Ethyl Disulfide Research Articles

Synthesis and Self-Assembly of Hyperbranched Multiarm Copolymer Lysozyme Conjugates Based on Light-Induced Metal-Free Atrp

In recent years, the coupling of structurally and functionally controllable polymers with biologically active protein materials to obtain polymer-protein conjugates with excellent overall properties and good biocompatibility has been important research in the field of polymers. In this study, the hyperbranched polymer hP(DEGMA-co-OEGMA) was first prepared by combining self-condensation vinyl polymerization (SCVP) with photo-induced metal-free atom transfer radical polymerization (ATRP), with 2-(2-bromo-2-methylpropanoyloxy) ethyl methacrylate (BMA) as inimer, and Di (ethylene glycol) methyl ether methacrylate (DEGMA) and (oligoethylene glycol) methacrylate (OEGMA, Mn = 300) as the copolymer monomer. Then, hP(DEGMA-co-OEGMA) was used as a macroinitiator to continue the polymerization of a segment of pyridyl disulfide ethyl methacrylate (DSMA) monomer to obtain the hyperbranched multiarm copolymers hP(DEGMA-co-OEGMA)-star-PDSMA. Finally, the lysozyme with sulfhydryl groups was affixed to the hyperbranched multiarm copolymers by the exchange reaction between sulfhydryl groups and disulfide bonds to obtain the copolymer protein conjugates hP(DEGMA-co-OEGMA)-star-PLZ. Three hyperbranched multiarm copolymers with relatively close molecular weights but different degrees of branching were prepared, and all three conjugates could self-assemble to form nanoscale vesicle assemblies with narrow dispersion. The biological activity and secondary structure of lysozyme on the assemblies remained essentially unchanged.

Dual-Responsive Glycopolymers for Intracellular Codelivery of Antigen and Lipophilic Adjuvants.

Traditional approaches to vaccines use whole organisms to trigger an immune response, but they do not typically generate robust cellular-mediated immunity and have various safety risks. Subunit vaccines composed of proteins and/or peptides represent an attractive and safe alternative to whole organism vaccines, but they are poorly immunogenic. Though there are biological reasons for the poor immunogenicity of proteins and peptides, one other key to their relative lack of immunogenicity could be attributed to the poor pharmacokinetic properties of exogenously delivered proteins and peptides. For instance, peptides often aggregate at the site of injection and are not stable in biological fluids, proteins and peptides are rapidly cleared from circulation, and both have poor cellular internalization and endosomal escape. Herein, we developed a delivery system to address the lack of protein immunogenicity by overcoming delivery barriers as well as codelivering immune-stimulating adjuvants. The glycopolymeric nanoparticles (glycoNPs) are composed of a dual-stimuli-responsive block glycopolymer, poly[2-(diisopropylamino)ethyl methacrylate]-b-poly[(pyridyl disulfide ethyl methacrylate)-co-(methacrylamidoglucopyranose)] (p[DPA-b-(PDSMA-co-MAG)]). This polymer facilitates protein conjugation and cytosolic release, the pH-responsive release of lipophilic adjuvants, and pH-dependent membrane disruption to ensure cytosolic delivery of antigens. We synthesized p[DPA-b-(PDSMA-co-MAG)] by reversible addition-fragmentation chain transfer (RAFT) polymerization, followed by the formation and physicochemical characterization of glycoNPs using the p[DPA-b-(PDSMA-co-MAG)] building blocks. These glycoNPs conjugated the model antigen ovalbumin (OVA) and released OVA in response to elevated glutathione levels. Moreover, the glycoNPs displayed pH-dependent drug release of the model hydrophobic drug Nile Red while also exhibiting pH-responsive endosomolytic behavior as indicated by a red blood cell hemolysis assay. GlycoNPs coloaded with OVA and the toll-like receptor 7/8 (TLR-7/8) agonist Resiquimod (R848) activated DC 2.4 dendritic cells (DCs) significantly more than free OVA and R848 and led to robust antigen presentation of the OVA epitope SIINFEKL on major histocompatibility complex I (MHC-I). In sum, the dual-stimuli-responsive glycopolymer introduced here overcomes major protein and peptide delivery barriers and could vastly improve the immunogenicity of protein-based vaccines.

