Dynamic Acylhydrazone Metal Ion Complex Libraries: A Mixed–Ligand Approach to Increased Selectivity in Extraction

Abstract

Metal ion coordination chemistry is well suited to dynamic combinatorial chemistry approaches. [1±3] Diverse metal ion complex libraries can be created simply by mixing a labile metal ion with different ligands. [4] If ligand exchange is rapid, these metal ion complexes form the equilibrating components of a dynamic library. The equilibrium between complexes may be shifted upon addition of molecular targets. For example, small molecule or biopolymer targets perturb the equilibrium between metal ion complexes to increase the concentration of the metal ion complex that best binds the target. [5±7] We previously reported on dynamic combinatorial libraries of metal ion Schiff-base complexes of limited diversity. [8] Our selection protocol utilizes extraction of metal ion complex libraries from aqueous into organic solvent. In this method, the organic solvent is the ultimate target and complexes with the greatest stability and solubility in organic solvent versus aqueous solution are selected. [9] Here we present studies using acylhydrazone ligand libraries and show that these libraries lead to improvements in efficiency and selectivity of metal ion extraction in comparison to single ligand systems.Acylhydrazone ligands (Scheme 1) were chosen to explore the possibility of forming a double-orthogonal library [4] by exchange at metal±ligand (MÀL) and C¼N bonds. [10±13] Initial studies were carried out to establish the feasibility of using these exchange processes. Zn II extracts into chloroform from a buffered aqueous solution in the presence of two equivalents of acylhydrazone ligand 1 (Table 1, Scheme 1). The predominant complex that extracts into chloroform is the neutral complex [Zn(1 À ) 2 ] as determined by comparison of 1 H NMR and mass spectral data to that of an authentic sample. After two hours, the extent of extraction of Zn II from a water/chloroform mixture containing 0.0500 mm [Zn(1 À ) 2 ] is identical within experimental error to a second experiment containing 0.0500 mm Zn(NO 3 ) 2 and 0.100 mm 1, confirming that our system is at equilibrium. Addition of a different acylhydrazone ligand (13) to either of the solutions above followed by stirring for 2 h increases the amount COMMUNICATIONS 4096

ROS-Mediated Cytotoxic Effect of Copper(II) Hydrazone Complexes against Human Glioma Cells

“…2-Acetylpyridine acetylhydrazone (H2AcMe), 2-benzoylpyridine acetylhydrazone (H2BzMe) and complexes 1 and 2 were prepared as previously reported by some of us [13] and by other authors [14,15]. The synthetic routes for the ligands and their Cu(II) complexes are outlined in Scheme 1.…”

Dynamic Combinatorial Chemistry

“…For hydrazones that are highly stable even at elevated temperature or in the presence of acid (e.g., hydrazones prepared from pyridine-derived difunctionalized hydrazine and carbaldehyde buiding blocks), exchange can be catalyzed using Lewis acids in CHCl 3 . 168 Recent studies on hydrazone-based DCLs aimed at developing new extraction agents for metal ions 169 and studies on nucleic acid replication under dilute conditions (0.01 mM) 170 demonstrate that the exchange can take place in aqueous medium close to neutrality in a reasonable time scale. However, the presence of an appropriate template is partly responsible for the relatively fast rate of equilibration.…”

Weak intermolecular hydrogen and halogen interactions in an isomorphous halogen series of pseudoterpyridine ZnIIcomplexes

“…Metal centers and the nature of the arms of the ligands forming the complex can be varied. Diverse metallosupramolecular combinatorial libraries can easily be generated by simply mixing a metal ion with different ligands (Legrand et al, 2007;Lehn, 1999;Kramer et al, 1993;Barboiu, 2010;Brady & Sanders, 1997;Storm & Luning, 2002;Goral et al, 2001;Choudhary & Morrow, 2002;Dumitru et al, 2005;Barboiu, Petit et al, 2006;Barboiu, Ruben et al, 2006). The constitutional self-organization into metallosupramolecular architectures around a metal ion center might be related to direct suitable ligands by reading out the structural information (intrinsic information -electronic and steric factors, i.e.…”