Gas phase attachment of water and methanol to Ag(I) complexes with α‐amino acids in an ion trap mass spectrometer

Collision-induced dissociation experiments on the Ag ϩ -phenylalanine complex using several collision energies were shown to yield ten different fragment ions. Unambiguous assignment of these fragment ions were made by careful analysis of deuterium labeling experiments. The losses of H 2 O, CO, CO 2 , and AgH were commonly observed; also encountered were the losses of H 2 , Ag, and H. Deuterium labeling experiments and density functional calculations have been employed to probe fragmentation mechanisms that account for all experimental results. (J Am Soc Mass Spectrom 2002, 13, 408 -416) © 2002 American Society for Mass Spectrometry T he interactions of metal ions with amino acids and peptides in the gas phase is a topic of much current interest [1][2][3]. Attempts have been made to further our understanding of complicated biological processes by modeling them using carefully planned gas-phase studies. In the absence of solvent, one may study the intrinsic modes of binding governing metalamino acid complexes. Mass spectrometric experiments thus offer great potential for exploring the formation and reactivity of isolated cationic species.Amino acid complexes of transition metal ions were first observed and studied using fast atom bombardment (FAB) [4,5]. However, the limited solubility of metal salts and poor sensitivity prevented widespread systematic study of these complexes. Sensitivity is not typically an issue in matrix-assisted laser desorption/ ionization (MALDI) [6,7], but the fragmentation yields of its metastably decomposing ions are often poor. As the fragment ions potentially give information on atom connectivity and hence structure, MALDI is therefore non-ideal for examining fragmentation pathways. One technique that has proven effective for the study of metal-containing amino acids and peptides, and the one employed here, is electrospray tandem mass spectrometry. First, electrospray ionization [8] is a soft ionization method and one that is efficient at producing gas-phase metal-containing ions [9 -15], whose solubility in water or water/methanol is typically high. Second, fragmentation is efficient and is easily controlled via collision-induced dissociation, the energy of which is crucial in directing fragmentation products and their yield.Molecular orbital calculations are frequently combined with experiments in studies to obtain a better understanding of the structure and thermochemistry of the organometallic species of interest [1,2,16,17]. Recent density functional molecular orbital studies have shown that Ag ϩ can be mono-, di-, or tricoordinate in complexes with ␣-amino acids [18]; tetracoordinate Ag ϩ has been postulated for relatively small peptides [19,20]. The binding of silver(I) to glycine, diglycine, and triglycine, and to a number of other polypeptides, has been investigated [19,20]. In particular, the structures of argentinated glycine and its oligomers have been examined in detail by means of density functional theory [21].The focus of this paper is the Ag ϩ -phenylalanine complex. ...

Section: Resultssupporting

confidence: 87%

Section: Resultssupporting

confidence: 62%

Gas-phase fragmentation of the Ag⁺—phenylalanine complex: Cation—π interactions and radical cation formation

Shoeib

Cunje

Hopkinson

et al. 2002

“…Likely, the attached water molecule is dislodged during collisional activation, but then rapidly reattaches before ion detection. This type of solvent adduction process has been commonly observed for transition-metal complexes in a quadrupole ion trap [23][24][25][26][27]. This was the same fragmentation pattern observed for the dissociation of the watersolvated 1:1 complexes containing 6, 7, and 8 and a transition-metal.…”

Section: Ligand Binding To Metalssupporting

confidence: 76%

Evaluation of metal-mediated DNA binding of benzoxazole ligands by electrospray ionization mass spectrometry

