| 1. |
- Arkhypchuk, Anna I., et al.
(author)
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Investigation of the demetallation of 10-aryl substituted synthetic chlorins under acidic conditions
- 2020
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In: Journal of Inorganic Biochemistry. - : ELSEVIER SCIENCE INC. - 0162-0134 .- 1873-3344. ; 205
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Journal article (peer-reviewed)abstract
- The acidic demetallation of a series of sparsely substituted Zn(II) chlorins is reported. The chlorins were functionalized in the 10-position with substituents ranging from strongly electron donating mesityl and p-methoxyphenyl to electron-withdrawingp-nitrophenyl and pentafluorophenyl groups. The demetallation kinetics were investigated using UV-Visible absorption spectroscopy. Demetallation was carried out by exposing the metallochlorins dissolved in CH2Cl2 to an excess of trifiuoroacetic acid. Reasonable correlation was found between the Hammett constant of the 10-substituent and the rate constant of the loss of the metal ion. The largest differences were observed between the p-methoxyphenyl and p-nitrophenyl-substituted Zn(II) chlorins, undergoing loss of Zn(II) with pseudo first order rate constants of 0.0789 x 10(-3) and 3.70 x 10(-3) min(-1), respectively. Taken together, these data establish the dramatic influence even subtle changes can have in altering the electronic properties of chlorins, which in turn impacts metallochlorin function.
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| 2. |
- Bornhof, Anna-Bea, et al.
(author)
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Rational Synthesis of 2-Bromoporphyrins and 2,12-Dibromoporphyrins
- 2017
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In: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 82:23, s. 12908-12913
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Journal article (peer-reviewed)abstract
- Bromoporphyrins were prepared by the metal-mediated self-condensation of brominated 1-formyldipyrromethanes. Depending on the conditions, Mg(II)-2,12-dibromoporphyrin and Mg(II)-2-bromoporphyrin could be obtained in up to 11% and 17% isolated yield, respectively. Zn(II) was also a viable templating metal. The positions of the bromine substituents were confirmed by 2D-NMR spectroscopic analysis and the X-ray crystal structure of a derivative. Suzuki and Sonogashira reactions of the bromoporphyrins yielded 2-substituted or 2,12-disubstituted porphyrins with red-shifted absorption and emission spectra. This method provides access to the minimalist core of beta-mono- and beta,beta'-disubstituted porphyrins from readily available starting materials.
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| 3. |
- Cornelius Chukwu, Eugenia, et al.
(author)
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Engineered Aldolases Catalyzing Stereoselective Aldol Reactions Between Aryl-Substituted Ketones and Aldehydes
- 2023
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In: Catalysis Science & Technology. - : Royal Society of Chemistry. - 2044-4753 .- 2044-4761.
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Journal article (peer-reviewed)abstract
- An A129G/R134V/S166G triple mutant of fructose 6-phosphate aldolase (FSA) from Escherichia coli was further engineered with the goal to generate new enzyme variants capable of catalyzing aldol reactions between aryl substituted ketones and aldehydes. Residues L107 and L163 were subjected to saturation mutagenesis and the resulting library of FSA variants was screened for catalytic activity with 2-hydroxyacetophenone and phenylacetaldehyde as substrates. A selection of aldolase variants was identified that catalyze the synthesis of 2,3-dihydroxy-1,4-diphenylbutanone. The most active enzyme variants contained an L163C substitution. An L107C/L163C variant was further tested for activity with substituted phenylacetaldehydes, and was shown to afford the production of the corresponding diphenyl substituted butanones with good diastereoselectivities (anti : syn dr of 10 to 30) and reasonable to good enantioselectivities of syn enantiomers (er of 5 to 25).
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Sethio, Daniel, et al.
(author)
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Simulation Reveals the Chameleonic Behavior of Macrocycles
- 2023
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In: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 63:1, s. 138-146
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Journal article (peer-reviewed)abstract
- Conformational analysis is central to the design of bioactive molecules. It is particularly challenging for macrocycles due to noncovalent transannular interactions, steric interactions, and ring strain that are often coupled. Herein, we simulated the conformations of five macrocycles designed to express a progression of increasing complexity in environment-dependent intramolecular interactions and verified the results against NMR measurements in chloroform and dimethyl sulfoxide. Molecular dynamics using an explicit solvent model, but not the Monte Carlo method with implicit solvation, handled both solvents correctly. Refinement of conformations at the ab initio level was fundamental to reproducing the experimental observations-standard state-of-the-art molecular mechanics force fields were insufficient. Our simulations correctly predicted the intramolecular interactions between side chains and the macrocycle and revealed an unprecedented solvent-induced conformational switch of the macrocyclic ring. Our results provide a platform for the rational, prospective design of molecular chameleons that adapt to the properties of the environment.
