ESI-FTICR mass spectrometric study of alcohol complexation properties of mono- and diphosphonate-bridged cavitands

Alcohol complexation properties of eight mono- and diphenyl phosphonate-bridged cavitands were studied by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR) and theoretical calculations. The cavitands varied in number and position of phenyl phosphonate bridges and their orientation with respect to the cavity, length of the lower rim alkyl chains, and substituents at apical positions of the resorcarene skeleton. The specificities of the different cavitands toward primary, secondary, and tertiary alcohols varying long of the alkyl chain were investigated, together with the stabilities of the formed complexes. The number, position, and orientation of the P = O moieties affected the complex formation of the cavitands and stability of the complexes dramatically. Methyl groups at apical positions of the resorcarene skeleton also affected the complexation properties. Although length and branching of the alkyl chain of the alcohol influenced the complex formation, the effect on stability of the complexes was negligible.     

Mass spectrometric investigation of noncovalent complexation between a tetratosylated resorcarene and alkyl ammonium ions

Noncovalent complexation between tetratosylated tetraethyl resorcarene (1) and primary, secondary, and tertiary alkyl ammonium ions (mMe, dMe, tMe, mEt, dEt, tEt, dBu, and dHex) was studied by electrospray ionization Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry. Interactions of the noncovalent complexes were investigated by means of competition experiments, collision-induced dissociation (CID) experiments, ion-molecule reactions with tripropylamine and gas phase H/D-exchange reactions with deuteroammonia. Gas phase ion-molecule reactions gave especially valuable information about the structure and properties of the complexes. Resorcarene 1 formed relatively stable 1:1 complexes with all aliphatic alkyl ammonium ions. Steric properties of the alkyl ammonium ions and proton affinities of the conjugate amines noticeably affected the complexation properties, indicating the importance of hydrogen bonding in these complexes. According to the competition experiments, the thermodynamically most stable host-guest complexes were formed with alkyl ammonium ions that were most substituted and had the longest alkyl chains. In CID experiments, release of an intact free guest ion or dissociation of the host was observed to depend on the proton affinity of the amine and the strength of the hydrogen bond that was formed. In ion-molecule reactions with tripropylamine, a guest exchange reaction occurred with all alkyl ammonium ion complexes with reaction rates mostly dependent on the steric properties of the original guest ion. In H/D-exchange reactions the N-H hydrogen atoms of the guest ion were exchanged with deuterium, whereas the resorcinol hydrogen atoms remained unchanged.     

Complexation of metal ions in Langmuir films formed with two amphiphilic dioxadithia crown ethers

The two new crown ethers presented in this study were synthesized in order to investigate two important features of ionophores, namely metal cation complexation and interfacial properties, and the way in which they interrelate. The two derivatives were conceived as analogs of membrane phospholipids with respect to their amphiphilicity and geometry. They contain a hydrophilic 1,1'-dioxo-3,3'-dithio-14-crown ether headgroup and bear two myristoyl or stearoyl lateral chains. The length of the myristoyl and stearoyl derivatives in an extended conformation is comparable with the thickness of the individual leaflets of cell membranes. The membrane-related and complexation properties of the two crown ether derivatives were studied in monomolecular films spread on pure water and on aqueous solutions of mono-, di-, and trivalent metal salts. The properties of the monolayers are described quantitatively using thermodynamic models. The compression isotherms of the monolayers formed on different subphases show a clear-cut differentiation of the monovalent and di- or trivalent cations with both ligands. This differentiation was interpreted in terms of conformational changes occurring in the crown ether derivatives upon complexation. Molecular modeling indicates that the mono- and divalent cations are coordinated differently by the ligands, yielding complexes with different conformations. The differences of the conformations of the mono- and di- or trivalent cation complexes may be important from the point of view of the interactions with lipid membranes and the biological activity of these potential ionophores.     

