Real-time investigation of lung surfactant respreading with surface vibrational spectroscopy

The respreading of a lung surfactant monolayer at the air-water interface is investigated with broad bandwidth sum frequency generation (BBSFG) spectroscopy. The lung surfactant mixture contains chain perdeuterated dipalmitoylphosphatidylcholine (DPPC-d62), palmitoyloleoylphosphatidylglycerol (POPG), palmitic acid (PA), and KL4 (a 21-residue polypeptide analogue to the surfactant protein SP-B). DPPC-d62 serves as a probe molecule for the spectroscopic investigation. The BBSFG spectra of DPPC-d62 in the lung surfactant mixture are obtained in the C-D stretching region in real-time during film compression and expansion in a Langmuir trough. The BBSFG intensity of the CD3 stretch peak from DPPC-d62 terminal methyl groups is used as a measure of the interfacial density of DPPC-d62 after careful consideration of orientation effects. For the first time, the interfacial loss of DPPC in a complex lung surfactant mixture is quantified. Spectroscopic results reveal that there is an 18% DPPC-d62 interfacial loss during film respreading. However, the surface pressure-area isotherm measurements demonstrate that there is a rather large trough area reduction (37%) during film expansion. The relatively small interfacial loss of DPPC-d62 and the rather large trough area reduction indicate that the respreading of DPPC and non-DPPC components in the lung surfactant is not uniform and a surface refinement process exists during film compression and expansion. This refinement process results in a DPPC-enriched monolayer with a significant depletion of non-DPPC components after film respreading. Implication for replacement surfactant design from this work is discussed.     

Synthesis of enantioenriched γ-quaternary cycloheptenones using a combined allylic alkylation/Stork-Danheiser approach: preparation of mono-, bi-, and tricyclic systems

A general method for the synthesis of β-substituted and unsubstituted cycloheptenones bearing enantioenriched all-carbon γ-quaternary stereocenters is reported. Hydride or organometallic addition to a seven-membered ring vinylogous ester followed by finely tuned quenching parameters achieves elimination to the corresponding cycloheptenone. The resulting enones are elaborated to bi- and tricyclic compounds with potential for the preparation of non-natural analogs and whose structures are embedded in a number of cycloheptanoid natural products.     

Similarity searching in databases of three-dimensional molecules and macromolecules.

This paper discusses algorithmic techniques for measuring the degree of similarity between pairs of three-dimensional (3-D) chemical molecules represented by interatomic distance matrices. A comparison of four methods for the calculation of 3-D structural similarity suggests that the most effective one is a procedure that identifies pairs of atoms, one from each of the molecules that are being compared, that lie at the center of geometrically-related volumes of 3-D space. This atom mapping method enables the calculation of a wide range of types of intermolecular similarity coefficient, including measures that are based on physicochemical data. Massively-parallel implementations of the method are discussed, using the AMT Distributed Array Processor, that achieve a substantial increase in performance when compared with a sequential implementation on a UNIX workstation. Current work involves the use of angular information and the extension of the method to field-based similarity searching. Similarity searching in 3-D macromolecules is effected by the use of a maximal common subgraph (MCS) isomorphism algorithm with a novel, graph-based representation of the tertiary structures of proteins. This algorithm is being used to identify similarities between the 3-D structures of proteins in the Brookhaven Protein Data Bank; its use is exemplified by searches involving the NAD-binding fold motif.     

The theory of absolute surface shear viscosity V. The effect of finite ring thickness

In the theory of Couette surface viscometers it is convenient to idealize a rotating ring thrust into a fluid interface supporting an adsorbed surface film as making a knife-edge contact of zero thickness. The validity of this assumption is examined by calculating from theory the flow patterns to be expected when the ring makes a contact of finite thickness with the interface. The zero thickness idealization is found to be valid for films of moderate to large surface viscosity, but it fails badly for films of low surface viscosity and places a limit upon the sensitivity of the ring method.     

