Electronic Supplementary Information Research Articles

Assessing molecular simulation for the analysis of lipid monolayer reflectometry

Using molecular simulation to aid in the analysis of neutron reflectometry measurements is commonplace. However, reflectometry is a tool to probe large-scale structures, and therefore the use of all-atom simulation may be irrelevant. This work presents the first direct comparison between the reflectometry profiles obtained from different all-atom and coarse-grained molecular dynamics simulations. These are compared with a traditional model layer structure analysis method to determine the minimum simulation resolution required to accurately reproduce experimental data. We find that systematic limits reduce the efficacy of the MARTINI potential model, while the Berger united-atom and Slipids all-atom potential models agree similarly well with the experimental data. The model layer structure gives the best agreement, however, the higher resolution simulation-dependent methods produce an agreement that is comparable. Finally, we use the atomistic simulation to advise on possible improvements that may be offered to the model layer structures, creating a more realistic monolayer model. Usage: Electronic Supplementary Information (ESI) including all analysis/plotting scripts and figure files, allowing for a fully reproducible, and automated, analysis workflow for the work presented is available at https://github.com/arm61/sim_vs_trad (DOI: 10.5281/zenodo.3254719) under a CC BY-SA 4.0 license. Reduced experimental datasets are available at DOI: 10.15125/BATH-00586, under a CC-BY 4.0 license.

Triboelectric generator based on a moving charged bead**Electronic supplementary information (ESI) available: More detailed information for analytic calculation via COMSOL about available charge distance between the PTFE bead and Cu electrode, illustration of the speed-dependence contact area, and time dependent long-term stability.

An energy harvesting system using a triboelectric generator (TEG), which converts a small amount of mechanical energy to available electrical energy, has recently been developed by combining a simple one-directional mechanical force (contact and separation or sliding back and forth) with a 2D device materials. However, with regard to using the TEG in real world applications, there is no TEG design suitable for utilizing a variety of mechanical forces and for generating triboelectric charge in various environmental conditions, especially under high relative humidity. In this work, we introduce a design for a humidity-independent triboelectric generator (HITEG) that can generate triboelectric charges with a granular system by simple rotating or shaking under high relative humidity conditions. The HITEG can generate an open-circuit voltage of 81.63 V and a short-circuit current of 213.9 nA using 80 polytetrafluoroethylene beads.

Correction: Design, synthesis and anti-inflammatory effects of novel 9-O-substituted-berberine derivatives electronic supplementary information

Correction for ‘Design, synthesis and anti-inflammatory effects of novel 9-O-substituted-berberine derivatives’ by Mei-Yan Huang et al., MedChemComm, 2016, DOI: 10.1039/c5md00577a.

An overview of nanoparticles commonly used in fluorescent bioimaging.

This article gives an overview of the various kinds of nanoparticles (NPs) that are widely used for purposes of fluorescent imaging, mainly of cells and tissues. Following an introduction and a discussion of merits of fluorescent NPs compared to molecular fluorophores, labels and probes, the article assesses the kinds and specific features of nanomaterials often used in bioimaging. These include fluorescently doped silicas and sol-gels, hydrophilic polymers (hydrogels), hydrophobic organic polymers, semiconducting polymer dots, quantum dots, carbon dots, other carbonaceous nanomaterials, upconversion NPs, noble metal NPs (mainly gold and silver), various other nanomaterials, and dendrimers. Another section covers coatings and methods for surface modification of NPs. Specific examples on the use of nanoparticles in (a) plain fluorescence imaging of cells, (b) targeted imaging, (c) imaging of chemical species, and (d) imaging of temperature are given next. A final section covers aspects of multimodal imaging (such as fluorescence/nmr), imaging combined with drug and gene delivery, or imaging combined with therapy or diagnosis. The electronic supplementary information (ESI) gives specific examples for materials and methods used in imaging, sensing, multimodal imaging and theranostics such as imaging combined with drug delivery or photodynamic therapy. The article contains 273 references in the main part, and 157 references in the ESI.

