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

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 amine-terminated (PAMAMG1NH2) and generation 2 hydroxyl-terminated (PAMAMG2OH) dendrimers. At Ag(+)/PAMAMG2OH molar ratios of 1, 2:1 and low abundance 3:1 complexes emerge. Similar results were observed for PAMAMG1NH2. 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+/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+-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 PAMAMG1NH2, 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+, Cu2+, and Pt2+ binding to PAMAMG2OH were also done, but reduced metal clusters were not observed in the mass spectra after the addition of hydrazine.     

Structural characterization of hexoses and pentoses using lead cationization. An electrospray ionization and tandem mass spectrometric study

The analytical potential of the complexation of isomeric underivatized hexoses (D-glucose, D-galactose, D-mannose, D-talose, D-fructose), methylglycosides (1-O-methyl-alpha-D-glucose and 1-O-methyl-beta-D-glucose) and pentoses (D-ribose, D-xylose, D-arabinose and D-lyxose) by Pb(2+) ions, was investigated by electrospray ionization and tandem mass spectrometry (MS/MS). Pb(2+) ions react mainly with monosaccharides by proton abstraction to generate [Pb(monosaccharide)(m) - H](+) ions (m = 1-3). At low cone voltage, a less abundant series of doubly charged ions of general formula [Pb(monosaccharide)(n)](2+) is also observed. The maximum number n of monosaccharides surrounding a single Pb(2+) ion depends on the metal : monosaccharide ratio. Our study shows that MS/MS experiments have to be performed to differentiate Pb(2+)-coordinated monosaccharides. Upon collision, [Pb(monosaccharide) - H](+) species mainly dissociate according to cross-ring cleavages, leading to the elimination of C(n)H(2n)O(n) neutrals. The various fragmentation processes observed allow the C(1), C(2) and C(4) stereocenters of aldohexoses to be characterized, and also a clear distinction aldoses and fructose. Furthermore, careful analysis of tandem mass spectra also leads to successful aldopentose distinction. Lead cationization combined with MS/MS therefore appears particularly useful to identify underivatized monosaccharides.     

Silver complexation and tandem mass spectrometry for differentiation of triterpenoid saponins from the roots of Pulsatilla chinensis (Bunge) Regel

For detection and differentiation of two types of triterpenoid saponins based on different aglycons of the lupane and oleanane skeleton from the roots of Pulsatilla chinensis (Bunge) Regel, the silver ion was introduced and electrospray ionization multi-stage tandem mass spectrometry was applied to analyze eleven triterpenoid saponin silver complexes. The quasi-molecular ion [M+Ag](+) was observed in the full-scan MS spectra of all the silver complexes. The MS(2) data of the [M+Ag](+) ion provided structural information on the sugar sequence of the oligosaccharide chains and the aglycon of the saponins. There are two patterns in the cleavage pathway of oleanane-type saponins. One is elimination of the sugar chain and subsequent loss of the carboxylic group which is the same as the cleavage of lupine-type saponins. The other is loss of the distinguishing ions at m/z 72 and 28 (C(2)H(4)) followed by loss of the carboxylic group. Diagnostic fragmentation pathways of the silver complexes of the saponins allow successful identification of the two types of saponins from the roots of Pulsatilla chinensis (Bunge) Regel.     

Complexes of silver(I) with peptides and proteins as produced in electrospray mass spectrometry

Silver(I) forms aqueous phase complexes with both sulfur and nonsulfur containing peptides and proteins. These complexes were introduced into the gas phase via electrospray, and their structures probed by means of tandem mass spectrometry. Experiments with di-, tri-, and oligopeptides show that the abundance of silver(I)-containing ions increases relative to that of proton-containing ions as peptide length increases. This increase is much more dramatic for methionine-containing peptides. Collision-induced dissociation of silver-peptide complexes yields a multitude of product ions that are silver containing. However, even for methioninecontaining peptides, very few of these product ions contain the methionine residue. The solution-phase structure and the gas-phase structure of the silver/peptide complex are not identical. The methionine sulfur acts as the silver anchoring point in solution. Desolvation in the gas phase leads to a rearrangement of the silver/peptide complex such that the silver ion becomes chelated to the nitrogen and oxygen atom on the peptide backbone in addition to the methionine sulfur. This rearrangement decreases the importance of the silver/sulfur bond to the extent that it is frequently broken upon collision activation and leads to the formation of silver/peptide product ions that are nonsulfur bearing.     

