skip to main content


Title: Increasing the structural boundary of quasiracemate formation: 4-substituted naphthylamides
Quasiracemates – materials consisting of pairs of near enantiomers – form crystalline motifs that mimic the inversion relationships observed for their racemic counterparts. Recent investigations from our group explored a family of chiral ( N -benzoyl)methylbenzylamines to understand the structural boundary of cocrystallization. This investigation extends these earlier studies to include naphthylamide quasiracemates, where the molecular framework is ∼20% larger by volume than the previous diarylamides. A family of naphthylamides was prepared where the pendant functional group differs incrementally in size ( i.e. , H to C 6 H 5 ) to give 55 possible unique pairs of racemic and quasiracemic combinations. Data collected from these materials using X-ray crystallography, thermal analysis methods and lattice energy calculations offer important insight into how a spatially larger naphthylamide molecular framework promotes greater structural variance of substituents during the pairwise assembly of quasienantiomers.  more » « less
Award ID(s):
1904651 1827313
NSF-PAR ID:
10271901
Author(s) / Creator(s):
; ; ; ; ;
Date Published:
Journal Name:
CrystEngComm
Volume:
23
Issue:
1
ISSN:
1466-8033
Page Range / eLocation ID:
210 to 215
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. 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
  2. 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⋯OC 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. 
    more » « less
  3. 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. 
    more » « less
  4. 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
  5. Decavanadate (V 10 O 28 6− or V10) is a paradigmatic member of the polyoxidometalate (POM) family, which has been attracting much attention within both materials/inorganic and biomedical communities due to its unique structural and electrochemical properties. In this work we explored the utility of high-resolution electrospray ionization (ESI) mass spectrometry (MS) and ion exclusion chromatography LC/MS for structural analysis of V10 species in aqueous solutions. While ESI generates abundant molecular ions representing the intact V10 species, their isotopic distributions show significant deviations from the theoretical ones. A combination of high-resolution MS measurements and hydrogen/deuterium exchange allows these deviations to be investigated and interpreted as a result of partial reduction of V10. While the redox processes are known to occur in the ESI interface and influence the oxidation state of redox-active analytes, the LC/MS measurements using ion exclusion chromatography provide unequivocal evidence that the mixed-valence V10 species exist in solution, as extracted ion chromatograms representing V10 molecular ions at different oxidation states exhibit distinct elution profiles. The spontaneous reduction of V10 in solution is seen even in the presence of hydrogen peroxide and has not been previously observed. The susceptibility to reduction of V10 is likely to be shared by other redox active POMs. In addition to the molecular V10 ions, a high-abundance ionic signal for a V 10 O 26 2− anion was displayed in the negative-ion ESI mass spectra. None of the V 10 O 26 cations were detected in ESI MS, and only a low-abundance signal was observed for V 10 O 26 anions with a single negative charge, indicating that the presence of abundant V 10 O 26 2− anions in ESI MS reflects gas-phase instability of V 10 O 28 anions carrying two charges. The gas-phase origin of the V 10 O 26 2− anion was confirmed in tandem MS measurements, where mild collisional activation was applied to V10 molecular ions with an even number of hydrogen atoms (H 4 V 10 O 28 2− ), resulting in a facile loss of H 2 O molecules and giving rise to V 10 O 26 2− as the lowest-mass fragment ion. Water loss was also observed for V 10 O 28 anions carrying an odd number of hydrogen atoms ( e.g. , H 5 V 10 O 28 − ), followed by a less efficient and incomplete removal of an OH˙ radical, giving rise to both HV 10 O 26 − and V 10 O 25 − fragment ions. Importantly, at least one hydrogen atom was required for ion fragmentation in the gas phase, as no further dissociation was observed for any hydrogen-free V10 ionic species. The presented workflow allows a distinction to be readily made between the spectral features revealing the presence of non-canonical POM species in the bulk solution from those that arise due to physical and chemical processes occurring in the ESI interface and/or the gas phase. 
    more » « less