Investigation of silver binding to polyamidoamine (PAMAM) dendrimers by ESI tandem mass spectrometry

Abstract

Electrospray ionization tandem mass spectrometry (ESI-MS/MS) was used to probe the binding of silver ions and reduced silver species with polyamidoamine generation 1 amineterminated (PAMAMG1NH 2 ) and generation 2 hydroxyl-terminated (PAMAMG2OH) dendrimers. At Ag ϩ /PAMAMG2OH molar ratios of Յ1, 1:1 complexes are observed, while at ratios Ͼ1, 2:1 and low abundance 3:1 complexes emerge. Similar results were observed for PAMAMG1NH 2 . The collisional activated dissociation (CAD) patterns of the dendrimer ions are characterized by losses of amidoamine branches resulting largely from hydrogen migration and cleavage reactions. Ag ϩ /dendrimer complexes are characterized by the loss of a dendrimer branch from the complex, with the silver ion remaining bound to a dendrimer fragment. When the Ag ϩ -bound dendrimer complexes are reduced by hydrazine, low abundance complexes, whose m/z values are consistent with ones containing zerovalent silver species, are observed in the mass spectra. Complexes with three silver atoms are observed in the spectrum containing PAMAMG1NH 2 , and complexes with four and five silver atoms are observed with PAMAMG2OH. The CAD fragmentation patterns of the complexes formed after the silver reduction are different than those observed for complexes containing one silver ion and are characterized by the ejection of all silver species, possibly as a cluster, leaving the intact dendrimer ion. Experiments with Cu ϩ , Cu 2ϩ , and Pt 2ϩ binding to PAMAMG2OH were also done, but reduced metal clusters were not observed in the mass spectra after the addition of hydrazine. . In addition to numerous applications in fields such as medicine, chemistry, materials science, biology, and physics, there is interest in the use of dendrimers as templates for metal nanoparticle synthesis [3,4]. The ability to synthesize metal nanoparticles with well-defined core sizes has important implications for the study of the sizedependent photochemical, electrochemical, and optical behavior of metal clusters.Polyamidoamine (PAMAM) dendrimers [5,6] (Figure 1 [7][8][9][10][11][12]. Upon chemical reduction of the metal ion/ dendrimer complexes, the PAMAM polymer matrix encapsulates and subsequently stabilizes the metal clusters, thus preventing agglomeration [12]. These intradendrimer metal nanoparticles are soluble and have well defined sizes due to the uniform three-dimensional structure and functional group composition of the dendrimers. Interest in the formation of intradendrimer metal nanoparticles has stimulated the need for analytical methods that are capable of characterizing the dendrimer host structure and the corresponding metal/ dendrimer complexes. Electrospray ionization mass spectrometry (ESI) [13][14][15][16][17] and matrix assisted laser desorption ionization (MALDI) [18 -25] mass spectrometry have been established as powerful techniques for the analysis of dendrimer macromolecules as a result of their ability to gently transfer species from solution to the gas-phase while minimizing the fragmentation of the an...

Electron capture dissociation, electron detachment dissociation, and collision-induced dissociation of polyamidoamine (PAMAM) dendrimer ions with amino, amidoethanol, and sodium carboxylate surface groups

“…In all dissociation reactions, hydrogen migration followed by cleavage at tertiary amine (fragments B G2 , B G1 , B G0 ) or between two carbon atoms (fragments A G2 , A G1 , A G0 ) leads to losses of amidoamine branches from different generations. Comparison of our results for [M + 6H] 6+ ions with those obtained for both singly and doubly charged precursors by Brodbelt et al [15] suggests that CID of PAMAM dendrimers does not depend on the number of mobile protons present.…”

“…In the present case of quapruply protonated PAMAMG1NH 2 ions, four protons are present and a maximum of four molecules of water are eliminated during CID. In contrast, CID of both singly and doubly charged PAMAMG1NH 2 ions resulted in loss of ammonia but not loss of water [15]. Neutral losses observed in the CID of PAMAMG1NH 2 depend on the charge state; for higher charge states, the dominant process is loss of water and, for lower charge states, elimination of NH 3 is observed.…”

“…Structural deviations in PAMAM dendrimers have been investigated by use of MALDI-TOF mass spectrometry [12, 13], as has their fragmentation [13, 14]. The collision-induced dissociation (CID) of electrosprayed PAMAM dendrimers and their Ag + complexes has been investigated by Brodbelt and colleagues [15]. The CID of anionic PAMAM dendrimers was studied by McLuckey et al [16].…”

Rapid characterization of cross-links, mono-adducts, and non-covalent binding of psoralens to deoxyoligonucleotides by LC-UV/ESI-MS and IRMPD mass spectrometry

“…Spectra were acquired by summing 20 scans. The extent of DNA binding, expressed as a “relative binding percentage” that equates with the relative binding affinity of each psoralen analog, was determined based on the following equation: 63 $$\text{Relative Binding Percentage}=\frac{{\mathrm{normalA}}_{(1:1)}+{\mathrm{normalA}}_{(1:2)}+{\mathrm{normalA}}_{(1:3)}+\dots }{{\mathrm{normalA}}_{\left(\mathrm{DNA}\right)}+{\mathrm{normalA}}_{(1:1)}+{\mathrm{normalA}}_{(1:2)}+{\mathrm{normalA}}_{(1:3)}+\dots }\mathrm{x}100\%$$ where A DNA is the peak area of the free duplex and A (1:n) are the peak areas of all DNA/psoralen complexes in the ESI-mass spectra. All calculated relative binding percentages of bound DNA assume the peak areas of the free and bound DNA ions are proportional to their relative concentrations in solution.…”

An investigation of the dissociation of complexes of triethylene tetramine with first-row transition-metal dications by electrospray ionization tandem mass spectrometry: Remote CC bond activation

“…ESI/MS was used to prove the existence of a complex containing Cu and Zn dications in the environment of diethylenetriamine, deprotanated imidazole and tris(2-aminoethylamine) [12]. ESI/MS/MS also has been used to investigate the binding of Ag + , Cu + , Cu 2+ and Pt 2+ with polyamidoamine generation 1 amine terminated PAMAMG1NH 2 [13]. Triethylene tetramine, a member of the polyamine family, is particularly interesting due to the fact that it is used for the treatment of Wilson's disease, an autosomal recessive disorder characterized by copper accumulation in various organs, such as the liver, kidney and brain [14].…”