Mechanistic investigations reveal that dibromobimane extrudes sulfur from biological sulfhydryl sources other than hydrogen sulfide†Electronic supplementary information (ESI) available: Experimental details, pH stability data for BTE, NMR spectra. See DOI: 10.1039/c4sc01875cClick here for additional data file.

Hydrogen sulfide (H2S) has emerged as an important biological signaling molecule in the last decade. During the growth of this field, significant controversy has arisen centered on the physiological concentrations of H2S. Recently, a monobromobimane (mBB) method has been developed for the quantification of different biologically-relevant sulfide pools. Based on the prevalence of the mBB method for sulfide quantification, we expand on this method to report the use of dibromobimane (dBB) for sulfide quantification. Reaction of H2S with dBB results in formation of highly-fluorescent bimane thioether (BTE), which is readily quantifiable by HPLC. Additionally, the reaction of sulfide with dBB to form BTE is significantly faster than the reaction of sulfide with mBB to form sulfide dibimane. Using the dBB method, BTE levels as low as 0.6 pM can be detected. Upon use of the dBB method in wild-type and CSE-/- mice, however, dBB reports significantly higher sulfide levels than those measured using mBB. Further investigation revealed that dBB is able to extract sulfur from other sulfhydryl sources including thiols. Based on mechanistic studies, we demonstrate that dBB extracts sulfur from thiols with α- or β-hydrogens, thus leading to higher BTE formation than from sulfide alone. Taken together, the dBB method is a highly sensitive method for H2S but is not compatible for use in studies in which other thiols are present.

Studying the active-site loop movement of the São Paolo metallo-β-lactamase-1†Electronic supplementary information (ESI) available: Procedures for protein expression and purification, 19F-labelling, crystallisation, data collection, and structure determination, table of crystallographic data, table of crystallographic parameters and refinement statistics, figures showing binding mode and distances, procedures for mass spectrometry measurements, differential scanning fluorimetry measurements, stopped-flow measurements and other kinetics measurements. See

Metallo-β-lactamases (MBLs) catalyse the hydrolysis of almost all β-lactam antibiotics. We report biophysical and kinetic studies on the São Paulo MBL (SPM-1), which reveal its Zn(ii) ion usage and mechanism as characteristic of the clinically important di-Zn(ii) dependent B1 MBL subfamily. Biophysical analyses employing crystallography, dynamic 19F NMR and ion mobility mass spectrometry, however, reveal that SPM-1 possesses loop and mobile element regions characteristic of the B2 MBLs. These include a mobile α3 region which is important in catalysis and determining inhibitor selectivity. SPM-1 thus appears to be a hybrid B1/B2 MBL. The results have implications for MBL evolution and inhibitor design.

Microporous device for local electric recordings on model lipid bilayers**Electronic Supplementary Information (ESI) available: See DOI: 10.1039/b000000x/

A powerful approach for characterizing lipid membranes and embedded proteins is the reconstitution of model lipid bilayers. The extreme fragility of 5 nm thick bilayers is a challenge for device design and requires a trade off of stability against accessibility. We here present a microporous lab-on-chip device that allows us to form stable, solvent-free lipid bilayers from giant unilamellar vesicles (GUVs) in a geometry that provides a unique set of access possibilities. The device is constructed around a micro-fabricated silicon chip with clusters of 1 µm-diameter pores and provides optical access to the lipid bilayers for high-NA epifluorescence imaging. At the same time, solvent exchange is possible on both sides of the lipid bilayer. Complete coverage can be achieved with GUVs, so that voltages can be applied across the lipid bilayer and single-channel currents can be measured using external or integrated silver/silver chloride electrodes. We describe the micro-fabrication by standard cleanroom techniques and the characterization of the device by atomic force microscopy, scanning electron microscopy and impedance spectroscopy. In proof-of-concept experiments we demonstrate that the device is capable of low-noise, single-ion-channel recordings.