Borate-nucleotide complex formation depends on charge and phosphorylation state

Flow injection analysis with electrospray ionization mass spectrometry was used to investigate borate-nucleotide complex formation. Solutions containing 100 microM nucleotide and 500 microM boric acid in water-acetonitrile-triethylamine (50:50:0.2, v/v/v; pH 10.3) showed that borate complexation with nicotinamide nucleotides was significantly influenced by the charge on the nicotinamide group and the number of phosphate groups on the adenine ribose. Borate binding decreased in the order of NAD(+), NADH, NADP(+) and NADPH. To investigate the relationship between complex formation and phosphorylation, association constants (K(A)) of borate-adenine (AMP, ADP, ATP), -guanine (GMP, GDP, GTP), -cytidine (CMP, CDP, CTP) and -uridine (UMP, UDP, UTP) complexes were compared. The results showed that the number of nucleotide phosphate groups was inversely proportional to the relative abundance of the borate complexes, with the K(A) of borate-nucleotide complex decreasing in the order mono-, di- and tri-phosphates (AMP approximately GMP approximately CMP approximately UMP > ADP approximately GDP approximately CDP approximately UDP > GTP > ATP approximately CTP approximately UTP). At pH 7.4, using ammonium bicarbonate buffer, only borate-NAD(+) complex was observed. This indicates that the borate-NAD(+) complex may be the most physiologically relevant of those studied.     

Noncovalent complex formation of tetratosylated resorcarene with aromatic,aliphatic, and cyclic alkyl ammonium ions: a mass spectrometric study of complex properties

The ability of tetratosylated resorcarene to form complexes with aromatic ammonium ions was investigated by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. The formation of noncovalent complexes, [1+guest]⁺ and [1 · 1+guest]⁺, as observed with singly charged aromatic anilinium and phenylene aminoammonium guests. Comparison of the complexation efficiencies of the aromatic and aliphatic ammonium ions showed the importance of proton affinity of conjugate amines in complex formation. In collision‐induced dissociation experiments, gas‐phase stability was found to be lower for complexes formed with aromatic ions and this behavior was not found to depend on the proton affinity of conjugate amines. Fast oxidation of the para and ortho aminoammonium ions and complexation of these ions with tetratosylated resorcarene was observed. Copyright © 2005 John Wiley & Sons, Ltd.     

Ammonium ion mediated resorcarene capsules: ESI-FTICRMS study on gas-phase structure and ammonium ion affinity of tetraethyl resorcarene and its per-methylated derivative

The ammonium ion binding affinities of tetraethyl resorcarene (1) and its per-methylated derivative (2) were studied by electrospray ionization Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry. Ten different ammonium ions were tested as guests for the resorcarenes. A strong tendency for complex formation was observed with all ammonium ions of size and charge distribution suitable for noncovalent interactions with the cavities of the resorcarene hosts 1 and 2. Although differences in ammonium ion affinities were observed between 1 and 2 due to the dissimilar conformations, the overall tendency was that increase in the degree of substitution and the length of carbon chain of the ammonium cation facilitated the complex formation until the sterical hindrance impeded the complexation. Dimeric as well as monomeric ammonium ion complexes were formed with resorcarene 1, but resorcarene 2 was unable to form the dimeric capsules because of the lack of H-bond donor possibilities. The nature of binding of the guest was further investigated with ion-molecule reactions and by determination of the single crystal X-ray structure of host 1 complexed with tetramethyl ammonium bromide.     

Investigation of heptakis(2,6-di-O-methyl)-beta-cyclodextrin inclusion complexes with flavonoid glycosides by electrospray ionization mass spectrometry

The non-covalent complexes between three flavonoid glycosides (quercitrin, hyperoside and rutin) and heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CD) were investigated by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS). The 1:1 complexation of each flavonoid glycoside (guest) to the DM-beta-CD (host) was monitored in the negative ion mode by mixing each guest with an up to 30-fold molar excess of the host. The binding constants for all complexes were calculated by a linear equation in the order: DM-beta-CD:quercitrin > DM-beta-CD:rutin > DM-beta-CD:hyperoside. A binding model for the complexes has also been proposed based on the binding constants and tandem mass spectrometric data of these complexes.     

Preparation of partially functionalised resorcinarene derivatives

The conditions for synthesis of mono-, di- and trifunctionalised resorcinarenes by catalysed Mannich reaction are described. A series of these compounds are functionalised with different functional groups.     