Synthesis, characterization, and antimicrobial activity of silver carbene complexes derived from 4,5,6,7-tetrachlorobenzimidazole against antibiotic resistant bacteria

Silver N-heterocyclic carbene complexes have been shown to have great potential as antimicrobial agents, affecting a wide spectrum of both Gram-positive and Gram-negative bacteria. A new series of three silver carbene complexes (SCCs) based on 4,5,6,7-tetrachlorobenzimidazole has been synthesized, characterized, and tested against a panel of clinical strains of bacteria. The imidazolium salts and their precursors were characterized by elemental analysis, mass spectrometry, (1)H and (13)C NMR spectroscopy, and single crystal X-ray diffraction. The silver carbene complexes, SCC32, SCC33, and SCC34 were characterized by elemental analysis, (1)H and (13)C NMR spectroscopy, and single crystal X-ray diffraction. These complexes proved highly efficacious with minimum inhibitory concentrations (MICs) ranging from 0.25 to 6 μg mL(-1). Overall, the complexes were effective against highly resistant bacteria strains, such as methicillin-resistant Staphylococcus aureus (MRSA), weaponizable bacteria, such as Yersinia pestis, and pathogens found within the lungs of cystic fibrosis patients, such as Pseudomonas aeruginosa, Alcaligenes xylosoxidans, and Burkholderia gladioli. SCC33 and SCC34 also showed clinically relevant activity against a silver-resistant strain of Escherichia coli based on MIC testing.     

Study of the structure and thermal behaviour of intercalated kaolinites

Intercalation complexes of three different Hungarian kaolinites with hydrazine and potassium acetate were investigated by FT-IR (DRIFT) spectrometry, X-ray diffraction, and thermogravimetry combined with mass spectrometry. Differences were found in the thermal behaviour of the complexes as well as in the rehydration — reexpansion patterns of the heated intercalates. An XRD method is proposed for the distinction of kaolinite and 7.2 Å halloysite present in the same mineral.The authors wish to thank Dr. E. Máttyás for providing the kaolinite samples and for carrying out their chemical analysis. Financial support from the Hungarian Scientific Research Fund under grant No. OTKA-014179 is gratefully acknowledged.     

Synthesis and characterization of transition metal complexes of dimeric N-confused porphyrin linked by an o-xylene fragment

Insertion of nickel(II), zinc, cadmium, or silver(III) into both macrocyclic crevices of 2,2'-o-xylene-bis(5,10,15,20-tetrakis(p-tolyl)-2-aza-21-carbaporphyrin) results in homometallic dimeric complexes which were isolated and characterized by NMR, UV-vis, mass spectrometry, and cyclic voltammetry. The 1H NMR study of these systems at low temperatures (203-233 K) allowed determination of most stable conformers with respect to a rotational freedom around the xylene bridge. An unfolded conformation for the dicationic bis(silver(III)) complex was determined on the basis of 2D nuclear Overhauser effect spectrometry experimentation. A mixture of nonequally populated diastereomers is observed for bis(zinc) and bis(cadmium) complexes due to a possibility of two different orientations of the apical anionic ligands with respect to the bridge. In a reaction of 5,10,15,20-tetrakis(p-tolyl)-2-aza-21-carbaporphyrinato nickel(II) with 2-(o-bromoxylene)-5,10,15,20-tetrakis(p-tolyl)-2-aza-21-carbaporphyrin in the presence of a proton scavenger, two isomeric bis(N-confused porphyrin) complexes with one subunit "empty" and the other metalated by nickel(II) were obtained. In the product 10, the o-xylene links external nitrogens of the subunits while product 11 consists of the xylene bridge between external nitrogen of the nonmetalated subunit and internal carbon of the fragment containing a nickel(II) ion. The products were characterized by mass spectrometry, UV-vis, NMR, and, in the case of complex 11, also by X-ray crystallographic analysis (space group P1, a =17.007(3), b = 18.130(3), c = 18.797(2) A, alpha = 105.856(13) degrees, beta = 107.447(13) degrees, gamma = 98.818(15) degrees, V = 5141.1(15) A3, Z = 2). Insertion of zinc or silver(III) into an empty crevice of 10 resulted in heterometallic zinc-nickel(II) or silver(III)-nickel(II) complexes 12 or 13, respectively, which were characterized by NMR, UV-vis, and cyclic voltammetry. The subunits in the bis(porphyrin) systems retain spectroscopic and redox properties typical for monomeric complexes.     

