Cation binding by a crown-capped porphyrin

The crown ether capped metalloporphyrins (6) form complexes with metal cations; complex formation may be detected by fluorescence quenching for (6, M=ZnII or CuII) and paramagnetic guest cations or, in some cases, by FAB mass spectrometry. Complexation with alkyl ammonium cations was also examined using absorption spectrometry.     

Study of Host-Guest Complexation of Alkaline Earth Metal Ion,Aluminum Ion and Transition Metal Ions with Crown Ethers by Fast Atom Bombardment Mass Spectrometry

Complexations of crown ethers with alkali metal ions have been investigated extensively by FAB mass spectrometry over the past decade, but very little attention has been paid to reactions of crown ethers with other classes of metal ions such as alkaline earth metal ions, transition metal ions and aluminum ions. Although fast atom bombardment ionization mass spectrometry has proven to be a rapid and convenient method to determine the binding interactions of crown ethers with metal ions, problems in reliabilities for quantitative measurements of” binding strength for the host-guest complexes have been described in the literature. Thus, in this paper, applications of FAB/MS for investigating the complexation of crown ethers with various classes of metal ions is discussed. Extensive fragmentations for neutral losses such as C₂H₄O or C₂H₄ molecules from the host-guest complexes could be observed. The reason is attributed to the energetic bombardment processes of FAB occuring in the formation of these complexes. Complexes of cyclen with metal ions also show neutral losses of C₂H₄NH molecules leading to fragment ions. Transition metal ions usually form (Crown + MCl)⁺ type of ions, alkaline earth metal ions can form both (Crown + MCl)⁺ and (Crown + MOH)⁺ type of ions. But for aluminum ions, only (Crown + Al(OH)₂)⁺ type of ions could he observed.     

Stoichiometry, complex stability, molecular size and conformational variations of metal ion crown ether complexes subject to diffusion coefficients in nonaqueous solutions

Both the stoichiometry and complex stability constants of crown ether complexes with metal ions have been determined by examining gradual changes in their diffusional behavior in nonaqueous solution. Diffusion coefficients, D, were evaluated by pulsed field gradient (PFG) NMR titration experiments whilst complex stability constants were determined by nonlinear curve-fitting procedures, D versus c_sol., which also allow the treatment of multiple complexation equilibria (1:1 to 1:2 stoichiometries). Differences in the diffusion coefficients of the various free crown ethers with respect to their metal ion complexes indicate great sensitivity to both conformational changes and changes in molecular size upon complexation.     

Metal displacement and stoichiometry of protein‐metal complexes under native conditions using capillary electrophoresis/mass spectrometry

Increases in the study of protein‐metal complexes, as well as in metal displacement in protein‐metal complexes under native conditions for optimum catalytic properties in drug research and catalyst design, demands a separation/detection technology that can accurately measure metal displacement and stoichiometry in protein‐metal complexes. Both nuclear magnetic resonance (NMR) and X‐ray diffraction techniques have been used for this purpose; however, these techniques lack sensitivity. Electrospray ionization mass spectrometry (ESI‐MS) using direct infusion offers higher sensitivity than the former techniques and provides molecular distribution of various protein‐metal complexes. However, since protein‐metal complexes under native conditions usually are dissolved in salt solutions, their direct ESI‐MS analysis requires off‐line sample clean‐up prior to MS analysis to avoid sample suppression during ESI. Moreover, direct infusion of the salty solution promotes non‐specific salt adduct formation by the protein‐metal complexes under ESI‐MS, which complicates the identification and stoichiometry measurements of the protein‐metal complexes. Because of the high mass of protein‐metal complexes and lack of sufficient resolution by most mass spectrometers to separate non‐specific from specific metal‐protein complexes, accurate protein‐metal stoichiometry measurements require some form of sample clean up prior to ESI‐MS analysis. In this study, we demonstrate that capillary electrophoresis/electrospray ionization in conjunction with a medium‐resolution (～10 000) mass spectrometer is an efficient and fast method for the measurement of the stoichiometry of the protein‐metal complexes under physiological conditions (pH ～7). The metal displacement of Co²⁺ to Cd²⁺, two metal ions necessary for activation in the monomeric AHL lactonase produced by B. thuringiensis, has been used as a proof of concept. Copyright © 2010 John Wiley & Sons, Ltd.     

