Observation of an Organic Acid Mediated Spin State Transition in a Co(II)-Schiff Base Complex: An EPR, HYSCORE, and DFT Study

The interactions of a weak organic acid (acetic acid, HOAc) with a toluene solution of the Co(II)-Schiff base type complex, (R,R')-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexane-diamino Co(II) (labeled [Co(1)]), was investigated using EPR, HYSCORE, and DFT computations. This activated [Co(II)(1)] system is extremely important within the context of asymmetric catalysts (notably the hydrolytic kinetic resolution of epoxides) despite the lack of detailed structural information about the nature of the paramagnetic species present. Under anaerobic conditions, the LS [Co(II)(1)] complex with a |yz, (2)A(2)? ground state is converted into a low-spin (LS) and a high-spin (HS) complex in the presence of the acid. The newly formed LS state is assigned to the coordinated [Co(II)(1)]-(HOAc) complex, possessing a |z(2), (2)A(1)? ground state (species A; g(x) = 2.42, g(y) = 2.28, g(z) = 2.02, A(x) = 100, A(y) = 120, A(z) = 310 MHz). The newly formed HS state is assigned to an acetate coordinated [Co(II)(1)]-(OAc(-)) complex, possessing an S = (3)/(2) spin ground state (species B, responsible for a broad EPR signal with g ≈ 4.6). These spin ground states were confirmed with DFT calculations using the hybrid BP86 and B3LYP functionals. Under aerobic conditions, the LS and HS complexes (species A and B) are not observed; instead, a new HS complex (species C) is formed. This complex is tentatively assigned to a paramagnetic superoxo bridged dimer (AcO(-))[Co(II)(1)···O(2)(-)Co(III)(1)](HOAc), as distinct from the more common diamagnetic peroxo bridged dimers. Species C is characterized by a very broad HS EPR signal (g(x) = 5.1, g(y) = 3.9, g(z) = 2.1) and is reversibly formed by oxygenation of the LS [Co(II)(1)]-(HOAc) complex to the superoxo complex [Co(III)(1)O(2)(-)](HOAc), which subsequently forms the association complex C by interaction with the HS [Co(II)(1)](OAc(-)) species. The LS and HS complexes were also identified using other organic acids (benzoic and propanoic acid). Thermal annealing-quenching experiments revealed the additional presence of [Co(III)(1)O(2)(-)](HOAc) adducts, corroborating the presence of species C and the presence of diamagnetic dimer complexes in the solution, such as the EPR silent (HOAc)[Co(III)(1)(O(2)(2-))Co(III)(1)](HOAc). Overall, it appears that a facile interconversion of the [Co(1)] complex, possessing a LS ground state, occurs in the presence of acetic acid, producing both HS and LS Co(II) states, prior to formation of the oxidized active form of the catalyst, [Co(III)(1)](OAc(-)).     

Amarisolide monohydrate,a 2‐(β‐glu­cosyl)­neoclerodane

The absolute configuration of the neoclerodane glycoside amarisolide, presented here as the monohydrate, C₂₆H₃₆O₉·H₂O, has been determined by association with the known configuration of the glucose moiety. Its structure was established as 2β‐(O‐β‐d ‐gluco­pyran­osyl)­neocleroda‐3,13(16),14‐trien‐15,16‐epoxy‐18,19‐olide. Extensive hydrogen bonding among the hydroxyl groups of the sugar moiety forms layers which are interconnected by water mol­ecules.     

Aldehyde-functional thermoresponsive diblock copolymer worm gels exhibit strong mucoadhesion

A series of thermoresponsive diblock copolymer worm gels is prepared via reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 2-hydroxypropyl methacrylate using a water-soluble methacrylic precursor bearing pendent cis-diol groups. Selective oxidation using an aqueous solution of sodium periodate affords the corresponding aldehyde-functional worm gels. The aldehyde groups are located within the steric stabilizer chains and the aldehyde content can be adjusted by varying the periodate/cis-diol molar ratio. These aldehyde-functional worm gels are evaluated in terms of their mucoadhesion performance with the aid of a fluorescence microscopy-based assay. Using porcine urinary bladder mucosa as a model substrate, we demonstrate that these worm gels offer a comparable degree of mucoadhesion to that afforded by chitosan, which is widely regarded to be a ‘gold standard’ positive control in this context. The optimum degree of aldehyde functionality is approximately 30%: lower degrees of functionalization lead to weaker mucoadhesion, whereas higher values compromise the desirable thermoresponsive behavior of these worm gels.

Optimizing the aldehyde content of thermoresponsive diblock copolymer worm gels via periodate oxidation leads to mucoadhesion performance comparable to that of chitosan (a gold standard positive control) in a fluorescence assay using porcine mucosa.     

The RHIM of the Immune Adaptor Protein TRIF Forms Hybrid Amyloids with Other Necroptosis-Associated Proteins

TIR-domain-containing adapter-inducing interferon-β (TRIF) is an innate immune protein that serves as an adaptor for multiple cellular signalling outcomes in the context of infection. TRIF is activated via ligation of Toll-like receptors 3 and 4. One outcome of TRIF-directed signalling is the activation of the programmed cell death pathway necroptosis, which is governed by interactions between proteins that contain a RIP Homotypic Interaction Motif (RHIM). TRIF contains a RHIM sequence and can interact with receptor interacting protein kinases 1 (RIPK1) and 3 (RIPK3) to initiate necroptosis. Here, we demonstrate that the RHIM of TRIF is amyloidogenic and supports the formation of homomeric TRIF-containing fibrils. We show that the core tetrad sequence within the RHIM governs the supramolecular organisation of TRIF amyloid assemblies, although the stable amyloid core of TRIF amyloid fibrils comprises a much larger region than the conserved RHIM only. We provide evidence that RHIMs of TRIF, RIPK1 and RIPK3 interact directly to form heteromeric structures and that these TRIF-containing hetero-assemblies display altered and emergent properties that likely underlie necroptosis signalling in response to Toll-like receptor activation.     

