Charged supramolecular assemblies of surfactant molecules in gas phase.

The aim of this review is to critically analyze recent literature on charged supramolecular assemblies formed by surfactant molecules in gas phase. Apart our specific interest on this research area, the stimuli to undertake the task arise from the widespread theoretical and applicative benefits emerging from a comprehensive view of this topic. In fact, the study of the formation, stability, and physicochemical peculiarities of non-covalent assemblies of surfactant molecules in gas phase allows to unveil interesting aspects such as the role of attractive, repulsive, and steric intermolecular interactions as driving force of supramolecular organization in absence of interactions with surrounding medium and the size and charge state dependence of aggregate structural and dynamical properties. Other interesting aspects worth to be investigated are joined to the ability of these assemblies to incorporate selected solubilizates molecules as well as to give rise to chemical reactions within a single organized structure. In particular, the incorporation of large molecules such as proteins has been of recent interest with the objective to protect their structure and functionality during the transition from solution to gas phase. Exciting fall-out of the study of gas phase surfactant aggregates includes mass and energy transport in the atmosphere, origin of life and simulation of supramolecular aggregation in the interstellar space. Moreover, supramolecular assemblies of amphiphilic molecules in gas phase could find remarkable applications as atmospheric cleaning agents, nanosolvents and nanoreactors for specialized chemical processes in confined space. Mass spectrometry techniques have proven to be particularly suitable to generate these assemblies and to furnish useful information on their size, size polydispersity, stability, and structural organization. On the other hand molecular dynamics simulations have been very useful to rationalize many experimental findings and to furnish a vivid picture of the structural and dynamic features of these aggregates. Thus, in this review, we will focus on the most important achievements gained in recent years by both these investigative tools.

Micelles of the chiral biocompatible surfactant (1R,2S)-dodecyl(2-hydroxy-1-methyl-2-phenylethyl)dimethylammonium bromide (DMEB): molecular dynamics and fragmentation patterns in the gas phase.

RATIONALE: The study of self-assembly processes of surfactant molecules in the gas phase is of great interest for several theoretical and technological reasons related to their possible exploitation as drug carriers, protein shields and cleaning agents in the gas phase. METHODS: The stability and fragmentation patterns of singly and multiply charged (either positively or negatively) aggregates of the surfactant (1R,2S)-dodecyl(2-hydroxy-1-methyl-2-phenylethyl)dimethyl ammonium bromide (DMEB) in the gas phase have been studied by ion mobility mass spectrometry and tandem mass spectrometry. Molecular dynamics (MD) simulations of positively and negatively singly and multiply charged DMEB aggregates have been performed to obtain structural and energetics information. Finally, in order to ascertain some clues on the DMEB growth mechanism, quantum mechanics calculations were carried out. RESULTS: It has been evidenced that positively and negatively singly charged aggregates at low collision energy decompose preferentially by loss of only one DMEB molecule. Increasing the collision energy, the loss of neutrals becomes increasingly abundant. Multiply charged DMEB aggregates are unstable and decompose forming singly charged monomers or dimers. MD simulations show reverse micelle-like structures with polar heads somewhat segregated into the aggregate interior. Finally, a good correlation between experimental and calculated collisional cross sections (CCS) was found. CONCLUSIONS: The fragmentation pathways of DMEB charged species evidenced for singly charged aggregates exhibit features similar to that of other detergent aggregates, but multiply charged aggregates showed a system-specific behavior. QM calculations on the optimized structures (21+ , 31+ , 11- and 21- ) indicate that the most determinant interactions are due to an OH---Br hydrogen bonding that is also involved in the link between monomeric DMEB units. The MD models gave CCS values in good agreement with experimental ones, evidenced by a less strict reverse micelle-like structure and a reasonably spread bromine anion distribution Copyright © 2017 John Wiley & Sons, Ltd.

Molecular dynamics and metadynamics simulations of electrosprayed water nanodroplets including sodium bis(2-ethylhexyl)sulfosuccinate micelles.