The distinction of underivatized monosaccharides using electrospray ionization ion trap mass spectrometry

A convenient method for distinguishing underivatized isomeric monosaccharides has been established using electrospray ionization ion trap mass spectrometry (ESI-ITMS). Mass spectra of hexoses (glucose, galactose, and mannose), N-acetylhexosamines (N-acetylglucosamine, N-acetylgalactosamine, and N-acetylmannosamine) and hexosamines (glucosamine, galactosamine, and mannosamine) dissolved in solvent containing 1 mM ammonium acetate were obtained in the positive ion mode. Glucose was distinguished from galactose and mannose in the MS(2) spectrum of the [M+NH(4)](+) ion at m/z 198. The MS(3) spectra generated from [M+NH(4)-H(2)O-NH(3)](+) at m/z 163 showed that galactose and mannose could be distinguished by the ratio of peak intensities at m/z 145 and 127, while the three N-acetylhexosamine and hexosamine stereochemical isomers could be identified by the relative abundance ratios of product ions observed in MS(3) spectra. The investigation of MS and MS(2) spectra from complexes of these monosaccharides with Na(+) and Pb(2+) failed to distinguish these monosaccharide isomers. Therefore, multiple stage mass analysis by ESI-ITMS using either [M+NH(4)](+) or [M+H](+) was useful to distinguish between the isomers of monosaccharides.     

Investigation of Metal Ion Complexation of π-Coordinate Calixarene Derivatives by Electrospray-Ionization Mass Spectrometry

Complexation of π-coordinate calix[4]arene derivatives toward soft metal ions, silver and thallium (I) ions, has been studied by electrospray-ionization mass spectrometry. Competitive metal–ion complexation of three calix[4]arene derivatives demonstrates a significant effect of olefinic substituents and its location on the silver ion complexation, but there was no effect of them on the thallium ion complexation. The stability constants for the metal ion complexes of the calixarene derivatives in methanol have been successfully determined by a mass-spectrometric method using 18-crown-6 as the reference ligand.     

Reactions of anionic porphyrin with group 11 elements: a spectrophotometric and electrospray ionization mass spectrometry study

The reaction of 3,8,13,18-tetramethyl-21H,23H-porphine-2,7,12,17-tetrapropionic acid or coproporphyrin-I (CPI) with the elements of 11 group have been studied. CPI is an anionic porphyrin that slowly reacts with copper ion to form Cu^IICPI and with silver ions to form Ag^IICPI, Ag^IIICPI complexes and colloidal silver. Gold ions do not form complexes with CPI, but, in the main, colloidal gold and some CPI-N-oxide. The kinetics of the reactions with copper and silver were spectrophotometerically studied and the rate constants were calculated. The identification and characterization of this water-soluble anionic porphyrin and its metal complexes have been performed by electrospray mass spectrometry (ESI-MS) that proved to be an excellent method for these determinations. The multiple charged parent ions for metal free ligand and their metal complexes were identified.     