Direct analysis of oligosaccharides and alpha hydroxy acids in fruits using electrosonic spray ionization mass spectrometry

Electrosonic spray ionization (ESSI) is a derivative technique of electrospray ionization (ESI) for mass spectrometry (MS) in which droplets are charged in the course of sonic spray. In this study, we applied ESSI MS to direct analysis of oligosaccharides and alpha hydroxy acids (AHAs) in fruits. The components were extracted from fruit fleshes by a feasible method prior to ESSI MS analysis, but the fruit juices were analyzed without further pretreatment. The results demonstrate that mainly alkali metal adducts of oligosaccharides are favorably produced in positive ion mode, while deprotonated AHAs and oligosaccharides are produced in negative ion mode. Compared with mass spectra obtained using electrospray droplet impact/secondary ion mass spectrometry (EDI/SIMS), mass spectra using ESSI make the identification of oligosaccharides more straightforward in positive ion mode than in negative ion mode.     

Influence of Equilibration Time in Solution on the Inclusion/Exclusion Topology Ratio of Host–Guest Complexes Probed by Ion Mobility and Collision‐Induced Dissociation

Host–guest complexes are formed by the creation of multiple noncovalent bonds between a large molecule (the host) and smaller molecule(s) or ion(s) (the guest(s)). Ion‐mobility separation coupled with mass spectrometry nowadays represents an ideal tool to assess whether the host–guest complexes, when transferred to the gas phase upon electrospray ionization, possess an exclusion or inclusion nature. Nevertheless, the influence of the solution conditions on the nature of the observed gas‐phase ions is often not considered. In the specific case of inclusion complexes, kinetic considerations must be taken into account beside thermodynamics; the guest ingression within the host cavity can be characterized by slow kinetics, which makes the complexation reaction kinetically driven on the timescale of the experiment. This is particularly the case for the cucurbituril family of macrocyclic host molecules. Herein, we selected para‐phenylenediamine and cucurbit[6]uril as a model system to demonstrate, by means of ion mobility and collision‐induced dissociation measurements, that the inclusion/exclusion topology ratio varies as a function of the equilibration time in solution prior to the electrospray process.     

Complexation of zinc octaalkylporphyrin with mono-, di-, and triethylenediamines in toluene

The complexation of zinc octaalkylporphyrin with mono-, di-, and triethylenediamines in toluene was studied by spectrophotometry using the molar ratio method and by ¹H NMR. The effect of the structure of the two-center organic base on the formation of 1 : 1 or 2 : 1 metal porphyrin-ligand complex was established. The stability constants of the resulting complexes were calculated and the concentration ranges of their existence were determined.     

ESI-MS studies of mixed-ligand Fe(II) complexes containing 1,10-phenanthroline and 1,10-phenanthroline-5,6-dione as ligands

In order to monitor the progression of the synthesis and the separation of novel mixed-ligand iron complexes containing 1,10-phenanthroline, 1,10-phenanthroline-5,6-dione, and NCS- as ligands all products were mass analyzed by electrospray ionization ion trap MS/MS. The spectra of methanol (MeOH), acetonitrile (ACN), water, and ethanol (EtOH) solutions were collected and the results were compared. It was detected under applied electrospray ionization mass spectrometry (ESI-MS) conditions that MeOH, water, and EtOH formed solvent clusters around the free or complexed 1,10-phenanthroline-5,6-dione. Owing to the solvent-ligand hydrogen-bond formation, the solvent-ligand clusters were formed in the polar protic solvents. The number of protic solvent molecules per complex ion in cluster depended on the number of 1,10-phenanthroline-5,6-dione ligands in the complex ion. Unlike MeOH, EtOH, or water, ACN was not involved in the formation of the solvent clusters with the iron complexes containing 1,10-phenanthroline-5,6-dione as ligand. We also showed that the NCS- group under certain solvent conditions served as a bidentate ligand.     

