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Cyclic peptide structures of the type -Lys-R1—Rn-Glu- can be synthesized on the Merrifield resin by assembling the peptide chain using Nα-Fmoc-amino acids and Boc and tert.-butyl protection for the side-chains of Lys and Glu, respectively. If residues R1 to Rn contain side-chain functional groups, TFA-resistant protection is required. After TFA treatment cyclization on the resin can be performed with appropriate coupling reagents. The formation of such cyclic structures may be preceded or followed by peptide chain assembly using Nα-Boc-amino acids and the entire peptide chain containing the cyclic portion is finally cleaved by HF treatment. Using this principle we synthesized the following opioid peptide related cyclic analogs: H-Tyr-d-Lys-Gly-Phe-Glu-NH2 (I), H-Tyr-Lys-Gly-Phe-Glu-NH2 (II), H-Tyr-d-Lys-Phe-Glu-NH2 (III), H-Tyr-d-Glu-Gly-Phe-Lys-NH2 (IV), H-Tyr-d-Glu-Phe-Lys-NH2 (V), H-Tyr-d-Orn-Gly-Glu-NH2 (VI) and H-Tyr-d-Ala-Lys-Phe-Glu-NH2 (VII). Cyclic monomers were obtained in all cases, as demonstrated by mass spectrometry. Analysis of side-products revealed a slow-down of the HF deprotection of O-benzylated tyrosine as a consequence of hydrophobic interactions as well as the formation of a side-chain-linked antiparallel cyclic dimer in the case of compound VI. In conclusion, the described method permits the convenient preparation of peptide analogs cyclized via amide bond formation between side-chain amino and carboxyl groups in reasonable yield.

We describe the characterization of the B-type procyanidins in wine and the B-type dehydrodicatechins (dimeric flavan-3-ols) obtained for the autoxidation of (+)-catechin and (-)-epicatechin by tandem mass spectrometry (MS/MS) coupled to reversed-phase high-performance liquid chromatography (HPLC). The MS/MS analysis demonstrates that the interesting major fragments derive from the dissociations of the C-ring on the catechin or epicatechin unit, such as retro-Diels-Alder reactions. The two kinds of dimers give completely different fragmentations because of the striking effect of the C-C interflavan linkage (IFL). For the natural dimers in wine, a catechin or epicatechin unit linking to the C-4 position stabilizes the product ions by forming a large pi-pi hyperconjugated system, whereas a similar pi-pi system is formed within dehydrodicatechin B through the C-C IFL. Thus dissociation in MS/MS experiments was inhibited. Apparently, the fragmentations of the dimers differ from that of the monomer, which is very important in the study of the gas-phase ion behaviour of the polymeric flavan-3-ols. In addition, two specific fragment ions at m/z 451 for native dimers and at m/z 393 for autoxidation species in HPLC/MS/MS were found to be very useful for analysing mixtures of B-type procyanidins and B-type dehydrodicatechins in food and beverages.

A detailed study of the solution chemistry and mass spectrometry of six carboxylato-organogermanium compounds in aqueous solution has been carried out using electrospray ionization and MSn techniques. The different types of hydrolysis products and their probable structures, which include the oligomers and their fragment ions plus water adduct ions formed by ion-molecule reactions, are presented, e.g., HO-cyclic-(-Ge(O−)CH2CH2COO) A, HO-cyclic-(-Ge(O-cyclic-(Ge(O−)CH2CH2COO)CH2CH2COO) B, −OGeO-cyclic-(-Ge(OH)CH2CH2COO) C, and −CH=CHGeO-cyclic-(-Ge(OH)CH2CH2COO) D, etc. The proposed cyclic structures are confirmed by theoretical calculations. Copyright © 2001 John Wiley & Sons, Ltd.

Complexation of aluminum ions {Al(III) in glycerol} with α-amino acids has been studied by FAB mass spectrometry. Twelve α-amino acids and cysteine methyl ester interact with different Al(III)-containing ions and form several cluster ions such as [M+117]+, [117={A1(III)+glycerol−2H}]; [M+231]+, [231={Al(III)+glycerol+ trifluoroacetic acid−2H}]; [M+233]+, [233={2Al(III)+2glycerol−5H}]; [2M+Al−2H]+ and [2M+117]+. Fragmentation of these adduct ions led to the formation of mainly metal-containing product ions. Fragmentation pathways were demonstrated with the help of the dissociation of Leu-d3, His-d4, Tyr-d4, Ser-d4, Cys-d4 and Cys methyl ester-d3 ion complexes in glycerol-d3. Aliphatic, aromatic and α-amino acids possessing functional side chains show differences in the fragmentation of [M+117]+ ions. Fourteen peptides of different chain lengths (two through six amino acids) also form adducts with Al(III)-glycerol. Dissociation of these complex ions, especially [M+Al−2H]+ ions provides information about side-chain functional groups and some sequence information. The site of the metal-ion interaction is mostly at the amide nitrogens.