Biologically active diterpenes containing a gem-dimethylcyclopropane subunit: an intriguing source of PKC modulators.

Covering: 1973 to 2013. The biological activities of tigliane, lathyrane, ingenane, casbane, jatropholane and premyrsinane diterpenoids which contain the gem-dimethylcyclopropyl unit are described. Particular attention is given to their anti-viral, anti-microbial and cytotoxic activities. In the main text there are 132 references. The electronic supplementary information contains tables listing 424 of these diterpenoids, their occurrence and biological activity together with the references.

Function through bio-inspired, synthesis-informed design: step-economical syntheses of designed kinase inhibitors†Dedicated to Max Malacria, a friend and scholar whose science and creative contributions to step-economical synthesis have inspired us all and moved the field closer to the ideal.‡Electronic supplementary information (ESI) available: Synthetic procedures and spectral data. See DOI: 10.1039/c4qo00228hClick here for additional data file.

The human kinome comprises over 500 protein kinases. When mutated or over-expressed, many play critical roles in abnormal cellular functions associated with cancer, cardiovascular disease and neurological disorders. Here we report a step-economical approach to designed kinase inhibitors inspired by the potent, but non-selective, natural product staurosporine, and synthetically enabled by a novel, complexity-increasing, serialized [5 + 2]/[4 + 2] cycloaddition strategy. This function-oriented synthesis approach rapidly affords tunable scaffolds, and produced a low nanomolar inhibitor of protein kinase C.

Orthogonal halogen and hydrogen bonds involving a peptide bond model†Electronic supplementary information (ESI) available: Experimental part, DSC, IR spectroscopic and crystallographic data. CCDC 899779-899785. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4ce01514bClick here for additional data file.Click here for additional data file.

The peptide bond model N-methylacetamide self-assembles with a range of dihalotetrafluorobenzenes forming co-crystals that all show the occurrence of orthogonal hydrogen and halogen bonds.

Chemically diverse polymer microarrays and high throughput surface characterisation: a method for discovery of materials for stem cell culture†Electronic supplementary information (ESI) available. See DOI: 10.1039/c4bm00054dClick here for additional data file.

Materials discovery provides the opportunity to identify novel materials that are tailored to complex biological environments by using combinatorial mixing of monomers to form large libraries of polymers as micro arrays. The materials discovery approach is predicated on the use of the largest chemical diversity possible, yet previous studies into human pluripotent stem cell (hPSC) response to polymer microarrays have been limited to 20 or so different monomer identities in each study. Here we show that it is possible to print and assess cell adhesion of 141 different monomers in a microarray format. This provides access to the largest chemical space to date, allowing us to meet the regenerative medicine challenge to provide scalable synthetic culture ware. This study identifies new materials suitable for hPSC expansion that could not have been predicted from previous knowledge of cell-material interactions.

Targeting the endoplasmic reticulum with a membrane-interactive luminescent ruthenium(ii) polypyridyl complex†Electronic supplementary information (ESI) available: Experimental details, characterization of 2 and Fig. S1-S6. See DOI: 10.1039/c3sc51725jClick here for additional data file.

The characterization and bioactivity of the dinuclear ruthenium(ii) complex [(Ru(DIP)2)2(tpphz)]4+ (DIP = 4,7-diphenyl-1,10-phenanthroline and tpphz = tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine) is reported. This new complex is found to be luminescent in acetonitrile, where excitation into MLCT (metal-to-ligand charge-transfer) bands in the visible area of the spectrum (λex = 450 nm, ε = 45 000 M-1 cm-1) result in red emission (λem,max = 620 nm, ΦMLCT = 0.017). Aqueous in vitro binding studies indicate that this complex binds to duplex DNA with an affinity of 1.8 × 106 M-1 through a non-classical groove-binding interaction, however, unlike the parent complex [(Ru(phen)2)2(tpphz)]4+ (phen = 1,10-phenanthroline), it also displays an increase in MLCT luminescence on addition of liposomes. Confocal microscopy and TEM studies show that this lipophilic complex targets the endoplasmic reticulum of eukaryotic cells, where it functions as an imaging agent for this organelle, and cytotoxicity studies in human cancer cell lines indicate a comparable potency to the anti-cancer drug cisplatin.

