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10.1039/c4sc01979b http://scihub22266oqcxt.onion/10.1039/c4sc01979b C5811126!5811126 !29560189     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\29560189 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Chem+Sci 2015 ; 6 (2 ): 1018-1026 Nephropedia Template TP {{tp|p=29560189 |t=2015. Chelation-induced diradical formation as an approach to modulation of the amyloid-? aggregation pathway |pdf=|usr=}}{{29560189 }} gab.com Text Chelation-induced diradical formation as an approach to modulation of the amyloid- aggregation pathway JO: Chem Sci http://www.kidney.de/pget.php?&tw=1&pmid=29560189 #FOAvip Current approaches toward modulation of metal-induced A? aggregation pathways involve the development of small molecules that bind metal ions, such as Cu(ii) and Zn(ii), and interact with A?. For this effort, we present the enediyne-containing ligand (Z)-N,N'-bis[1-pyridin-2-yl-meth(E)-ylidene]oct-4-ene-2,6-diyne-1,8-diamine (PyED), which upon chelation of Cu(ii) and Zn(ii) undergoes Bergman-cyclization to yield diradical formation. The ability of this chelation-triggered diradical to modulate A? aggregation is evaluated relative to the non-radical generating control pyridine-2-ylmethyl-(2-{[(pyridine-2-ylmethylene)-amino]-methyl}-benzyl)-amine (PyBD). Variable-pH, ligand UV-vis titrations reveal pK(a) = 3.81(2) for PyBD, indicating it exists mainly in the neutral form at experimental pH. Lipinski's rule parameters and evaluation of blood-brain barrier (BBB) penetration potential by the PAMPA-BBB assay suggest that PyED may be CNS+ and penetrate the BBB. Both PyED and PyBD bind Zn(ii) and Cu(ii) as illustrated by bathochromic shifts of their UV-vis features. Speciation diagrams indicate that Cu(ii)-PyBD is the major species at pH 6.6 with a nanomolar K(d), suggesting the ligand may be capable of interacting with Cu(ii)-A? species. In the presence of A?(40/42) under hyperthermic conditions (43 °C), the radical-generating PyED demonstrates markedly enhanced activity (2-24 h) toward the modulation of A? species as determined by gel electrophoresis. Correspondingly, transmission electron microscopy images of these samples show distinct morphological changes to the fibril structure that are most prominent for Cu(ii)-A? cases. The loss of CO(2) from the metal binding region of A? in MALDI-TOF mass spectra further suggests that metal-ligand-A? interaction with subsequent radical formation may play a role in the aggregation pathway modulation. Twit Text FOAVip Chelation-induced diradical formation as an approach to modulation of the amyloid- aggregation pathway ????Chem Sci http://www.kidney.de/pget.php?&tw=1&pmid=29560189 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29560189 #FOAvip English Wikipedia <ref>{{Cite pmid|29560189 }}</ref> Chelation-induced diradical formation as an approach to modulation of the amyloid-? aggregation pathway #MMPMID29560189 Porter MR ; Kochi A ; Karty JA ; Lim MH ; Zaleski JM Chem Sci 2015[Feb]; 6 (2 ): 1018-1026 PMID29560189 show ga Current approaches toward modulation of metal-induced A? aggregation pathways involve the development of small molecules that bind metal ions, such as Cu(ii) and Zn(ii), and interact with A?. For this effort, we present the enediyne-containing ligand (Z)-N,N'-bis[1-pyridin-2-yl-meth(E)-ylidene]oct-4-ene-2,6-diyne-1,8-diamine (PyED), which upon chelation of Cu(ii) and Zn(ii) undergoes Bergman-cyclization to yield diradical formation. The ability of this chelation-triggered diradical to modulate A? aggregation is evaluated relative to the non-radical generating control pyridine-2-ylmethyl-(2-{[(pyridine-2-ylmethylene)-amino]-methyl}-benzyl)-amine (PyBD). Variable-pH, ligand UV-vis titrations reveal pK(a) = 3.81(2) for PyBD, indicating it exists mainly in the neutral form at experimental pH. Lipinski's rule parameters and evaluation of blood-brain barrier (BBB) penetration potential by the PAMPA-BBB assay suggest that PyED may be CNS+ and penetrate the BBB. Both PyED and PyBD bind Zn(ii) and Cu(ii) as illustrated by bathochromic shifts of their UV-vis features. Speciation diagrams indicate that Cu(ii)-PyBD is the major species at pH 6.6 with a nanomolar K(d), suggesting the ligand may be capable of interacting with Cu(ii)-A? species. In the presence of A?(40/42) under hyperthermic conditions (43 °C), the radical-generating PyED demonstrates markedly enhanced activity (2-24 h) toward the modulation of A? species as determined by gel electrophoresis. Correspondingly, transmission electron microscopy images of these samples show distinct morphological changes to the fibril structure that are most prominent for Cu(ii)-A? cases. The loss of CO(2) from the metal binding region of A? in MALDI-TOF mass spectra further suggests that metal-ligand-A? interaction with subsequent radical formation may play a role in the aggregation pathway modulation. äChelation-induced diradical formation as an approach to modulation of (epmc).pdf DeepDyve Pubget Overpricing