The behavior of aqueous solutions of sodium bis(2-ethylhexyl)sulfosuccinate (AOTNa) under conditions of electrospray ionization (ESI) has been investigated by molecular dynamics (MD) and well-tempered metadynamics (WTM) simulations at 300 K and 400 K. We have examined water droplets with initial fixed numbers of water molecules (1000) and AOT- anions (100), and with sodium cations in the range of 70-130. At 300 K, all charged droplets show the water evaporation rate increasing with the absolute value of the initial droplet charge state (Z), accompanied by ejection of an increasing number of solvated sodium ions or by expulsion of AOT- anions depending on the sign of Z and by fragmentation in the case of high |Z|. At 400 K, the water evaporation becomes more rapid and the fission process more extensive. In all cases, the AOTNa molecules, arranged as a direct micelle inside the aqueous system, undergo a rapid inversion in vacuo so that the hydrophilic heads and sodium ions surrounded by water molecules move toward the droplet interior. At the end of the 100-ns MD simulations, some water molecules remain within the aggregates at both temperatures. The subsequent metadynamics simulations accelerate the droplet evolution and show that all systems become anhydrous, in agreement with the experimental results of ESI mass spectrometry. This complete water loss is accompanied by sodium counterion emission for positively charged aggregates at 300 K. The analysis shows how the temperature and droplet charge state affect the populations of the generated surfactant aggregates, providing information potentially useful in designing future ESI experimental conditions.

Electrospray ion mobility mass spectrometry of positively and negatively charged (1R,2S)-dodecyl(2-hydroxy-1-methyl-2-phenylethyl)dimethylammonium bromide aggregates.

RATIONALE: Self-assembling processes of surfactants in the gas phase constitute a developing research field of interest since they allow information to be gained on the peculiar structural organization of these aggregates, on their ability to incorporate from small molecules up to proteins and on their possible use as carriers of drugs in the gas phase or as cleaning agents and exotic reaction media. METHODS: The mass spectra of charged aggregates of the chiral surfactant (1R,2S)-dodecyl(2-hydroxy-1-methyl-2-phenylethyl)dimethylammonium bromide (DMEB) in the gas phase have been recorded using a Synapt G2-Si mass spectrometer in the positive and negative ion mode. For comparison purposes, the mass spectra of sodium bis(2-ethylhexyl)sulfosuccinate and sodium octane sulfonate aggregates have also been recorded under the same experimental conditions. The collisional cross sections of positively and negatively charged DMEB aggregates were obtained through an appropriate calibration of the measured drift times. RESULTS: For all the surfactants investigated, it has been found that there is a lowest and a highest limit of the aggregation number at each charge state: no aggregates are found outside this range. Moreover, the occurrence at each aggregation number and extra charge of a unique value of drift time points toward aggregates whose conformations do not show discernible shape change in the experiment time scale. The analysis of the collisional cross sections emphasizes that the DMEB aggregates are nearly spherical clusters somewhat affected by the charge state and constituted by interlaced polar and apolar domains. CONCLUSIONS: The analysis of all the experimental findings indicates that in the gas phase DMEB forms supramolecular aggregates characterized by an internal organization whose stability is triggered by the charge state. The comparison of the behavior of DMEB aggregates with that of sodium bis(2-ethylhexyl)sulfosuccinate and sodium octane sulfonate aggregates allows us to highlight the effects on the aggregate organization in gas phase due to nature of the head group and alkyl chain steric hindrance.

Structural organization of surfactant aggregates in vacuo: a molecular dynamics and well-tempered metadynamics study.

Experimental investigations using mass spectrometry have established that surfactant molecules are able to form aggregates in the gas phase. However, there is no general consensus on the organization of these aggregates and how it depends on the aggregation number and surfactant molecular structure. In the present paper we investigate the structural organization of some surfactants in vacuo by molecular dynamics and well-tempered metadynamics simulations to widely explore the space of their possible conformations in vacuo. To study how the specific molecular features of such compounds affect their organization, we have considered as paradigmatic surfactants, the anionic single-chain sodium dodecyl sulfate (SDS), the anionic double-chain sodium bis(2-ethylhexyl) sulfosuccinate (AOT) and the zwitterionic single-chain dodecyl phosphatidyl choline (DPC) within a wide aggregation number range (from 5 to 100). We observe that for low aggregation numbers the aggregates show in vacuo the typical structure of reverse micelles, while for large aggregation numbers a variety of globular aggregates occur that are characterized by the coexistence of interlaced domains formed by the polar or ionic heads and by the alkyl chains of the surfactants. Well-tempered metadynamics simulations allows us to confirm that the structural organizations obtained after 50 ns of molecular dynamics simulations are practically the equilibrium ones. Similarities and differences of surfactant aggregates in vacuo and in apolar media are also discussed.

