemates (±)- 1 and (±)- 2 . This study circumvented this challenge by generating multi-molecular assemblies using additional crystallizing agents capable of complementing the hydrogen-bond abilities of succinic acids 1 and 2 . Both imidazole (Im) and 4,4′-bipyridyl- N , N ′-dioxide (BPDO) served as tailor-made additives that effectively modified the crystal packing landscape of quasiracemate of (+)- 1 /(−)- 2 . Combining imidazole with the quasiracemate, racemate, and enantiopure forms of 1 and 2 resulted in crystal structures characterized as molecular salts with layered motifs formed from highly directional N + –H⋯carboxylate and carboxyl⋯carboxylate interactions. In contrast to the enantiopure [(+)- 1 ·Im and (−)- 2 ·Im] and racemic [(±)- 1 ·Im and (±)- 2 ·Im] systems, neighboring molecular layers observed in quasiracemate (+)- 1 /(−)- 2 ·Im are organized by approximate inversion symmetry. Assessment of the crystal packing efficiency for this series of molecular salts via crystal densities and packing coefficients ( C k ) indicates imidazole greatly alters the crystal landscape of the system in favor of racemic and quasiracemic crystal packing. A similar desymmetrized crystal environment was also realized for the ternary cocrystalline system of (+)- 1 /(−)- 2 ·BPDO where the components organize via N + –O − ⋯carboxyl contacts. This study underscores the importance of molecular shape to molecular recognition processes and the stabilizing effect of tailor-made additives for creating new crystalline phases of previously inaccessible crystalline materials.
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- Award ID(s):
- 1745368
- NSF-PAR ID:
- 10058474
- Date Published:
- Journal Name:
- RSC Advances
- Volume:
- 6
- Issue:
- 69
- ISSN:
- 2046-2069
- Page Range / eLocation ID:
- 64921 to 64929
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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ABSTRACT Zeolitic imidazolate frameworks (ZIFs) feature complex phase transitions, including polymorphism, melting, vitrification, and polyamorphism. Experimentally probing their structural evolution during transitions involving amorphous phases is a significant challenge, especially at the medium-range length scale. To overcome this challenge, here we first train a deep learning-based force field to identify the structural characteristics of both crystalline and non-crystalline ZIF phases. This allows us to reproduce the structural evolution trend during the melting of crystals and formation of ZIF glasses at various length scales with an accuracy comparable to that of ab initio molecular dynamics, yet at a much lower computational cost. Based on this approach, we propose a new structural descriptor, namely, the ring orientation index, to capture the propensity for crystallization of ZIF-4 (Zn(Im)2, Im = C3H3N2−) glasses, as well as for the formation of ZIF-zni (Zn(Im)2) out of the high-density amorphous phase. This crystal formation process is a result of the reorientation of imidazole rings by sacrificing the order of the structure around the zinc-centered tetrahedra. The outcomes of this work are useful for studying phase transitions in other metal-organic frameworks (MOFs) and may thus guide the development of MOF glasses.
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New additions to quasiracemic materials have been developed by cocrystallizing a ternary component – hydrogen oxalate – with pairs of amino acid quasienantiomers where at least one of the side-chain R groups contains a sulfur atom. Of the eight quasiracemates investigated, six exhibit crystal packing that drastically deviates from the expected centrosymmetric alignment present in the racemic counterparts and the extant database of quasiracemic materials. These structures were quantitatively assessed for conformational similarity (CCDC-Mercury structure overlay) and the degree of inversion symmetry (Avnir's Continuous Symmetry Measures) for each quasienantiomeric pair. Despite the variance in quasienantiomeric components, these structures exhibit a high degree of isostructurality where the principal components assemble by a complex blend of common N + –H⋯O and O–H⋯O − interactions. These charge-assisted hydrogen-bonded networks form thermodynamically favored crystal packing that promotes cocrystallization of a structurally diverse set of quasienantiomeric components.more » « less
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Abstract Bacterial poly(3-hydroxybutyrate) (P3HB) is a perfectly isotactic, crystalline material possessing properties suitable for substituting petroleum plastics, but high costs and low volumes of its production are impractical for commodity applications. The chemical synthesis of P3HB via ring-opening polymerization (ROP) of racemic
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Families of quasiracemic materials constructed from 3- and 4-substituted chiral diarylamide molecular frameworks were prepared, where the imposed functional group differences systematically varied from H to CF3–9 unique components for each isomeric framework. Cocrystallization from the melt via hot stage thermomicroscopy using all possible racemic and quasiracemic combinations probed the structural boundaries of quasiracemate formation. The crystal structures and lattice energies (differential scanning calorimetry and lattice energy calculations) for many of these systems showed that quasienantiomeric components organize with near inversion symmetry and lattice energetics closely resembling those found in the racemic counterparts. This study also compared the shape space of pairs of quasienantiomers using an in silico alignment-based method to approximate the differences in molecular shape and provide a diagnostic tool for quasiracemate prediction. Comparing these results to our recent report on related 2-substituted diarylamide quasiracemates shows that functional group position can have a marked effect on quasiracemic behavior and provide critical insight to a more complete shape space, essential for defining molecular recognition processes.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/C6RA08131B