Evaluation of photoinduced changes in stability constants for metal-ion complexes of crowned spirobenzopyran derivatives by electrospray ionization mass spectrometry

The photoinduced changes of metal-ion complexing ability of crowned spirobenzopyran derivatives were studied by using electrospray ionization mass spectrometry (ESI-MS). Stability constants for the complexation with various metal ions in methanol under visible-irradiation conditions were determined for the first time by ESI-MS. It was found that the stability constants of crowned bis(spirobenzopyran) derivatives with metal ions are decreased dramatically by visible irradiation due to the disappearance of powerful ionic interaction between phenolate anion(s) of the merocyanine form of their spirobenzopyran moiety and a metal ion bound to their crown ether moiety, and the decrease in the stability constants is more pronounced for the multivalent metal-ion complexes. A theoretical consideration was also made to attain reliable values of stability complexes for metal-ion complexes of crown compounds.     

Unusual behavior of pyrazolo[1,2-a]pyrazoles in fast atom bombardment (fab) and frit-fast atom bombardment (Frit-FAB) mass spectrometry. Influence of the matrix

The nature of the matrix used in Fast Atom Bombardment (FAB) mass spectrometry analyses of pyrazolo[1,2-a]pyrazoles was found to influence significantly their positive and negative ions mass spectra. Indeed the use of glycerol provided an abundant ion corresponding to the protonated molecule (M+H)⁺ whereas the meta-nitrobenzyl alcohol favored the formation of the radical ion M^+°. Such results which are in accordance with the oxidoreduction properties of the matrices studied were also established in Frit-FAB mass spectrometry analyses of pyrazolo[1,2-a]pyrazoles.     

The analysis of salen complexes by fast atom bombardment mass spectrometry and atmospheric pressure chemical ionization mass spectrometry

Fast atom bombardment (FAB) mass spectrometry provides useful structural information about salen complexes and salen-based oxo transfer catalysts that are not appreciably soluble in organic solvents. It was discovered that initial dissolution of these complexes in trifluoroacetic acid was crucial for producing good FAB mass spectra. Trifluoroacetic acid helps dissolve the salen-based catalysts, concentrates the analyte molecules at the matrix surface, and most importantly, suppresses the reduction process, which is a well-known phenomenon when protic matrices are used. The best FAB matrices for these catalysts were found to be thioglycerol and “magic bullet.” However, dechlorination occurred under the acid conditions for complexes containing iron chloride and manganese chloride. Demetalation also occurred for nickel-containing oxo transfer salen-based complexes. When the salen-based complexes are soluble in LC solvents, they can be analyzed easily by atmospheric pressure chemical ionization (APCI) mass spectrometry without the employment of relatively nonvolatile matrices. In addition, APCI/MS provides much more sensitive detection for manganese-salen complexes when compared with FAB results. No dechlorination or demetalation were observed when a negative ion mode APCI was employed. To our knowledge, this is the first time that an intact molecule of this type of complex has been observed by mass spectrometry.     

Ultramark 1621 as a reference compound for positive and negative ion fast-atom bombardment high-resolution mass spectrometry

Ultramark 1621, a commercially available mixture of fluorinated phosphazines, was found to bea a useful calibration compound for negative and positive ion fast-atom bombardment (FAB) high-resolution mass spectrometry. Ultramark 1621 worked very well with the most widely used matrices such as glycerol, nitrobenzyl alcohol, and triethanolamine. The negative and positive ion FAB mass spectra of Ultramark include a series of intense peaks extending from 700 to 1900 u.     

Comparative investigations of the secondary ion emission of metal complexes under MeV and keV ion bombardment

A series of ionic and neutral Group VIII transition metal complexes with molecular masses up to 2500 u were analysed by time-of-flight secondary ion mass spectrometry (SIMS) and plasma desorption mass spectrometry (PDMS). The secondary ion emission, the secondary ion yields and the yield ratios Y(PDMS)/Y(SIMS) of 20 ionic and neutral metal complexes were determined. Both techniques generally provide both molecular and fragment ion information. Characteristic fragmentation patterns give useful data for structural characterization. Additionally, the stabilities of different secondary ion species were compared by their half-lives. Both PDMS and SIMS are very sensitive, yielding optimum spectra from total sample sizes as low as 5 nmol, and the sample consumption is negligible.     

