A new synthesis of difluoromethanesulfonamides--a novel pharmacophore for carbonic anhydrase inhibition

Preparation of the key intermediate carboxydifluoromethanesulfonamide provides direct synthetic access to a wide range of novel difluoromethanesulfonamides, including the acetazolamide analogue (2-ethanoylamino-1,3,4-thiadiazol-5-yl)-difluoromethanesulfonamide. Their water solubility and stability, ether partition coefficient, pK(a) and submicromolar dissociation constants for human carbonic anhydrase isozyme II (HCA II) make them promising candidates for topical glaucoma therapy.     

Synthesis of substituted quinolines by electrophilic cyclization of N-(2-alkynyl)anilines

Quinolines substituted in the 3-position by an iodo or phenylseleno group are readily prepared in good to excellent yields by the reaction of propargylic anilines with appropriate electrophiles under mild reaction conditions. [reaction: see text]     

Synthesis of the eastern portion of ajudazol a based on Stille coupling and double acetylene carbocupration

[structure: see text] A strategy for the synthesis of ajudazol A, an unusual, pharmacologically active metabolite from myxobacteria, based on the Stille cross-coupling of a 2-stannyl-oxazole with a vinyl iodide unit is described; the vinyl halide unit containing a (Z,Z)-diene was prepared in one pot by the double acetylene carbocupration of a functionalized alkyl cuprate followed by trapping with 2,3-dibromopropene.     

Inhibition studies on salicylate synthase

Analogues of chorismate and isochorismate were designed and tested as potential inhibitors in the first inhibition study against a salicylate synthase.     

The mechanistic origin of regiochemical changes in the nitrosative N-dealkylation of N,N-dialkyl aromatic amines

The regioselectivity of the nitrous acid mediated dealkylation of 4-substituted-N-ethyl-N-methylanilines is a function of the acidity of the reaction mixture. At high acidity deethylation predominates, whereas demethylation is the predominant reaction in nitrosamine formation at pH 2 and above. In some cases the regioselectivity of nitrosative dealkylation changes as the run proceeds. Through the use of the corresponding 4-nitroaniline as the primary substrate, CIDNP, kinetics, kinetic deuterium isotope effects and other transformations involving nitrosations with NO2 or NOBF4 in aprotic solvents, a new mechanism of tertiary amine nitrosation has been deduced and proposed to explain regioselective deethylation. The mechanism involves the oxidation of the substrate to the amine radical cation by NO+. This is followed by the abstraction of a hydrogen atom from the carbon adjacent to the amine nitrogen by NO2 to produce an iminium ion which reacts further to produce the corresponding aldehyde and the nitrosamine. Depending upon the acidity, this process competes with three other mechanistic pathways, two of which give the nitrosamine through the iminium ion, and one leads to the formation of C-nitro compounds. The competing pathways to nitrosamine formation involve NOH elimination from a nitrosammonium ion and deprotonation of the radical cation to give an alpha-amino radical which rapidly oxidized to the iminium ion. Predominant, but not highly regioselective demethylation occurs by these pathways. Nitro compound formation principally arises from the reaction of NO2 with the radical cation followed by deprotonation, but also occurs by para C-nitrosation followed by oxidation.     

The significance of high-order resonances of spherical bubbles to the acoustic response of fish with swimbladders

The high-order resonant response of spherical gas bubbles in seawater, when insonified by an acoustic pulse of 12 cycles of 38 kHz, used for target strength measurements, shows substantial variation in shape with only small changes in bubble radius. In contrast, the amplitude response of a gas bubble near its fundamental resonance changes predominantly in magnitude as the radius changes. The fundamental response is very similar to that of a more rigid target such as a tungsten carbide sphere. It might initially be thought that the high-order resonant response of spherical gas bubbles in seawater would have little relevance to the response of a gas-filled spheroidal swimbladder immersed in a viscous fish body. However, target responses similar to those predicted theoretically for gas bubbles have been found in data collected in situ for estimating target strength from normal fish populations. With further theoretical and experimental work, high-order resonances could be a useful aid to estimating target size and possibly target species.     

The role of visual speech cues in reducing energetic and informational masking

Two experiments compared the effect of supplying visual speech information (e.g., lipreading cues) on the ability to hear one female talker's voice in the presence of steady-state noise or a masking complex consisting of two other female voices. In the first experiment intelligibility of sentences was measured in the presence of the two types of maskers with and without perceived spatial separation of target and masker. The second study tested detection of sentences in the same experimental conditions. Results showed that visual cues provided more benefit for both recognition and detection of speech when the masker consisted of other voices (versus steady-state noise). Moreover, visual cues provided greater benefit when the target speech and masker were spatially coincident versus when they appeared to arise from different spatial locations. The data obtained here are consistent with the hypothesis that lipreading cues help to segregate a target voice from competing voices, in addition to the established benefit of supplementing masked phonetic information.     

Fine-tuning molecular acoustic models: sensitivity of the predicted attenuation to the Lennard-Jones parameters

In a previous paper [Y. Dain and R. M. Lueptow, J. Acoust. Soc. Am. 109, 1955 (2001)], a model of acoustic attenuation due to vibration-translation and vibration-vibration relaxation in multiple polyatomic gas mixtures was developed. In this paper, the model is improved by treating binary molecular collisions via fully pairwise vibrational transition probabilities. The sensitivity of the model to small variations in the Lennard-Jones parameters--collision diameter (sigma) and potential depth (epsilon)--is investigated for nitrogen-water-methane mixtures. For a N2(98.97%)-H2O(338 ppm)-CH4(1%) test mixture, the transition probabilities and acoustic absorption curves are much more sensitive to sigma than they are to epsilon. Additionally, when the 1% methane is replaced by nitrogen, the resulting mixture [N2(99.97%)-H2O(338 ppm)] becomes considerably more sensitive to changes of sigma(water). The current model minimizes the underprediction of the acoustic absorption peak magnitudes reported by S. G. Ejakov et al. [J. Acoust. Soc. Am. 113, 1871 (2003)].     

Toward a theory of wave energy transport in large irregular structures

An ansatz is proposed by which the energy transport behavior observed at early times in a direct numerical simulation (DNS) of a large irregular structure may be extrapolated to arbitrary times. In the slow-transport limit, this ansatz leads to a diffusion-like equation, similar to that of time-domain statistical energy analysis (SEA), but it does not require substructuring. The model is successfully used to extract diffusion parameters from simulated data of unambiguously diffusive character. The model is then successfully used to extract diffusion parameters from data obtained in a DNS of a simple undamped two-room structure of a kind typically analyzed by SEA or room acoustics.