Computational and experimental investigation of factors affecting the quality of multi-component crystals

Simple item page
dc.contributor.advisorEsterhuysen, Catharineen_ZA
dc.contributor.advisorHaynes, Deliaen_ZA
dc.contributor.authorAkerele, Oluwatoyin Omolaraen_ZA
dc.contributor.otherStellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.en_ZA
dc.date.accessioned2022-03-11T08:01:19Zen_ZA
dc.date.accessioned2022-04-29T12:56:01Zen_ZA
dc.date.available2023-03-18T03:00:12Zen_ZA
dc.date.issued2022-03en_ZA
dc.descriptionThesis (PhD)--Stellenbosch University, 2022.en_ZA
dc.description.abstractENGLISH ABSTRACT: A series of six substituted benzoic acid and fifteen substituted pyridine compounds have been crystallised together to form multi-component co-crystals or salts. The crystal structures obtained from single-crystal X-ray diffraction show that the hydrogen bond between the carboxylic acid group and pyridine nitrogen is strong, resulting in a robust synthon that is present in all the co-crystals and salts formed. The nature of the synthon, including hydrogen bond strengths and geometries and the co-planar of the acid and base in the multi-component crystals was investigated using both experimental and computational approaches. The hydrogen-bond energy between the acid and base is related to the Npyr-Ocarb distance as we found low distances correspond to strong interactions and vice versa in both co-crystals and salts. It was found that in the presence of NH2 substituents ortho to the pyridine an 𝑅22(8) hydrogen-bonded ring forms that leads to co-planarity of the two molecules. This is likely to promote the formation of a slip plane, which in turn may improve the tabletability of such salts or co-crystals. These results were confirmed by a Cambridge Structural Database search that showed that the properties identified are also generally relevant for the 879 related multi-component crystal structures previously reported. These crystal structures were then used as a basis for the identification of intrinsic factors that affect the crystal quality. The hydrogen-bond energies between the acid-base unit in salts is stronger than those in co-crystals, suggesting that salts are more stable than co-crystals. Similar observations were obtained for the lattice energies, the free energies of interactions, polarisation energies, and the strengths of hydrogen bond donor and acceptor. This means the presence of ionic components makes these interactions stronger and thereby stabilises the multi-component crystal. However, in salts this does not automatically translate into a good-quality crystal as we observed good- and poor-quality crystals for both salts and co-crystals. This means ionicity does not determine the formation of quality crystals. Further investigation revealed that the factors influencing crystal quality depend on the chemical species involved; there is no common factor that cut across all the compounds. The interactions associated with the packing of the crystal structures, and not necessarily the hydrogen bond between the acid-base pair were most commonly found to be responsible for the formation of good-quality salt crystals. The quality of co-crystals is influenced by both the strength of the hydrogen bond within the acid-base unit and the interactions with molecules surrounding the unit. The absence of a substituent at the para position in the acid component was found to hinder the formation of good-quality co-crystals. Comparison of two similar compounds that produce crystals of different quality reveals that the strong lattice energy, electrostatic energy, a small difference in the strength of hydrogen bond donor and hydrogen bond acceptor of acid and base, the presence of strong interactions around the benzoic-acid…pyridine synthons, are the factors that influence the formation of good-quality crystals. These interactions that play a role are typically strong hydrogen bonds, π- π stacking, and C-H…O bonds; the greater the number of interactions with high energy in a complex, the better the quality of crystals that will be formed. Finally, the organic bases used in this study were found to impact crystal formation, for instance, 2-amino-4-methyl pyridine and 2-amino-5-nitropyridine are good co-formers that generally facilitate strong interactions and give rise to good-quality crystals, while co-formers such as 4-cyanopyridine and 2-amino-6-methylpyridine typically form weak interactions, resulting in poor-quality crystals.