Thompson, Alison
Permanent URI for this collectionhttps://hdl.handle.net/10222/27742
Alison Thompson
Professor
Faculty of Science Killam Professor 2012-2017
Email: Alison.Thompson@dal.ca
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Item Open Access A Series of Potent BODIPY Photosensitisers Featuring Tellurophene Motifs at Boron(2024-05-08) Campbel, J.W.; Tung, M.T.; Taylor, B.B.; Beharry, A.A.; Thompson, AlisonItem Open Access Synthesis and Evaluation of Telluorophene- 2 BODIPY Photosensitizers Appended to Estradiol(2025-05-05) Tung. M.T.; Taylor, B.B.; Beharry, A.A.; Thompson, AlisonItem Embargo Synthesis of chiral systems featuring the pyrrole unit: a review(Royal Society of Chemistry, 2024-09-18) Jacob W. Campbell; Michael J. Cotnam; Francisca R. Annan; James W. Hilborn; Alison ThompsonSynthetic strategies towards pyrroles within chiral frameworks are summarised, focussing on reports published 2010–2023. The synthesis of pyrroles featuring substituents bearing chiral centres are summarised, as are those whereby pyrroles are located within axially chiral systems courtesy of restricted bond rotation.Item Embargo BODIPYs a-appended with distyryl-linked aryl bisboronic acids: single-step cell staining and turn-on fluorescence binding with D-glucose(Royal Society of Chemistry, 2024-08-27) Adil Alkaş; Joshua M. Kofsky; Em C. Sullivan; Daisy Nebel; Katherine N. Robertson; Chantelle J. Capicciotti; David L. Jakeman; Erin R. Johnson; Alison ThompsonSmall-molecule sensors that are selective for particular sugars are rare. The synthesis of BODIPYs appended with two boronic acid units is reported, alongside cellular staining/labelling and turn-on fluorescence binding data for carbohydrates. The structural frameworks were designed using computational methods, leaning on the chelation characteristics of bis(boronic acids) and the photophysical properties of BODIPYs. Selective binding to glucose is demonstrated via emission and absorption methods, and the challenges of using NMR data for studying carbohydrate binding are discussed. Furthermore, crystal structures, cell permeability and imaging properties of the BODIPYs appended with two boronic acid units are described. This work presents boronic-acid-appended BODIPYs as a potential framework for tunable carbohydrate sensing and chemical biology staining.Item Open Access Synthesis and Properties of Tetra-aryl Azobispyrroles(Royal Society of Chemistry, 2025) Steve O. Sequeira; Roberto M. Diaz-Rodriguez; Mmasinachi Atansi; James W. Hilborn; Adil Alkaş; Rosinah Liandrah Gapare; Madeleine Dearden; Em C. Sullivan; Emily B. Brown; Katherine N. Robertson; Alison ThompsonAn unprecedented azobispyrrole framework is introduced, wherein two aryl-substituted pyrroles are joined by an azo (–N[double bond, length as m-dash]N–) linkage. Functionalisation was demonstrated via pyrrolic N-methylation and by –BF2 complexation using the coordinating abilities of the pyrrolic and azo nitrogen atoms. Control of co-planarity enables tunability with maximal absorption and emission spanning almost 300 nm.Item Open Access Introducing the Substituted Azobispyrrole Framework: Synthesis and Properties(2025-07-03) Alkaş, Adil; Diaz-Rodriguez, Roberto M.; Sequeira, Steve O.; Hilborn, James W.; Atansi, Mmasinachi; Sullivan, Em C.; Brown, Emily B.; Gapare, Rosinah Liandrah; Mutus, Bulent; Robertson, Katherine N.; Thompson, AlisonAn unprecedented azobispyrrole framework is introduced, wherein two aryl-substituted pyrroles are joined by an azo (-NN-) linkage. Functionalisation was demonstrated via pyrrolic N-methylation and by -BF2 complexation using the coordinating abilities of the pyrrolic and azo nitrogen atoms. Control of co-planarity enables tunability with maximal absorption and emission spanning almost 300 nm.Item Open Access The Suzuki–Miyaura Reaction of BPin-substituted F-BODIPYs with Aryl Halides(2021-01-12) Craig D. Smith; Alison ThompsonF-BODIPYs substituted with BPin functionality have been coupled to aryl halides using a mild and efficient catalyst system involving Pd2(dba)3 and XPhos. The methodology enables the Suzuki–Miyaura cross-coupling of electron-rich, electron-poor, and sterically encumbered BPin-substituted F-BODIPYs to aryl halides bearing various functional groups, thus presenting an opportunity for the preparation of highly functionalised F-BODIPYs without need for the corresponding aryl moiety to be available in borylated formItem Open