Evaluation of metal complexation as an alternative to protonation for electrospray ionization of pharmaceutical compounds

Alvarez, Erwin J.; Brodbelt, Jennifer S.

doi:10.1016/s1044-0305(98)00007-5

Cited by 49 publications

(50 citation statements)

References 40 publications

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“…Due to our previous studies in this area [53][54][55][56][57][58], 2,2Ј-bipyridine was selected as the first auxiliary ligand and CoBr 2 was used as the metal salt. For the flavonoids, acidic sites that may be deprotonated in solution and are adjacent to a second binding site (i.e., another oxygen atom) are the likely chelation sites for the metal ions.…”

Section: Metal Complexationmentioning

confidence: 99%

“…Although deprotonation results in more intense mass spectra in the negative ESI mode, the fragmentation patterns again frequently do not differentiate similar compounds or isomers. Metal complexation is an alternative ionization mode which has been explored in the Brodbelt group in the past [53][54][55][56][57][58]. It has been observed that metal complexation can both increase ion intensity and alter fragmentation pathways, resulting in many more structurally distinctive fragment ions.…”

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confidence: 99%

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Differentiation of flavonoid glycoside isomers by using metal complexation and electrospray ionization mass spectrometry

Pikulski

Brodbelt

2003

J. Am. Soc. Mass Spectrom.

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The elucidation of flavonoid isomers is accomplished by electrospray ionization tandem mass spectrometry (ESI-MS/MS) via formation and collisional activated dissociation (CAD) of metal/flavonoid complexes containing an auxiliary ligand. Addition of a metal salt and a suitable neutral auxiliary ligand to flavonoids in solution results in the formation of [M(II) (flavonoid-H) ligand]+ complexes by ESI which, upon collisional activated dissociation, often result in more distinctive fragmentation patterns than observed for conventional protonated or deprotonated flavonoids. Previously, 2,2'-bipyridine was used as an auxiliary ligand, and now we compare and explore the use of alternative pyridyl ligands, including 4,7-diphenyl-1,10-phenanthroline. Using this technique, three groups of flavonoid glycoside isomers are differentiated, including glycosides of apigenin, quercetin, and luteolin.

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Section: Metal Complexationmentioning

confidence: 99%

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confidence: 99%

Differentiation of flavonoid glycoside isomers by using metal complexation and electrospray ionization mass spectrometry

Pikulski

Brodbelt

2003

J. Am. Soc. Mass Spectrom.

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“…We have reported previously on the formation and dissociations of ternary complexes with Cu 2+ and diimine ligands of amino acids19–22 and several dipeptides 23–25. Ternary complexes of other biomolecules containing polar groups have also been studied by mass spectrometry and found to be useful for structure elucidation 26–29. The complexes self‐assemble in aqueous methanol solution upon mixing peptides with Cu 2+ salts and 2,2′‐bipyridine (bpy) or 1,10‐phenanthroline (phen) and provide abundant gas‐phase ions by electrospray ionization (ESI)30 that are analyzed by tandem mass spectrometry.…”

Section: Introductionmentioning

confidence: 99%

Sequence information, distinction and quantitation of C‐terminal leucine and isoleucine in ternary complexes of tripeptides with Cu(II) and 2,2′‐bipyridine

et al. 2001

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Tripeptides form ternary complexes with Cu(2+) and 2,2'-bipyridine (bpy) that self-assemble upon mixing the components in aqueous methanol solution. Electrospray ionization (ESI) of the complex solutions provides abundant singly charged [Cu(peptide -- H)bpy](+) and doubly charged [Cu(peptide)bpy](2+) ions. Collision-induced dissociation (CID) at low ion kinetic energies of several tripeptides, AGG, GGA, LGG, GGL, GGI, FGG, GGF, LGF, GLF, GFL, GYA and GAY, showed fragments that were indicative of the amino acid sequence in the peptide. In addition, CID of single and doubly charged complexes of isomeric tripeptides GGL and GGI provided unambiguous distinction of the isomeric leucine and isoleucine residues. Leucine peptides eliminated C(3)H(7) radicals from the amino acid side-chain whereas isoleucine eliminated C(2)H(5) radicals. CID of gas-phase doubly charged peptide complexes in a quadrupole ion trap produced a series of singly charged sequence fragments that following isolation and further CID furnished distinct fragments that allowed quantitation of leucine and isoleucine-containing peptides in mixtures.

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“…A number of groups have studied metal complexes by mass spectrometry and found that the fragmentation pathways of analytes can be significantly altered, allowing new opportunities for structural determination [55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71]. The Brodbelt group has shown that metal complexation combined with the use of a neutral auxiliary ligand dramatically increases sensitivity for detection of flavonoids while also providing a richer array of fragments to aid in isomer differentiation [50 -52, 72].…”

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Determination of the glycosylation site of flavonoid monoglucosides by metal complexation and tandem mass spectrometry

Davis

Brodbelt

2004

J. Am. Soc. Mass Spectrom.

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Metal complexation and tandem mass spectrometry were used to differentiate C-and O-bonded flavonoid monoglucoside isomers. Electrospray ionization of solutions containing a flavonoid glycoside and a metal salt led to the generation of the key [M(II) (L) (L-H)] ϩ complexes, where M is the metal ion and L is the flavonoid glycoside. Thirteen flavonoid monoglucosides were examined in combination with Ca(II), Mg(II), Co(II), Ni(II), and Cu(II). Collisional activated dissociation (CAD) of the [M(II) (L) (L-H)] ϩ complexes resulted in diagnostic mass spectra, in contrast to the CAD mass spectra of the protonated, deprotonated, and sodium-cationized flavonoid glucosides. Five common sites of glycosylation could be predicted based on the fragmentation patterns of the flavonoid glucoside/magnesium complexes, while flavonoid glucoside/calcium complexes also were effective for location of the glycosylation site when MS 3 was employed. Cobalt, nickel and copper complexation had only limited success in this application. The metal complexation methods were also applied for characterization of a flavonoid rhamnoside, and the dissociation pathways of the metal complexes indicate that flavonoid rhamnosides have distinctive dissociation features from flavonoid glucosides. (J Am Soc Mass Spectrom 2004, 15, 1287-1299

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Evaluation of metal complexation as an alternative to protonation for electrospray ionization of pharmaceutical compounds

Cited by 49 publications

References 40 publications

Differentiation of flavonoid glycoside isomers by using metal complexation and electrospray ionization mass spectrometry

Differentiation of flavonoid glycoside isomers by using metal complexation and electrospray ionization mass spectrometry

Sequence information, distinction and quantitation of C‐terminal leucine and isoleucine in ternary complexes of tripeptides with Cu(II) and 2,2′‐bipyridine

Determination of the glycosylation site of flavonoid monoglucosides by metal complexation and tandem mass spectrometry

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