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| 8. |
- Umereweneza, Daniel, et al.
(author)
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Macrocyclic Pyrrolizidine Alkaloids and Silphiperfolanol Angelate Esters from Solanecio mannii
- 2023
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In: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; 26:8
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Journal article (peer-reviewed)abstract
- Three new compounds, the silphiperfolanol angelate ester umutagarananol (1), the macrocyclic pyrrolizidine alkaloids umutagarinine A and B (2-3), and five known secondary metabolites (4-8) were isolated from the CH2Cl2-MeOH (1 : 1) extract of the roots and the stem bark of Solanecio mannii (Hook. f.) (Asteraceae). The isolated compounds were characterized by NMR and IR spectroscopic, and mass spectrometric analyses, whereas the relative stereochemistry of 4 was established by NAMFIS-based combined computational and solution NMR analysis. Synthetic modification of 5 provided two new compounds, 2-angeloyloxy-4,8-epoxypresilphiperfolane (9) and 2-angeloyloxy-4,8-epoxypresilphi-perfolane (10). The crude extracts and the isolated constituents showed weak antibacterial activities (EC50 0.7-13.3 mM) against the Gram-negative Escherichia coli and the Gram-positive Bacillus subtilis. Compounds 2, 3 and 4 exhibited strong cytotoxicity against MCF-7 human breast cancer cells, with EC50 values of 35.6, 21.7 and 12.5 mu M, respectively.
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| 9. |
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| 10. |
- Xiong, Ruisheng, et al.
(author)
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Attempted syntheses of N-confused hydroporphyrins through modified Lindsey routes
- 2019
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In: Journal of Porphyrins and Phthalocyanines. - : WORLD SCI PUBL CO INC. - 1088-4246 .- 1099-1409. ; 23:4-5, s. 589-598
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Journal article (peer-reviewed)abstract
- Unlike N-confused porphyrins which are well-known and extensively studied tetrapyrroles, N-confused hydroporphyrins are almost unknown, largely because so far they have resisted attempts at rational synthesis. Here, we report our efforts towards the total synthesis of N-confused hydroporphyrins. We have prepared N-confused building blocks analogous to the non-N-confused substrates in the Lindsey synthesis of sparsely substituted chlorins. We have systematically flipped the A, B and C pyrrole rings in the dipyrrolic precursors of the target N-confused macrocycles, preparing in total an N-confused "Western half' (tetrahydrodipyrrin) and two N-confused "Eastern halves" (brominated formyldipyrromethanes). These were subjected to a range of cyclization conditions. While we successfully isolated and identified three macrocyclic products, none of these proved to be the desired N-confused hydroporphyrin.
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| 11. |
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| 12. |
- Xiong, Ruisheng
(author)
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Development of Novel Hydroporphyrins for Light Harvesting and Sensitising NIR Lanthanide Luminescence
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Chlorins, as the core structures of chlorophylls, have been extensively studied for harvesting solar energy, fluorescent imaging and photodynamic therapy against cancer. This thesis is concerned with design and synthesis of novel chlorins as antennae for harvesting light and sensitising near infrared lanthanide luminescence.In the first part, a series of chlorin monomers, dimers and polymers were synthesised and their photophysical properties were characterised. The chlorin monomers were substituted with five-membered heterocycles, such as thiophenes and furans. These heterocycles function as auxochromes analogous to the natural ones in chlorophylls, and extend chlorin absorption and emission strongly to the red (up to λem = 680 nm). A borylation method was developed to prepare borylated chlorins, which gave access to directly linked chlorin dimers through Suzuki coupling reaction. Different regioisomers of chlorin dimer were prepared, including β-meso homodimers, meso-meso homodimers and heterodimers. The dimerisation resulted in red-shifted absorption and emission. Chlorin polymerisations were performed both electrochemically and chemically. Bis-thienylchlorins yielded chlorin films and an organic solvent soluble copolymer with hexylthiophene, respectively. These polymers from both polymerisations have red absorptions beyond 700 nm, and might be used as light-harvesting antennae.In the second part, chlorins were used as chromophores to sensitise near infrared lanthanide luminescence. Two types of chlorin-lanthanide dyads were prepared through lanthanide coordination with cyclen derivatives and dipicolinic acids (DPA). The cyclen-based dyads were poorly soluble in water, thus their near infrared emissions were not observed. The other type of complexes was fully soluble in H2O and THF. Both Nd and Yb emission were recorded even upon excitation into the Q bands of chlorins. In the dyads with free base chlorins, the singlet state of chlorins might be involved in the sensitisation of lanthanide luminescence. These DPA-based dyads presented two-color emission based on one chlorin and two-color excitation based on one lanthanide ion. These dyads would enable in theory 4-color imaging.In the last part, a microwave-assisted two-step synthesis was described to prepare dipyrromethanes, which are the key intermediates in the chlorin synthesis. This mild method took advantage of the nucleophilicity of pyrrole and the electrophilicity of N,N-dimethylaminomethyl pyrroles. The usually used acid catalysis is detrimental to many functionalities, thus our methods enable the synthesis of dipyrromethanes with acid sensitive groups or a formyl group.