Access Substitution at Boron in BODIPYs(Chemical Communications (ChemComm), 2022-06-20) Rosinah Liandrah Gapare; Alison ThompsonRecent synthetic achievements have led to 4,4-disubstituted-4-bora-3a,4a-diaza-s-indacenes (BODIPYs) with varying substituents at the meso, pyrrolic and/or boron sites, with each influencing photophysical properties and utility. This Feature article gives an overview of chemistry at the boron atom in BODIPYs, highlighting our contributions that evolved from synthetic curiosities and now offer this dipyrrolic skeleton potential across a wider range of applications. We first summarise preparative routes to BODIPYs through complexation of boron with the dipyrrinato ligand. The role of boron in protecting dipyrrins is then discussed, followed by strategies by which to achieve facile substitution at the boron atom.Item Open Access Introducing the tellurophene-appended BODIPY: PDT agent with mass cytometry tracking capabilities(American Chemical Society, 2021-11-22) Jacob W. Campbell; Matthew T. Tung; Roberto M. Diaz-Rodriguez; Katherine N. Robertson; Andrew A. Beharry; Alison ThompsonThe synthesis and characterization of the first BODIPY appended to the five-membered heterocylic tellurophene [Te] moiety is reported. By incorporating tellurophene at the meso position, the tellurophene-appended boron-dipyrromethene dye (BODIPY) acts as a multimodal agent, becoming a potent photosensitizer with a mass cytometry tag. To synthesize the compound, we developed a method to enable late-stage Suzuki–Miyaura coupling by preparing and isolating tellurophene-2-BPin in a one-step procedure from the parent tellurophene. Coupling to a meso-substituted BODIPY functionalized with a pendant aryl bromide provides the desired tellurophene-appended BODIPY. This compound demonstrated a singlet oxygen quantum yield of 0.26 ± 0.01 and produced a light dose-dependent cytotoxicity with nanomolar IC50 values against 2D cultured HeLa cells and high efficacy against 3D cultured HeLa tumor spheroids, proving to be a strong photosensitizer. The presence of the tellurophene moiety could be detected using mass cytometry, thus showcasing the ability of a tellurophene-appended BODIPY as a novel photodynamic-therapy–mass-cytometry theranostic agent.Item Open Access Regioselective Substituent Effects upon the Synthesis of Dipyrrins from 2-Formyl Pyrroles(2018-03-26) Michael H.R. Beh; Carlotta Figliola; Kate-Lyn A.R. Lund; Aleksandra K. Kajetanowicz; Ann E. Johnsen; Elise M. Aronitz; Alison ThompsonThe synthesis of symmetric α-free meso-H-dipyrrin hydrobromides from 5-H-2-formyl pyrroles was investigated. The self-condensation produces regioisomeric dipyrrins through adoption of two mechanistic pathways. The key difference between the two pathways lies in which position of the pyrrole directs nucleophilic attack. Through a systematic study involving various substituted and (or) isotopically labelled 5-H-2-formyl pyrroles, we herein provide evidence to suggest that not only do two mechanistic pathways exist, but the steric bulk of the substituent adjacent to the 5-unsubstituted position influences which pathway dominates.Item Embargo A mild synthetic route to α-nitroso diaryl pyrroles (Postprint)(2024) Brown, Emily B.; Gapare, Rosinah Liandrah; Campbell, Jacob W.; Alkaş, Adil; Sequeira, Steve; Hilborn, James W.; Greening, Sarah M.; Robertson, Katherine N.; Thompson, AlisonA new synthetic method to access α-nitroso pyrroles is presented. This method utilises the nitrosonium salt NOBF4, enabling short reaction times (<10 minutes) and avoiding the harsh acidic conditions usually associated with pyrrole nitrosation. Application of this procedure to diarylated pyrroles yielded several novel nitroso-pyrroles. Modifications to the method, through exclusion of air and inclusion of a mild base, allowed for the nitrosation of pyrroles bearing aryl groups substituted with electron-donating groups. Attempts to nitrosylate pyrroles bearing alkyl substituents resulted in the formation of a dimeric material composed of a pyrrolic unit and a 2-hydroxyimino-protected 1,5-dihydro-2H-pyrrol-2-one.Item Open Access BODIPYs with Chalcogenophenes at Boron: Synthesis and Properties. Postprint(J. Org. Chem., 2023-07-13) Campbell, J.W.; Tung, M.T.; Robertson, K.N.; Beharry, A.A.; Thompson, A.Reported herein are the synthesis and characterization of BODIPYs bearing heterocycles at boron. To synthesize this series, various