Asymmetric Synthesis of Heterocyclic Chloroamines and Aziridines by Enantioselective Protonation of Catalytically Generated Enamines**

We report a method for the synthesis of chiral vicinal chloroamines via asymmetric protonation of catalytically generated prochiral chloroenamines using chiral Brønsted acids. The process is highly enantioselective, with the origin of asymmetry and catalyst substituent effects elucidated by DFT calculations. We show the utility of the method as an approach to the synthesis of a broad range of heterocycle-substituted aziridines by treatment of the chloroamines with base in a one-pot process, as well as the utility of the process to allow access to vicinal diamines.     

Expediting the identification of impaired channels in cochlear implants via analysis of speech-based confusion matrices

There is significant variability in the benefit provided by cochlear implants to severely deafened individuals. The reasons why some subjects exhibit low speech recognition scores are unknown; however, underlying physiological or psychophysical factors may be involved. Certain phenomena, such as indiscriminable electrodes and nonmonotonic pitch rankings, might hint at limitations in the ability of individual channels in the cochlear implant and/or sensorineural pathway to convey speech information. In this paper, four approaches for analyzing the results of a simple listening test using speech stimuli are investigated for the purpose of targeting channels of concern in order for follow-on psychophysical experiments to correctly identify channels performing in an "impaired" or anomalous manner. Listening tests were first conducted with normal-hearing subjects and acoustic models simulating channel-specific anomalies. Results indicate that these proposed analyses perform significantly better than chance in providing information about the location of anomalous channels. Vowel and consonant confusion matrices from six cochlear implant subjects were also analyzed to test the robustness of the proposed analyses to variability intrinsic to cochlear implant data. The current study suggests that confusion matrix analyses have the potential to expedite the identification of impaired channels by providing preliminary information prior to exhaustive psychophysical testing.     

Predictions of psychophysical measurements for sinusoidal amplitude modulated (SAM) pulse-train stimuli from a stochastic model

Two approaches have been proposed to reduce the synchrony of the neural response to electrical stimuli in cochlear implants. One approach involves adding noise to the pulse-train stimulus, and the other is based on using a high-rate pulse-train carrier. Hypotheses regarding the efficacy of the two approaches can be tested using computational models of neural responsiveness prior to time-intensive psychophysical studies. In our previous work, we have used such models to examine the effects of noise on several psychophysical measures important to speech recognition. However, to date there has been no parallel analytic solution investigating the neural response to the high-rate pulse-train stimuli and their effect on psychophysical measures. This work investigates the properties of the neural response to high-rate pulse-train stimuli with amplitude modulated envelopes using a stochastic auditory nerve model. The statistics governing the neural response to each pulse are derived using a recursive method. The agreement between the theoretical predictions and model simulations is demonstrated for sinusoidal amplitude modulated (SAM) high rate pulse-train stimuli. With our approach, predicting the neural response in modern implant devices becomes tractable. Psychophysical measurements are also predicted using the stochastic auditory nerve model for SAM high-rate pulse-train stimuli. Changes in dynamic range (DR) and intensity discrimination are compared with that observed for noise-modulated pulse-train stimuli. Modulation frequency discrimination is also studied as a function of stimulus level and pulse rate. Results suggest that high rate carriers may positively impact such psychophysical measures.     

Implementation and analysis of spectral subtraction in deterministic wide‐band anti‐jamming scenarios

In this paper, we propose an approach for mitigating deterministic and partially deterministic jamming signals from the received signal space, thus yielding recoverable signal vectors at a target receiver. Aimed at friendly or self‐jamming environments, where enemy communication jamming is paramount. The proposed approach employs a concept called spectral subtraction, where one or more known signals can be removed from the received signal space via the subtraction of their spectral characteristics from the received composite signal. Although spectral subtraction is used in a variety of speech communication scenarios, it has not been extensively employed in wireless applications because of several practical challenges, such as achieving both sufficient time alignment and accurate waveform characterization of the signal to be removed. In order to assess these challenges, as well as analyze the potential benefits of the proposed approach, validation was performed using actual over‐the‐air experimentation using software‐defined radio technology. The feasibility study of the proposed approach for achieving sufficient signal removal was examined for a constrained operating scenario, and experimental results show that spectral subtraction can be achieved in a physical transmission environment. Although physical simulations were limited, they provide baseline results for a previously untested method of jammer suppression. Copyright © 2016 John Wiley & Sons, Ltd.     

