Mechanistic investigation of the interaction between bisquaternary antimicrobial agents and phospholipids by liquid secondary ion mass spectrometry and differential scanning calorimetry

Heuvel

et al. 2006

Self Cite

The effect of cone voltage (CV) variation on the mass spectral pattern of the bisquaternary ammonium salt decamethoxinum in the electrospray ionization (ESI) mode was studied. The advantage of decamethoxinum as a test compound in ESI mass spectrometry lies in the production of two types of precursor ions, i.e. the doubly charged organic dication Cat 2R and its singly charged cluster with a Cl S counterion, Cat Á Cl R . This makes it possible to monitor the fragmentation patterns of these ions under identical experimental conditions. Pronounced qualitative and quantitative changes in the ESI mass spectra were observed upon a gradual increase of the CV. The model compound decamethoxinum allowed us to reveal the extreme situation, in which the mass spectra at a CV below and over approximately 100 V look quite different, in that they contain different product ions of Cat 2R and Cat Á Cl R . While this effect may be much less pronounced for other classes of organic compounds, it should be properly taken into account for the adequate description of fragmentation pathways of bisquaternary ammonium compounds with ESI. Comparison of ESI, FAB-SIMS and MALDI mass spectra of decamethoxinum shows that taking into account CV effects also permits us to gain information on energy deposition into ions generated with the different ionization techniques. 10,[37][38][39][40][41][42] It is believed that the CV effect is due to an in-source collision-induced dissociation (CID) (up-front CID) process. The initially sprayed charged species can undergo collisions with the residual or bath gas on their path between the nozzle and the skimmer, and the change of the ion velocity caused by CV variation affects their kinetic energy and, consequently, their collision energy. 18The possibility of controlling the charge state of the ions, the desolvation process and the degree of fragmentation of the ions by CV variation offers the prospect of many useful applications of this technique, mainly in studies of supramolecular noncovalent complexes. [25][26][27][28][29][30][31][32][33][34][35][36] For example, a method was suggested for evaluating the stability of chemotherapeutic non-intercalating drugs binding to DNA on the basis of monitoring DNA-drug complex decomposition upon CV increase, which correlates with the thermal decomposition of the complex. 25,26 CV adjustment is also of critical importance in probing the structures of surfactant micelles generated under ESI conditions. 30,31 In-source CID is used along with collision-cell tandem mass spectrometric (MS/MS) CID in studies of protein structures. [19][20][21][32][33][34][35][36] Comparison of in-cell CID and in-source CID 32 permits us to obtain more comprehensive information on the molecular structures of analytes. A method, denoted as energydependent ESI mass spectrometry (EDESI-MS), employing CV variation, has been reported for fragmentation studies of metalloorganic compounds.

Section: Resultsmentioning

confidence: 97%

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confidence: 99%

The effect of cone voltage on electrospray mass spectra of the bisquaternary ammonium salt decamethoxinum

Pashynska

Heuvel

et al. 2006

Self Cite

“…It was decided to compare positive and negative ion LSIMS spectra of cationic and anionic surfactants and their binary mixtures. We selected two bisquaternary ammonium salts, decamethoxinum and aethonium, well studied in our previous works,18–21 as cationic surfactants and the widely used sodium dodecyl sulfate (SDS) as an anionic surfactant. The data obtained were interpreted by applying the notions of surface and colloid chemistry concerning the interfacial EDL.…”

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confidence: 99%

Is there a ‘matrix suppression effect’ under fast‐atom bombardment liquid secondary ion mass spectrometry of ionic surfactants in glycerol?

