School of Chemistry - Research Publications
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ItemCompetitive Triplet Formation and Recombination in Crystalline Films of Perylenediimide Derivatives: Implications for Singlet Fission(AMER CHEMICAL SOC, 2020-05-28)Developing photostable compounds that undergo quantitative singlet fission (SF) is a key challenge. As SF necessitates electron transfer between neighboring molecules, the SF rate is highly sensitive to intermolecular coupling in the solid state. We investigate SF in thin films for a series of perylenediimide (PDI) molecules. By adding different substituents at the imide positions, the packing of the molecules in the solid state can be changed. The relationship between SF parameters and the stacked geometry in PDI films is investigated, with two-electron direct coupling found to be the main SF mechanism. Time-resolved emission and transient absorption data show that all of the PDI films undergo SF although with different rates and yields varying from 35 to 200%. The results show that PDI1 and 2, which are stacked PDI pairs twisted out of alignment along the highest occupied molecular orbital to lowest unoccupied molecular orbital transition, exhibit faster and more efficient SF up to 200% yield. We demonstrate that both triplet formation and decay rates are highly sensitive to the ordering of the molecules within a film. The results of this study will assist in the design of optimized structures with a fast SF rate and low recombination rate that are required for useful light harvesting applications.
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ItemFRET-enhanced photoluminescence of perylene diimides by combining molecular aggregation and insulation(Royal Society of Chemistry, 2020-07-14)The photoluminescence quantum yield (ϕPL) of perylene diimide derivatives (PDIs) is often limited by aggregation caused quenching (ACQ) at high concentration or in the neat solid-state. Energy transfer in high dye concentration systems is also a key factor in determining ϕPL as a result of energy funneling to trap sites in the sample. By tuning the substituents, we present two classes of PDIs with aggregation and insulation of the PDI core. By combining these fluorophores in a polymer film, we demonstrate highly emissive samples (85% ϕPL) at high concentration (140 mM or 20% w/w). Experimental and theoretical studies provide insight into why such a combination is necessary to achieve high ϕPL. While insulated fluorophores maintain respectable ϕPL at high concentration, an improved ϕPL can be achieved in the presence of appropriately oriented fluorophore aggregates as emissive traps. The theoretical calculations show that the relative orientation of aggregated monomers can result in energetic separation of localized states from the charge-transfer and bi-excitonic states thereby enabling high ϕPL.
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ItemOxidative damage of proline residues by nitrate radicals (NO3): a kinetic and product study(ROYAL SOC CHEMISTRY, 2020-09-21)Tertiary amides, such as in N-acylated proline or N-methyl glycine residues, react rapidly with nitrate radicals (NO3˙) with absolute rate coefficients in the range of 4-7 × 108 M-1 s-1 in acetonitrile. The major pathway proceeds through oxidative electron transfer (ET) at nitrogen, whereas hydrogen abstraction is only a minor contributor under these conditions. However, steric hindrance at the amide, for example by alkyl side chains at the α-carbon, lowers the rate coefficient by up to 75%, indicating that NO3˙-induced oxidation of amide bonds proceeds through initial formation of a charge transfer complex. Furthermore, the rate of oxidative damage of proline and N-methyl glycine is significantly influenced by its position in a peptide. Thus, neighbouring peptide bonds, particularly in the N-direction, reduce the electron density at the tertiary amide, which slows down the rate of ET by up to one order of magnitude. The results from these model studies suggest that the susceptibility of proline residues in peptides to radical-induced oxidative damage should be considerably reduced, compared with the single amino acid.
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ItemOptimising molecular rotors to AIE fluorophores for mitochondria uptake and retention(ROYAL SOC CHEMISTRY, 2020-12-07)Molecular rotors exhibit fluorescence enhancement in a confined environment and thus have been used extensively in biological imaging. However, many molecular rotors suffer from small Stokes shift and self-aggregation caused quenching. In this work, we have synthesised a series of red emissive molecular rotors based on cationic α-cyanostilbene. Profoundly enhanced aggregation-induced emission (AIE) properties and greatly widened Stokes shifts can be achieved by molecular engineering. With specificity to stain mitochondria, we demonstrate a simple approach to achieve cell uptake and retention upon tuning the pyridinium substituent of the dyes.
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ItemOxidative Repair of Pyrimidine Cyclobutane Dimers by Nitrate Radicals (NO3•): A Kinetic and Computational Study(MDPI, 2020-06)Pyrimidine cyclobutane dimers are hazardous DNA lesions formed upon exposure of DNA to UV light, which can be repaired through oxidative electron transfer (ET). Laser flash photolysis and computational studies were performed to explore the role of configuration and constitution at the cyclobutane ring on the oxidative repair process, using the nitrate radical (NO3•) as oxidant. The rate coefficients of 8–280 × 107 M−1 s−1 in acetonitrile revealed a very high reactivity of the cyclobutane dimers of N,N’-dimethylated uracil (DMU), thymine (DMT), and 6-methyluracil (DMU6-Me) towards NO3•, which likely proceeds via ET at N(1) as a major pathway. The overall rate of NO3• consumption was determined by (i) the redox potential, which was lower for the syn- than for the anti-configured dimers, and (ii) the accessibility of the reaction site for NO3•. In the trans dimers, both N(1) atoms could be approached from above and below the molecular plane, whereas in the cis dimers, only the convex side was readily accessible for NO3•. The higher reactivity of the DMT dimers compared with isomeric DMU dimers was due to the electron-donating methyl groups on the cyclobutane ring, which increased their susceptibility to oxidation. On the other hand, the approach of NO3• to the dimers of DMU6-Me was hindered by the methyl substituents adjacent to N(1), making these dimers the least reactive in this series.