Decoupling of dynamic processes in surfactant-based liquid mixtures: the case of lithium-containing bis(2-ethylhexyl)phosphoric acid/bis(2-ethylhexyl)amine systems.

Pure surfactant liquids and their binary mixtures, because of the amphiphilic nature of the molecules involved, can exhibit nanosegregation and peculiar transport properties. The idea that inspired this work is that the possibility of including in such media salts currently used for technological applications should lead to a synergy between the properties of the salt and those of the medium. Therefore, the dynamic features of bis(2-ethylhexyl)amine (BEEA) and bis(2-ethylhexyl)phosphoric acid (HDEHP) liquid mixtures were investigated as a function of composition and temperature by (1)H nuclear magnetic resonance (NMR) spectroscopy and rheometry. Inclusion of litium trifluoromethanesulfonate (LiT) has been investigated by infrared spectroscopy, pulsed field gradient NMR, and conductimetry methods to highlight the solubilizing and confining properties of these mixtures as well as the lithium conductivity. It was found that BEEA/HDEHP binary liquid mixtures show zero-threshold percolating self-assembly with a maximum in viscosity and a minimum in molecular diffusion at a 1:1 composition. Dissolution of LiT in such system can occur via confinement in the locally self-assembled polar domains. Despite this confinement, Li(+) conduction is scarcely dependent on the medium composition because of the possibility of a field-induced hopping decoupled by the structural and dynamical features of the medium.

Self-assembly and intra-cluster reactions of erbium and ytterbium bis(2-ethylhexyl)sulfosuccinates in the gas phase.

RATIONALE: The study of surfactant organization in vacuum allows surfactant-surfactant interaction to be unveiled in the absence of surrounding solvent molecules. Knowledge on their chemical-physical properties may also lead to the definition of more efficient gas-phase carriers, air-cleaning agents and nanoreactors. In addition, the presence of lanthanide-group ions adds unique photochemical properties to surfactants. METHODS: The structural features, stability and fragmentation patterns of charged aggregates formed by lanthanide-functionalized surfactants, ytterbium and erbium bis(2-ethylhexyl)sulfosuccinate ((AOT)3Yb and (AOT)3Er), have been investigated by electrospray ionization mass spectrometry (ESI-MS), tandem mass spectrometry (ESI-MS/MS) and energy-resolved mass spectrometry (ER-MS). RESULTS: The experimental data indicate that the self-assembling of (AOT)3Yb and (AOT)3Er in the gas phase leads to the formation of a wide range of singly charged aggregates differing in their aggregation number, relative abundance and stability. In addition to specific effects on aggregate organization due to the presence of lanthanide ions, ER-MS experiments show rearrangements and in-cage reactions activated by collision, eventually including alkyl chain intra-cluster migration. CONCLUSIONS: Analysis of the experimental findings suggests that the observed chemical transformations occur within an organized supramolecular assembly rather than in a random association of components. The fragmentation pathways leading to the neutral loss of a fragment of nominal mass 534 Da, assigned as C28 H54 O7 S, from some positively charged aggregates has been rationalized.

Morphology and local organization of water-containing (1R,2S)-dodecyl(2-hydroxy-1-methyl-2-phenylethyl)dimethylammonium bromide reverse micelles dispersed in toluene.

