Chemistry of 4-alkylaryloxenium ion "precursors": sound and fury signifying something?

Quinol esters 2b, 2c, and 3b and sulfonamide 4c were investigated as possible precursors to 4-alkylaryloxenium ions, reactive intermediates that have not been previously detected. These compounds exhibit a variety of interesting reactions, but with one possible exception, they do not generate oxenium ions. The 4-isopropyl ester 2b predominantly undergoes ordinary acid- and base-catalyzed ester hydrolysis. The 4-tert-butyl ester 2c decomposes under both acidic and neutral conditions to generate tert-butanol and 1-acetyl-1,4-hydroquinone, 8, apparently by an SN1 mechanism. This is also a minor decomposition pathway for 2b, but the mechanism in that case is not likely to be SN1. Decomposition of 2c in the presence of N3- leads to formation of the explosive 2,3,5,6-tetraazido-1,4-benzoquinone, 14, produced by N3--induced hydrolysis of 8, followed by a series of oxidations and nucleophilic additions by N3-. No products suggestive of N3--trapping of an oxenium ion were detected. The 4-isopropyl dichloroacetic acid ester 3b reacts with N3- to generate the two adducts 2-azido-4-isopropylphenol, 5b, and 3-azido-4-isopropylphenol, 11b. Although 5b is the expected product of N3- trapping of the oxenium ion, kinetic analysis shows that it is produced by a kinetically bimolecular reaction of N3- with 3b. No oxenium ion is involved. The sulfonamide 4c predominantly undergoes a rearrangement reaction under acidic and neutral conditions, but a minor component of the reaction yields 4-tert-butylcresol, 17, and 2-azido-4-tert-butylphenol, 5c, in the presence of N3-. These products may indicate that 4c generates the oxenium ion 1c, but they are generated in very low yields (ca. 10%) so it is not possible to definitively conclude that 1c has been produced. If 1c has been generated, the N3--trapping data indicate that it is a very short-lived and reactive species in H2O. Comparisons with similarly reactive nitrenium ions indicate that the lifetime of 1c is ca. 20-200 ps if it is generated, so it must react by a preassociation process. Density functional theory calculations at the B3LYP/6-31G*//HF/6-31G* level coupled with kinetic correlations also indicate that the aqueous solution lifetimes of 1a-c are in the picosecond range.     

Increasing Convex-Along-Rays Functions with Applications to Global Optimization

Increasing convex-along-rays functions are defined within an abstract convexity framework. The basic properties of these functions including support sets and subdifferentials are outlined. Applications are provided to unconstrained global optimization using the concept of excess function.     

Dual conditions characterizing optimality for convex multi-objective programs

Received June 13, 1995 / Revised version received February 6, 1998 Published online August 18, 1998     

Cis→Trans Isomerization of Pro<Superscript>7</Superscript> in Oxytocin Regulates Zn<Superscript>2+</Superscript> Binding

Ion mobility/mass spectrometry techniques are employed to investigate the binding of Zn²⁺ to the nine-residue peptide hormone oxytocin (OT, Cys¹-Tyr²-Ile³-Gln⁴-Asn⁵-Cys⁶-Pro⁷-Leu⁸-Gly⁹-NH₂, having a disulfide bond between Cys¹ and Cys⁶ residues). Zn²⁺ binding to OT is known to increase the affinity of OT for its receptor [Pearlmutter, A. F., Soloff, M. S.: Characterization of the metal ion requirement for oxytocin-receptor interaction in rat mammary gland membranes. J. Biol. Chem. 254, 3899–3906 (1979)]. In the absence of Zn²⁺, we find evidence for two primary OT conformations, which arise because the Cys⁶–Pro⁷ peptide bond exists in both the trans- and cis-configurations. Upon addition of Zn²⁺, we determine binding constants in water of K_A = 1.43 ± 0.24 and 0.42 ± 0.12 μM^?1, for the trans- and cis-configured populations, respectively. The Zn²⁺ bound form of OT, having a cross section of Ω = 235 Ų, has Pro⁷ in the trans-configuration, which agrees with a prior report [Wyttenbach, T., Liu, D., Bowers, M. T.: Interactions of the hormone oxytocin with divalent metal ions. J. Am. Chem. Soc. 130, 5993–6000 (2008)], in which it was proposed that Zn²⁺ binds to the peptide ring and is further coordinated by interaction of the C-terminal, Pro⁷-Leu⁸-Gly⁹-NH₂, tail. The present work shows that the cis-configuration of OT isomerizes to the trans-configuration upon binding Zn²⁺. In this way, the proline residue regulates Zn²⁺ binding to OT and, hence, is important in receptor binding.

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Graphical Abstract ?