A computational study on pi and sigma modes of metal ion binding to heteroaromatics (CH)(5-m)X(m) and (CH)(6-m)X(m) (X = N and P): contrasting preferences between nitrogen- and phosphorous-substituted rings

The pi and sigma complexation energy of various heteroaromatic systems which include mono-, di-, and trisubstituted azoles, phospholes, azines and phosphinines with various metal ions, viz. Li(+), Na(+), K(+), Mg(2+), and Ca(2+), was calculated at the post Hartree-Fock MP2 level, MP2(FULL)/6-311+G(2d,2p)//MP2/6-31G. The azoles and azines were found to form stronger sigma complexes than the corresponding pi complexes, whereas the phospholes and phosphinines had higher pi complexation energy with Li(+), Mg(2+), and Ca(2+) while their pi and sigma complexation energies were very comparable with Na(+) and K(+). The strongest pi complex among the five-membered heteroaromatic system was that of pyrrole with all the metals except with Mg(2+), while benzene formed the strongest pi complex among the six-membered heterocyclic systems. The nitrogen heterocyclic system 4H-[1,2,4] triazole and pyridazine formed the strongest sigma complex among the five- and six-membered heteroaromatic systems considered. The complexation energy of the pi and sigma complexes of the azoles and azines was found to decrease with the increase in the heteroatom substitution in the ring, while that of phospholes and phosphinines did not vary significantly. The azoles and azines preferred to form sigma complexes wherein the metal had bidentate linkage, while the phospholes and phosphinines did not show binding mode preference. In the sigma complexes of both azoles and phospholes, the metal binds away form the electron-deficient nitrogen or phosphorus center.     

电喷雾离子化飞行时间质谱研究鸡蛋清溶菌酶与β－环糊精 的新型复合物

运用电喷雾离子化飞行时间质谱分析鸡蛋清溶菌酶与β－环糊精的复合物。通过减少β－环糊精的配制浓度至原来的1/5,发现形成1:2和1:3复合比的溶菌酶-β-环糊精复合物的离丰度减弱,但化学计量比为1:1的复合物变化不大,证明该新型复合物为非特异性非共价复合物。此外还对质谱参数、分析条件对复合物离子化的影响作了详尽的考察,得出在nozzle电压为200V时复合物信号最强,在不影响生物分子高级结构的前提下添加少量的有机溶剂如甲醇、乙腈等能较明显地改善质谱信号。     

Nebulization ionization and desorption ionization analysis of reactive organofunctionalized silanes in nanofilm products

Three different and recently developed desorption ionization techniques, transmission-mode desorption electrospray ionization (TM-DESI), low temperature plasma (LTP) ionization and nano-assisted laser desorption ionization (NALDI), are compared with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) for the analysis of two nanofilm products (NFPs) for surface coating, which contain hydrolysates and condensates of organo-functionalized silanes. The NFPs were characterized in different states from the liquid phase to the fully formed surface film. The LTP spectra were dominated by the silanes, while the corresponding di-, tri- and tetrasiloxanes were common in ESI, APCI and TM-DESI. This indicates readily condensation of the silanes during the ESI and APCI ionization processes leading to the observed siloxanes. NALDI showed larger siloxane structures than the other techniques, indicating film formation on the NALDI target. Real-time monitoring of the film formation on a glass surface by LTP showed a decreasing abundance of the silanes, while the abundances of the di-, tri and tetrasiloxanes increased significantly within the first 100 s. LTP was superior in showing the non-reacted content of the NFPs, while ESI, APCI and TM-DESI were characterized by artefact formation of siloxanes. NALDI was ideal for showing the siloxane structures of the formed film. The applicabilities of each of the ionization techniques were examined, showing the advantage of utilizing more than one ionization technique for the analysis of reactive species.     

Electrospray mass spectrometric studies of noncovalent complexes of buspirone hydrochloride and other serotonin 5-HT(1A) receptor ligands containing arylpiperazine moieties

Noncovalent complexes consisting of two protonated amines and a chloride anion were observed under electrospray ionization mass spectrometry (ESI-MS) conditions. The observed phenomenon was investigated for the hydrochlorides of buspirone, a well-known anxiolytic drug, and 23 other arylpiperazine derivatives that had been developed as serotonin 5-HT(1A) receptor ligands. Due to the major role of ionic interactions in a vacuum, it was proposed that the detected complexes were formed by NH(+)---Cl(-)---NH(+) bridges. It was found that complexation depended on structural features of the analyzed compounds. For derivatives with a shorter linker (three methylene groups) containing a terminal cyclic amide fragment, complex ions were not observed. It was postulated that, in the latter case, steric hindrance due to a terminal group could disturb ionic bridge formation. Since both the observed complexation and ligand-binding processes are driven by noncovalent forces, and a qualitative relationship between them was found (compounds with a 4-carbon chain always display higher affinity for 5-HT(1A) receptors than do their 3-carbon analogues), such ESI-MS studies may yield valuable information on ligand-receptor interactions.     