Combined convection and wall conduction effects in laminar pipe flow: numerical predictions and experimental validation under uniform wall heating

Laminar combined convection in horizontal circular ducts is investigated both numerically and experimentally, under uniform wall heating. A series of experiments for the heating of water in a long horizontal copper tube are simulated numerically in order to assess the reliability of the theoretical results. Peripheral and axial wall conduction effects, inherently present in the experiments, are accounted for in the numerical model. The cross validation of experimental and numerical data allows significant conclusions to be reached on conjugate conduction and convection with buoyancy effects in horizontal duct flows. Buoyancy is considered for values of the modified Rayleigh number,Ra _qo , up to 5·10⁶; the forced convection contribution is considered for two values of the entry Reynolds number,Re _o=500 and 1000.     

[Rh2(MEPY)4] and [BiRh(MEPY)4]: Convenient Syntheses and Computational Analysis of Strikingly Dissimilar Siblings

[Rh₂(MEPY)₄] is a versatile catalyst for asymmetric synthesis but its preparation requires purification by chromatography on surface-modified silica. A higher yielding procedure based on a more convenient work-up is presented herein. Moreover, a much improved method for the preparation of [BiRh(OTfa)₄] is described, which makes this heterobimetallic complex readily available. Subsequent exchange of the trifluoroacetate ligands opens access to a so far underappreciated family of (chiral) paddlewheel complexes. While [BiRh] complexes comprising four carboxylate ligands are highly adequate for intermolecular asymmetric cyclopropanation reactions, [BiRh(MEPY)₄] as the heterobimetallic cousin of [Rh₂(MEPY)₄] was found to be surprisingly unreactive; DFT calculations uncover the reasons for this inertia.     

Mononuclear Polypyridylruthenium(II) Complexes with High Membrane Permeability in Gram‐Negative Bacteria—in particular Pseudomonas aeruginosa

Ruthenium(II) complexes containing the tetradentate ligand bis[4(4′‐methyl‐2,2′‐bipyridyl)]‐1,n‐alkane (“bb_n”; n=10 and 12) have been synthesised and their geometric isomers separated. All [Ru(phen)(bb_n)]²⁺ (phen=1,10‐phenanthroline) complexes exhibited excellent activity against Gram‐positive bacteria, but only the cis‐α‐[Ru(phen)(bb₁₂)]²⁺ species showed good activity against Gram‐negative species. In particular, the cis‐α‐[Ru(phen)(bb₁₂)]²⁺ complex was two to four times more active than the cis‐β‐[Ru(phen)(bb₁₂)]²⁺ complex against the Gram‐negative strains. The cis‐α‐ and cis‐β‐[Ru(phen)(bb₁₂)]²⁺ complexes readily accumulated in the bacteria but, significantly, showed the highest level of uptake in Pseudomonas aeruginosa. Furthermore, the accumulation of the cis‐α‐ and cis‐β‐[Ru(phen)(bb₁₂)]²⁺ complexes in P. aeruginosa was considerably greater than in Escherichia coli. The uptake of the cis‐α‐[Ru(phen)(bb₁₂)]²⁺ complex into live P. aeruginosa was confirmed by using fluorescence microscopy. The water/octanol partition coefficients (log P) were determined to gain understanding of the relative cellular uptake. The cis‐α‐ and cis‐β‐[Ru(phen)(bb_n)]²⁺ complexes exhibited relatively strong binding to DNA (K_b≈10⁶ M ^?1), but no significant difference between the geometric isomers was observed.     