chalcogenophenes (furan, thiophene, selenophene, and tellurophene) were lithiated and then used as nucleophiles to attack the boron center of a parent F-BODIPY. Compounds in the series were compared with respect to their photophysical and structural properties, and trends were discussed. By virtue of the “heavy atom effect”, as the mass of the heterocycle appended to the BODIPY core increases, compounds exhibit a higher singlet oxygen quantum yield. The BODIPY with tellurophene at boron exhibits the highest quantum yield (ΦΔ = 0.68) in the series and reduced emission (Φf = 0.01).Item Open Access Bridging and Conformational Control of Porphyrin Units through Non-Traditional Rigid Scaffolds(2019-11-07) Grover, Nitika; Locke, Gemma M.; Flanagan, Keith J.; Beh, Michael H. R.; Thompson, Alison; Senge, Mathias O.Connecting two porphyrin units in a rigid linear fashion, without any undesired electron delocalization or communication between the chromophores, remains a synthetic challenge. Herein, a broad library of functionally diverse multi-porphyrin arrays that incorporate the non-traditional rigid linker groups cubane and bicyclo[1.1.1]pentane (BCP) is described. A robust, reliable, and versatile synthetic procedure was employed to access porphyrin-cubane/BCPporphyrin arrays, representing the largest non-polymeric structures available for cubane/BCP derivatives. These reactions demonstrate considerable substrate scope, from utilization of small phenyl moieties to large porphyrin rings, with varying lengths and different angles. To control conformational flexibility, amide bonds were introduced between the bridgehead carbon of BCP/cubane and the porphyrin rings. Through varying the orientation of the substituents around the amide bond of cubane/BCP, different intermolecular interactions were identified through single crystal X-ray analysis. These studies revealed non-covalent interactions that are the first-of-their-kind including a unique iodine-oxygen interaction between cubane units. These supramolecular architectures indicate the possibility to mimic a protein structure due to the sp3 rigid scaffolds (BCP or cubane) that exhibit the essential conformational space for protein function while simultaneously providing amide bonds for molecular recognition.Item Open Access Synthesis, properties and reactivity of BCl2 aza-BODIPY complexes and salts of the aza-dipyrrinato scaffold(Royal Society of Chemistry, 2020-02-25) Diaz-Rodriguez, Roberto M.; Burke, Luke; Robertson, Katherine N.; Thompson, AlisonThe synthesis and characterisation of the BCl2-chelated complexes of both archetypal aza-dipyrrin sub- types are presented. A stepwise halogen exchange, leading to a mixed-halide Cl–B–F intermediate, is implicated in the conversion of F-aza-BODIPYs to Cl-aza-BODIPYs upon treatment with BCl3. The utility of the Cl-aza-BODIPY scaffold to facilitate substitutions at boron is demonstrated under mild conditions through treatment with aryl Grignard reagents. Additionally, the lability of the B–Cl bond enables facile removal of the BCl2 group, i.e. deprotection of F-aza-BODIPYs, under aqueous conditions. Three aza- dipyrrin HX salts were also synthesised and characterised. The pKa of the protonated aza-dipyrrin was determined to be 4, thereby providing insight regarding the storage and stability of such species.Item Open Access Bridging and Conformational Control of Porphyrin Units through Non-Traditional Rigid Scaffolds(Wiley, 2019-11) Grover, Nitika; Locke, Gemma M.; Flanagan, Keith J.; Beh, Michael H. R.; Thompson, Alison; Senge, Mathias O.Connecting two porphyrin units in a rigid linear fashion, without any undesired electron delocalization or communication between the chromophores, remains a synthetic challenge. Herein, a broad library of functionally diverse multi-porphyrin arrays that incorporate the non-traditional rigid linker groups cubane and bicyclo[1.1.1]pentane (BCP) is described. The reactions demonstrate wide substrate scope, from utilization of small phenyl to large porphyrin rings, with varying lengths and different angles. To control conformational flexibility, amide bonds were introduced between the bridgehead carbon of BCP/cubane and the porphyrin rings. Through varying the orientation of the substituents around the amide bond of cubane/BCP, different intermolecular interactions were identifiedItem Open Access Bis[Pyrrolyl Ru(II)] Triads: a New Class of Photosensitizers for Metal-Organic