- Hydrogen-bonded cyclic dimers at large compression: The case of 1h-pyrrolo[3,2-h]quinoline and 2-(2′-pyridyl)pyrrole
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1H-pyrrolo[3,2-h]qinoline (PQ) and 2-(2′-pyridyl)pyrrole (PP) are important systems in the study of proton-transfer reactions. These molecules possess hydrogen bond donor (pyrrole) and acceptor (pyridine) groups, which leads to the formation of cyclic dimers in their crystals. Herein, we present a joint experimental (Raman scattering) and computational (DFT modelling) study on the high-pressure behaviour of PQ and PP molecular crystals. Our results indicate that compression up to 10 GPa (100 kbar) leads to considerable strengthening of the intermolecular hydrogen bond within the cyclic dimers. However, the intramolecular N–H···N interaction is either weakly affected by pressure, as witnessed in PQ, or weakened due to compression-induced distortions of the molecule, as was found for PP. Therefore, we propose that the compression of these systems should facilitate double proton transfer within the cyclic dimers of PQ and PP, while intramolecular transfer should either remain unaffected (for PQ) or weakened (for PP).
- Chumak, Taisiia,Kurzyd?owski, Dominik,Listkowski, Arkadiusz,Rogo?a, Jakub
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supporting information
(2021/07/10)
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- Pyrroloquinoline scaffold-based 5-HT6R ligands: Synthesis, quantum chemical and molecular dynamic studies, and influence of nitrogen atom position in the scaffold on affinity
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Based on pyrroloquinoline scaffold bearing 5-HT2C agonists, a series of arylsulfonamide derivatives of 1H-pyrrolo[2,3-f]quinoline and 1H-pyrrolo[3,2-h]quinoline, substituted at position 3 with tetrahydropyridine, were synthesized and evaluated in vitro for their affinity for 5-HT6 receptors. A structure–activity relationship study showed that the 1H-pyrrolo[3,2-h]quinoline scaffold was more favorable for 5-HT6R binding than the 1H-pyrrolo[2,3-f]quinoline one, suggesting dependence upon the type of condensation of the pyrrole and quinoline rings. As revealed by quantum-chemical calculations and molecular dynamic studies, position of the quinoline nitrogen atom in the planar pyrroloquinoline skeleton might affect the spatial orientation of the arylsulfonyl fragment, as a result of structure stabilization by internal hydrogen bonds.
- Grychowska, Katarzyna,Kurczab, Rafa?,?liwa, Pawe?,Sata?a, Grzegorz,Dubiel, Krzysztof,Mat?oka, Miko?aj,Moszczyński-P?tkowski, Rafa?,Pieczykolan, Jerzy,Bojarski, Andrzej J.,Zajdel, Pawe?
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p. 3588 - 3595
(2018/05/31)
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- Pyrrolo(iso)quinoline derivatives as 5-HT2C receptor agonists
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A series of 1-(1-pyrrolo(iso)quinolinyl)-2-propylamines was synthesised and evaluated as 5-HT2C receptor agonists for the treatment of obesity. The general methods of synthesis of the precursor indoles are described. The functional efficacy and
- Adams, David R.,Bentley, Jonathan M.,Benwell, Karen R.,Bickerdike, Michael J.,Bodkin, Corinna D.,Cliffe, Ian A.,Dourish, Colin T.,George, Ashley R.,Kennett, Guy A.,Knight, Antony R.,Malcolm, Craig S.,Mansell, Howard L.,Misra, Anil,Quirk, Kathleen,Roffey, Jonathan R.A.,Vickers, Steven P.
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p. 677 - 680
(2007/10/03)
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- Microwave assisted Leimgruber-Batcho reaction for the preparation of indoles, azaindoles and pyrroylquinolines
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The development of enhanced conditions for Lewis acid catalysed Leimgruber-Batcho indole synthesis using microwave acceleration is described. This approach has permitted the preparation of a variety of heteroaromatic enamine intermediates in good yield and high purities. Subsequent catalytic hydrogenation reactions, under various conditions including the use of a solid-phase encapsulated catalyst, furnish the corresponding indole derivatives in good yields.
- Siu, Jason,Baxendale, Ian R.,Ley, Steven V.
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p. 160 - 167
(2007/10/03)
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- A new ring-forming methodology for the synthesis of bioactive pyrroloquinoline derivatives
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A new, efficient, two-step method for the synthesis of bioactive pyrroloquinolines is described. Readily available nitroquinolines, bearing the nitro moiety in the carbocyclic ring, are treated with 4-chlorophenoxyacetonitrile in the presence of potassium tert-butoxide/THF to give the analogous vicarious nucleophilic substitution products (5, 8 and 11). These, in turn, are subjected to catalytic hydrogenation to produce 1H-pyrrolo[2,3-f]quinoline (6), 3H-pyrrolo[3,2-f]quinoline (9) and 1H-pyrrolo[3,2-h]quinoline (12) in good yields and relatively short reaction times. The differential activity of two N-alkylated 1H-pyrrolo[2,3-f]quinolines (1) in cisplatin resistant cell lines compared to the corresponding parent lines suggests that these might be useful leads for developing agents for use in drug resistant diseases.
- Vlachou, Margarita,Tsotinis, Andrew,Kelland, Lloyd R.,Thurston, David E.
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p. 129 - 133
(2007/10/03)
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- 2-Substituted 1H-pyrrolo [3,2-h] quinoline derivatives: Synthesis and aspects of their biological activity
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Certain 2-substituted 1H-pyrrolo [3,2-h] quinolines have been prepared and their biological activity in mammalian cells and in some microrganisms have been studied. These compounds represent a simplified ellipticine heterocyclic moiety: in addition they have a different ring condensation, leading to an angular molecular structure instead of a linear one. In mammalian cells all compounds appeared to be able of inducing an antiproliferative effect and an extensive DNA fragmentation, similarly to ellipticine, even if to a reduced extent. The new derivatives behaved in a comparable way also on some microrganisms, such as T2 bacteriophage (which appears to be less sensitive than mammalian cells) and in mutagenesis tests carried out with E. coli WP2 TM9 and S. typhimurium TA 98, which are reverted by base substitution and frame-shift mutagens, respectively. Similarly to the reference compound, all ellipticine analogues appeared to be no mutagenic. The obtained results suggest that they induce the antiproliferative activity in mammalian cells mainly as topoisomerase inhibitors, similarly to ellipticine itself. Therefore, they represent an interesting model to design new potential anticancer drugs.
- Grazia Ferlin,Chiarelotto,Baccichetti,Carlassare,Toniolo,Bordin
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p. 1513 - 1528
(2007/10/02)
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