Synthesis of exopolysaccharide-based organo-montmorillonite with improved affinity towards carbon dioxide and hydrophilic character

Grafting of a bio-sourced exopolysaccharide (EPS) using a disulfide ethyl moiety with two ammonium ends as interface on Na + -exchanged montmorillonite (NaMt) turned out to be a “green” route to produce an OH-enriched organoclay with improved affinity towards CO 2 and moisture. Characterization through X-ray diffraction, infrared spectroscopy and thermogravimetric analysis revealed an organized structure with an increased basal spacing that facilitates the diffusion of CO 2 and water molecules and thermal stability up to 190 °C. Measurements through thermal programmed desorption (TPD) showed that at least 16 CO 2 molecules are adsorbed per OH group incorporated via HO:CO 2 interactions between CO 2 molecules and both EPS, and adsorbed water molecules. Adsorbed CO 2 can be completely released below 190 °C. This opens promising prospects for designing respiratory devices that support vegetal-derived moieties that can capture non-stoichiometric amounts of CO 2 in CO 2 -rich gas mixtures and enclosures with non-thermal regeneration.

Biodegradable Phosphocholine Cross‐Linker With Ion‐Pair Design for Tough Zwitterionic Hydrogel

AbstractHydrogels have been widely used in various biomedical applications based on their ability to provide 3D frames with tissue‐like elasticity and high water content. However, the role of the cross‐linking agents in the hydrogels was undervalued in terms of biocompatibility, mechanical properties, degradability, and hydration of gels. In this study, an innovative zwitterionic dimethacrylate 2‐[2‐{2‐(Methacryloyloxy)ethyldimethylammonium}ethyl‐phosphate]ethyl disulfide (MPCSS) for the development of biodegradable and biocompatible hydrogels with entirely bio‐inspired PC structure is reported. The MPCSS cross‐linker includes the zwitterionic group providing nonfouling properties and a disulfide bond that can be degraded by reducing agents and enzymes. Moreover, MPCSS has an opposite arrangement of charged groups to that in the 2‐methacryloyloxyethyl phosphorylcholine (MPC) monomer. The hydrogels developed from MPCSS and MPC allow the stronger mechanical properties upon electrostatic interaction between the oppositely charged groups and the higher water content than the MPC gels with the conventional cross‐linker. The biocompatibility and fouling characteristics of MPC/MPCSS hydrogels are systematically investigated. Moreover, the degradation of MPCSS cross‐linked hydrogels is evaluated through their weight loss and rheological data. Ultimately, MPC/MPCSS hydrogel is demonstrated to in situ encapsulate NIH‐3T3 fibroblasts and provide an excellent 3D environment, facilitating cell remodeling and growth as a tissue scaffold.

Cobalt(II)-disulfide compounds with the unusual PF2O2– anion. ligand-dependent redox conversion to a cobalt(III)-thiolate complex

Herein we describe the synthesis of the cobalt(II) disulfide compounds [CoII2(LxSSLx)(μ–PO2F2)2](PF6)2 and [CoII2(LxSSLx)(NO3)4] (x = 1: di-2-(bis(2-pyridylmethyl)amino)-ethyl disulfide; x = 2: di-2-((6-methyl-2-pyridylmethyl)(2-pyridylmethyl)amino)-ethyl disulfide). The crystal structures show the cobalt(II) centers in [CoII2(LxSSLx)(μ-PO2F2)2](PF6)2 to be in distorted octahedral geometries, whereas in [CoII2(L1SSL1)(NO3)4] the geometries are distorted trigonal bipyramidal. The cobalt(II) centers in [CoII2(LxSSLx)(PO2F2)2](PF6)2 are coordinated by three nitrogen and one sulfur donor atom of the disulfide ligand, and two oxygen atoms of two bridging difluoridophosphate anions. The cobalt(II) centers in [CoII2(L1SSL1)(NO3)4] are coordinated by three nitrogen donors of the ligand and three oxygen atoms of one monodentate and one bidentate nitrate anion, the latter two oxygen atoms together occupying one of the equatorial sites of the trigonal bipyramid. It was found that the dinuclear compound [CoII2(L1SSL1)(PO2F2)2](PF6)2 is stable as such in methanol and dichloromethane solution, but in acetonitrile redox conversion occurs forming the cobalt(III) thiolate compound [CoIII(L1S)(MeCN)2]2+. The compound [CoII2(L1SSL1)(NO3)4] and the disulfide compounds of the ligand L2SSL2 do not show this redox conversion and remain in the disulfide form in all investigated solvents.