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| 13. |
- Xiong, Ruisheng, 1985-, et al.
(author)
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Directly linked hydroporphyrin dimers
- 2016
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In: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; 52, s. 9056-9058
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Journal article (peer-reviewed)abstract
- Directly linked hydroporphyrin (chlorin) dimers were accessed regioselectively from bromochlorins. Versatile 15-borylated chlorins were prepared in excellent yield via Miyaura borylation. Suzuki coupling yielded meso-meso-linked homo- and heterodimers, and meso-beta-linked dimers. The photophysical and electrochemical properties of the dimers are reported.
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| 14. |
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| 15. |
- Xiong, Ruisheng, 1985-, et al.
(author)
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Excitation- and emission wavelength-based multiplex imaging using red-absorbing near infrared-emitting lanthanide complexes
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Other publication (other academic/artistic)abstract
- : Multiplex luminescence imaging in the red and near infrared (NIR) should be an enabling tool for the real-time investigation of complex biological systems. Current probes have numerous limitations including low photostability, short luminescent lifetime, overlapping absorption and emission bands, and small Stokes shift, the combination of which limits multiplexing in this region to two colors. Here we report emitters based on near infrared (NIR) emitting luminescent lanthanides (Ln) sensitized by hydroporphyin antennae. The narrow and intense absorption bands of hydroporphyrins are in the red, and their porisiotns are readily tunable. These dyads enable both emission- and excitation-based multiplexing; the former by combining either the same antenna with different Ln’s, the latter by attaching chlorin antennae with non-overlapping absorptions to the same Ln-complex. Up to 4 different species could be discerned without tedious data manipulation.
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| 16. |
- Xiong, Ruisheng, et al.
(author)
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Excitation- and Emission-Wavelength-Based Multiplex Spectroscopy Using Red-Absorbing Near-Infrared-Emitting Lanthanide Complexes
- 2018
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 140:35, s. 10975-10979
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Journal article (peer-reviewed)abstract
- Multiplex imaging in the red and near-infrared (NIR) should be an enabling tool for the real-time investigation of biological systems. Currently available emitters have short luminescent lifetimes, broad absorption and emission bands, and small Stokes shifts, which limits multiplexing in this region to two colors. NIR-emitting luminescent lanthanide (Ln) complexes carrying hydroporphyrin (chlorin) sensitizing antennae are excitable in the red through the narrow, intense and tunable chlorin absorptions. Both emission- and excitation-based multiplexing are possible, the former by exciting the same antenna appended to different Lns, the latter by attaching different chlorins with nonoverlapping absorptions to the same Ln. The combination of excitation and emission spectroscopies allows for the straightforward differentiation of up to four different complexes.
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| 17. |
- Xiong, Ruisheng, et al.
(author)
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Furan- and Thiophene-Based Auxochromes Red-shift Chlorin Absorptions and Enable Oxidative Chlorin Polymerizations
- 2017
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In: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 23:17, s. 4089-4095
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Journal article (peer-reviewed)abstract
- The de novo syntheses of chemically stable chlorins with five-membered heterocyclic (furane, thiophene, formylfurane and formylthiophene) substituents in selected meso- and beta-positions are reported. Heterocycle incorporation in the 3- and 13-positions shifted the chlorin absorption and emission to the red (up to lambdaem =680 nm), thus these readily incorporated substituents function analogously to auxochromes present in chlorophylls, for example, formyl and vinyl groups. Photophysical, theoretical and X-ray crystallographic experiments revealed small but significant differences between the behavior of the furan- and the thiophene-based auxochromes. Four regioisomeric bis-thienylchlorins (3,10; 3,13, 3,15 and 10,15) were oxidatively electropolymerized; the chlorin monomer geometry had a profound impact on the polymerization efficiency and the electrochemical properties of the resulting material. Chemical co-polymerization of 3,13-bis-thienylchlorin with 3-hexylthiophene yielded an organic-soluble red-emitting polymer.
