Localization and delocalization in a mixed-valence dicopper helicate

The coordination chemistry of the tetradentate pyridyl-thiazole (py-tz) N-donor ligand 6,6'-bis(4-phenylthiazol-2-yl)-2,2'-bipyridine (L1) has been investigated. Reaction of L1 with equimolar copper(II) ions results in the formation of the single-stranded mononuclear complex [Cu(L1)(ClO4)2] (1), whereas reaction with copper(I) ions results in the double-stranded dinuclear helicate [Cu2(L1)2][PF6]2 (2). Both complexes were characterized by X-ray crystallography, UV-vis spectroscopy, and electrospray ionization mass spectroscopy (as well as 1H NMR spectroscopy for diamagnetic 2). Complex 2 is redox-active and, upon one-electron oxidation, forms the stable tricationic mixed-valence helicate [Cu2(L1)2]3+ (3). This species can also be prepared in situ by combining [Cu(MeCN)4][BF4], [Cu(H2O)6][BF4]2, and L1 in a 1:1:2 ratio in nitromethane. X-ray crystallographic analysis of 3 provides structural evidence for the presence of an internuclear Cu-Cu bond, with an even distribution of spin density across the two Cu centers. Room-temperature UV-vis spectroscopy is consistent with this finding; however, frozen-glass EPR spectroscopic investigations suggest solvatochromic behavior at 110 K, with the [Cu2]3+ core varying from localized to delocalized depending on the solvent polarity.     

Control of S-based aggregation: designed synthesis of NiM2 and Ni2M trinuclear complexes

Modification of the nickel dithiolate metalloligand, Ni(bme-daco) [where bme-daco = bis(mercaptoethyl)diazacyclooctane] or Ni-1, by oxygenation of one thiolate into a sulfinate, Ni(mese-daco) [where mese-daco = (mercaptoethyl)(sulfinatoethyl)diazacyclooctane] or Ni-2, restricts the ligating ability to monodentate and is expected to reduce the donor ability of the remaining thiolate S. Nevertheless, the Ni-2 complex forms a stable thiolate S-bound adduct of W0(CO)5, (Ni-2)W(CO)5, a complex whose upsilon(CO) IR spectrum reports insignificant differences in the donor abilities of Ni-1 and Ni-2 in (eta1-NiN2S2)W(CO)5 complexes. In the presence of the strong sulfophile CuI, a CuNi2 trimetallic, (Ni-2)2CuBr, was isolated. Another trimetallic, (mu-eta2-Ni-1)[W(CO)5]2, demonstrated the Ni(bme-daco), Ni-1, unit to bridge low-valent metals in a transoid configuration, yielding W-W distances of over 5 A.     

Relating PAC damping to EFG fluctuation rates through the PAC relaxation peak

A perturbed angular correlation (PAC) experiment that measures dynamic damping also needs information about the fundamental quadrupole frequency to relate the damping as a function of temperature to the EFG fluctuation rate. When the experiment is unable to access slow electric field gradient (EFG) fluctuations that show the fundamental quadrupole frequency directly, one needs additional information to determine the hyperfine field parameters and thereby the connection between observed damping and EFG fluctuation rates. One way to solve this problem is to estimate the hyperfine parameters from the fluctuation rate for maximum damping (i.e. at the relaxation peak) or from the rate of maximum damping. This work relates both the maximum damping rate and the fluctuation rate at the relaxation peak to EFG magnitudes (or quadrupole frequencies) for five dynamic N-state symmetric models of fluctuating EFGs.     

Methods for the Analysis of High Precision Differential Hydrogen Deuterium Exchange Data

Hydrogen/deuterium exchange (HDX) mass spectrometry has been widely applied to the characterization of protein dynamics. More recently, differential HDX has been shown to be effective for the characterization of ligand binding. Previously we have described a fully automated HDX system for use as a ligand screening platform. Here we describe and validate the required data analysis workflow to facilitate the use of HDX as a robust approach for ligand screening. Following acquisition of HDX data at a single on-exchange time point (n ≥ 3), one way analysis of variance in conjunction with the Tukey multiple comparison procedure is used to establish the significance of any measured difference. Analysis results are graphed with respect to a single peptide, ligand or group of ligands, or displayed as an overview within a heat map. For the heat map display, only Δ%D values with a Tukey-adjusted P value less than 0.05 are colored. Hierarchical clustering is used to bin compounds with highly similar HDX signatures. The workflow is evaluated with a small data set showing the ligand binding domain (LDB) of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) screened against 10 functionally selective ligands. More significantly, data for the vitamin D receptor (VDR) in complex with 87 ligands are presented. To highlight the robustness and precision of our automated HDX platform we analyzed the data from 4191 replicate HDX measurements acquired over an eight month timeframe. Ninety six percent of these measurements were within 10 percent of the mean value. Work has begun to integrate these analysis and graphing components within our HDX software suite.     

