eprintid: 1472682 rev_number: 24 eprint_status: archive userid: 608 dir: disk0/01/47/26/82 datestamp: 2015-11-18 14:01:16 lastmod: 2021-09-19 23:59:33 status_changed: 2015-11-18 14:01:16 type: article metadata_visibility: show creators_name: Hylton, RK creators_name: Tizzard, GJ creators_name: Threlfall, TL creators_name: Ellis, AL creators_name: Coles, SJ creators_name: Seaton, CC creators_name: Schulze, E creators_name: Lorenz, H creators_name: Seidel-Morgenstern, A creators_name: Stein, M creators_name: Price, SL title: Are the crystal structures of enantiopure and racemic mandelic acids determined by kinetics or thermodynamics? ispublished: pub divisions: UCL divisions: B04 divisions: C06 divisions: F56 note: This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. abstract: Mandelic acids are prototypic chiral molecules where the sensitivity of crystallized forms (enantiopure/racemic compound/polymorphs) to both conditions and substituents provides a new insight into the factors that may allow chiral separation by crystallization. The determination of a significant number of single crystal structures allows the analysis of 13 enantiopure and 30 racemic crystal structures of 21 (F/Cl/Br/CH3/CH3O) substituted mandelic acid derivatives. There are some common phenyl packing motifs between some groups of racemic and enantiopure structures, although they show very different hydrogen-bonding motifs. The computed crystal energy landscape of 3-chloromandelic acid, which has at least two enantiopure and three racemic crystal polymorphs, reveals that there are many more possible structures, some of which are predicted to be thermodynamically more favorable as well as slightly denser than the known forms. Simulations of mandelic acid dimers in isolation, water, and toluene do not differentiate between racemic and enantiopure dimers and also suggest that the phenyl ring interactions play a major role in the crystallization mechanism. The observed crystallization behavior of mandelic acids does not correspond to any simple "crystal engineering rules" as there is a range of thermodynamically feasible structures with no distinction between the enantiopure and racemic forms. Nucleation and crystallization appear to be determined by the kinetics of crystal growth with a statistical bias, but the diversity of the mandelic acid crystallization behavior demonstrates that the factors that influence the kinetics of crystal nucleation and growth are not yet adequately understood. date: 2015-09-02 date_type: published official_url: http://dx.doi.org/10.1021/jacs.5b05938 oa_status: green full_text_type: pub primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1047818 doi: 10.1021/jacs.5b05938 language_elements: eng lyricists_name: Price, Sarah lyricists_id: SLPRI40 actors_name: Price, Sarah actors_name: Poirier, Elizabeth actors_id: SLPRI40 actors_id: EPPOI23 actors_role: owner actors_role: impersonator full_text_status: public publication: Journal of the American Chemical Society volume: 137 number: 34 pagerange: 11095-11104 event_location: United States issn: 1520-5126 citation: Hylton, RK; Tizzard, GJ; Threlfall, TL; Ellis, AL; Coles, SJ; Seaton, CC; Schulze, E; ... Price, SL; + view all <#> Hylton, RK; Tizzard, GJ; Threlfall, TL; Ellis, AL; Coles, SJ; Seaton, CC; Schulze, E; Lorenz, H; Seidel-Morgenstern, A; Stein, M; Price, SL; - view fewer <#> (2015) Are the crystal structures of enantiopure and racemic mandelic acids determined by kinetics or thermodynamics? Journal of the American Chemical Society , 137 (34) pp. 11095-11104. 10.1021/jacs.5b05938 <https://doi.org/10.1021/jacs.5b05938>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1472682/1/jacs.5b05938.pdf