Specific VOC-Profile of Decomposed Sasquatch Remains

A method using a thermal desorber combined with a gas chromatograph coupled to a mass spectrometer was proposed to identify the volatile organic compounds (VOCs) released in decomposed Sasquatch remains. It is known that specific VOCs are generated during the decomposition of Sasquatch and animal corpses that allow us to determine to which species the remains correspond, and the time elapsed since their dead. We found a combination of 8 compounds (ethyl propionate, propyl propionate, propyl butyrate, ethyl pentanoate, pyridine, diethyl disulfide, methyl (methylthio) ethyl disulfide and 3-methylthio1-propanol) that led to the distinction of Sasquatch remains from another animal remains. These markers would allow a more efficiently training of cadaver dogs or portable detection devices could be developed.

Poly(ethylene disulfide)/carbon fiber composites: cure and effect of fiber content on mechanical and thermal properties

In this paper, poly(ethylene disulfide) (PEDS) and carbon fiber (CF) composites were synthesized using in situ polymerization. Then, synthesized composites, sulfur, zinc oxide (ZnO), stearic acid, and N-cyclohexyl-2-benzothiazole sulfenamide (CBS) were compounded using a two-roll mill and cured by a rheometer at 140°C. PEDS characteristics were investigated by Fourier transform infrared (FTIR), Raman spectroscopies, X-ray diffraction (XRD), proton nuclear magnetic resonance (1H NMR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Also, cured samples were investigated by scanning electron microscopy (SEM), FTIR, Raman spectroscopies, XRD, DSC, and TGA. Moreover, the mechanical properties and hardness of the samples were investigated by tensile test and Shore A. The results showed that after the curing process, due to the cross-links, the structure is completely amorphous and no melting temperature (T m) has been observed. Also, by increasing CFs in composites, the glass transition temperature occurs at higher temperatures. Moreover, the thermal stability of composites by increasing CFs was enhanced. Furthermore, by an increase of CFs in matrix, hardness, and elastic modulus, as well as strength, were increasing.

Identification of Volatile Sulfur Compounds Produced by Schizophyllum commune.

Schizophyllum commune is a causative agent of allergic bronchopulmonary mycosis, allergic fungal rhinosinusitis, and basidiomycosis. Diagnosis of these diseases remains difficult because no commercially available tool exists to identify the pathogen. Unique volatile organic compounds produced by a pathogen might be useful for non-invasive diagnosis. Here, we explored microbial volatile organic compounds produced by S. commune. Volatile sulfur compounds, dimethyl disulfide (48 of 49 strains) and methyl ethyl disulfide (49 of 49 strains), diethyl disulfide (34 of 49 strains), dimethyl trisulfide (40 of 49 strains), and dimethyl tetrasulfide (32 of 49 strains) were detected from headspace air in S. commune cultured vials. Every S. commune strain produced at least one volatile sulfur compound analyzed in this study. Those volatile sulfur compounds were not detected from the cultures of Aspergillus spp. (A. fumigatus, A. flavus, A. niger, and A. terreus), which are other major causative agents of allergic bronchopulmonary mycosis. The last, we examined H2S detection using lead acetate paper. Headspace air from S. commune rapidly turned the lead acetate paper black. These results suggest that those volatile sulfur compounds are potent targets for the diagnosis of S. commune and infectious diseases.

The Reactivity of FeII and CoII Disulfide Compounds with Dihydrogen Peroxide

The reactivity of two metal disulfide compounds [MII2(L1SSL1)Cl4] {M = Fe and Co, L1SSL1 = di‐2‐[bis(2‐pyridylmethyl)amino]ethyl disulfide} with dihydrogen peroxide has been investigated. Reaction of the iron(II) disulfide compound [FeII2(L1SSL1)Cl4] with H2O2 results in the formation of the mononuclear iron(III) sulfonate compound [FeIII(L1SO3)Cl2]. The crystal structure combined with EPR spectroscopy confirms that a high‐spin (S = 5/2) iron(III) center was generated, which is coordinated by three nitrogen donors and one oxygen atom of the sulfonate group of the tetradentate ligand, and two chloride ions in an octahedral geometry. In contrast, reaction of compound [CoII2(L1SSL1)Cl4] with H2O2 yielded the mononuclear cobalt(III) sulfinate compound [CoIII(L1SO2)Cl2]. The crystal structure and NMR spectroscopy show that in this case a low‐spin (S = 0) cobalt(III) center was obtained, which is coordinated by three nitrogen donors and one sulfur atom of the sulfinate group of the tetradentate ligand and two chloride ions in an octahedral geometry.

