Improved mass accuracy for higher mass peptides by using SWIFT excitation for MALDI-FTICR mass spectrometry

Stepwise-external calibration has previously been shown to produce sub part-per-million (ppm) mass accuracy for the MALDI-FTICR/MS analyses of peptides up to m/z 2500. The present work extends these results to ions up to m/z 4000. Mass measurement errors for ions of higher mass-to-charge are larger than for ions below m/z 2500 when using conventional chirp excitation to detect ions. Mass accuracy obtained by using stored waveform inverse Fourier transform (SWIFT) excitation was evaluated and compared with chirp excitation. Analysis of measurement errors reveals that SWIFT excitation provides smaller deviations from the calibration equation and better mass accuracy than chirp excitation for a wide mass range and for widely varying ion populations.     

Comparative thermodynamic studies of aqueous glutaric acid, ammonium sulfate and sodium chloride aerosol at high humidity

Aerosol optical tweezers are used to simultaneously characterize and compare the hygroscopic properties of two aerosol droplets, one containing inorganic and organic solutes and the second, referred to as the control droplet, containing a single inorganic salt. The inorganic solute is either sodium chloride or ammonium sulfate and the organic component is glutaric acid. The time variation in the size of each droplet (3-7 microm in radius) is recorded with 1 s time resolution and with nanometre accuracy. The size of the control droplet is used to estimate the relative humidity with an accuracy of better than +/-0.09%. Thus, the Kohler curve of the multicomponent inorganic/organic droplet, which characterizes the variation in equilibrium droplet size with relative humidity, can be determined directly. The measurements presented here focus on high relative humidities, above 97%, in the limit of dilute solutes. The experimental data are compared with theoretical treatments that, while ignoring the interactions between the inorganic and organic components, are based upon accurate representations of the activity-concentration relationships of aqueous solutions of the individual salts. The organic component is treated by a parametrized fit to experimental data or by the UNIFAC model and the water activity of the equilibrium solution droplet is calculated using the approach suggested by Clegg, Seinfeld and Brimblecombe or the Zdanovskii-Stokes-Robinson approximation. It is shown that such an experimental strategy, comparing directly droplets of different composition, enables highly accurate measurements of the hygroscopic properties, allowing the theoretical treatments to be rigorously tested. Typical deviations of the experimental measurements from theoretical predictions are shown to be around 1% in equilibrium size, comparable to the variation between the theoretical frameworks considered.     

Preparation and biological properties of inclusion compounds of calix[4]arene and 1,4-benzodiazepinone derivatives

The possibility of enhancing the oral bioavailability of certain 1,4-benzodiazepinones by using them as complexes with a series of calix[4]arene derivatives was examined. All the inclusion compounds prepared exhibit anticonvulsant activity by antagonism with Corazol spasmodic agent. Complexes with 25,27-bis[(hydrazinocarbonyl)methoxy]-26,28-dihydroxy-p-tert-butylcalix[4]arene exhibit higher pharmacological activity compared to the starting 7-bromo-5-(o-chloro)phenyl-and 1-hydrazinocarbonylmethyl-7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-ones.     

An isoform-selective, small-molecule inhibitor targets the autoregulatory mechanism of p21-activated kinase

Autoregulatory domains found within kinases may provide more unique targets for chemical inhibitors than the conserved ATP-binding pocket targeted by most inhibitors. The kinase Pak1 contains an autoinhibitory domain that suppresses the catalytic activity of its kinase domain. Pak1 activators relieve this autoinhibition and initiate conformational rearrangements and autophosphorylation events leading to kinase activation. We developed a screen for allosteric inhibitors targeting Pak1 activation and identified the inhibitor IPA-3. Remarkably, preactivated Pak1 is resistant to IPA-3. IPA-3 also inhibits activation of related Pak isoforms regulated by autoinhibition, but not more distantly related Paks, nor >200 other kinases tested. Pak1 inhibition by IPA-3 in live cells supports a critical role for Pak in PDGF-stimulated Erk activation. These studies illustrate an alternative strategy for kinase inhibition and introduce a highly selective, cell-permeable chemical inhibitor of Pak.     

Reactions of actinide metal atoms with ethane: computation and observation of new Th and U ethylidene dihydride, metallacyclopropane dihydride, and vinyl metal trihydride complexes

A combined computational and experimental investigation provides evidence that excited thorium and uranium atoms activate ethane to form the vinyl metal trihydride, metallacyclopropane dihydride, and ethylidene metal dihydride for thorium and the latter complex and the inserted ethyl metal hydride for uranium. These products are trapped in solid argon and identified through deuterium isotopic substitution and vibrational frequencies calculated by density functional theory. Comparisons are made with group 4 and methane reaction products. Numerous calculations using several methods show that these simple ethylidene complexes are more distorted by the agostic interaction than the corresponding methylidene species. This enhanced agostic interaction probably arises from methyl hydrogen to alpha-H repulsions, which leads to a substantial decrease in the alpha-H to Th agostic interaction distance, and contributes to our understanding of agostic distortion in organometallic complexes.     