A single-scattering correction for large contrasts in elastic layers

The single-scattering solution is implemented in a formulation that makes it possible to accurately handle solid-solid interfaces with the parabolic equation method. Problems involving large contrasts across sloping stratigraphy can be handled by subdividing a vertical interface into a series of two or more scattering problems. The approach can handle complex layering and is applicable to a large class of seismic problems. The solution of the scattering problem is based on an iteration formula, which has improved convergence in the new formulation, and the transverse operator of the parabolic wave equation, which is implemented efficiently in terms of banded matrices. Accurate solutions can often be obtained by using only one iteration.     

Shape selectivity versus functional group pre-organization in molecularly imprinted polymers

A systematic survey of related molecular probes differing in shape or functional group orientation was used to compare the effects of shape selectivity versus pre-organization of functional monomers on imprinting and rebinding performance of molecularly imprinted polymers (MIPs). These studies revealed that templates with two functional group interactions with the MIPs are influenced to a larger degree by shape selective interactions than templates with three functional group interactions. For example, with two functional group interactions, increasing side chain size of compounds 1-5 increased selectivity 5-fold; while the same size change for compounds with three functional group interactions leads to a maximum 2-fold increase. Thus, the effects of shape selectivity and pre-organization of functional groups do not appear to work in concert with each other during the imprinting process or in the rebinding behavior. Furthermore, greater selectivity is generally found for templates with two functional groups, where the dominant mode of molecular recognition is shape selectivity. For example, the α value for the MIP elicited toward template compound 5 with two hydrogen bonding groups was 5-12-fold higher than equivalently shaped compounds 6-8 that have three non-covalent binding interactions (Table 3). On the other hand, pre-organization of functional groups dominated the performance of MIPs elicited toward templates with three template-functional group interactions. This is observed in Tables 6-8, where compounds with identical positioning of three functional groups all show less than an order of magnitude change in α values despite changes in shape.     

Dinuclear ruthenium(II) complexes as potential probes for RNA bulge sites

1H NMR spectroscopy and molecular modelling have been used to investigate the binding of the DeltaDelta-and LambdaLambda-enantiomers of the dinuclear ruthenium(II) complex [[Ru(Me2bpy)2]2(mu-bpm)]4+ [Me2bpy = 4,4'-dimethyl-2,2'-bipyridine; bpm = 2,2'-bipyrimidine] to an RNA tridecanucleotide duplex containing a single-base bulge [r(CCGAGAAUUCCGG)2]], and the corresponding control dodecanucleotide [r(CCGGAAUUCCGG)2]. Both enantiomers bound the control RNA sequence weakly. From upfield shifts of the metal complex H3 and H3' protons throughout the titration of the control dodecanucleotide with DeltaDelta-[[Ru(Me2bpy)2]2(mu-bpm)]4+, a binding constant of 1 x 10(3) M(-1) was determined. In NOESY spectra of the control sequence with added DeltaDelta-[[Ru(Me2bpy)2]2(mu-bpm)]4+, NOEs were only observed to protons from the terminal base-pair residues. No significant changes in chemical shift were observed for either the metal complex or RNA protons upon addition of the LambdaLambda-enantiomer to the control dodecanucleotide. The DeltaDelta-[[Ru(Me2bpy)2]2(mu-bpm)]4+ complex bound the bulge-containing RNA with a significantly greater affinity (6 x 10(4) M(-1)) than the non-bulge control RNA duplex. Competition binding experiments indicated that the LambdaLambda-isomer bound the tridecanucleotide with similar affinity to the DeltaDelta-enantiomer. Addition of DeltaDelta-[[Ru(Me2bpy)2]2(mu-bpm)]4+ to the bulge-containing tridecanucleotide induced selective changes in chemical shift for the base H8 and sugar H1' resonances from the adenine bulge residue, and resonances from nucleotide residues adjacent to the bulge site. Intermolecular NOEs observed in NOESY spectra of the tridecanucleotide with added DeltaDelta-[[Ru(Me2bpy)2]2(mu-bpm)]4+ confirmed the selective binding of the ruthenium complex at the bulge site. Preliminary binding models, consistent with the NMR data, showed that the ruthenium complex could effectively associate in the RNA minor groove at the bulge site.