Separation of components of the solution modeling PUREX raffinate via extraction by crown ethers to 1,1,7-trihydrododecafluoroheptanol

We study the extraction of strontium, cesium, and some other elements by dicyclohexano-18-crown-6 (DCH18C6) and its di-tert-butyl derivative (DTBDCH18C6) in the system 1,1,7-trihydrododecafluoroheptanol-water from the solution modeling PUREX raffinate. We show that strontium under these conditions is extracted in a single contact with distribution ratios of 100–200 and separates from sodium, whose distribution ratio is less than 0.01. Strontium extraction in a single contact reaches 99.5%. The stoichiometry and stability constants are determined for nitric acid complexes of the crown ethers studied with coextraction of nitric acid (1: 1). The mutual solubilities of the components in the system 1,1,7-trihydrododecafluoroheptanol-water are calculated using chromatography/mass spectrometry: water in alcohol is 0.5 wt %, and alcohol in water is 0.16 wt %.     

Partial methanolysis and fast atom bombardment mass spectrometry of peptides containing sulphurated ammo acids

Sequence determination by partial methanolysis and fast atom bombardment (FAB) mass spectrometry of peptides containing cysteine and methionine was investigated. Cysteine-containing peptides require methylation of the sulphydryl group by methyl iodide to give a stable S-methylcysteinyl residue prior to partial methanolysis and mass spectrometry. Methionine-containing peptides undergo partially a methylation on sulphur during methanolysis, with formation of an S-methylsulphonium ion which under FAB conditions is extracted from the matrix and eliminates methyl sulphide in the gas phase. The presence of additional peaks due to chemical modifications or gas-phase fragmentations, however, does not interfere with the sequence information of the spectra.     

Antifungal active tetraaza macrocyclic transition metal complexes: Designing, template synthesis, and spectral characterization

Eight novel macrocyclic complexes as candidates of antifungal agent were designed and synthesized by incorporating an N₄ donor site via the template condensation of 4,4′-diaminodiphenylmethane, formaldehyde. p-anisidine, and metal salts. The structural features were determined on the basis of their elemental analyses, magnetic susceptibility, molar conductance, FAB Mass, UV-Vis, and IR spectral data. Electronic absorption spectral data of the complexes suggest a square-planar geometry around the central metal ion except the VO(IV) complex, which shows square-pyramidal geometry. The stoichiometry of the complexes had been found to be 1: 1 (metal: ligand). Electrolytic nature of the complexes is assessed from their high conductance data. Monomeric nature of the complexes is confirmed from magnetic susceptibility values. The X-band ESR spectra of the Cu(II) and VO(IV) complexes in DMSO at 300 and 77 K were recorded, and their salient features are reported. The antifungal activity of the macrocyclic metal complexes were screened in vitro against Aspergillus niger, Aspergillus fluvus, Trichoderma harizanum, Trichoderma viridae, and Rhizoctonia solani. The data showed that they possessed antifungal activity. The article is published in the original.     

Ion formation in fast atom bombardment mass spectrometry: a divided probe investigation of gas-phase reactions

Some ion-formation processes during fast atom bombardment (FAB) are discussed, especially the possibility of reactions in the gas phase. Divided (two halves) FAB probe tips were used for introducing two different samples into the source at the same time. Our results showed [M + A]⁺ ions (where M = crown ethers and A = alkali metal ions), can be produced, at least in part, in the gas phase when crown ethers and sources of alkali metal ion are placed on two halves of the FAB probe tip. The extent of this ion formation depends on the volatility of the crown ether and on steric factors. Cluster ions such as (M + LiCl)Li⁺, (2M + LiCl)Li⁺, [2M + K]⁺ and [2M + Na]⁺ are also observed to form in the gas phase. Unimolecular decompositions contribute to some ions detected in FAB. When the alkali ion salt and the crown ether are mixed together the probability of [M + A]⁺ ion formation increases significantly, regardless of the volatility of the crown ether.     