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ItemGallium Fluoride Complexes with Acyclic Bispicolinic Ligands as Potential New Fluorine-18 Labelled Imaging Agents(WILEY-V C H VERLAG GMBH, 2020-09-22)The positron‐emitting radionuclide, fluorine‐18, is used to radiolabel molecules to develop tracers for diagnostic imaging with positron‐emission tomography. There is growing interest in the potential of using strong coordinate bonds between electropositive Ga(III) and electronegative fluoride (≈ 557 kJ/mol) to provide new methods of incorporating fluorine‐18 into molecules. The potential of gallium(III) complexes with acyclic pentadentate bispicolinic acid containing ligands (H2L1–3) to form ternary complexes with fluoride, [GaL1–3F] was investigated with a view to developing new methods for fluorine‐18 radiolabelling. A solid‐phase peptide synthesis approach was used to produce a bispicolinic acid chelator with a lysine residue. Characterisation of [GaL1X] (X = OH, Cl, F) by X‐ray crystallography revealed that L1 acted as dianionic N2O2 donor to the Ga(III) with the fifth site occupied by a monodentate anion (OH–, Cl– or F–). Despite its high stability in aqueous mixture and [D6]DMSO and the straightforward synthesis of [GaL1F], it was only possible to form the radioactive analogue [18F][GaL1F] in low radiochemical yields.
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ItemEvidence that pi-ligand exchange reactions of chalcogen iranium ions proceed via Huckel pseudocoarctate transition states(Wiley, 2020-12)Despite numerous computational and experimental studies on the π‐ligand exchange reactions of chalcogen iranium ions, a classification of the reaction class has yet to be made. The characteristics of the transition states presented thus far suggested a coarctate nature with two bonds breaking and forming simultaneously at the chalcogen centre. The change in barrier height, depending on the nature of the chalcogen and the alkene, was initially attributed as a shift in the degree of aromaticity moving from pseudocoarctate to coarctate reactions. However, this paper suggests that all 12 reactions under consideration are pseudocoarctate with a Hückel number of delocalised π electrons based on comprehensive studies of the orbital interactions and magnetic properties both at the transition state and along the reaction path. The change in barrier height was largely driven by the electrophilicity of the chalcogen and the strain present in the three‐membered ring rather than a shift in the degree of aromaticity.
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ItemA Molecular Chameleon for Mapping Subcellular Polarity in an Unfolded Proteome Environment(WILEY-V C H VERLAG GMBH, 2020-06-15)Environmental polarity is an important factor that drives biomolecular interactions to regulate cell function. Herein, a general method of using the fluorogenic probe NTPAN-MI is reported to quantify the subcellular polarity change in response to protein unfolding. NTPAN-MI fluorescence is selectively activated upon labeling unfolded proteins with exposed thiols, thereby reporting on the extent of proteostasis. NTPAN-MI also reveals the collapse of the host proteome caused by influenza A virus infection. The emission profile of NTPAN-MI contains information of the local polarity of the unfolded proteome, which can be resolved through spectral phasor analysis. Under stress conditions that disrupt different checkpoints of protein quality control, distinct patterns of dielectric constant distribution in the cytoplasm can be observed. However, in the nucleus, the unfolded proteome was found to experience a more hydrophilic environment across all the stress conditions, indicating the central role of nucleus in the stress response process.
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ItemA Molecular Chameleon for Mapping Subcellular Polarity in an Unfolded Proteome Environment(Wiley, 2020-06-15)Abstract Environmental polarity is an important factor that drives biomolecular interactions to regulate cell function. Herein, a general method of using the fluorogenic probe NTPAN‐MI is reported to quantify the subcellular polarity change in response to protein unfolding. NTPAN‐MI fluorescence is selectively activated upon labeling unfolded proteins with exposed thiols, thereby reporting on the extent of proteostasis. NTPAN‐MI also reveals the collapse of the host proteome caused by influenza A virus infection. The emission profile of NTPAN‐MI contains information of the local polarity of the unfolded proteome, which can be resolved through spectral phasor analysis. Under stress conditions that disrupt different checkpoints of protein quality control, distinct patterns of dielectric constant distribution in the cytoplasm can be observed. However, in the nucleus, the unfolded proteome was found to experience a more hydrophilic environment across all the stress conditions, indicating the central role of nucleus in the stress response process.
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ItemAutomated synthesis of 18F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry(SPRINGERNATURE, 2020-11-09)BACKGROUND: Oncrasin-1 is a small molecule which was identified from a screen of KRAS mutant cancer cells and has shown specificity for KRAS mutant cell killing. We aimed to develop a radiolabelled form of Oncrasin-1 to enable in-vivo imaging of mutant KRAS expression in malignant tumours. This work outlines the synthesis of 3 fluorinated derivatives and development of iodonium salt and boronic ester precursors for radiolabelling with the 18F isotope. RESULTS: In our hands, synthesis of iodonium salts were not easily accessible due to the 3-carbaldehyde indole structure being preferentially oxidized by conditions required for iodonium salt formation, rather than benzyl iodide. Synthesis and radiolabelling of boronic acid pinacol ester precursors were successful, with the products being obtained in yields of 10.76% ± 0.96% (n = 5), 14.7% ±8.58% (n = 3) and 14.92% ±3.9% (n = 3) for 18F KAM001, 18F KAM002 and 18F KAM003 respectively, with radiochemical purity of greater than 99%. CONCLUSIONS: The successful synthesis of these tracers has been undertaken utilizing boronic ester radio-fluorination methods and will allow for investigation of Oncrasin based molecules as potential diagnostics for cancers expressing mutant KRAS protein.