Extent of Nucleophilic Participation in the Solvolyses of Alkyl Chloromethyl Ethers and Sulfides

The specific rates of solvolysis have been determined for chloromethyl ethyl ether (3) and chloromethyl octyl ether (4) at −10.0 °C and for chloromethyl methyl sulfide (5) at 25.0 °C in a variety of pure and binary solvents. These values were used for a correlation analysis treatment using the extended Grunwald–Winstein equation incorporating literature values for solvent nucleophilicity ( NT) and solvent ionising power ( YCl). Appreciable values were found for the sensitivities towards changes in both NT and YCl values. Using a literature specific rate of hydrolysis at 25.0 °C for fluoromethyl methyl ether (2), the required value for chloromethyl methyl ether (1) was obtained from use of NT and YCl values and the sensitivities for 3 to changes in their values, to adjust an experimental specific rate value for 1 in 100% ethanol to the corresponding value in 100% water. In this way, an estimated kCl/ kF of 1.2 × 105 was obtained, essentially identical to values for the solvolyses of tert-butyl halides. A unimolecular mechanism for the solvolyses, with appreciable nucleophilic solvation of the developing carbocation, is proposed. Electronic supplementary information provides, for several solvents, specific rates of solvolysis for 3, 4, and 5 at additional temperatures and the calculated activation parameters.

6]Saddlequat: a [6]helquat captured on its racemization pathway

A dicationic [6]helicene congener captured on the racemization pathway in its saddle-shaped geometry is introduced. Synthesis, structure, resolution, and dynamic properties of this chiral [6]saddlequat in-between and its highly stereocontrolled transformation into enantiopure [6]helquat are discussed and demonstrated. The dynamic aspects established by experiment and supported by detailed DFT-D calculations are presented visually in the form of a movie (electronic table-of-contents and electronic supplementary information). The title [6]saddlequat was found to be an isolable chiral species on the entirely chiral enantiomerization pathway of a [6]helquat that is discussed as an example of Mislow's “rubber glove” molecule.

Selective aerobic oxidation of para-xylene in sub- and supercritical water. Part 2. The discovery of better catalysts

An extensive and systematic study has been carried out on the catalytic effect of more than 20 elements on the aerobic oxidation of p-xylene to terephthalic acid in super- and subcritical water. Reactions have been performed in a continuous reactor under catalyst unsaturated conditions. Reaction product, by-products and intermediates have been quantified as well as the burn (the amount of CO2 originating from total oxidation of p-xylene). CuBr2 has been found to be a superior catalyst to MnBr2, which has been widely used in the literature for this reaction in water at high temperatures. At catalyst unsaturated conditions (i.e. with low concentrations of catalyst), MnBr2 gives a terephthalic acid yield of 36.1% whereas CuBr2 enhances this value to 55.6%. A strong synergistic effect has been found between CuBr2 and other metals and sources of bromide. Indeed, we show that Cu/Co/Br, Cu/Co/NH4/Br and other mixtures give better results than CuBr2 reaching a terephthalic acid yield of 70.5% for the four component catalyst. The compositions of the catalyst as well as the reactor temperature have been optimized and their effects on the analyzed compounds are discussed. A substantial amount of additional data is included in the electronic supplementary information.

