the content of each peptide flask was dissolved by addition of hepes buffer 100  mm , ph  7.4 ( a128 ) or ultrapure milli - q water ( a116 ) .
the concentration of a was then measured by uv - visible spectroscopy ( 276  nm ( tyr10)=1410  m  cm ) .
uv - visible spectra were recorded on a biochrom libra s50 or a specord 205 spectrophotometer ( analytik jena , germany ) .
fluorescence spectra were recorded on a flsp920 spectrometer ( edinburgh instruments ltd , uk ) , with bandwidth for excitation and emission=2  nm .
a complex was first prepared by mixing equimolar amounts of a128 and cucl2 in hepes buffer 50  mm , ph  7.4 .
the metalation of a was monitored by the decrease of fluorescence ( see ref .  ) .
a solution of ligand 1 or cq in dmso was then added ( 1 or 2  mol  equiv , respectively ) , and the reaction was monitored by uv - visible spectroscopy .
final concentrations were [ a128]=[cu]==20  m , [ cq]=40  m ; dmso / hepes buffer=5:95 v / v . the 50  % decrease of fluorescence of a upon metalation by copper was confirmed in buffered mixture containing up to 10  vol  % of an organic solvent , namely ch3cn ( ref .  ) , or dmso ( present report , data not shown ) .
x - band ( 9.525  ghz ) esr spectra were recorded in quartz tubes at 120  k , using a bruker elexsys - ii e500 spectrometer . for experiments with ligand 1 ,
the solvent was hepes buffer 100  mm , ph  7.4 , containing 13  vol  % of dmso .
[ a116]=185  m ; a116/cu molar ratio=1:1 ( figure  3  a ) , a116/cu/1=1:1:0.5 ( figure  3  b ) , a116/cu/1=1:1:1 ( figure  3  c ) , cu/1=1:1 ( figure  3  d ) .
the addition of 16  vol  % of dmso in hepes did not induce modification of the spectrum of cu 
the solvent was dmso / hepes buffer 100  mm , ph  7.4 , 90:10 v / v .
a116/cu molar ratio=1:1 ( figure  5  a ) , a116/cu / cq=1:1:1 ( figure  5  b ) , a116/cu / cq=1:1:2 ( figure  5  c ) , cu / cq=1:2 ( figure  5  d ) .
the sample solutions were injected ( 7.5  l ) using a mobile phase ch3oh / h2o ( 90:10 v / v ) , flow rate=0.15  ml  min .
the cone voltage was 15  v , and spectra were acquired in the positive ion mode , in the m / z range 1002500 .
the mixture of a116/cucl2/cq ( 1:1:1 mol ratio ) was prepared in ultrapure milli - q water ( ph  5.8)/meoh ( 1:1 v / v ) .
final concentration was 100  m , injected volume was 7.5  l . the series of multicharged patterns at m / z=1161.9 , 774.9 , and 581.4 was not detected in the absence of cu .
as a service to our authors and readers , this journal provides supporting information supplied by the authors .
such materials are peer reviewed and may be re - organized for online delivery , but are not copy - edited or typeset . technical support issues arising from supporting information ( other than missing files ) should be addressed to the authors .
 the accumulation of redox - active metal ions , in particular copper , in amyloid plaques is considered to the cause of the intensive oxidation damage to the brain of patients with alzheimers disease ( ad ) . 
 drug candidates based on a bis(8-aminoquinoline ) tetradentate ligand are able to efficiently extract cu2 + from copper - loaded amyloids ( cu  a ) . 
 contrarily , in the presence of a bidentate hydroxyquinoline , such as clioquinol , the copper is not released from a , but remains sequestrated within a acu  clioquinol ternary complex that has been characterized by mass spectrometry . 
 facile extraction of copper(ii ) at a low amyloid / ligand ratio is essential for the re - introduction of copper in regular metal circulation in the brain . 
 as , upon reduction , the cu+ is easily released from the bis(8-aminoquinoline ) ligand unable to accommodate cui , it should be taken by proteins with an affinity for copper . 
 so , the tetradentate bis(8-aminoquinoline ) described here might act as a regulator of copper homeostasis . 
Experimental Section
Supporting Information