A Practical Synthesis of ω-Aminoalkanoic Acid Derivatives from Cycloalkanones

A practical synthetic route to N-Boc protected or Boc-amino acid coupled ω-aminoalkanoic acids is reported and exemplified by the preparation of 8-(t-butoxycarbonylamino)caprylic acid 2 and (N-t-butoxycarbonylphenylalanyl)-8-aminocaprylic acid 3. The sequence does not involve column chromatography, hydrogenation, azide or bromine related rearrangements, and therefore is amenable to scale-up. Homologues of the ω-aminoalkanoic acid derivatives may also be prepared by using different cycloalkanones.     

Temporary hearing loss influences post-stimulus time histogram and single neuron action potential estimates from human compound action potentials

An analytic compound action potential (CAP) obtained by convolving functional representations of the post-stimulus time histogram summed across auditory nerve neurons [P(t)] and a single neuron action potential [U(t)] was fit to human CAPs. The analytic CAP fit to pre- and postnoise-induced temporary hearing threshold shift (TTS) estimated in vivo P(t) and U(t) and the number of neurons contributing to the CAPs (N). The width of P(t) decreased with increasing signal level and was wider at the lowest signal level following noise exposure. P(t) latency decreased with increasing signal level and was shorter at all signal levels following noise exposure. The damping and oscillatory frequency of U(t) increased with signal level. For subjects with large amounts of TTS, U(t) had greater damping than before noise exposure particularly at low signal levels. Additionally, U(t) oscillation was lower in frequency at all click intensities following noise exposure. N increased with signal level and was smaller after noise exposure at the lowest signal level. Collectively these findings indicate that neurons contributing to the CAP during TTS are fewer in number, shorter in latency, and poorer in synchrony than before noise exposure. Moreover, estimates of single neuron action potentials may decay more rapidly and have a lower oscillatory frequency during TTS.     

Proton-detected heteronuclear single quantum correlation NMR spectroscopy in rigid solids with ultra-fast MAS

In this article, we show the potential for utilizing proton-detected heteronuclear single quantum correlation (HSQC) NMR in rigid solids under ultra-fast magic angle spinning (MAS) conditions. The indirect detection of carbon-13 from coupled neighboring hydrogen nuclei provides a sensitivity enhancement of 3- to 4-fold in crystalline amino acids over direct-detected versions. Furthermore, the sensitivity enhancement is shown to be significantly larger for disordered solids that display inhomogeneously broadened carbon-13 spectra. Latrodectus hesperus (Black Widow) dragline silk is given as an example where the sample is mass-limited and the sensitivity enhancement for the proton-detected experiment is 8- to 13-fold. The ultra-fast MAS proton-detected HSQC solid-state NMR technique has the added advantage that no proton homonuclear decoupling is applied during the experiment. Further, well-resolved, indirectly observed carbon-13 spectra can be obtained in some cases without heteronuclear proton decoupling.     

Stabilizing effect of oxygen on thermal degradation of poly(methyl methacrylate)

The thermal degradation of poly(methyl methacrylate) has been studied under nitrogen and air. The presence of oxygen increases the initial decomposition temperature by 70°C. The stabilizing effect of oxygen is explained by the formation of thermally stable radical species that suppress unzipping of the polymer. This assumption is supported by the experimental fact that introduction of NO into the gaseous atmosphere increases the initial decomposition temperature by more than 100°C.     

Tailored polymers by free radical processes

This paper describes a versatile and effective method for the control of free radical polymerization and its use in the preparation of narrow polydispersity polymers of various architectures. Living character is conferred to conventional free radical polymerization by the addition of a thiocarbonylthio compound of general structure S=C(Z)SR, for example, S=C(Ph)SC(CH₃)₂Ph. The mechanism involves Reversible Addition-Fragmentation chain Transfer and, for convenience of referral, we have designated it the RAFT polymerization. The process is compatible with a very wide range of monomers including functional monomers such as acrylic acid, hydroxyethyl methacrylate, and dimethylaminoethyl methacrylate. Examples of narrow polydispersity (≤1.2) homopolymers, copolymers, gradient copolymers, end-functional polymers, star polymers, A-B diblock and A-B-A triblock copolymers are presented.