Synthesis and characterization of a series of transition metal compounds of thioether and disulfide ligands

A series of mononuclear metal compounds [MII(L1SCH3)Cl2] (M = Co, Cu, Fe, Mn, L1SCH3 = 2-(methylthio)-N,N-bis(pyridin-2-ylmethyl)aminoethane) has been synthesized and characterized. The structures and spectroscopic properties of these compounds are compared to the related dinuclear compounds [MII2(L1SSL1)Cl4] (M = Co, Cu, Fe), which were obtained from the reactions of disulfide ligand L1SSL1 with the corresponding metal chloride salts (L1SSL1 = di-2-(bis(2-pyridylmethyl)amino)-ethyl disulfide). The crystal structures show that the metal centers in the mononuclear compounds [CoII(L1SCH3)Cl2], [CuII(L1SCH3)Cl2] and [MnII(L1SCH3)Cl2] are in trigonal-bipyramidal geometries coordinated by three nitrogen donors of the tetradentate ligand and two chloride ions, with configurations similar to that of metal centers in [CoII2(L1SSL1)Cl4] and [CuII2(L1SSL1)Cl4]. In contrast, the iron(II) center in [FeII(L1SCH3)Cl2] is coordinated by three nitrogen donors and one sulfur atom of the tetradentate ligand and two chloride ions in an octahedral geometry, which is similar to the geometry of one of the Fe(II) centers in the dinuclear compound [FeII2(L1SSL1)Cl4], where two iron(II) centers are in different geometries. UV–vis spectra of the mononuclear compounds are comparable to those of the related dinuclear compounds.

Redox Interconversion between Cobalt(III) Thiolate and Cobalt(II) Disulfide Compounds

The redox interconversion between Co(III) thiolate and Co(II) disulfide compounds has been investigated experimentally and computationally. Reactions of cobalt(II) salts with disulfide ligand L1SSL1 (L1SSL1 = di-2-(bis(2-pyridylmethyl)amino)-ethyl disulfide) result in the formation of either the high-spin cobalt(II) disulfide compound [CoII2(L1SSL1)Cl4] or a low-spin, octahedral cobalt(III) thiolate compound, such as [CoIII(L1S)(MeCN)2](BF4)2. Addition of thiocyanate anions to a solution containing the latter compound yielded crystals of [CoIII(L1S)(NCS)2]. The addition of chloride ions to a solution of [CoIII(L1S)(MeCN)2](BF4)2 in acetonitrile results in conversion of the cobalt(III) thiolate compound to the cobalt(II) disulfide compound [CoII2(L1SSL1)Cl4], as monitored with UV–vis spectroscopy; subsequent addition of AgBF4 regenerates the Co(III) compound. Computational studies show that exchange by a chloride anion of the coordinated acetonitrile molecule or thiocyanate anion in compounds [CoIII(L1S)(MeCN)2]2+ and [CoIII(L1S)(NCS)2] induces a change in the character of the highest occupied molecular orbitals, showing a decrease of the contribution of the p orbital on sulfur and an increase of the d orbital on cobalt. As a comparison, the synthesis of iron compounds was undertaken. X-ray crystallography revealed that structure of the dinuclear iron(II) disulfide compound [FeII2(L1SSL1)Cl4] is different from that of cobalt(II) compound [CoII2(L1SSL1)Cl4]. In contrast to cobalt, reaction of ligand L1SSL1 with [Fe(MeCN)6](BF4)2 did not yield the expected Fe(III) thiolate compound. This work is an unprecedented example of redox interconversion between a high-spin Co(II) disulfide compound and a low-spin Co(III) thiolate compound triggered by the nature of the anion.