The fast atom bombardment (FAB)mass spectra of a series of dinucleotide analogs, compounds 1-8 with alkaline earth metal chlorides (CaCl 2 , MgCl 2 , SrCl 2 and BaCl 2 ) were studied in a thioglycerol matrix. The positive-ion FAB mass spectra of 1-8 with CaCl 2 gave [M + Ca - H] + , [M + CaCl] + and [M + Ca 2 Cl - 2H] + ions. The formulae of [M + Ca - H] + and [M + Ca 2 Cl - 2H] + ions from 2 were confirmed with high-resolution measurements. Compounds 1-8 with alkaline earth metal ions also give metal chelated dimerized species [2M + Ca 3 Cl - 4H] + , [2M + Ca 2 - 3H] + and [2M + Ca - H] + ], a process which is independent of the size of the polyether chain. The negative-ion FAB spectra also produce bimetallic ions with all substrates studied. Experiments with D 2 O addition using CaCl 2 with compounds 2 and 6 suggested the elimination of acidic protons (amide and/or amine) in the formation of [M + Met x Cl y - nH) ions in either positive or negative modes. The site of the metal chelation was the same in both positive-and negative-ion mass spectra. The collision-activated dissociation data suggest the covalent bonding of the metal to the nitrogen base and coordination with the polyether chain.

The electron impact (EI) mass spectra of alkyltriphenylphosphonium and alkyltriphenylarsonium salts were compared with fast atom bombardment (FAB) mass spectra in a 3-nitrobenzyl alcohol matrix. It is clearly demonstrated that FAB is an effective ionization method compared with EI for analysis of these non-volatile and thermally labile compounds, particularly triphenylarsonium salts. In FABMS, the spectra generally show the intact cations (C+) as the base peaks, in addition to the singly charged cluster ions (C2A)+. High-resolution mass spectrometry was used to determine the elemental composition of the ions at m/z 277 for some phosphonium salts in the EI mode and the results show that the formation of (O(double bond)PPh3 − 1)+ (m/z 277) involves an oxygen rearrangement as a possible reaction pathway. B/E linked scans of the intact cations of triphenylarsonium salts generated by FABMS were studied in detail both to illustrate the dissociation pathways and to compare the reaction mechanism with that occurring for triphenylphosphonium salts.

In this paper we report our studies of reduction phenomena in a high performance liquid chromatography/particle beam interface-mass spectrometer system (HPLC/PB-MS). It is shown that reduction takes place in the ion source of the mass spectrometer, but that the particle beam interface plays an important role in the reduction process since the HPLC mobile phase is involved in the reduction. HPLC flow rate and desolvation-chamber temperature have significant effects on the reduction extent, while ion-source temperature has only a minor effect. All the nitro compounds and sulfoxides tested in this work showed reduction in the system. There was no observed reduction for sulfones. 1,4-Naphthaquinone showed significant reduction, while no reduction was observed for anthraqunone.

The tris(acetylacetonate) (L3) and tris(1,1,1-trifluoromethyl-2,4-pentanedionate) (L′3) complexes of transition metals V, Cr, Mn, Fe, Co, Ru and Os in their +3 oxidation states were studied under fast-atom bombardment (FAB) conditions using 3-nitrobenzyl alcohol as a matrix. All complexes showed the formation of molecular ion and protonated molecules [ML2]+ and [ML′2]+ are the most abundant ions in the spectra of all the metal acetylacetonates (L) and trifluoroacetylacetonates (L′) studied. Interaction of matrix with metal complexes and polynuclear metal complexes led to the formation of polynuclear species with significant abundance especially for manganese and iron complexes. Formation of these metal ions was observed with relative intensities from 3–30%. Ions corresponding to ligand-exchange reactions were observed with moderate to high abundance in all metal complexes studied except those of ruthenium and osmium. Experiments carried out with a split FAB probe tip suggested ligand–ligand exchange reactions were not due to gas-phase reactions but only due to solution-phase exchanges. Osmium and ruthenium complexes do not yield polynuclear species or ions due to matrix clustering. Instead they show neutral ligand losses and formation of acetyl ion.