Ion-induced nucleation in solution: promotion of solute nucleation in charged levitated droplets

We have investigated the nucleation and growth of sodium chloride in both single quiescent charged droplets and charged droplet populations that were levitated in an electrodynamic levitation trap (EDLT). In both cases, the magnitude of a droplet's net excess charge (ions(DNEC)) influenced NaCl nucleation and growth, albeit in different capacities. We have termed the phenomenon ion-induced nucleation in solution. For single quiescent levitated droplets, an increase in ions(DNEC) resulted in a significant promotion of NaCl nucleation, as determined by the number of crystals observed. For levitated droplet populations, a change in NaCl crystal habit, from regular cubic shapes to dome-shaped dendrites, was observed once a surface charge density threshold of -9 x 10(-4) e.nm(-2) was surpassed. Although promotion of NaCl nucleation was observed for droplet population experiments, this can be attributed in part to the increased rate of solvent evaporation observed for levitated droplet populations having a high net charge. Promotion of nucleation was also observed for two organic acids, 2,4,6-trihydroxyacetophenone monohydrate (THAP) and alpha-cyano-4-hydroxycinnamic acid (CHCA). These results are of direct relevance to processes that occur in both soft-ionization techniques for mass spectrometry and to a variety of industrial processes. To this end, we have demonstrated the use of ion-induced nucleation in solution to form ammonium nitrate particles from levitated droplets to be used in in vitro toxicology studies of ambient particle types.     

Anionic hyperconjugation

Although hyperconjugation involving alkyl groups to a carbocation is a well-established concept, the analogous charge delocalization generated in anions by electronegative substitution has long been a subject of controversy. We have investigated this phenomenon for the β-hydroxyethyl and β-trifluoroethyl anions using ab initio electronic structure calculations. Split valence basis sets augmented by diffuse functions were used with fully optimized geometries. Three dimensional molecular orbital plots clearly show an in-plane HOMO-LUMO mixing of a C-X σ antibonding orbital with the carbon lone pair which yields hyperconjugative π bonding in the anti conformation. Deformation density maps further demonstrate that this delocalization leads to the development of a π component as well as a previously unrecognized sigma enhancement. These results support and extend the work of Apeloig and that of Schleyer and Kos, but are in opposition to the induction hypothesis of Streitwieser and Holtz. The recent experimental determination of the acidity of (CF₃)₃CH by Tatlow $\text{et al}$ and their interpretation in terms of fluorine hyperconjugation are also in accord with this work.     

A millimeter/sub-millimeter-wave spectroscopic study of the FeCl radical (XΔi)

Pure rotational spectroscopy of the FeCl radical (X⁶Δ_i) has been carried out using millimeter/sub-millimeter direct absorption techniques. The species was created by the reaction of chlorine with iron vapor. All six spin-orbit components were observed in the majority of the twenty-one rotational transition recorded. Chlorine hyperfine structure was resolved in the Ω = 9/2 and 7/2 components, and lambda-type doubling observed in the Ω = 3/21/2, and −1/2 ladders. The data were analyzed with a ⁶Δ Hamiltonian, and rotational, fine structure, lambda-doubling, and hyperfine parameters determined. The hyperfine and lambda-doubling interactions in FeCl appear to be different from those in the FeF radical.     

Nested-channel for on-demand alternation between electrospray ionization regimes

On-demand electrospray ionization from different liquid channels in the same emitter was realized using filamented capillary and gas phase charge supply. The solution sub-channel was formed when back-filling solution to the emitter tip by capillary action along the filament. Gas phase charge carriers were used to trigger electrospray ionization from the solution meniscus at the tip. The meniscus at the tip opening may be fully filled or partially empty to generate electrospray ionization in main-channel regime and sub-channel regime, respectively. For emitters with 4 μm tip opening, the two nested electrospray (nested-ESI) channels accommodated ESI flow rates ranging from 50 pL min⁻¹ to 150 nL min⁻¹. The platform enabled on-demand regime alternations within one sample run, in which the sub-channel regime generated smaller charged droplets. Ionization efficiencies for saccharides, glycopeptide, and proteins were enhanced in the sub-channel regime. Non-specific salt adducts were reduced and identified by regime alternation. Surprisingly, the sub-channel regime produced more uniform responses for a peptide mixture whose relative ionization efficiencies were insensitive to ESI conditions in previous picoelectrospray study. The nested channels also allowed effective washing of emitter tip for multiple sampling and analysis operations.

Nested electrospray ionization alternates on-demand between microscale main-channel and nanscale sub-channels.