The structure of (1R,2S)-dodecyl(2-hydroxy-1-methyl-2-phenylethyl)dimethylammonium bromide (DMEB) reverse micelles, at various water-to-surfactant molar ratio (Rw, Rw = [water]/[DMEB]) and DMEB concentrations, has been investigated by small angle X-ray scattering (SAXS) and extended X-ray absorption fine structure spectroscopy (EXAFS). SAXS data of dry reverse micelles are consistent with a model of spherical hydrophilic core surrounded by DMEB alkyl chains whose polydispersity decreases significantly with surfactant concentration. By adding water, a sphere to cylinder transition occurs leading to a one-dimensional growth of reverse micellar cores with Rw and surfactant concentration. The observed behavior was taken as an indication that water molecules are confined in the core of DMEB reverse micelles, quite uniformly distributed among them and mainly located among surfactant head groups. EXAFS data allow to focus within the hydrophilic micellar core to solve the short range local environment around the Br(-) counterion and to follow its changing with surfactant concentration and Rw. Analysis of Fourier transform of the EXAFS spectra indicates the existence of a local order nearby the bromide ions; pointing toward a quite structured hydrophilic core of DMEB reverse micelles. However, as a consequence of the fluid nature of reverse micelles, such local order is lower than that found in the lamellar structure of solid DMEB. Water confinement within the reverse micellar cores induces an increase of the local disorder suggesting an enhancement of the micellar core dynamics.

Chiroptical phenomena in reverse micelles: the case of (1R,2S)-dodecyl (2-hydroxy-1-methyl-2-phenylethyl)dimethylammonium bromide (DMEB).

(1R,2S)-Dodecyl(2-hydroxy-1-methyl-2-phenylethyl)dimethylammonium bromide (DMEB) aggregates dispersed in carbon tetrachloride have been investigated by Fourier transform infrared (FT-IR), vibrational circular dichroism (VCD) and (1)H nuclear magnetic resonance (NMR) spectroscopy at various surfactant concentration and water-to-surfactant molar ratio. Experimental data indicate that, even at the lowest investigated concentration and in absence of added water, DMEB molecules associate in supramolecular assemblies. At higher DMEB concentration the aggregates can confine water molecules, making it plausible to think that DMEB form reverse micelles and that water molecules are quite uniformly distributed among them and mainly located in the proximity of surfactant head groups. Moreover, the water state in DMEB reverse micelles has been found to be different from that in pure water, due to system-specific water/surfactant head group interactions. (1)H NMR diffusion measurements of both water and DMEB emphasize their joined translational motion characterized by a diffusion rate one order of magnitude lower than that of free molecules. Finally, VCD allowed us to show some characteristics of the association of optically active DMEB molecules as reverse micelles and water confinement inside; namely, we monitored the vibrational optical activity of deuterated hydroxyl bonds of the self-assembled DMEB molecules and their interaction with D(2)O molecules.

A molecular dynamics study of structure, stability and fragmentation patterns of sodium bis(2-ethylhexyl)sulfosuccinate positively charged aggregates in vacuo.

Positively charged supramolecular aggregates formed in vacuo by n AOTNa (sodium bis(2-ethylhexyl)sulfosuccinate) molecules and n(c) additional sodium ions, i.e. [AOT(n)Na(n+n(c))](n(c)), have been investigated by molecular dynamics (MD) simulations for n = 1-20 and n(c) = 0-5. Statistical analysis of physical quantities like gyration radii, atomic B-factors and moment of inertia tensors provides detailed information on their structural and dynamical properties. Even for n(c) = 5, all stable aggregates show a reverse micelle-like structure with an internal solid-like core including sodium counterions and surfactant polar heads surrounded by an external layer consisting of the surfactant alkyl chains. Moreover, the aggregate shapes may be approximated by rather flat and elongated ellipsoids whose longer axis increases with n and n(c). The fragmentation patterns of a number of these aggregates have also been examined and have been found to markedly depend on the aggregate charge state. In one particular case, for which experimental findings are available in the literature, a good agreement is found with the present fragmentation data.

Supramolecular aggregates in vacuum: positively monocharged sodium alkanesulfonate clusters.

The formation and structural features of positively monocharged aggregates of sodium bis(2-ethylhexyl) sulfosuccinate (AOT) and sodium methane--(MetS), butane--(ButS) and octane--(OctS) sulfonate molecules in gas phase have been investigated by electrospray ionization mass spectrometry, energy resolved mass spectrometry and density functional theory (DFT) calculations. The experimental results show that the center-of-mass collision energy required to dissociate 50% of these monocharged aggregates scantly depends on the length of the alkyl chain as well as on the aggregation number. This, together with the large predominance of monocharged species in the mass spectra, was rationalized in terms of an aggregation pattern mainly driven by the counter ions and head groups electrostatic interactions while minor effects were attributed to the steric hindrance caused by the size of the surfactant head group and alkyl chain. DFT calculations show that the most favoured structural arrangement of these aggregates is always characterized by an internal polar core constituted by the sodium counter ions and surfactant head groups surrounded by an external layer composed by the surfactant alkyl chains.