Conversion of Ca2+ salt of an organic compound to its Li+ salt to simplify the fast atom bombardment mass spectrum

The FAB mass spectrum of the Ca(2+) salt of RK-682 (1, MW 368), a potent protein tyrosine phosphatase inhibitor, shows a complex pattern due to Ca(2+) adduct ions with multimers of 1 and their decomposition ions. Addition of LiCl greatly simplified the FAB mass spectrum, providing a prominent Li(+) adduct ion of 1 at m/z 381 [M+2Li-H](+). The addition of LiCl also greatly simplified the FAB mass spectrum of calcium pantothenate. This approach may be generally useful for molecular weight determination of multivalent metal salts of organic compounds, or organic compounds that can form Li salts, by FAB mass spectrometry.     

N-Alkylnicotinium halides: A class of cationic matrix additives for enhancing the sensitivity in negative ion Fast-Atom bombardment mass spectrometry of polyanionic analytes

The addition of some surfactants to the fast-atom bombardment (FAB) matrix previously has been demonstrated to enhance analyte signals in fast-atom bombardment mass spectrometry. In particular, cationic surfactants appear to enhance the negative ion FAB detectability of analytes that exist as anionic species in the matrix solution. It has been proposed that the charged surfactant concentrates the oppositely charged analyte near the surface, which results in larger signals for the analyte. Cationic surfactants that contain a fixed positive charge and an additional basic site were prepared with different hydrophobic moieties and were evaluated for their effectiveness as FAB matrix additives. The compound N-octylnico-tinium bromide (ONBr) is shown to improve greatly the analyte-related signals in negative ion fast-atom bombardment mass spectrometry for a variety of polyanionic analytes, relative to other surfactants (e.g., cetylpyridinium salts). This surfactant not only enhances detectability, but also simplifies the pseudomolecular ion region of the resulting spectra by reducing or eliminating metal cation adduct peaks. The simple mechanism of enhancement via surface activity is evaluated, and alternative mechanisms are considered. It is clearly shown that ONBr, as a FAB matrix additive, will allow mass spectrometry to be used for the analysis of anionic compounds that normally exhibit very low responses.     

Continuous-flow fast atom bombardment mass spectrometry of oligonucleotides

Although frit-fast atom bombardment (frit-FAB) and continuous-flow FAB mass spectrometry have become standard methods for the analysis of peptides and peptide mixtures, these techniques have not been applied previously to the analysis of oligonucleotides. Mobilephase composition, flow rate, and sample size were optimized for the analysis of oligonucleotides by negative ion frit-FAB mass spectrometry (a type of continuous-flow FAB mass spectrometry). With a mobile phase consisting of methanol/water/triethanolamine (80:20:0.5, v/v/w), flow injection frit-FAB analysis of oligonucleotides showed lower limits of detection compared to standard probe FAB mass spectrometry. For example, in order to obtain a signal-to-noise ratio of 3:1, 38 prnol of d(GTIAAC) were required for frit-FAB mass spectrometry and 62 pmol were required for standard probe FAB mass spectrometry. The largest difference between frit-FAB and standard probe FAB was observed for d(pC)₅, for which the limit of detection by frit-FAB was approximately 11-fold lower than by standard FAB mass spectrometry. Adjustment of the mobile phase to pH 7 with trifluoroacetic acid increased the limit of detection (reduced sensitivity) a minimum of sixfold. Equimolar mixtures of two or three oligonucleotides produced deprotonated molecules in identical relative abundances whether analyzed by frit-FAB or standard probe FAB mass spectrometry. Finally, frit-FAB liquid chromatography mass spectrometry was demonstrated by separating mixtures of oligonucleotides on a β -cyclodextrin high-performance liquid chromatography column with a mobile phase containing methanol, water, and triethanolamine.     