Mazzitelli

Rodriguez

Kerwin

et al. 2008

The binding of a series of benzoxazole analogs with different amide-and ester-linked side chains to duplex DNA in the absence and presence of divalent metal cations is examined. All ligands were found to form complexes with Ni 2ϩ , Cu 2ϩ , and Zn 2ϩ , with 2:1 ligand/metal cation binding stoichiometries dominating for ligands containing shorter side chains (2, 6, 7, and 8), while 1:1 complexes were the most abundant for ligands with long side chains (9, 10, and 11). Ligand binding with duplex DNA in the absence of metal cations was assessed, and the long side-chain ligands were found to form low abundance complexes with 1:1 ligand/ DNA binding stoichiometries. The ligands with the shorter side chains only formed DNA complexes in the presence of metal cations, most notably for 7 and 8 binding to DNA in the presence of Cu 2ϩ . The binding of long side-chain ligands was enhanced by Cu . As a topoisomerase II inhibitor, one of the unique properties of UK-1 is its ability to bind biologically important divalent metal cations [3] and its metalmediated DNA binding [3,7]. While UK-1 has demonstrated cytotoxicity against a number of cell lines, it does not inhibit the growth of bacteria, yeast, or fungi [1,8], making the mechanism of this selective cytotoxic activity and the metal binding properties of UK-1 and new analogs of great interest.In a recent study, we used electrospray ionization mass spectrometry (ESI-MS) in conjunction with cytotoxicity assays to examine several simple analogs of UK-1 to explore the metal ion binding requirements of these compounds, assess metal-mediated DNA binding and evaluate anticancer and antibacterial activity [6]. Interestingly, the only ligand that exhibited anticancer activity, 2 (Figure 1), was also the only metal-mediated DNA binder with a preference for Ni 2ϩ as determined by ESI-MS experiments. Two other compounds, 4 and 5, formed complexes with DNA in a nonspecific, nonmetalmediated manner, and showed antibacterial but not cytotoxic behavior. These results suggested a correlation between metal-mediated binding and anticancer activity of the compounds. To improve upon the solubility of the benzoxazoles in aqueous solutions and to allow further examination of the metal-mediated DNA binding and anticancer activity, a series of analogs of 2 have been synthesized with different ester and amidelinked side chains (Figure 1) [9].In the present study, ESI-MS was used to screen the binding of the new ligands to a series of divalent metals including Mg 2ϩ , Ni 2ϩ , Cu 2ϩ , and Zn 2ϩ . Ligand binding to duplex DNA in the presence and absence of metal ions was also assessed. ESI-MS has been shown to be a useful tool for the analysis of noncovalent ligand/DNA

“…During the isolation step, all ionized species except the one chosen for storage are resonantly ejected from the ion trap. The appearance of peaks 18 u higher than the isolated ion is indicative of the formation of H 2 O adducts [23][24][25]; the abundance of the adducts increased as the isolation and storage time was extended. The formation of abundant H 2 O adducts indicates that several of the uranyl complex ions show a significant tendency to accept ligands via gas-phase association reactions in the ion trap.…”

Section: Resultsmentioning

confidence: 99%

“…To gain a better understanding of the intrinsic interactions between different uranyl species and solvent, we have begun an investigation of uranyl-anion complexes in the gas phase using ion-trap mass spectrometry (IT-MS). Several recent reports have demonstrated that intrinsic metal and metal complex chemistry can be investigated by the (controlled) addition of reagent gas to an ion trap [12][13][14][15][16][17][18][19][20][21][22], or by way of the presence of H 2 O and other small molecule contaminants within the He bath gas used to collisionally cool ions and improve trapping efficiency [23][24][25]. The reactions of uranium ions in the gas phase have been the subject of several earlier investigations.…”

mentioning

confidence: 99%

Elucidation of the collision induced dissociation pathways of water and alcohol coordinated complexes containing the uranyl cation

Stipdonk

Anbalagan

Chien

et al. 2003

Multiple-stage tandem mass spectrometry was used to characterize the dissociation pathways for complexes composed of (1) the uranyl ion, (2) nitrate or hydroxide, and (3) water or alcohol. The complex ions were derived from electrospray ionization (ESI) ϩ . The abundance of the species was greater than expected based on previous experimental measurements of the (slow) hydration rate for UO 2 ϩ when stored in the ion trap. To account for the production of the hydrated product, a reductive elimination reaction involving reactive collisions with water in the ion trap is proposed. T he speciation and reactivity of uranium is a topic of sustained interest because species-dependent chemistry [1] controls processes ranging from nuclear fuel processing [2] to mobility and fate in the geologic subsurface [3,4]. The solution chemistry of uranium is dominated by the uranyl dication, UO 2 2ϩ , which is known to form complexes with a range of ligands [1]. Specific interaction with solvent will significantly influence the physico-chemical behavior of the uranyl ion and its complexes, and this has motivated investigations of complex composition and stability using infrared spectroscopy and extended X-ray absorption fine structure [5][6][7][8][9][10][11]. Unfortunately, explicit control over the interactions of solvent and nonsolvent ligands with the uranyl ion is difficult, which makes the study of species-dependent uranium behavior complicated. To gain a better understanding of the intrinsic interactions between different uranyl species and solvent, we have begun an investigation of uranyl-anion complexes in the gas phase using ion-trap mass spectrometry (IT-MS). Several recent reports have demonstrated that intrinsic metal and metal complex chemistry can be investigated by the (controlled) addition of reagent gas to an ion trap [12][13][14][15][16][17][18][19][20][21][22], or by way of the presence of H 2 O and other small molecule contaminants within the He bath gas used to collisionally cool ions and improve trapping efficiency [23][24][25]. The reactions of uranium ions in the gas phase have been the subject of several earlier investigations. Studies by , and by Schwarz and coworkers [30] have probed the reactions between U ϩ and UO ϩ and organic compounds such as alkanes and alcohols. Armentrout and Beauchamp [31] investigated the oxidation of U ϩ using small molecules such as O 2 , CO, CO 2 , COS, and