Partitioning study of polycyclic aromatic hydrocarbons between water and some selected water-insoluble phases.

An investigation on the partitioning of naphthalene and phenanthrene between water and some water-insoluble phases has been carried out by Uv-vis-NIR spectrophotometry. The analysis of the experimental results emphasized the role of intermolecular interactions and structural features of the hosting phases as driving forces of the partitioning of these polycyclic aromatic hydrocarbons. The critical comparison of the resulting distribution constants allowed to evaluate the potentials of some extracting phases to set up sensitive analytical methods and/or effective environment remediation technologies.

Entrapment of amino acids in gas phase surfactant assemblies: The case of tryptophan confined in positively charged (1R,2S)-dodecyl (2-hydroxy-1-methyl-2-phenylethyl) dimethylammonium bromide aggregates.

The ability of positively charged aggregates of the surfactant (1R,2S)-dodecyl(2-hydroxy-1-methyl-2-phenylethyl)dimethylammonium bromide (DMEB) to incorporate D-tryptophan or L-tryptophan in the gas phase has been investigated by electrospray ion mobility mass spectrometry (ESI-IM-MS). Strongly impacted by the pH of the electrosprayed solutions, both protonated (T+ ) and deprotonated (T- ) tryptophan are effectively included into the aggregates, whereas, tryptophan in zwitterionic (T0 ) form is practically absent in singly charged DMEB aggregates but can be found in multiply charged ones. The ability to incorporate tryptophan increases with the aggregation number and charge state of aggregates. More than 1 tryptophan species can be entrapped (aggregates including up to 5 tryptophan are observed). Collision induced dissociation experiments performed on the positively singly charged DMEB hexamer containing 1 T- show that at low collision energies the loss of a DMEB molecule is preferred with respect to the loss of the DMEB cation plus T- species which, in turn, is preferred with respect to the loss of mere tryptophan, suggesting that the deprotonated amino acid is preferentially located in proximity of a DMEB head group and with the ionic moiety pointing towards the core of the aggregate. The analysis of the collision cross sections (CCS) of bare and tryptophan containing aggregates allowed evaluating the contributions of tryptophan and bromide ions to the total aggregate CCS. No significant discrimination between D-tryptophan and L-tryptophan by the chiral DMEB aggregates has been evidenced by mass spectra data, CID experiments, and CCS values.

Structural and physicochemical characterization of the inclusion complexes of cyclomaltooligosaccharides (cyclodextrins) with melatonin.

The stoichiometry, geometry, stability, and solubility of the inclusion complexes of melatonin (MLT) with native cyclomaltooligosaccharides (alpha-, beta- or gamma-cyclodextrins, CDs) are determined experimentally by high-resolution NMR spectroscopy, calorimetric and solubility measurements, and mass spectrometry. The observed differences are discussed in terms of molecular recognition expression of the host-guest (h-g) interactions within the hydrophobic CDs cavities of different size. The 1:1 h-g stoichiometry in water solution prevails at low CD concentrations; the trend to form higher order associations is observed at increasing CD concentrations. The stability order beta-CD>gamma-CD>alpha-CD for the complexes in water solution and beta-CD>alpha-CD>gamma-CD for the protonated or alkali-cationated complexes in the gas phase are rationalized on the grounds of the structural data from NMR spectroscopy and of the thermodynamic parameters from calorimetric measurements.

Structure, stability, and fragmentation of sodium bis(2-ethylhexyl)sulfosuccinate negatively charged aggregates in vacuo by MD simulations.