Evaluation and determination of the cyclofructans–amino acid complex binding pattern by electrospray ionization mass spectrometry

The noncovalent complex interactions between cyclofructans, a new class of cyclic oligosaccharide hosts, and various amino acids have been characterized by means of electrospray ionization mass spectrometry and nuclear magnetic resonance. The 1 : 1 stoichiometry of cyclofructans and amino acid complexes was confirmed by their mass‐to‐charge ratio in positive mode. Cyclofructans (CFs)–amino acid complexes and cyclodextrin–amino acid complexes exhibited distinctive different fragment behaviors in collision‐induced dissociation experiments. Coupled with the results of ¹H NMR and nuclear overhauser effect spectroscopy, cyclofructan–amino acid complexes were deduced to be rim complexes via formation hydrogen bonding and ion–dipole forces. The interaction pattern could be controlled by changing the pH condition. In neutral solution, amino acids are located on the positive side of CFs, although moved to the negative side pocket constructed by 3‐OH oxygen of furanose ring and the crown ether oxygen in acid condition. In addition, theory calculation for geometry optimization of Trp and CFs was performed, which was in good agreement with the experimental results. Copyright © 2014 John Wiley & Sons, Ltd.     

Transition metal complexes of 2-acetylpyridine o-hydroxybenzoylhydrazone (APo-OHBH): their preparation, characterisation and antimicrobial activity.

Coordination compounds of some transition metal ions with 2-acetylpyridene-o-hydroxybenzoylhydrazone (APo-OHBH) were synthesized. Their structures have been characterised by elemental analyses, electrical conductance, magnetic moments (at 25 degrees C) and spectral (IR, UV, NMR) studies. The fast atom bombardment (FAB) method was used for obtaining mass spectra of the positive ion FAB studies of the ligand and some metal complexes. The thermal behaviour of selected complexes was investigated by thermal gravimetrical analysis (TGA) and differential thermal analysis (DTA) techniques. The IR spectra show that the ligand acts in a neutral bidentate, neutral tridentate and/or mononegative tridentate fashion depending on the metal salt used and the medium of the reaction. Preliminary pharmacological tests on the ligand and its complexes showed some antimicrobial activity.     

Determination of binding selectivities in host-guest complexation by electrospray/quadrupole ion trap mass spectrometry

The quantifiable relationship between the equilibrium solution composition and electrospray (ESI) mass spectral peak intensities of simple host-guest complexes was investigated. Specifically, host-guest complexes of simple crown ethers or glymes with alkali metals and ammonium ions were studied. Comparisons were made between the theoretical concentrations of host-guest complexes derived in solution from known stability constants and the peak intensities for the complexes observed by ESI mass spectrometry (ESI-MS). Two types of complexation experiments were undertaken. First, complexation of a single guest ion, such as an alkali metal, and two crown ethers was studied to evaluate the determination of binding selectivities. Second, complexation of two different guest ions by a single polyether host was also examined. In general, solvation was found to play an integral part in the ability to quantify binding selectivities by ESI-MS. The more similar the solvation energies of the two complexes in the mixture, the more quantifiable their binding selectivities by ESI-MS. In some cases, excellent correlation was obtained between the theoretically predicted selectivity ratios and the ESI mass spectral ratios, in particular when the ESI ratios were adjusted based on evaluation of ESI response factors for the various host-guest complexes.     

Selective detection of specific protein-ligand complexes by electrosonic spray-precursor ion scan tandem mass spectrometry

A novel mass spectrometric method for the selective detection of specific protein-ligand complexes is presented. The new method is based on electrosonic spray ionization of samples containing protein and ligand molecules, and mass spectrometric detection using the precursor ion scanning function on a triple quadrupole instrument. Mass-selected intact protein-ligand complex ions are subjected to fragmentation by means of collision-induced dissociation in the collision cell of the instrument, while the second mass analyzer is set to the m/z of protonated ligand ions or their alkali metal adducts. The method allows for the detection of only those ions which yield ions characteristic of the ligand molecules upon fragmentation. Since the scan range of first analyzer is set well above the m/z of the ligand ion, and the CID conditions are established to permit fragmentation of only loosely bound, noncovalent complexes, the method is specific to the detection of protein-ligand complexes under described conditions. Behavior of biologically specific and nonspecific complexes was compared under various instrumental settings. Parameters were optimized to obtain maximal selectivity for specific complexes. Specific and nonspecific complexes were found to show markedly different fragmentation characteristics, which can be a basis for selective detection of complexes with biological relevance. Preparation of specific and nonspecific complexes containing identical building blocks was attempted. Complex ions with identical stoichiometry but different origin showed the expected difference in fragmentation characteristics, which gives direct evidence for the different mechanism of specific versus nonspecific complex ion formation.