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.     

Electrospray ionization of alkali and alkaline earth metal species. Electrochemical oxidation and pH effects

The utility of electrospray ionization mass spectrometry (ESI-MS) for characterizing dissolved metal species has generated considerable interest in the use of this technique for metal speciation. However, the development of accurate speciation methods based on ESI-MS requires a detailed understanding of the mechanisms by which dissolved metal species are ionized during electrospray. We report how the analysis of alkali and alkaline earth metal species provides new information about some of the processes that affect electrospray ion yield. Selected metal ions and organic ligands were combined in 50 : 50 water-acetonitrile buffered with acetic acid or ammonium acetate and analyzed by flow injection ESI-MS using mild electrospray conditions. Species formed by alkali metal ions with thiol and oxygen-donating ligands were detected in acidic and neutral pH solutions. Electrochemical oxidation of N, N-diethyldithiocarbamate and glutathione during electrospray was indicated by detection of the corresponding disulfides as protonated or alkali metal species. The extent of ligand oxidation depended on solution pH and the dissociation constant of the thiol group. Tandem mass spectrometric experiments suggested that radical cations such as [NaL](+.) (where L=N,N-diethyldithiocarbamate) can be generated by in-source fragmentation of disulfide species. Greater complexation of alkali metals at neutral pH was indicated by a corresponding decrease in the relative abundance of the free metal ion. The number of alkali metal ions bound by glutathione and phthalic acid also increased with increasing pH, in accordance with thermodynamic equilibrium theory. Alkaline earth metal species were detected only in acidic solutions, the absence of 8-hydroxyquinoline complexes being attributed to their relative instability and subsequent dissociation during electrospray. Hence, accurate speciation by ESI-MS depends on experimental conditions and the intrinsic properties of each analyte. Copyright 2000 John Wiley & Sons, Ltd.     

Mesomorphous structure change by tail chain number in ionic liquid crystalline complexes of linear polymer and amphiphiles

Three polymer-amphiphile complexes were prepared by combining poly(allylamine hydrochloride)(PAH) with the potassium salt of mono-,di-,and trisubstituted benzoic acid dendrons(4-octyloxybenzoic acid,3,5-dioctyloxybenzoic acid,and 3,4,5- trioctyloxybenzoic acid).The solid structure and properties were monitored with FT-IR,XRD,TG,DSC,and polarized optical microscope(POM).Difference in the tail chain number of the dendritic amphiphile induced two different mesomorphous structures: lamella for the mono-,disubstituted dendron containing complexes and hexagonal column for the trisubstituted dendron containing complexes.These corresponded to the ionic thermotropic liquid crystal SmA andΦ_h phases,respectively.This finding is significant for design of functional nanostructures based on the ionic complexation of polymers and amphiphiles.     

Gas-phase binding of non-covalent protein complexes between bovine pancreatic trypsin inhibitor and its target enzymes studied by electrospray ionization tandem mass spectrometry

The potential of electrospray ionization (ESI) mass spectrometry (MS) to detect non-covalent protein complexes has been demonstrated repeatedly. However, questions about correlation of the solution and gas-phase structures of these complexes still produce vigorous scientific discussion. Here, we demonstrate the evaluation of the gas-phase binding of non-covalent protein complexes formed between bovine pancreatic trypsin inhibitor (BPTI) and its target enzymes over a wide range of dissociation constants. Non-covalent protein complexes were detected by ESI-MS. The abundance of the complex ions in the mass spectra is less than expected from the values of the dissociation constants of the complexes in solution. Collisionally activated dissociation (CAD) tandem mass spectrometry (MS/MS) and a collision model for ion activation were used to evaluate the binding of non-covalent complexes in the gas phase. The internal energy required to induce dissociation was calculated for three collision gases (Ne, Ar, Kr) over a wide range of collision gas pressures and energies using an electrospray ionization source. The order of binding energies of the gas-phase ions for non-covalent protein complexes formed by the ESI source and assessed using CAD-MS/MS appears to differ from that of the solution complexes. The implication is that solution structure of these complexes was not preserved in the gas phase.