     

Hadamard-encoded sub-slice fMRI for reduced signal dropout

T2?-weighted blood oxygen level-dependent functional magnetic resonance imaging is adversely affected by susceptibility-induced field gradients in brain regions adjoining air interfaces that cause image distortion and signal dropout. Reducing slice thickness diminishes signal dropout but is accompanied by reduced signal-to-noise ratio (SNR). This study proposes simultaneous excitation of subslices with total width equal to the desired slice thickness, employing alternating Hadamard-encoded radiofrequency pulses coupled with incoherent addition of the subslices to achieve reduction of through-plane dephasing with minimal SNR loss but at the expense of a reduction in temporal resolution. Using a sensory task and hypercapnic challenge with breathholding (BH), results with two subslices per slice and a twofold reduction in temporal resolution show improved activation relative to a conventional acquisition. Average (eight subjects) T-scores in the BH task increased by 16% (P<.0003), and activation extent increased by 12% (not significant). In frontal brain regions, significant improvements in BH activation extent (11.4%, P<.05) and T-scores (18%, P<.0002) were demonstrated. Higher temporal resolution can be achieved by tradeoff of SNR.     

Adsorption of sulfur dioxide by CoFe2O4 spinel ferrite nanoparticles and corresponding changes in magnetism

Adsorption of sulfur dioxide on 10 nm CoFe(2)O(4) spinel ferrite nanoparticles was examined. Adsorption loadings of sulfur dioxide at breakthrough conditions were determined to be approximately 0.62 mol/kg, which is significant given the 150 m(2)/g surface area of the nanoparticles. Adsorption proceeds through a chemisorption mechanism with sulfur dioxide forming a sulfate upon adsorption on the particle surface, which leads to a 23% decrease in the remnant magnetization, a 20% decrease in the saturation magnetization, and a 9% decrease in the coercivity of the magnetic nanoparticles. Adsorbent materials that provide a magnetic signal when adsorption occurs could have broad implications on adsorption-based separations.     

Path relinking for unconstrained binary quadratic programming

This paper presents two path relinking algorithms to solve the unconstrained binary quadratic programming (UBQP) problem. One is based on a greedy strategy to generate the relinking path from the initial solution to the guiding solution and the other operates in a random way. We show extensive computational results on five sets of benchmarks, including 31 large random UBQP instances and 103 structured instances derived from the MaxCut problem. Comparisons with several state-of-the-art algorithms demonstrate the efficacy of our proposed algorithms in terms of both solution quality and computational efficiency. It is noteworthy that both algorithms are able to improve the previous best known results for almost 40 percent of the 103 MaxCut instances.     

Reliable determination of amidicity in acyclic amides and lactams

Two independent computational methods have been used for determination of amide resonance stabilization and amidicities relative to N,N-dimethylacetamide for a wide range of acyclic and cyclic amides. The first method utilizes carbonyl substitution nitrogen atom replacement (COSNAR). The second, new approach involves determination of the difference in amide resonance between N,N-dimethylacetamide and the target amide using an isodesmic trans-amidation process and is calibrated relative to 1-aza-2-adamantanone with zero amidicity and N,N-dimethylacetamide with 100% amidicity. Results indicate excellent coherence between the methods, which must be regarded as more reliable than a recently reported approach to amidicities based upon enthalpies of hydrogenation. Data for acyclic planar and twisted amides are predictable on the basis of the degrees of pyramidalization at nitrogen and twisting about the C-N bonds. Monocyclic lactams are predicted to have amidicities at least as high as N,N-dimethylacetamide, and the β-lactam system is planar with greater amide resonance than that of N,N-dimethylacetamide. Bicyclic penam/em and cepham/em scaffolds lose some amidicity in line with the degree of strain-induced pyramidalization at the bridgehead nitrogen and twist about the amide bond, but the most puckered penem system still retains substantial amidicity equivalent to 73% that of N,N-dimethylacetamide.     

An Experimental Evaluation of a Scatter Search for the Linear Ordering Problem

Scatter search is a population-based method that has recently been shown to yield promising outcomes for solving combinatorial and nonlinear global optimization problems. Based on formulations originally proposed in the 1960s for combining decision rules and problem constraints, such as in generating surrogate constraints, scatter search uses strategies for combining solution vectors that have proved effective in a variety of problem settings. In this paper, we present a scatter search implementation designed to find high quality solutions for the NP-hard linear ordering problem, which has a significant number of applications in practice. The LOP, for example, is equivalent to the so-called triangulation problem for input-output tables in economics. Our implementation incorporates innovative mechanisms to combine solutions and to create a balance between quality and diversification in the reference set. We also use a tracking process that generates solution statistics disclosing the nature of combinations and the ranks of antecedent solutions that produced the best final solutions. Extensive computational experiments with more than 300 instances establishes the effectiveness of our procedure in relation to approaches previously identified to be best.