Ultrasensitive absorption spectroscopy of optically-trapped aerosol droplets

High-sensitivity optical absorption measurements on individual sub-picoliter aqueous droplets are reported using aerosol optical tweezers to simultaneously manipulate and characterize a sample droplet and a control droplet for comparison. It is demonstrated that the detection sensitivity to trace analytes is set by the weak absorption by the solvent, water, and that absorbances less than 5 x 10(-7) can be measured over pathlengths of less than 10 microm. The potential applications of this approach to analyze aerosol particle composition and to perform trace analysis are discussed.     

Chemoenzymatic acylation of aminoglycoside antibiotics

The chemoenzymatic installation of the clinically valuable (S)-4-amino-2-hydroxybutyryl side chain onto a number of 2-deoxystreptamine-containing aminoglycosides is described using the purified Bacillus circulans biosynthetic enzymes BtrH and BtrG in combination with a synthetic acyl-SNAC surrogate substrate.     

Electronic Characterization of Vis–NIR Absorbing Noninnocent Ruthenium Oxyquinolate–merocyanine Complexes and their Photoacoustic Emission in Aqueous Micellar Solution†

The electronic and photophysical properties for a series of ruthenium(II) polypyridyl dyes are presented where a π-accepting 5-(vinyl-cyanine)-8-oxyquinolate class of ligand is incorporated to yield an improved vis–NIR absorption. A combination of computational, UV–vis–NIR absorption, phosphorescence emission and cyclic voltammetry studies are used to probe the influence of these ligands on complex electronic and photophysical properties. To assess their potential as vis–NIR photoacoustic contrast agents, select complexes were formulated in a PBS buffer/Tween® 20 solvent system. The p-quinolin-1-ium, 1,3,3-trimethyl-3H-indol-1-ium and 1,1,3-trimethyl-1H-benzo[e]indol-3-ium acceptor groups each impart a strong 680 nm optical absorption and photoacoustic emission on par with the performance exhibited by both the methylene blue and cryptocyanine commercial dyes.     

Alkaline-Earth Metal Mediated Benzene-to-Biphenyl Coupling

Complex [(^DIPePBDI)Ca]₂(C₆H₆), with a C₆H₆²⁻ dianion bridging two Ca²⁺ ions, reacts with benzene to yield [(^DIPePBDI)Ca]₂(biphenyl) with a bridging biphenyl²⁻ dianion (^DIPePBDI=HC[C(Me)N-DIPeP]₂; DIPeP=2,6-CH(Et)₂-phenyl). The biphenyl complex was also prepared by reacting [(^DIPePBDI)Ca]₂(C₆H₆) with biphenyl or by reduction of [(^DIPePBDI)CaI]₂ with KC₈ in presence of biphenyl. Benzene-benzene coupling was also observed when the deep purple product of ball-milling [(^DIPPBDI)CaI(THF)]₂ with K/KI was extracted with benzene (DIPP=2,6-CH(Me)₂-phenyl) giving crystalline [(^DIPPBDI)Ca(THF)]₂(biphenyl) (52 % yield). Reduction of [(^DIPePBDI)SrI]₂ with KC₈ gave highly labile [(^DIPePBDI)Sr]₂(C₆H₆) as a black powder (61 % yield) which reacts rapidly and selectively with benzene to [(^DIPePBDI)Sr]₂(biphenyl). DFT calculations show that the most likely route for biphenyl formation is a pathway in which the C₆H₆²⁻ dianion attacks neutral benzene. This is facilitated by metal-benzene coordination.     

Cover Picture: Supramolecular Self-Assembly as a Tool To Preserve the Electronic Purity of Perylene Diimide Chromophores (Angew. Chem. Int. Ed. 12/2023)

Organic semiconductors are promising for efficient, printable optoelectronics. However, strong excited-state quenching due to uncontrolled aggregation limits their use in devices. We report on the self-assembly of a supramolecular pseudo-cube formed from six perylene diimides (PDIs). The rigid, shape-persistent cage sets the distance and orientation of the PDIs and suppresses intramolecular rotations and vibrations, leading to non-aggregated, monomer-like properties in solution and the solid state, in contrast to the fast fluorescence quenching in the free ligand. The stabilized excited state and electronic purity in the cage enables the observation of delayed fluorescence due to a bright excited multimer, acting as excited-state reservoir in a rare case of benign inter-chromophore interactions in the cage. We show that self-assembly provides a powerful tool for retaining and controlling the electronic properties of chromophores, and to bring molecular electronics devices within reach.