Pore structures in an implantable sol-gel titania ceramic device used in controlled drug release applications: A modeling study

Several process variables, which may be helpful in optimizing the rate at which drugs are released from implantable, sol-gel titania devices have been identified in this study. The controlled rate of drug release is compared for two different anticonvulsant drugs, valproic acid and sodic phenytoin. Contrary to what one might expect, when the concentration is increased in the titania reservoir the rate of initial drug delivery decreases. This is a desirable result, because it may reduce the danger of a high initial discharge, which may harm the epileptic rat. The structure of the porous structure within the titania network has been studied using a generalized form of the BET equation which considers only n layers. In general, following an initial discharge, the rate at which the drug is released will increase with the increasing concentration. Pore mouth blocking can present a problem. However, this problem tends to disappear following the initial discharge. The extent of drug loading is a useful variable parameter, which can be adjusted in order to deliver the amount of drug required in a given application.     

A novel derivative for the assessment of urinary and salivary nitrate using gas chromatography/mass spectrometry

Previous gas chromatography/mass spectrometry (GC/MS) methods for determining nitrate in biological samples involve either hazardous chemicals or produce multiple isomers that can be difficult to quantitate. Modification of these methods, by the nitration of mesitylene instead of benzene and in the presence of trifluoroacetic anhydride rather than sulphuric acid, should enable simple isotopic quantitation for use in tracer studies, for example, in the measurement of nitric oxide production. Desiccated urine and saliva samples, in addition to aqueous labelled and unlabelled nitrate standards, were treated with trifluoroacetic anhydride and mesitylene at 70°C for 1 h, cooled, then sequentially washed with deionised water and aqueous sodium bicarbonate. The solution of nitromesitylene in mesitylene was separated, dried and analysed by GC/MS. The full mass spectra exhibited abundant ions at m/z 165 and 166 corresponding to the unlabelled and labelled molecular species of nitromesitylene, respectively. Selected ion monitoring of these masses for a series of gravimetrically prepared standards indicated good agreement with isotopic enrichments in the range 0.0625–5 mole % excess, and at nitrate concentrations within the physiological range of 0.078–2 mmol/L. Derivatised samples were stable with respect to isotopic enrichments and nitrate concentrations at −20°C for up to 21 days and exhibited excellent repeatability. Nitration of mesitylene proved to be a simple and rapid method for the measurement of isotope ratios in aqueous nitrates by GC/MS, which has applications in tracer studies and in concentration determinations by isotope dilution techniques for nitric oxide production. Copyright © 2008 John Wiley & Sons, Ltd.     

Very high resolution CO laser spectrometer and first sub-Doppler line-shape studies near 60 THz (5 μm)

2 laser standards. Using this technique, we can tune the CO laser frequency with absolute frequency control within the gain profile of each laser transition. The frequency uncertainty is smaller than 15 kHz, corresponding to Δν/ν=2.5×10^-10. Moreover, we obtain a reduction of the CO laser linewidth by a factor of 2 down to 65 kHz, corresponding to a spectral resolution of δν/ν=1×10^-9. With this outstanding accuracy and resolution we studied the shape of saturation dips in rovibrational lines of CO and carbonyl sulfide (OCS) at low pressure (<5 Pa). The self-pressure-broadening rate of CO was found to be γ_c=+83(7) kHz/Pa in this pressure region. This value is about four times higher than values resulting from previous measurements at much higher pressures. To our knowledge the measurements described here are the first line-shape studies with sub-Doppler resolution in the 5 μm spectral region. Received: 4 November 1996     

A New Mechanism for β‐Lactamases: Class D Enzymes Degrade 1β‐Methyl Carbapenems through Lactone Formation

β‐Lactamases threaten the clinical use of carbapenems, which are considered antibiotics of last resort. The classical mechanism of serine carbapenemase catalysis proceeds through hydrolysis of an acyl‐enzyme intermediate. We show that class D β‐lactamases also degrade clinically used 1β‐methyl‐substituted carbapenems through the unprecedented formation of a carbapenem‐derived β‐lactone. β‐Lactone formation results from nucleophilic attack of the carbapenem hydroxyethyl side chain on the ester carbonyl of the acyl‐enzyme intermediate. The carbapenem‐derived lactone products inhibit both serine β‐lactamases (particularly class D) and metallo‐β‐lactamases. These results define a new mechanism for the class D carbapenemases, in which a hydrolytic water molecule is not required.     

An empirical study of the effect of the variables in a flash vacuum pyrolysis (FVP) experiment

The effect of the variation of the experimental parameters on the conversion of precursor to products in a typical flash vacuum pyrolysis (FVP) experiment was investigated empirically. Temperature-conversion plots can be used to optimise FVP conditions and their mechanistic significance is exemplified. At a given temperature, the conversion can be increased by an increase in the background pressure, or by packing a section of the furnace tube with inert material (particularly when placed at the trap end of the furnace tube) or by employing a catalyst. Despite the prevailing view that only intramolecular reactions take place by FVP, it has been shown by a 'dual-FVP' cross-over experiment that the dimerisation of benzyl radicals occurs in the gas-phase, before the cold trap, under standard conditions. However, reduction in through-put rate, increase in furnace temperature and reduction in background pressure all reduce the amount of gas-phase coupling.