A tetranuclear fluorido-bridged iron compound: Fluoride abstraction from the tetrafluoridoborate anion

The novel iron(II) fluoride cluster [FeII4(L1SSL1)2F6(MeCN)2](BF4)2 (L1SSL1 = di‑2‑(bis(2‑pyridylmethyl)amino)ethyl disulfide) has been synthesized by reaction of the ligand L1SSL1 with [Fe(MeCN)6](BF4)2. The crystal structure shows that a tetranuclear iron(II) compound is formed through the bridging of two dinuclear iron(II) units by four fluoride anions. The 19F NMR spectrum distinguishes both the terminal and bridging fluoride ions in this compound. The new compound is a rare FeII fluoride cluster with four FeII and four F− ions arranged in a nearly perfect square plane, which obtained its fluoride ions from the tetrafluoridoborate anion.

Stabilization of Glucagon by Trehalose Glycopolymer Nanogels

AbstractGlucagon is a peptide hormone used for the treatment of hypoglycemia; however, its clinical potential is limited by its insolubility and instability in solution. Herein, the encapsulation, stabilization, and release of glucagon by trehalose glycopolymer nanogels are reported. Methacrylate‐functionalized trehalose is copolymerized with pyridyl disulfide ethyl methacrylate using free radical polymerization conditions to form trehalose glycopolymers with thiol‐reactive handles. Glucagon is chemically modified to contain two thiol groups and is subsequently utilized as the cross‐linker to form redox‐responsive trehalose nanogels with greater than 80% conjugation yield. Nanogel formation and subsequent glucagon stabilization are characterized using polyacrylamide gel electrophoresis, dynamic light scattering, and transmission electron microscopy. It is determined that the solution stability of the glucagon increased from less than 24 h to at least three weeks in the nanogel form. Additionally, in vitro activity of the synthesized glucagon analog and released glucagon is investigated, demonstrating that the glucagon remains active after modification. It is anticipated that these glucagon–nanogel conjugates will be useful as a stabilizing glucagon formulation, allowing for cargo release under mild reducing conditions.

Differentiation between decomposed remains of human origin and bigger mammals

This study is a follow-up study in the search for a human specific marker in the decomposition where the VOC-profile of decomposing human, pig, lamb and roe remains were analyzed using a thermal desorber combined with a gas chromatograph coupled to a mass spectrometer in a laboratory environment during 6 months. The combination of 8 previously identified human and pig specific compounds (ethyl propionate, propyl propionate, propyl butyrate, ethyl pentanoate, 3-methylthio-1-propanol, methyl(methylthio)ethyl disulfide, diethyl disulfide and pyridine) was also seen in these analyzed mammals. However, combined with 5 additional compounds (hexane, heptane, octane, N-(3-methylbutyl)- and N-(2-methylpropyl)acetamide) human remains could be separated from pig, lamb and roe remains. Based on a higher number of remains analyzed, as compared with the pilot study, it was no longer possible to rely on the 5 previously proposed esters to separate pig from human remains. From this follow-up study reported, it was found that pyridine is an interesting compound specific to human remains. Such a human specific marker can help in the training of cadaver dogs or in the development of devices to search for human remains. However, further investigations have to verify these results.

Fatty Acid-Mimetic Micelles for Dual Delivery of Antigens and Imidazoquinoline Adjuvants.

Vaccine design has undergone a shift towards the use of purified protein subunit vaccines, which offer increased safety and greater control over antigen specificity, but at the expense of immunogenicity. Here we report the development of a new polymer-based vaccine delivery platform engineered to enhance immunity through the co-delivery of protein antigens and the Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ). Owing to the preferential solubility of IMQ in fatty acids, a series of block copolymer micelles with a fatty acid-mimetic core comprising lauryl methacrylate (LMA) and methacrylic acid (MAA), and a poly(ethylene glycol) methyl ether methacrylate (PEGMA) corona decorated with pyridyl disulfide ethyl methacrylate (PDSM) moieties for antigen conjugation were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Carriers composed of 50 mole% LMA (LMA50) demonstrated the highest IMQ loading (2.2 w/w%) and significantly enhanced the immunostimulatory capacity of IMQ to induce dendritic cell maturation and proinflammatory cytokine production. Conjugation of a model antigen, ovalbumin (OVA), to the corona of IMQ-loaded LMA50 micelles enhanced in vitro antigen uptake and cross-presentation on MHC class I (MHC-I). A single intranasal (IN) immunization of mice with carriers co-loaded with IMQ and OVA elicited significantly higher pulmonary and systemic CD8+ T cell responses and increased serum IgG titer relative to a soluble formulation of antigen and adjuvant. Collectively, these data demonstrate that rationally designed fatty acid-mimetic micelles enhance intracellular antigen and IMQ delivery and have potential as synthetic vectors for enhancing the immunogenicity of subunit vaccines.

