| 1. |
- Hammarström, Lars G. J., et al.
(författare)
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The Oncolytic Efficacy and in Vivo Pharmacokinetics of [2-(4-Chlorophenyl)quinolin-4-yl](piperidine-2-yl)methanol (Vacquinol-1) Are Governed by Distinct Stereochemical Features
- 2016
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 59:18, s. 8577-8592
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma remains an incurable brain cancer. Drugs developed in the past 20 years have not improved the prognosis for patients, necessitating the development of new treatments. We have previously reported the therapeutic potential of the quinoline methanol Vacquinol-1 (1) that targets glioblastoma cells and induces cell death by catastrophic vacuolization. Compound 1 is a mixture of four stereoisomers due to the two adjacent stereogenic centers in the molecule, complicating further development in the preclinical setting. This work describes the isolation and characterization of the individual isomers of 1 and shows that these display stereospecific pharmacokinetic and pharmacodynamic features. In addition, we present a stereoselective synthesis of the active isomers, providing a basis for further development of this compound series into a novel experimental therapeutic for glioblastoma.
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| 2. |
- Hammarström, Leif, et al.
(författare)
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Time-Resolved Laser Spectroscopy in Molecular Devices for Solar Energy Conversion
- 2017
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Ingår i: Molecular Devices for Solar Energy Conversion and Storage. - Singapore : Springer Singapore. - 2196-6990 .- 2196-6982. - 9789811059230 - 9789811059247 ; , s. 385-432
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- A complete characterization of solar energy conversion devices and the processes underlying their function is a challenge, and require a multitude of different experimental methods. This chapter discusses investigations of molecular solar cells and solar fuels devices by time-resolved laser spectroscopic methods. These methods have established important concepts we now use for understanding the function of devices for solar energy conversion into primary products. We give examples of scientific insight provided by ultrafast methods using detection in the regions from X-ray to THz radiation, and particularly highlight the case where the use of different methods has provided complementary information. Charge collection and solar fuel catalysis on the other hand occur on longer time scales, which opens for the use of time-resolved magnetic resonance and microwave conductivity methods. We also point out that, with suitable precautions, time-resolved laser spectroscopy is able to give information relevant for in operando device conditions
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| 3. |
- Herrmann, Uli S., et al.
(författare)
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Structure-based drug design identifies polythiophenes as antiprion compounds
- 2015
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Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 7:299, s. 299ra123-
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Tidskriftsartikel (refereegranskat)abstract
- Prions cause transmissible spongiform encephalopathies for which no treatment exists. Prions consist of PrPSc, a misfolded and aggregated form of the cellular prion protein (PrPC). We explore the antiprion properties of luminescent conjugated polythiophenes (LCPs) that bind and stabilize ordered protein aggregates. By administering a library of structurally diverse LCPs to the brains of prion-infected mice via osmotic minipumps, we found that antiprion activity required a minimum of five thiophene rings bearing regularly spaced carboxyl side groups. Solid-state nuclear magnetic resonance analyses and molecular dynamics simulations revealed that anionic side chains interacted with complementary, regularly spaced cationic amyloid residues of model prions. These findings allowed us to extract structural rules governing the interaction between LCPs and protein aggregates, which we then used to design a new set of LCPs with optimized binding. The new set of LCPs showed robust prophylactic and therapeutic potency in prion-infected mice, with the lead compound extending survival by greater than80% and showing activity against both mouse and hamster prions as well as efficacy upon intraperitoneal administration into mice. These results demonstrate the feasibility of targeted chemical design of compounds that may be useful for treating diseases of aberrant protein aggregation such as prion disease.
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| 4. |
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| 5. |
- Huang, Jing, et al.
(författare)
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Covalently linking CuInS2 quantum dots with a Re catalyst by click reaction for photocatalytic CO2 reduction
- 2018
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Ingår i: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9226 .- 1477-9234. ; 47:31, s. 10775-10783
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Tidskriftsartikel (refereegranskat)abstract
- Covalently linking photosensitizers and catalysts in an inorganic-organic hybrid photocatalytic system is beneficial for efficient electron transfer between these components. However, general and straightforward methods to covalently attach molecular catalysts on the surface of inorganic semiconductors are rare. In this work, a classic rhenium bipyridine complex (Re catalyst) has been successfully covalently linked to the low toxicity CuInS2 quantum dots (QDs) by click reaction for photocatalytic CO2 reduction. Covalent bonding between the CuInS2 QDs and the Re catalyst in the QD-Re hybrid system is confirmed by UV-visible absorption spectroscopy, Fourier-transform infrared spectroscopy and energy-dispersive X-ray measurements. Time-correlated single photon counting and ultrafast time-resolved infrared spectroscopy provide evidence for rapid photo-induced electron transfer from the QDs to the Re catalyst. Upon photo-excitation of the QDs, the singly reduced Re catalyst is formed within 300 fs. Notably, the amount of reduced Re in the linked hybrid system is more than that in a sample where the QDs and the Re catalyst are simply mixed, suggesting that the covalent linkage between the CuInS2 QDs and the Re catalyst indeed facilitates electron transfer from the QDs to the Re catalyst. Such an ultrafast electron transfer in the covalently linked CuInS2 QD-Re hybrid system leads to enhanced photocatalytic activity for CO2 reduction, as compared to the conventional mixture of the QDs and the Re catalyst.
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| 6. |
- Schlotthauer, Tina, et al.
(författare)
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A multidonor-photosensitizer-multiacceptor triad for long-lived directional charge separation
- 2017
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 19:42, s. 28572-28578
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Tidskriftsartikel (refereegranskat)abstract
- The modular assembly of a directional photoredox-active multidonor-photosensitizer-multiacceptor (Dn-P-A(m)) architecture is presented. The triad assembly features a central Ru(II) sensitizer equipped with pendant polymer chains consisting of multiple triarylamine (pTARA) and naphthalene diimide (pNDI) units, respectively. Upon excitation, the efficient formation (496%) of charge separation (CS) was observed featuring similar CS lifetimes (400 ns) as related molecular triads. In contrast, a significant additional longer-lived CS component (2400 ns, 30%) is observed indicating multiple contributing pathways.
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| 7. |
- Schlotthauer, Tina, et al.
(författare)
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Aryl-Decorated Ru-II Polypyridyl-type Photosensitizer Approaching NIR Emission with Microsecond Excited State Lifetimes
- 2016
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 55:11, s. 5405-5416
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Tidskriftsartikel (refereegranskat)abstract
- Bis-tridentate Ru-II complexes based on the dqp scaffold (dqp is 2,6-di(quinolin-8-yl)pyridine) with multiple aryl substituents were explored to tailor the absorption and emission properties. A synthetic methodology was developed for the facile synthesis and purification of homo- and heteroleptic bis-tridentate Ru complexes. The effect of the aryl substituents in the para positions of the pyridine and quinoline subunits was detailed by X-ray crystallography, steady state and time-resolved spectroscopy, electrochemistry, and computational methods. The attachment of the aryl groups results in enhanced molar extinction coefficients with the largest effect in the pyridine position, whereas the quinoline substituent leads to red-shifted emission tailing into the NIR region (up to 800 nm). Notably, the excited state lifetimes remain in the microsecond time scale even in the presence of O-2, whereas the emission quantum yields are slightly increased with respect to the parental complex [Ru(dqp)(2)](2+). The peripheral functional groups (Br, Me, OMe) have only a minor impact on the optical properties and are attractive to utilize such complexes as functional building blocks.
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