Metabonomics study of urine and plasma in depression and excess fatigue rats by ultra fast liquid chromatography coupled with ion trap-time of flight mass spectrometry

A novel metabonomic method based on fast liquid chromatography coupled with ion trap-time of flight mass spectrometry (UFLC/MS-IT-TOF) was applied to study the metabolic changes of plasma and urine in depression and excess fatigue rats. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were applied for classifying the depression, excess fatigue and the control rats. Metabolites which were important for the classification in the three groups of rats were selected as potential biomarkers and identified by MS(n) information achieved from UFLC/MS-IT-TOF analysis. Spermine, propionylcarnitine, butyrylcarnitine, phenylalanine, lysophosphatidylcholine (LPC) C14:0 and LPC C18:2 were down-regulated, methyl-hippuric acid and chenodeoxycholic acid (CDCA) were up-regulated significantly in plasma of the excess fatigue rats. Spermine, leucine, propionylcarnitine, and butyrylcarnitine decreased, hippuric acid, methyl-hippuric acid, cholic acid, CDCA and LPC C16:0 increased markedly in plasma of the depression rats. Ethyl N2-acetyl-L-argininate and N-methyl-2-pyridone-5-carboxamide (2-PY) (or N-methyl-4-pyridone-3-carboxamide (4-PY)) were down-regulated, leucylproline and pantothenic acid were up-regulated remarkably both in urine of depression and excess fatigue rats. The concentration of kynurenic acid and N2-succinyl-L-ornithine was low in urine of depression rats compared with control rats. Based on the data, correlation networks for depression and excess fatigue rats revealed the abnormality of nicotinate and nicotinamide metabolism, arginine metabolism, cholesterol metabolism, tryptophan metabolism and kynurenine metabolism in depression rats, and in excess fatigue rat alterations of energy metabolism, nicotinate and nicotinamide metabolism and lecithin metabolism. Our results provide novel insights in the complex metabolic mechanisms occurring in depression and excess fatigue rats.

Synthesis of polycaprolactone: a review

Polycaprolactone (PCL) is an important polymer due to its mechanical properties, miscibility with a large range of other polymers and biodegradability. Two main pathways to produce polycaprolactone have been described in the literature: the polycondensation of a hydroxycarboxylic acid: 6-hydroxyhexanoic acid, and the ring-opening polymerisation (ROP) of a lactone: epsilon-caprolactone (epsilon-CL). This critical review summarises the different conditions which have been described to synthesise PCL, and gives a broad overview of the different catalytic systems that were used (enzymatic, organic and metal catalyst systems). A surprising variety of catalytic systems have been studied, touching on virtually every section of the periodic table. A detailed list of reaction conditions and catalysts/initiators is given and reaction mechanisms are presented where known. Emphasis is put on the ROP pathway due to its prevalence in the literature and the superior polymer that is obtained. In addition, ineffective systems that have been tried to catalyse the production of PCL are included in the electronic supplementary information for completeness (141 references).

Sc(OTf)3-catalyzed condensation of 2-alkyl-N-tosylaziridine with aldehydes or ketones: an efficient synthesis of 5-alkyl-1,3-oxazolidines

Sc(OTf)(3) effectively catalyzes the condensation of 2-alkyl-N-tosylaziridine with a wide variety of aldehydes and ketones, producing 5-alkyl-1,3-oxazolidines in good yields and excellent regioselectivity at catalyst loadings as low as 1 mol%.

Membrane flow patterns in multicomponent giant vesicles induced by alternating electric fields†Electronic supplementary information (ESI) available: Vesicle preparation procedure, numerical calculations and confocal microscopy movies of domain motion. See DOI: 10.1039/b811876kClick here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file.

Alternating electric (AC) fields induce circular patterns of lipid transport in membranes of giant vesicles. The flow is visualized by fluorescently labelled lipid domains.

The Protein Society: Celebrating 20 years in 2006—The founding and early years

A person is clearly identified as “old” when he begins to get requests to write a history of an organization with which he has been associated for many years. So it was not exactly a surprise when The Protein Society requested that I write a history of the Society and its journal upon the occasions of the 20th yearly American Symposium of The Protein Society and my announced retirement as Editor of Protein Science, since I have been active in both throughout their entire histories and am certifiably at an age that most of the attendees of the 20th Symposium will consider advanced.