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: ’n Reeks van ses gesubstitueerde bensoësuur- en vyftien gesubstitueerde piridienverbindings is saam gekristalliseer om multi-komponent ko-kristalle of soute te vorm. Die kristalstrukture verkry uit enkelkristal X-straaldiffraksie toon dat die waterstofbinding tussen die karboksielsuurgroep en piridienstikstof sterk is, wat lei tot ‘n robuuste sinton wat teenwoordig is in al die medekristalle en soute wat gevorm word. Die aard van die sinton, insluitende waterstofbindingsterktes en geometrieë en die ko-planariteit van die suur en basis in die multi-komponent kristalle, is ondersoek deur gebruik te maak van beide eksperimentele en berekeningsmetodes. Die waterstofbindingsenergie tussen die suur en basis hou verband met die Npyr-Okarb-afstand aangesien ons gevind het dat lae afstande ooreenstem met sterk interaksies en omgekeerd in beide medekristalle en soute. Daar is gevind dat in die teenwoordigheid van NH2-substituente orto tot die piridien ‘n R22(8) waterstofgebinde ring vorm wat lei tot ko-planariteit van die twee molekules. Dit sal waarskynlik die vorming van ‘n glyvlak bevorder, wat op sy beurt die tableteerbaarheid van sulke soute of medekristalle kan verbeter. Hierdie resultate is bevestig deur ‘n Cambridge Strukturele Databasis-soektog wat getoon het dat die eienskappe wat geïdentifiseer is ook oor die algemeen relevant is vir die 879 verwante multi-komponent kristalstrukture wat voorheen gerapporteer is. Hierdie kristalstrukture is dan gebruik as basis vir die identifisering van intrinsieke faktore wat die kristalkwaliteit beïnvloed. Die waterstofbindingsenergieë tussen die suur-basis-eenheid in soute is sterker as vir medekristalle, wat daarop dui dat soute meer stabiel is as medekristalle. Soortgelyke waarnemings is verkry vir die roosterenergieë, die vrye energieë van interaksies, polarisasie-energieë en die sterktes van die waterstofbindingsdonor en -akseptor. Dit beteken die teenwoordigheid van ioniese komponente maak hierdie interaksies sterker en stabiliseer daardeur die multi-komponent kristal. In soute vertaal dit egter nie outomaties in ‘n goeie kwaliteit kristal nie, aangesien ons goeie- en swak-kwaliteit kristalle vir beide soute en medekristalle waargeneem het. Dit beteken ionisiteit bepaal nie die vorming van kwaliteit kristalle nie. Verdere ondersoek het aan die lig gebring dat die faktore wat kristalkwaliteit beïnvloed, afhang van die betrokke chemiese spesies; daar is geen gemeenskaplike faktor wat deur al die verbindings sny nie. Die interaksies wat geassosieer word met die pakking van die kristalstrukture, en nie noodwendig die waterstofbinding tussen die suur-basis-paar nie, is mees algemeen gevind om verantwoordelik te wees vir die vorming van goeie kwaliteit soutkristalle. Die kwaliteit van ko-kristalle word beïnvloed deur beide die sterkte van die waterstofbinding binne die suur-basis-eenheid en die interaksies met molekules wat die eenheid omring. Daar is gevind dat die afwesigheid van ‘n substituent by die para-posisie in die suurkomponent die vorming van goeie kwaliteit medekristalle belemmer. Vergelyking van twee soortgelyke verbindings wat kristalle van verskillende kwaliteit produseer, onthul dat ‘n sterk roosterenergie en elektrostatiese energie, ‘n klein verskil in die sterkte van die waterstofbindingsdonor en waterstofbindingsakseptor van die suur en basis en die teenwoordigheid van sterk interaksies rondom die bensoësuur…piridien-sintone is die faktore wat die vorming van goeie kwaliteit kristalle beïnvloed. Die interaksies wat ‘n rol speel is tipies sterk waterstofbindings, π-π stapeling en CH-O bindings; hoe groter die aantal interaksies met hoë energie in ‘n kompleks, hoe beter is die kwaliteit van kristalle wat gevorm sal word. Laastens is gevind dat die organiese basisse wat in hierdie studie gebruik is om kristalvorming te beïnvloed, byvoorbeeld, 2-amino-4-metielpiridien en 2-amino-5-nitropiridien is goeie medevormers wat oor die algemeen sterk interaksies fasiliteer en aanleiding gee tot goeie-kwaliteit kristalle, terwyl medevormers soos 4-sianopiridien en 2-amino-6-metielpiridien tipies swak interaksies vorm, wat lei tot swak kwaliteit kristalle.af_ZA
dc.description.versionDoctorateen_ZA
dc.embargo.terms2023-03-10en_ZA
dc.format.extentxii, 181 pages : illustrationsen_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/125147en_ZA
dc.language.isoEnglish (British)en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.rights.holderStellenbosch Universityen_ZA
dc.subject.lcshCrystallizationen_ZA
dc.subject.lcshBenzoic aciden_ZA
dc.subject.lcshPyridinium compoundsen_ZA
dc.subject.lcshUCTDen_ZA
dc.titleComputational and experimental investigation of factors affecting the quality of multi-component crystalsen_ZA
dc.typeThesisen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
akerele_computational_2022.pdf
Size:
10.77 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Doctoral Degrees (Chemistry and Polymer Science)