Negatively charged supramolecular aggregates formed in vacuo by n bis(2-ethylhexyl)sulfosuccinate (AOT(-)) anions and n + n(c) sodium counterions (i.e., [AOT(n) Na(n+nc)](nc)) have been investigated by molecular dynamics (MD) simulations for n = 1 to 20 and n(c) = -1 to -5. By comparing the maximum excess charge values of negatively and positively charged AOTNa aggregates, it is found that the charge storage capability is higher for the latter systems, the difference decreasing as the aggregation number increases. Statistical analysis of physical properties like gyration radii and moment of inertia tensors of aggregates provides detailed information on their structural properties. Even for n(c) = -5, all stable aggregates show a reverse micelle-like structure with an internal core, including sodium counterions and surfactant polar heads, surrounded by an external layer consisting of the surfactant alkyl chains. Interestingly, the reverse micelle-like structure is retained also in proximity of fragmentation. Moreover, the aggregate shapes may be approximated by elongated ellipsoids whose longer axis increases with n and |n(c)|. The fragmentation patterns of a number of these aggregates have also been examined and have been found to markedly depend on the aggregate charge state. The simulated fragmentation patterns of a representative aggregate show good agreement with experimental data obtained using low collision voltages.

Degrees of freedom effect on fragmentation in tandem mass spectrometry of singly charged supramolecular aggregates of sodium sulfonates.

The characteristic collision energy (CCE) to obtain 50% fragmentation of positively and negatively single charged noncovalent clusters has been measured. CCE was found to increase linearly with the degrees of freedom (DoF) of the precursor ion, analogously to that observed for synthetic polymers. This suggests that fragmentation behavior (e.g. energy randomization) in covalent molecules and clusters are similar. Analysis of the slope of CCE with molecular size (DoF) indicates that activation energy of fragmentation of these clusters (loss of a monomer unit) is similar to that of the lowest energy fragmentation of protonated leucine-enkephalin. Positively and negatively charged aggregates behave similarly, but the slope of the CCE versus DoF plot is steeper for positive ions, suggesting that these are more stable than their negative counterparts.

DNA binding and antiproliferative activity toward human carcinoma cells of copper(II) and zinc(II) complexes of a 2,5-diphenyl[1,3,4]oxadiazole derivative.

The interaction of calf thymus DNA with [CuL(ClO(4))]ClO(4)·H(2)O (1) and [ZnLBr]Br·H(2)O (2) (L = 9,12,15,18,27,28-hexaaza-29-oxatetracyclo[24.2.1.0(2,7).0(20,25)]enneicosa-2,4,6,20,22,24,26,28(1)-octaene) dicationic complexes in aqueous solution at neutral pH, was investigated by variable-temperature UV-vis absorption, circular dichroism and fluorescence spectroscopy. The values of the DNA-binding constants of these complexes, determined by competitive binding spectrofluorimetric titrations of ethidium bromide (EB)-DNA solutions, are (6.7 ± 0.5) × 10(6) M(-1) for CuL(2+) and (4.7 ± 0.5) × 10(5) M(-1) for ZnL(2+). These data together with a through analysis of the spectroscopic behaviour consistently suggest that both compounds are effective DNA binders. Interestingly, the DNA-binding strength of these complexes has been found to be correlated to their in vitro cytotoxic activity toward human breast carcinoma cells, although the complex with lower DNA-binding affinity is more active. In fact, biological studies showed that when the compounds are delivered through the cell membrane by a lipidic carrier, the cell survival is sensibly reduced, up to 58% with 1 and to 31% with 2.

Complex permittivity of FeCl3/AOT/CCl4 microemulsions probed by AC impedance spectroscopy.

The complex permittivity of FeCl(3)/AOT/CCl(4) microemulsions in the 1-10(5) Hz frequency range has been measured by the conventional AC complex impedance technique. Measurements as a function of the volume fraction of the dispersed phase (FeCl(3)+AOT) and temperature at fixed salt-to-AOT molar ratio (R, R = 0.5) show that the entrapment of FeCl(3) clusters significantly enhances the local permittivity of the AOT reverse micelles and the number density of charge carriers resulting from the peculiar state of the confined inorganic salt. An estimate of the apparent static permittivity of the FeCl(3) ionic clusters entrapped in the core of AOT reverse micelles gives the very high and quite surprisingly value of about 237. Moreover, a thorough analysis of conductivity data and of their temperature dependence strongly supports the hypothesis that the charge transport in these systems is mainly sustained by a mechanism of hopping consisting in the continuous jumping of charged species within supra-micellar aggregates of AOT reverse micelles whose aggregation is driven by fluctuating opposite charges on contacting micelles.