Density Functional Theory and Mass Spectrometry of Phthalate Fragmentations Mechanisms: Modeling Hyperconjugated Carbocation and Radical Cation Complexes with Neutral Molecules

This is the first ab initio study of the energetics of the fragmentation mechanisms of phthalate, by mass spectrometry, leading to protonated phthalic anhydride (m/z 149). Phthalates fragment by two major pathways; namely, the McLafferty + 1 rearrangement and the loss of alkoxy. Both pathways involve a carbonyl oxygen attack to the ortho-carbonyl carbon leading to structures with tetrahedral carbon intermediates that eventually give m/z 149. These pathways were studied by collision induced dissociation (CID) using triple quadrupole mass spectrometry. The proposed McLafferty + 1 pathway proceeds through a distonic M^•+, leading to the loss of an allylic-stabilized alkene radical. The McLafferty rearrangement step proceeds through a six-membered ring transition state with a small activation energy ranging 0.4–6.2 kcal/mol; the transfer of a second H from the distonic ion of the rearrangement step proceeds through a radical cation molecule complex. Based on quantum chemical modeling of the cation molecule complexes, two kinds of cation molecule complexes were identified as radical cation molecule complex and hyperconjugated cation molecule complex. This distinction is based on the cation and simplifies future modeling of similar complexes. Optimization of important fragments in these pathways showed cyclized and hydrogen-bonded structures to be favored. An exception was the optimized structure of the protonated phthalic anhydride (m/z 149) that showed a structure with an open anhydride ring.     

Luminescent, three-coordinate azadipyrromethene complexes of d(10) copper, silver, and gold

Boron azadipyrromethenes are red-light-absorbing dyes with chromophoric capabilities deriving from a conjugated, chelating framework. Reported here are tricoordinate copper(I), silver(I), and gold(I) complexes of a tetraphenylazadipyrromethene ligand. The new complexes are characterized by optical absorption and emission spectroscopy, multinuclear NMR, mass spectrometry, elemental analysis, and X-ray diffraction crystallography. Time-dependent density functional theory calculations indicate that the principal absorption features in azadipyrromethene complexes result from optically allowed intraligand transitions that undergo configuration interaction.     

Substituent effects on the structures of silver complexes with monoazatrithia-12-crown-4 ethers bearing substituted aromatic rings

New 4'-methoxybenzyl-, 4'-methylbenzyl-, benzyl-, 3',5'-difluorobenzyl-, 3',5'-dichlorobenzyl-, and 4'-nitrobenzyl-armed monoazatrithia-12-crown-4 ethers were prepared by the reductive amination of monoazatrithia-12-crown-4 with the appropriate benzenecarbaldehyde in the presence of NaBH(OAc)3. Cold electrospray ionization mass spectrometry and X-ray crystallography show that silver complexes with armed monoazatrithia-12-crown-4 ethers bearing aromatic side arms with electron-donating groups or electron-withdrawing groups are coordination polymers and trimers, respectively. The structures of the silver complexes were strongly dependent on the strength of the CH...pi interactions, which are controlled by substituent effects on the aromatic side arms.     

Meso-四(对烷氧苯基)卟啉金属银配合物的激光解吸电离飞行时间质谱表征

通过激光解吸电离飞行时间质谱对meso-四(对烷氧苯基)卟啉金属银配合物进行了表征.样品溶解在氯仿中,以正离子方式记录谱图,结果发现除了产生目标化合物分子离子峰外,没有任何碎片峰.激光解吸电离飞行时间质谱是表征这种meso-四(对烷氧苯基)卟啉金属银配合物有效的方法.     

New riches in carbaporphyrin chemistry: silver and gold organometallic complexes of benzocarbaporphyrins