Various methods of suppression of the reduction process occurring in fast-atom bombardment (FAB) mass spectrometry have been studied, using the organic dyes rhodamine B and methylene blue as reference compounds. Our results indicate that transition metal chlorides have a strong influence on the suppression of the reduction process, while stannous chloride exhibits a remarkable suppression effect despite being a strong reducing agent. We suggest that the metal radicals generated in glycerol solution are responsible for these suppression effects. This phenomenou strongly supports the mechanism of hydrogen radical addition to the substrate molecules, postulated earlier as the cause of the reduction process. Co-solvents in the matrix have also been found to suppress the reduction ions along with other matrix-interfering ions. These studies help shed some light on the FAB ionization mechanism.

In this Communication we report, for the first time, a direct method for the determination of benomyl (methyl [1-(butylcarbamoyl)-1H-benzimidazol-2-yl]carbamate) in wettable powder formulations by fast-atom bombard-ment mass spectrometry (FAB-MS). Solutions of desired concentrations of benomyl were prepared in 5 M hydrochloric acid. The matrix compound, glycerol, was added at 10% (v/v) to these solutions for obtaining FAB mass spectra. The results of the analysis of wettable powder samples, carried out by FAB-MS, compared well (p > 0.05) with those obtained by reversed-phase high performance liquid chromatography.

ZnF2, CdF2, and CuF2 have been adsorbed onto the surface of montmorillonite K10, and the infrared and 19F, 27Al, and 29Si MAS NMR spectra of the resulting reagents over a range of loadings and activation temperatures have been obtained. CuF2 was observed to attack the SiO2 layer and form the complex CuSiF6, ZnF2 tends to attack the aluminium oxide layer, in which Zn isomorphously replaces Al, and forms AlF3 and AlF4− complexes. The spectroscopic evidence rules out the formation of any Al–F and (or) Si–F species as CdF2 is adsorbed on the surface of montmorillonite K10. The reactivity of MF2–K10 reagents towards the Friedel–Crafts reaction of benzene with benzyl chloride varies from one reagent to another. ZnF2–K10 was observed to be the most reactive and CuF2 was the least reactive.

The relative metal ion (Ni+, Co+, CoCl+) affinities of twelve alkylamines have been estimated using Cooks' kinetic method in a FAB mass spectrometer. The results are compared with proton affinities and with two-ligand dissociation enthalpies. An approximate ordering for the relative metal ion affinities of the amines is given and discussed. The RNH2-Ni+ bond is found to be slightly weaker than RNH2-CoCl+ but stronger than RNH2-Co+. The effective temperature (T) of the metal-bound dimer ions may fall in the range 298 K ≤ T

The relative metal ion (Ni+ and Co+) affinities of 14 alkanenitriles, alkenenitriles and benzonitrile were estimated using Cooks' kinetic method in a fast atom bombardment mass spectrometer. The results are compared with proton affinities, affinities for other metal ions, two-ligand dissociation enthalpies and the dipole moments of the nitriles. The RCNCo+ bond is found to be close to the RCNNi+ bond but weaker than the RCNAl+ bond. The effective temperature (T) of the metal-bound dimer ions falls in the range 298 K < T < 400 K.

The formation of transition-metal ion (M+Fe+, CO+, Ni+ and Mn+) complexes with cyclohexylamine (1) in a modified fast-atom bombardment (FAB) source, and the reactions of various ion/molecule complexes, have been studied by FAB MASS spectrometry combined with metastable ion and collisional activation techniques. Multiples dehydrogenations to produce [(aniline)·M]+ and consecutive [2H2+NH3] elimination to afford [(benzene)·M]+ from 1 prevail for all the metal ions studied. Furthermore, [(1)·][Ni]+ and [(1)2·Co]+ ions underwent an unusual NH3 loss. Relative reactivities of the metal ions and complicated ligand effects are presented.

The relative CoCI+ ion affinities of six alkylnitriles have been estimated using Cooks' kinetic method in mass spectrometer using fast-atom bombardm ent ionization. An approximate ordering for the relative affinities is given and discussed.

Trifluoromethylthiocopper(I) has been readily prepared from the silver analogue, using a metathetical reaction with copper(I) bromide. Homogeneous CuSCF 3 and the supported reagent CuSCF 3 -alumina have been compared in their reactivity towards aryl iodides, in order to form trifluoromethylaryl sulphides in good yields.

The Mass spectral fragmentation processes for a number of alkyl and aryl subtituted phosphinyl and phosphonyllk halides and their thio analogs are discussed with respect to two intramolecular rearrangment processes. The first is aryl fluorine transfer to phosphorus and the second concerns a rearrangement depicted as follows, i.e. a reverse Arbuzov reaction RR′XPS→RXPSR′. Both pathways are supported by evidence obtained form metastable ions and mass analyzed ion kinentic energay spectra. The previously observed phenomenon of subtituent coupling is also describedc where ita occurs in the phosphinyl compounds. The mass spectra of a number of mixed fluoro-pebtafkuorophenyl phosphorances are also discussed.