Photodynamic Therapy(2020) Smithen, Deborah A.; Monro, Susan; Pinto, Mitch; Roque III, John; Diaz- Rodriguez, Roberto M.; Yin, Huimin; Cameron, Colin G.; Thompson, Alison; McFarland, Sherri A.A new family of ten dinuclear Ru(II) complexes based on the bis[pyrrolyl Ru(II)] triad scaffold, where two Ru(bpy)2 centers are separated by a variety of organic linkers, was prepared to evaluate the influence of the organic chromophore on the spectroscopic and in vitro photodynamic therapy (PDT) properties of the compounds. The bis[pyrrolyl Ru(II)] triads absorbed strongly throughout the visible region, with several members having molar extinction coefficients (e) ≥104 at 600–620 nm and longer. Phosphorescence quantum yields (Fp) were generally less than 0.1% and in some cases undetectable. The singlet oxygen quantum yields (FD) ranged from 5% to 77% and generally correlated with their photocytotoxicities toward human leukemia (HL-60) cells regardless of the wavelength of light used. Dark cytotoxicities varied ten-fold, with EC50 values in the range of 10– 100 μM and phototherapeutic indices (PIs) as large as 5,400 and 260 with broadband visible (28 J cm-2, 7.8 mW cm-2) and 625-nm red (100 J cm-2, 42 mW cm-2) light, respectively. The bis[pyrrolyl Ru(II)] triad with a pyrenyl linker (5h) was especially potent, with an EC50 value of 1 nM and PI >27,000 with visible light and subnanomolar activity with 625-nm light (100 J cm-2, 28 mW cm- 2). The lead compound 5h was also tested in a tumor spheroid assay using the HL60 cell line and exhibited greater photocytotoxcicity in this more resistant model (EC50=60 nM and PI>1,200 with 625-nm light) despite a lower dark cytotoxicity. The in vitro PDT effects of 5h extended to bacteria, where submicromolar EC50 values and PIs >300 against S. mutans and S. aureus were obtained with visible light. This activity was attenuated with 625-nm red light, but PIs were still near 50. The ligand-localized 3ππ* state contributed by the pyrenyl linker of 5h likely plays a key role in its phototoxic effects toward cancer cells and bacteria.Item Open Access Synthesis of sulfenyl dipyrroles via reaction of a-free pyrroles with thionyl chloride(2020-09) Beh, Michael H. R.; Smith, Craig D.; Robertson, Katherine N.; Thompson, AlisonItem Open Access Facile Deprotection of F-BODIPYs using Methylboronic Acid(2020) Smith, Craig D.; Thompson, Alison4,4-Difluoro-4-bora-3a,4a-diaza-s-indacenes (F-BODIPYs) are deprotected through removal of the –BF2 moiety upon treatment with methylboronic acid. The tolerance of various substitution patterns about the dipyrrinato core is demonstrated via the deprotection of thirteen F-BODIPYs and an F-aza-BODIPY. Work-up with aq. HBr affords the desired dipyrrin HBr salt in quantitative yield without need for purification.Item Open Access Synthesis and reactivity of 2-thionoester pyrroles: a route to 2-formyl pyrroles(RSC Advances, 2019) Kim, Min Joon; Gaube, Sophie M.; Beh, Michael H. R.; Smith, Craig D.; Thompson, Alison2-Functionalised pyrroles exhibit considerable synthetic utility. Herein, the synthesis and reactivity of 2-thionoester (-C(S)OR) pyrroles is reported. 2-Thionoester pyrroles were synthesized using a Knorr-type approach from aliphatic starting materials. 2-Thionoester pyrroles were reduced to the corresponding 2-formyl pyrroles, or the deuterated formyl variant, in one step using Raney nickel, thereby removing the need for the much-utilized hydrolysis/decarboxylation/formylation steps that are typically required to convert Knorr-type 2-carboxylate pyrroles into 2-formyl pyrroles. 2-Thionoester pyrroles proved tolerant of typical functional group interconversions for which the parent 2-carboxylate pyrroles have become known.Item Open Access The Photodecarboxylation of Substituted Naphthylmethyl Arylacetate Esters: Synthesis of Naphthylarylethanes(2019) Hilborn, James W.; Moya-Barrios, Reinaldo; Thompson, AlisonThe synthesis of naphthylarylethanes via the photodecarboxylation of naphthylmethyl arylacetate esters is reported where the aryl group is able to stabilize a charge transfer reaction. The reaction proceeds via intramolecular charge transfer from the donor to acceptor thereby enhancing a pathway to produce, within the solvent cage, the desired diarylethane products. These in-cage naphthylarylethanes are produced in good yields, in a single photochemical step, with the use of cyclohexane as solvent providing optimal yields.