An improved synthesis of 5,6,7,8‐tetrahydro‐1,7‐naphthyridine ‐ a conformationally‐restricted analog of 2‐(3‐pyridyl)ethylamine

The 5,6,7,8‐tetrahydro‐1,7‐naphthyridine ( 7 ) pharmacophore has the potential to serve as a confor‐mationally‐locked analog of the pharmacologically active 2‐(3‐pyridyl)ethylamine ( 1 ) core structure. This paper describes the synthesis of 5,6,7,8‐tetrahydro‐1,7‐naphthyridine ( 7 ) via a five‐step sequence, which affords a significant improvement over previously reported syntheses.     

Laser-induced acoustic desorption (LIAD) mass spectrometry

Large thermally labile molecules were not amenable to mass spectrometric analysis until the development of atmospheric pressure evaporation/ionization methods, such as electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI), since attempts to evaporate these molecules by heating induces degradation of the sample. While ESI and MALDI are relatively soft desorption/ionization techniques, they are both limited to preferential ionization of acidic and basic analytes. This limitation has been the driving force for the development of other soft desorption/ionization techniques. One such method employs laser-induced acoustic desorption (LIAD) to evaporate neutral sample molecules into mass spectrometers. LIAD utilizes acoustic waves generated by a laser pulse in a thin metal foil. The acoustic waves travel through the foil and cause desorption of neutral molecules that have been deposited on the opposite side of the foil. One of the advantages of LIAD is that it desorbs low-energy molecules that can be ionized by a variety of methods, thus allowing the analysis of large molecules that are not amenable to ESI and MALDI. This review covers the generation of acoustic waves in foils via a laser pulse, the parameters affecting the generation of acoustic waves, possible mechanisms for desorption of neutral molecules, as well as the various uses of LIAD by mass spectrometrists. The conditions used to generate acoustic or stress waves in solid materials consist of three regimes: thermal, ablative, and constrained. Each regime is discussed, in addition to the mechanisms that lead to the ablation of the metal from the foil and generation of acoustic waves for two of the regimes. Previously proposed desorption mechanisms for LIAD are presented along with the flaws associated with some of them. Various experimental parameters, such as the exact characteristics of the laser pulse and foil used, are discussed. The internal and kinetic energy of the neutral desorbed molecules are also considered. Our research group has been instrumental in the development and use of LIAD. For example, we have systematically examined the influence of many parameters, such as the type of the foil and its thickness, as well as the analyte layer's thickness, on the efficiency of desorption of neutral molecules. The coupling of LIAD with different instruments and ionization techniques allows for broad use of LIAD in our research laboratories. The most important applications involve analytes that cannot be analyzed by using other mass spectrometric methods, such as large saturated hydrocarbons and heavy hydrocarbon fractions of petroleum. We also use LIAD to characterize lipids, peptides, and oligonucleotides. Fundamental research on the reactions of charged mono-, bi-, and polyradicals with biopolymers, especially oligonucleotides, also requires the use of LIAD, as well as thermochemical measurements for neutral biopolymers. These are but a few of the uses of LIAD in our research group.     

Martin’s Axiom and separated mad families

Two families \(\mathcal{A}, \mathcal{B}\) of subsets of ω are said to be separated if there is a subset of ω which mod finite contains every member of \(\mathcal{A}\) and is almost disjoint from every member of \(\mathcal{B}\). If \(\mathcal{A}\) and \(\mathcal{B}\) are countable disjoint subsets of an almost disjoint family, then they are separated. Luzin gaps are well-known examples of ω ₁-sized subfamilies of an almost disjoint family which can not be separated. An almost disjoint family will be said to be ω ₁-separated if any disjoint pair of ≤ω ₁-sized subsets are separated. It is known that the proper forcing axiom (PFA) implies that no maximal almost disjoint family is ≤ω ₁-separated. We prove that this does not follow from Martin’s Axiom.     

Selective Oxidations of Alcohols by Bromine in Combination with Nickel(II) Benzoate

The combination of nickel(II) bromide with benzoyl peroxide serves as an effective reagent for the conversion of secondary alcohols to ketones and, when nickel(II) bromide is employed as an alcohol template, for the oxidation of primary alcohols to aldehydes.¹ The unique steric selectivity of the Bz₂O₂/NiBr₂ combination has recently been demonstrated in oxidations of 2,2-disubstituted-1, 4-butanediols to the corresponding β,β-disubstituted-γ-butyrolactones.² In the course of our investigation of this novel oxidative method, we have discovered that molecular bromine in combination with commercially available nickel(II) benzoate is a mild, effective, and selective oxidant for the conver-     

Design, Modeling, Fabrication, and Evaluation of the Air Amplifier for Improved Detection of Biomolecules by Electrospray Ionization Mass Spectrometry

Through a multi-disciplinary approach, the air amplifier is being evolved as a highly engineered device to improve detection limits of biomolecules when using electrospray ionization. Several key aspects have driven the modifications to the device through experimentation and simulations. We have developed a computer simulation that accurately portrays actual conditions and the results from these simulations are corroborated by the experimental data. These computer simulations can be used to predict outcomes from future designs resulting in a design process that is efficient in terms of financial cost and time. We have fabricated a new device with annular gap control over a range of 50 to 70 μm using piezoelectric actuators. This has enabled us to obtain better aerodynamic performance when compared to the previous design (2× more vacuum) and also more reproducible results. This is allowing us to study a broader experimental space than the previous design which is critical in guiding future directions. This work also presents and explains the principles behind a fractional factorial design of experiments methodology for testing a large number of experimental parameters in an orderly and efficient manner to understand and optimize the critical parameters that lead to obtain improved detection limits while minimizing the number of experiments performed. Preliminary results showed that several folds of improvements could be obtained for certain condition of operations (up to 34 folds).     

Discretely weak P-sets

A discretely weak P-set is a nowhere dense closed set which is disjoint from the closure of any countable discrete subset of its complement. We show that the Stone-?ech remainder N^∗ of the discrete space N of natural numbers cannot be covered by discretely weak P-sets when the continuum hypothesis is assumed.     

On the cofinality of the splitting number

The splitting number $\mathfrak{s}$ can be singular. The key method is to construct a forcing poset with finite support matrix iterations of ccc posets introduced by Blass and Shelah (1989).     

Instabilities and vortex-lattice formation in rotating conventional and dipolar dilute-gas Bose-Einstein condensates

A theoretical study of vortex-lattice formation in atomic Bose-Einstein condensates confined by a rotating elliptical trap is presented. For the conventional case of purely s-wave interatomic interactions, this is done through a consideration of both hydrodynamic equations and time-dependent simulations of the Gross-Pitaevskii equation. We discriminate three distinct, experimentally testable regimes of instability: ripple, interbranch, and catastrophic. Additionally, we generalize the classical hydrodynamical approach to include long-range dipolar interactions, showing how the static solutions and their stability in the rotating frame are significantly altered. This enables us to examine the routes towards unstable dynamics, which, in analogy to conventional condensates, may lead to vortex-lattice formation.