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

Analyses of a series of nitroaromatic compounds using fast atom bombardment (FAB) mass spectrometry are discussed. An interesting ion-molecule reaction leading to [M + O − H]− ions is observed in the negative ion FAB spectra. Evidence from linked-scan and collision-induced dissociation spectra proved that [M + O − H]− ions are produced by the following reaction: M + NO2− [M + NO2]− [M + O − H]−. These experiments also showed that M−˙ ions are produced in part by the exchange of an electron between M and NO2− species. All samples showed M−˙, [M − H]− or both ions in their negative ion FAB spectra. Not all analytes studied showed either [M + H]+ and/or M+˙ in the positive ion FAB spectra. No M+˙ ions were observed for ions having ionization energies above ∼9 eV.

The Fast Atom Bombardment (FAB) mass spectra of the alkali metal chlorides (Na, K, Cs) and fluorides (Na, K, Rb, Cs) were obtained from solids and a glycerol matrix, using a fast atom bombardment source. From solids the fluorides exhibited an ion abundance enhancement of the well-known [M(MF)4]+ cluster, which decreased with increasing cation size. A gradual decrease in the n=4 enhancement was observed as the salt was diluted with glycerol. In the chlorides only sodium chloride showed the n=4 relative enhancement. The mass spectra of the salts from a glycerol matrix at molar ratios of 1:1 to 1:10 showed that the spectra of the 1:1 solutions were similar to those from the solids, while glycerol adducts were found to increase with increasing glycerol concentration. A [M(MX)n(gly)]+ species that featured successive losses of HX was observed. It has not been established whether HX losses take place in solution, in the surface/vacuum interface and/or whether gas phase reactions might be responsible for the observation of the [M(MX)n(gly)–y HX]− species in the mass spectra of the MX/glycerol system.

The mass spectra of a series of ortho, meta and para substituted isopropyl benzene derivatives have been determined where the second substituent is COOH, C(O)NH2, C(O)C6H5, C(Ph)(=NPh) or CH(Ph)(NHPh). Two bis-isopropylbenzophenones have also been studied. The spectra are characterized by prominent ortho effects which distinguish the ortho derivatives from the meta and para.

The metastable ion supported fragmentations and fluorine transfer rearrangements of a series of fluoroaromatic heterocyclic derivatives of silicon, germanium and tin are reported. Of particular interest is the unique loss of neutral SiF4 from the parent ion of (C12F8)Si yielding the [C24F12]+˙ ion. These and similar rearrangements are discussed and structures are proposed for some of the ions observed. The general case of cyclic rearrangement intermediates prior to the loss of neutral metal fluorides from perfluoroaromatic derivatives is discussed. Losses of neutral metal fluorides from the parent ions appear to involve a species with increased co-ordination number about the central atom as an intermediate. In addition to (C12F8)2M, the following compound types were studied: (C6H5)2Ge(C12F8), (C12F8S)2M and R4Sn2(C6F4)2 (where M = a Group IV metal and R = CH3 or C6H5).

Nucleoside base analogs in which fluoro substituents replace the enolic hydroxy groups of uracil, thymine and cytosine have been prepared. Improved methods for the preparation and isolation of the known 2,4-di-fluoropyrimidine, 2,4-difluoro-6-methylpyrimidine and the new 2,4-difluoro-5-methylpyrimidine, 2-fluoro-4-aminopyrimidine, 4-fluoro-2-aminopyrimidine, and other alkylaminofluoropyrimidines are described.

Mass and NMR spectral data are presented for a number of dodecafluoro-1,6-disubstituted triptycenes. The epoxide OAs2(C6F4)2 can be made by heating together arsenic (As), arsenic(III) oxide (As2O3) and 1,2-di-iodotetrafluorobenzene (1,2-I2C6F4) in a sealed tube. The molecular structure of As2(C6F4)3 has been confirmed by X-ray crystallography.

The mass spectra of the compounds C12F8M2 (M = S, Se), (I), C12F8M (M = S, Se, Te), (II) and C12F8SX2 (X = Br, I), (III), have been measured. Results indicate that sulfur-carbon bonds are more stable under electron bombardment than either selenium-carbon or tellurium-carbon bonds. Numerous metastable-supported transitions are evident, which are incorporated into comprehensive fragmentation schemes for these compounds. Many metastable transitions, not previously reported, were observed for the fluorocarbon fragments and a fragmentation scheme is reported. The bromine and iodine-containing compounds behave remarkably like the heterocyclic systems, I and II, presumably due to initial loss of Br2 or I2 to form a ring system of type II.