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| 18. |
- Xiong, Ruisheng, 1985-, et al.
(author)
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Mild Microwave-Assisted Synthesis of Dipyrromethanes and Their Analogues
- 2014
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In: Synlett. - : Georg Thieme Verlag KG. - 0936-5214 .- 1437-2096. ; 26, s. 484-488
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Journal article (peer-reviewed)abstract
- The Mannich reaction between pyrroles or indoles and Eschenmoser’s salt (dimethylmethylideneammonium iodide) forms N,N-dimethylamino-methylated derivatives in good to excellent yields. The reaction is highly regioselective, and for pyrroles both 2- and 3-sub- stituted derivatives could be obtained. The N,N-dimethylaminometh- ylpyrroles and indoles underwent substitution with pyrrole under mi- crowave irradiation, affording the appropriate dipyrromethanes, N- confused, and indolo-dipyrromethanes in moderate to excellent overall yield.
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| 19. |
- Xiong, Ruisheng, et al.
(author)
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Paramagnetic lanthanide tags for identifying ligand-protein binding site
- 2018
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Conference paper (peer-reviewed)abstract
- Ligand-protein interactions are pivotal in living organisms. Knowing the binding sites of small-molecule ligands, especially low affinity ones, is an important step for modern drug discovery as it enables the development of high affinity lead compounds. Due to the lack of robust characterization approaches, the determination of weak binding is still cumbersome. We have reported a paramagnetic ligand tagging method by taking advantage of pseudo-contact shifts of protein NMR, which requires the ligand to be linked to a paramagnetic lanthanide complex.1 In this project we have improved the structure of our original paramagnetic tag to increase the accuracy of the NMR-based structure determination as compared to our previously presented approach.
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| 20. |
- Xiong, Ruisheng
(author)
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Paramagnetic ligand tagging to identify ligand-protein binding sites
- 2018
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Conference paper (peer-reviewed)abstract
- Ligand-protein interactions are pivotal in living organisms. Knowing the binding sites of small-molecule ligands, especially low affinity ones, is an important step for modern drug discovery as it enables the development of high affinity lead compounds. Due to the lack of robust characterization approaches, the determination of weak binding is still cumbersome. We have reported a paramagnetic ligand tagging method by taking advantage of pseudo-contact shifts of protein NMR, which requires the ligand to be linked to a paramagnetic lanthanide complex.1 In this project we have improved the structure of our original paramagnetic tag to increase the accuracy of the NMR-based structure determination as compared to our previously presented approach.
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| 21. |
- Xiong, Ruisheng, et al.
(author)
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Synthesis and characterisation of lanthanide-hydroporphyrin dyads
- 2015
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In: Dalton Transactions. - 1477-9226 .- 1477-9234. ; 44:6, s. 2541-2553
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Journal article (peer-reviewed)abstract
- Fluorescence spectroscopy is in many ways the ideal tool for the interrogation of complex biological systems, as it is non-invasive, sensitive, and offers high spatiotemporal resolution. For biomedical imaging luminescent probes absorbing and emitting in the red-to-near infrared (NIR) region are best suited to maximise tissue penetration and minimise damage to cellular components. NIR-emitting lanthanides (Ln) sensitised with red-absorbing antennae are promising candidates for these applications, assuming the challenges of poor photophysical properties and tedious syntheses of the complexes are overcome. Chlorins are porphyrin-type tetrapyrroles with intense red absorption. Recently chlorins have been shown to sensitise Yb and Nd emission when incorporated into Ln-complexes. Here we expand on our previous work, and explore the effect of chlorin structure, metallation state, chlorin–Ln-complex linker length and mode of attachment on the properties of chlorin–Ln complexes. As chlorin absorption bands are ∼20 nm fwhm and readily tunable, a deeper understanding of structure–property relationships would enable the use of chlorin–Ln complexes in multicolour imaging using antenna-specific excitation. A detailed description of antenna and complex syntheses and photophysical characterisation is given. A number of challenges were identified, which will have to be addressed in future studies to enable multicolour imaging using the NIR-emitting lanthanides.
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