Reactive Copolymers Based on N-Vinyl Lactams with Pyridyl Disulfide Side Groups via RAFT Polymerization and Postmodification via Thiol–Disulfide Exchange Reaction

Herein, we report the synthesis of a series of novel pyridyl disulfide (PDS)-functionalized statistical reactive copolymers that enable facile access to complex polymeric architectures through highly selective thiol–disulfide exchange reaction with thiol-containing ligands or proteins. Functional reactive poly(N-vinyl lactam)-based copolymers including poly(N-vinylpyrrolidone-co-pyridyl disulfide ethyl methacrylate) (PVPD), poly(N-vinylpiperidone-co-pyridyl disulfide ethyl methacrylate) (PVPID), and poly(N-vinylcaprolactam-co-pyridyl disulfide ethyl methacrylate) (PVD) with PDS side groups were synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization at 60 °C in anisole with methyl 2-(ethoxycarbonothioylthio)propanoate as chain transfer agent. The PDS contents in the synthesized copolymers were varied from 2 to 10 mol % (as confirmed by systematical characterization with FTIR/Raman and 1H NMR spectroscopy) using well-controlled continuous feeding method. The kinetics study suggested that copolymerizations were less favored with the enlargement of the lactam rings, indicated by lower conversions and larger dispersity indexes (Đ). The PDS-functionalized reactive polymers were amenable to functionalization with a variety of thiol-containing molecules, including 3-mercaptopropionic acid (3M), 2-phenylethanethiol (2P), methyl 3-mercaptopropionate (M3), 2-mercaptoethanol (2M), 2-aminoethanethiol (2A), poly(ethylene glycol) methyl ether thiol (PEG-SH), and enhanced green fluorescent protein (EGFP) via thiol–disulfide exchange reaction under mild conditions, confirmed by 1H NMR and SDS-PAGE. The conversions in all cases were higher than 95%, displaying that the thiol–disulfide exchange reaction to PDS groups with thiol-containing molecules is highly selective and tolerant to different ligands including amine, carboxyl, hydroxyl, phenyl, PEG and even polypeptides, providing a versatile scaffold for facile conjugation of various biological components. The contact angle measurement results and fluorescence microscopy study indicated that the reactive films based on the PDS-functionalized copolymers allowed facile, direct, and environmental-friendly surface engineering of surfaces from aqueous solution suggesting potential application in surface decoration of tissue-engineering scaffolds and medical implants. The initial cell culture experiments with HeLa cells displayed that the unmodified PVPD film was nontoxic and biocompatible while the film modified with PEG (a type of antifouling polymer) showed diminished cell attachment and growth, indicating that elegant engineering of the film surface can meet demands of particular applications.

Time-dependent VOC-profile of decomposed human and animal remains in laboratory environment

A validated method using a thermal desorber combined with a gas chromatograph coupled to a mass spectrometer was used to identify the volatile organic compounds released in decomposed human and animal remains after 9 and 12 months in glass jars in a laboratory environment. This is a follow-up study on a previous report where the first 6 months of decomposition of 6 human and 26 animal remains was investigated. In the first report, out of 452 identified compounds, a combination of 8 compounds was proposed as human and pig specific. The goal of the current study was to investigate if these 8 compounds were still released after 9 and 12 months. The next results were noticed: 287 compounds were identified; only 9 new compounds were detected and 173 were no longer seen. Sulfur-containing compounds were less prevalent as compared to the first month of decomposition. The appearance of nitrogen-containing compounds and alcohols was increasingly evident during the first 6 months, and the same trend was seen in the following 6 months. Esters became less important after 6 months. From the proposed human and pig specific compounds, diethyl disulfide was only detected during the first months of decomposition. Interestingly, the 4 proposed human and pig specific esters, as well as pyridine, 3-methylthio-1-propanol and methyl(methylthio)ethyl disulfide were still present after 9 and 12 months of decomposition. This means that these 7 human and pig specific markers can be used in the development of training aids for cadaver dogs during the whole decomposition process. Diethyl disulfide can be used in training aids for the first month of decomposition.