The mass spectra of several perfluoroaromatic nitrogen compounds, including primary and secondary amines, diamines, nitriles, hydrazines, azines and azo compounds, are presented. Fragmentation patterns of these compounds are described and the data are discussed in terms of comparisons amongst perfluoroaromatic nitrogen compounds, and with reference to the hydrogen substituted analogs, or to oxygen and sulfur analogs of a particular compound.

The uracil analog, 4-fluoro-2-pyridone was synthesized by ether cleavage of 4-fluoro-2-methoxypyridine with trimethylsilyl iodide. Improved procedures for the preparations of 2-methoxypyridine N-oxide hydrochloride and 2-methoxy-4-nitropyridine N-oxide are described.

Die Chinolinolato-Hg-Chelatkomplexe (I) werden durch Umsetzung von fluorierten Phenyl- Hg-chloriden mit Tl-chinolinolat oder von Methyl- bzw. Phenyl-HgOH mit Chinolinol oder seinem 2-Methyl-Derivat in Methanol dargestellt.

Tetraethylammonium fluoride in dimethylformamide promotes the alkylation of phenols with alkyl iodides and benzyl chloride to provide good yields of alkyl phenyl ethers. A number of phenols have be...

Solutions of alkali metal fluorides in aliphatic diols or carboxylic acids have been investigated by 19F n.m.r. at concentrations of ca. 0.5 mol kg–1 and greater. Heats of association of potassium fluoride with ethane-1,2-diol and methanoic acid are obtained from variable-temperature n.m.r. studies. The nature of the strong hydrogen bond and its influence on the n.m.r. spectra are discussed.

The powerful hydrogen bond electron donor fluoride ion assists the O-alkylation of 2-naphthols but inhibits the autoxidation of 1-alkyl-2-naphthols. These observations may be explained in terms of the nature of the OHF− hydrogen bond.

Charcoal supported copper(I) thiocyanate can be used to convert bromo- and iodo-benzenes into phenyl thiocyanates with no contamination from phenyl isothiocyanates.

Fast atom bombardment mass spectrometry (FABMS) has been used to investigate the hydrogen-bonding of pyridinium and trialkylammonium ions with a range of electron donors. We have studied the effects of matrix liquid, concentration, nature of the anion, and strength of the hydrogen-bond on the observed intensity of the complex peak. The results may be easily rationalized in hydrogen-bonding terms and are in excellent agreement with those of more ‘conventional’ techniques such as i.r. spectroscopy.

Reaction of tris(pentafluorophenyl)phosphine with various nucleophiles (DMF, HMPA, HEPA, diethylformamide, hydrazine, UDMH, phenylhydrazine, formamide, and aniline) gave exclusively the replacement...

The rhodium(I) carboxylates,trans-RhO2CR(CO)(PPh3)2 (R = C6F5, C6Cl5,p-HC6F4,m-HC6F4,o-HC6F4,p-McOC6F4, 4,5-H2C6F3, 3,5-H2C6F3, or 2,6-F2C6H3, have been prepared by reaction of RhH(CO)(PPh3)3 with the appropriate polyhalogenobenzoic acids in ethanol and/or by reaction oftrans-RhCl(CO)(PPh3)2 with the appropriate thallous carboxylates in benzene. Decarboxylations with formation of polyhalogenoarylrhodium(I) compounds,trans-RhR(CO)(PPh3)2 (R = C6F5, C6Cl5,p-HC6F4,m-HC6F4,p-MeOC6F4, 4,5-H2C6F3 or 3,5-H2C6F3), have been achieved either by decomposition of the corresponding rhodium(I) carboxylates in pyridine or by reaction oftrans-RhCl(CO)(PPh3)2 and the thallous carboxylates in pyridine, but the derivatives R =o-HC6F4 or 2,6-F2C6H3 could not be obtained by this method. The rate of decarboxylation decreased in the sequence R = C6F5 >p-MeOC6F4 >p-HC6F4 >m-HC6F4 > 4,5-H2C6F3 > 3,5-H2C6F3.

The hydrogen-bonded solvates formed between tetraethylammonium fluoride and a number of β-dicarbonyl compounds react at about room temperature with alkyl iodides to provide high yields of the mono-C-alkylated β-dicarbonyl products with no apparent contamination due to the formation of O-alkyl, dialkyl, or polymerisation products.