Chagovets

Shelkovsky

et al. 2007

Some features of a 'matrix suppression effect' caused by ionic surface-active compounds under fast-atom bombardment (FAB) liquid secondary ion mass spectrometry (LSIMS) are being revised. It is shown that abundant transfer of the glycerol matrix molecules to the gas phase does occur under FAB-LSIMS of ionic surfactants, contrary to popular belief. This process can be obscure because of the dependence of the charge state of the glycerol-containing cluster ions on the type of ionic surfactant. It is revealed that, while glycerol matrix signals are really completely suppressed in the positive ion mass spectra of cationic surfactants (decamethoxinum, aethonium), abundant deprotonated glycerol and glycerol-anion clusters are recorded in the negative ion mode. In the case of an anionic surfactant (sodium dodecyl sulfate), on the contrary, glycerol is completely suppressed in the negative ion mode, but is present in the protonated and cationized forms in the positive ion mass spectra. It is suggested that such patterns of positive and negative ion FAB-LSIMS spectra of ionic surfactants solutions reflect the structure and composition of the electric double layer formed at the vacuum-liquid interface by organic cations or anions and their counterions. Processes leading to the formation of the glycerol-containing ions preferentially of positive or negative charge are discussed. The most obvious of them is efficient binding of glycerol to inorganic counterions of the salts Cl S or Na R , which is confirmed by data from quantum chemical calculations. The high content of the counterions and relatively small content of glycerol in the sputtered zone may be responsible for the charge-selective suppression of neat glycerol clusters of opposite charge to the counterions. In the case of a mixture of cationic and anionic surfactants the substitution of inorganic counterions by organic ones was observed. The dependence of the exchange rate in the surface layer is not a linear function of the bulk solution concentration, and an effect of abrupt recharging of the surface can be registered. No both positively or negatively charged pure glycerol and glycerol-inorganic counterion clusters are recorded for the mixture. Correlations between the mass spectrometric observations and some phenomena of surface and colloid chemistry and physics are discussed.

“…In our earlier mass spectrometric study on molecular mechanisms of action of antimicrobial drugs based on bisquaternary ammonium compounds,31 we studied decamethoxinum which has shown strong dependence of the types of several precursor ions produced and of their fragmentation patterns on the desorption/ionization technique applied and on the variation of some experimental parameters within one technique 32. In this connection we have suggested that a more detailed study of this particular compound can contribute to clarification of the mechanism of the fragmentation of bisquaternary compounds and throw light on the question of the stability of the organic dications in the gas phase.…”

mentioning

confidence: 99%

On the stability of the organic dication of the bisquaternary ammonium salt decamethoxinum under liquid secondary ion mass spectrometry

Pashynska

Gömöry

et al. 2005

In the course of a liquid secondary ion mass spectrometric (SIMS) investigation on a bisquaternary ammonium antimicrobial agent, decamethoxinum, unusual pathways of fragmentation of the organic dication M2+ of this bisquaternary salt, with preservation of the doubly charged state of the fragments, were observed. To reveal the structural and electronic parameters of decamethoxinum, which are responsible for the stabilization of its organic dication in the gas phase, a comprehensive SIMS study using metastable decay, collision-induced dissociation and kinetic energy release techniques complemented by ab initio quantum chemical calculations was performed. Pathways of fragmentation of two main precursors originating from decamethoxinum-organic dication M2+ and its cluster with a Cl- counterion [M.Cl]+-and a number of their primary fragments were established and systematized. Differences in the pathways of fragmentation of M2+ and [M.Cl]+ were revealed: the main directions of [M.Cl]+ decay involve dequaternization similar to thermal degradation of this compound, while in M2+ fragmentation via loss of one and two terminal radicals with preservation of the doubly charged state of the fragments dominates over charge separation processes. It was shown that pairing of the dication with a Cl- anion does not preserve the complex from fragmentation via separation of two positively charged centers or neutralization (dequaternization) of one such center. At the same time the low abundance of M2+ in the SIMS spectra is to a larger extent controlled by a probability of M2+ association with an anion than by the decay of the dication per se. Quantum chemical calculations of the structural and electronic parameters of the decamethoxinum dication have revealed at least three features which can provide stabilization of the doubly charged state. Firstly, in the most energetically favorable stretch conformation the distance between the quaternary nitrogens (rN1-N2=1.39 nm) is relatively large. Secondly, an intramolecular solvation of quaternary groups by carbonyl oxygens of the adjacent groups of the dication occurs, which contribute to structural stabilization. Thirdly, an important feature of the electronic structure of the dication is the presence of a partial negative charge on the nitrogen atoms and smearing of a positive charge mainly over the hydrogens of alkyl groups attached to the quaternary nitrogens, which reduces the net repulsion between the quaternary groups. The possible influence of charge smearing on the kinetic energy released on the dication fragmentation is discussed.