The Search for a Volatile Human Specific Marker in the Decomposition Process.

In this study, a validated method using a thermal desorber combined with a gas chromatograph coupled to mass spectrometry was used to identify the volatile organic compounds released during decomposition of 6 human and 26 animal remains in a laboratory environment during a period of 6 months. 452 compounds were identified. Among them a human specific marker was sought using principle component analysis. We found a combination of 8 compounds (ethyl propionate, propyl propionate, propyl butyrate, ethyl pentanoate, pyridine, diethyl disulfide, methyl(methylthio)ethyl disulfide and 3-methylthio-1-propanol) that led to the distinction of human and pig remains from other animal remains. Furthermore, it was possible to separate the pig remains from human remains based on 5 esters (3-methylbutyl pentanoate, 3-methylbutyl 3-methylbutyrate, 3-methylbutyl 2-methylbutyrate, butyl pentanoate and propyl hexanoate). Further research in the field with full bodies has to corroborate these results and search for one or more human specific markers. These markers would allow a more efficiently training of cadaver dogs or portable detection devices could be developed.

Graphene/tri-block copolymer composites prepared via RAFT polymerizations for dual controlled drug delivery via pH stimulation and biodegradation

A novel tri-block copolymer poly(oxopentanoate ethyl methacrylate)-block-poly(pyridyl disulfide ethyl acrylate)-block-poly(ethylene glycol acrylate) [poly(OEMA-b-PDEA-b-PEGA)], retaining active keto groups and pyridyl disulfide (PDS) side functionalities, was synthesized as a drug delivery vehicle using reversible addition–fragmentation chain transfer (RAFT) polymerization method. One mimic drug pyridine-2-thione (PT) was introduced into the monomer, PDEA for copolymerization. The other mimic drug O-benzylhydroxylamine (BHA) was conjugated with tri-block copolymer via efficient oxime coupling chemistry, followed by the attachment onto graphene via π–π stacking interaction to obtain a graphene/tri-block copolymer composite. 1H NMR, UV–vis absorption spectroscopy, fluorescence spectroscopy, gel permeation chromatography (GPC), atomic force microscope (AFM) and transmission electron microscope (TEM) were used to verify the successful step-wise preparation of the tri-block copolymer and drug loaded composite. In vitro release behaviors of BHA and PT from graphene/tri-block copolymer composite via dual drug release mechanisms were investigated. BHA can be released under acid environment, while PT will be released in the presence of reducing agents, such as dithiothreitol (DTT) or glutathione (GSH). It can be envisioned that this novel composite could be exploited as a novel intracellular drug delivery system via dual release mechanisms.

Thermal performance of poly(ethylene disulfide)/expanded graphite nanocomposites

In this study, the influences of expanded graphite oxide (EG) nanosheets presence with and without surfactant on structural and thermal performance of poly(ethylene disulfide) (PEDS)-based nanocomposites are investigated. Sodium dodecylbenzenesulfonate (SDBS) is used as a surfactant for the preparation of modified-EG nanosheets. The structural, morphological, and thermal properties of prepared nanocomposites are studied using X-ray diffraction (XRD), scanning electron microscopy, and differential scanning calorimetry techniques, respectively. XRD patterns of nanocomposites reveal that a high degree of expanded graphite nanosheets dispersion is achieved with and without surface modification using in situ polymerization method. Moreover, the presence of immobilized polysulfide chains near the interface region of nanosheets is suggested as a possible reason for the observed increase in the number of semi-crystalline organic fractions in the structure of PEDS via EG nanosheets incorporation. In addition, the morphology of SDBS-modified-EG loaded nanocomposite shows a smoother fracture surface than unmodified-nanosheets reinforced nanocomposite. Therefore, more interactions between nanosheets and polysulfide chains are expected in the structure of unmodified-EG reinforced nanocomposite. Moreover, thermal resistance and degradation kinetics of prepared nanocomposites are studied using thermogravimetric analysis results and degradation activation energy calculations, respectively. The required activation energy for the degradation process of SDBS-EG loaded nanocomposite is about 140 kJ mol−1 lower than the required degradation activation energy of unmodified-nanosheets reinforced nanocomposite.