The NH-N-NH-N core of the porphyrin system represents one of the best studied and most versatile platforms for coordination chemistry. However, the replacement of one or more of the interior nitrogens with carbon atoms would be expected to diminish the ability of these systems to form metallo derivatives considerably. Despite this expectation, carbaporphyrinoid systems have been shown to form stable organometallic derivatives. Although azuliporphyrins and benziporphyrins act as dianionic ligands, benzocarbaporphyrins are trianionic ligands. Treatment of five different meso unsubstituted benzocarbaporphyrins and two different meso tetraarylbenzocarbaporphyrins with excess silver(I) acetate afforded 65-97% yields of the corresponding silver(III) organometallic derivatives. The insertion of silver metal was confirmed by mass spectrometry and X-ray crystallography. The UV-vis spectra showed a strong Soret band at wavelengths between 437 and 451 nm, together with a series of Q-type bands at longer wavelengths. The new metallo carbaporphyrins demonstrate the presence of a strong diatropic ring current in their proton NMR spectra, and carbon-13 NMR spectroscopy indicates that the derivatives retain a plane of symmetry. The reaction of meso tetraaryl carbaporphyrins with gold(III) acetate afforded the related gold(III) complexes, and these also showed strongly porphyrin-like aromatic characteristics. The UV-vis spectra for the gold complexes again showed a strong Soret band between 437-439 nm, but a secondary band near 400 nm is somewhat intensified for the gold species compared to the spectra for the related silver(III) meso tetrasubstituted carbaporphyrins. The ring currents observed for the gold(III) complexes by proton NMR spectroscopy were comparable to those of the silver(III) derivatives, implying that both series have similar macrocyclic conformations. Cyclic voltammetry was performed on two different carbaporphyrins, their silver(III) derivatives, and a gold(III) complex. The silver complexes display a reversible cathodic wave that is assigned to the Ag(III/II) couple. However, the gold porphyrinoid gave a value for the reductive wave that could be due to a gold(III/II) couple or a ligand-based process.     

Probing isomeric differences of phosphorylated carbohydrates through the use of ion/molecule reactions and FT-ICR MS

Through the use of ion/molecule reactions and tandem mass spectrometry, phosphate position is assigned in both phosphorylated monosaccharides and oligosaccharides. In previous work phosphate moieties of monosaccharides were stabilized under collisional activation, by first derivatizing the deprotonated monosaccharide with trimethyl borate through an ion/molecule reaction, and the phosphate position determined through marker ions generated in tandem mass spectra. In this work, the methodology is extended to larger phosphorylated oligomers employing chlorotrimethylsilane (TMSCl) as the ion/molecule reagent. Phosphorylated monosaccharides were first investigated to determine diagnostic ions for phosphate linkage in monomeric standards. It was observed that the diagnostic ions showed both linkage and some monosaccharide stereochemical information. Furthermore, it was observed that TMS addition stabilized the phosphate moiety under collisionally activated conditions. Upon identification of the diagnostic ions, the methodology was applied to lactose-1-phosphate. It was found that TMSCl, stabilized the phosphate moiety upon collisional activation, and furthermore, the phosphate linkage could be determined through tandem mass spectrometric analysis. As a further extrapolation to biologically relevant problems, the methodology was applied to a lipophosphoglycan analog from the protozoan parasite Leishmania. This sample contains bridging phosphates which were converted to terminal phosphates through collision induced dissociation. The sample was then analyzed in the same manner as lactose-1-phosphate, yielding phosphate linkage information and stereochemical information. This study showed that, using the developed methodology, phosphate linkage can be determined from both monosaccharides and larger oligosaccharides; furthermore it is applicable to samples in which the phosphates are either terminating or bridging.     

Time-of-flight mass spectrometric analysis of ion formation in hypervelocity impact of organic polymer microspheres: comparison with secondary ion mass spectrometry, (252)Cf mass spectrometry and laser mass spectrometry

Unisized 1.6-microm polystyrene microspheres coated with PEDOT (polyethylene-dioxythiophene) were accelerated to speeds of 6-16 km/s and shot onto a silver target. Either positive or negative ions, both instantaneously formed by the impact process, have been analyzed by time-of-flight mass spectrometry (TOF). Apparently, the processes that control the formation of ions of either polarity depend on the impact velocity. Comparing the results with those of secondary ion mass spectrometry with primary ion energy in both the elastic and the inelastic ((252)Cf-MS) energy loss regimes, some reaction mechanisms of the polymer ions for different energy densities could be elucidated. Some aspects of ion formation are also related to those found in pulsed laser ion generation from these microspheres. This investigation was performed in order to further improve the method of analyzing the organic fraction of interstellar, interplanetary, and cometary dust particles impinging on the targets of the "CIDA" time-of-flight (TOF) mass spectrometers on-board the NASA comet missions "STARDUST" and "CONTOUR".     

Tris{2‐[N‐(diethylaminothiocarbonyl)benz(‐amidino;‐imidoxy;‐imidothio)‐N′‐yl]ethyl}amine – neue tripodale Liganden. Darstellung,Komplexstabilität und Extraktionsverhalten ihrer Silber(I)‐Komplexe

Tris{2‐[ N ‐(diethylaminothiocarbonyl)benz(‐amidino; imidoxy; ‐imidothio)‐ N ′‐yl]ethyl}amines – New Tripodal Ligands. Synthesis, Complex Stability, and Extraction Behaviour of their Silver(I) Complexes N‐(Thiocarbamoyl)‐benzimidoylchlorides react with trivalent nucleophiles to give four novel tripodal ligands. Two of them have been characterized by X‐ray methods. The ligands form with silver(I) cationic mononuclear complexes in which the three arms of the ligand are coordinated monodentately via sulfur. The results of FAB and ESI mass spectrometry as well as ESCA and NMR investigations verify this binding mode. The protonation constants of the ligands and the stability constants of silver(I) complexes have been determined potentiometrically. The novel tripodal compounds behave as powerful extractands for silver(I).     

Studies of cisplatin and hemoglobin interactions using nanospray mass spectrometry and liquid chromatography with inductively-coupled plasma mass spectrometry

Interactions of cisplatin with hemoglobin (Hb) were studied using both nanoelectrospray mass spectrometry (nanoESI-MS) and a combination of size exclusion high performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICPMS). Size exclusion HPLC separation of free and protein-bound cisplatin followed by simultaneous monitoring of 195Pt and 57Fe demonstrated the presence of Hb-bound Pt complexes. Nanospray quadrupole time-of-flight mass spectrometry studies of the Hb-cisplatin complexes further demonstrated the specific binding of cisplatin to the alpha-chain, heme-alpha, beta-chain, and heme-beta units of hemoglobin. Accurate mass measurements and tandem mass spectrometry information confirmed the Hb-cisplatin complexes. The formation of Hb-cisplatin complexes was observed at the sub-microM to microM concentration levels of cisplatin, which are relevant to clinical levels. These findings and the techniques developed for cisplatin-Hb interaction studies are useful for understanding of drug-protein interactions.     

Ranking of gas-phase acidities and chloride affinities of monosaccharides and linkage specificity in collision-induced decompositions of negative ion electrospray-generated chloride adducts of oligosaccharides

Negative ion electrospray-tandem mass spectrometry has been employed to study chloride adducts of saccharide molecules. Decompositions of [M + Cl]- obtained under identical low-energy collision conditions allow the approximate ranking of chloride affinities and gas-phase acidities of a series of isomeric monosaccharides. The ketohexoses are found to be more acidic than the aldohexoses. Chloride adduct decompositions are examined for a glucopyranosyl fructose and a glucopyranosyl glucose series. For each disaccharide series, the linkage position is shown to markedly influence the favored pathways of [M + Cl]- decompositions, initiated either by loss of neutral HCl to form [M - H]- and possibly leading to further (consecutive) decompositions, or by loss of M to form Cl-. Upon formation of [M - H]-, both cross-ring cleavages and glycosidic bond decompositions were observed in varying degrees for the two series of disaccharides. Remarkably, for three non-reducing polysaccharides that each contain a terminal sucrose group at the "downstream" end, chlorine-containing product ions arising from cleavage of the Glcalpha-2Fru linkage have been observed. Apart from Cl-, chlorine-containing product ions are not observed for any of the other disaccharides investigated, and they appear to be specifically diagnostic of a terminal Glcalpha-2Fru linkage. Their appearance is rationalized based upon a substantially reduced tendency for HCl loss from these non-reducing polysaccharides.