Supramolecular Nature of Multicomponent Crystals Formed from 2,2'-Thiodiacetic Acid with 2,6-Diaminopurine or N9-(2-Hydroxyethyl)adenine.

The synthesis and characterization of the multicomponent crystals formed by 2,2'-thiodiacetic acid (H2tda) and 2,6-diaminopurine (Hdap) or N9-(2-hydroxyethyl)adenine (9heade) are detailed in this report. These crystals exist in a salt rather than a co-crystal form, as confirmed by single crystal X-ray diffractometry, which reflects their ionic nature. This analysis confirmed proton transfer from the 2,2'-thiodiacetic acid to the basic groups of the coformers. The new multicomponent crystals have molecular formulas [(H9heade+)(Htda-)] 1 and [(H2dap+)2(tda2-)]·2H2O 2. These were also characterized using FTIR, 1H and 13C NMR and mass spectroscopies, elemental analysis, and thermogravimetric/differential scanning calorimetry (TG/DSC) analyses. In the crystal packing the ions interact with each other via O-H⋯N, O-H⋯O, N-H⋯O, and N-H⋯N hydrogen bonds, generating cyclic hydrogen-bonded motifs with graph-set notation of R22(16), R22(10), R32(10), R33(10), R22(9), R32(8), and R42(8), to form different supramolecular homo- and hetero-synthons. In addition, in the crystal packing of 2, pairs of diaminopurinium ions display a strong anti-parallel π,π-stacking interaction, characterized by short inter-centroids and interplanar distances (3.39 and 3.24 Å, respectively) and a fairly tight angle (17.5°). These assemblies were further analyzed energetically using DFT calculations, MEP surface analysis, and QTAIM characterization.

H(N3)dap (Hdap = 2,6-Diaminopurine) Recognition by Cu2(EGTA): Structure, Physical Properties, and Density Functional Theory Calculations of [Cu4(µ-EGTA)2(µ-H(N3)dap)2(H2O)2]·7H2O.

Reactions in water between the Cu2(µ-EGTA) chelate (EGTA = ethylene-bis(oxyethyleneimino)tetraacetate(4-) ion) and Hdap in molar ratios 1:1 and 1:2 yield only blue crystals of the ternary compound [Cu4(µ-EGTA)2(µ-H(N3)dap)2(H2O)2]·7H2O (1), which has been studied via single-crystal X-ray diffraction and various physical methods (thermal stability, spectral and magnetic properties), as well as DFT theoretical calculations. In the crystal, uncoordinated water is disordered. The tetranuclear complex molecule also has some irrelevant disorder in an EGTA-ethylene moiety. In the complex molecule, both bridging organic molecules act as binucleating ligands. There are two distorted five- and two six-coordinated Cu(II) centers. Each half of EGTA acts as a tripodal tetradentate Cu(II) chelator, with a mer-NO2 + O(ether, distal) conformation. Hdap exhibits the tautomer H(N3)dap, with the dissociable H-atom on its less basic N-heterocyclic atom. These features favor the efficient cooperation between Cu-N7 or Cu-N9 bonds with appropriate O-EGTA atoms, as N6-H···O or N3-H···O interligand interactions, respectively. The bridging role of both organics determines the tetranuclear dimensionality of the complex. In this crystal, such molecules associate in zig-zag chains built by alternating π-π interactions between the five- or six-atom rings of Hdap ligands of adjacent molecules. DFT theoretical calculations (using two different theoretical models and characterized by the quantum theory of "atoms in molecules") reveal the importance of these π-π interactions between Hdap ligands, as well as those corresponding to the referred hydrogen bonds in the contributed tetranuclear molecule.

Onsite evaluation of endoscopic ultrasound fine needle aspiration: the endosonographer, the cytotechnologist and the cytopathologist.

Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) has become an essential tool in the management of multiple diseases. Its accuracy is related to different aspects of the technique, one of the most important being the experience and interaction of the endosonographer and pathologist. Certain studies over the past years have highlighted the importance of having rapid on-site evaluation (ROSE) of samples obtained at the time of EUS-FNA. We have reviewed the role of ROSE, performed by the same endosonographer, a cytotechnologist and an expert cytopathologist. The available data suggest that ROSE (either by the endosonographer, the cytotechnologist, or the cytopathologist) improves sample adequacy and diagnostic yield, with the best option to have ROSE performed by an expert cytopathologist. However, if non-ROSE accuracy is already very high, any improvement is harder to achieve.

Release of nanoclay and surfactant from polymer-clay nanocomposites into a food simulant.

Release assessment of organo-modified montmorillonite (O-MMT) nanoclay and the organo-modifiers (surfactants) was performed on two types of polymer­clay nanocomposites: polypropylene (PP) and polyamide 6 (PA6) with O-MMT. In accordance with ASTM D4754-11, nanocomposite films were exposed to ethanol as a fatty-food simulant at 70 °C. The release of O-MMT, with Si and Al used as the nanoclay markers, was evaluated by graphite furnace atomic absorption spectrometry. The nanoclay particles released in ethanol were visualized by transmission electron microscopy (TEM). More nanoclay particles were released from PP­clay films (0.15 mg L(­1)) than from PA6­clay films (0.10 mg L(­1)), possibly due to the lack of interaction between the nanoclay and PP as indicated by the structure and morphology in the TEM images. The surfactant release was quantified by a liquid chromatography tandem mass spectrometry (LC-MS/MS) method. A substantial amount of surfactant was released into ethanol (3.5 mg L(­1) from PP­clay films and 16.2 mg L(­1) from PA6­clay films), indicating changes in the nanoclay structure within the nanocomposite while it was exposed to ethanol. This research has provided information for the determination of exposure doses of nanoclay and surfactant in biosystems and the environment, which enabled the risk assessment.

Safety and impact of peripheral parenteral nutrition on nutrient delivery in patients with nutrition risk: A prospective observational study.

BACKGROUND: Malnutrition is common in hospitalized patients and strategies to improve energy and protein intake have a positive impact on outcome. Despite early evidence suggesting the usefulness of peripheral parenteral nutrition (PPN), its adoption has been hampered by concerns regarding safety and efficacy. This study addresses this issue. METHODS: This prospective observational study was performed in medical and surgical inpatients in who were screened for nutrition risk and assessed using Subjective Global Assessment (SGA). Data captured included nutrition status, energy and protein requirements, intravenous access, indications for PPN, use of supplemental micronutrients, and disposition of patients on PPN. RESULTS: Ninety-eight patients were recruited from two centers over 8 months. The average age was 61.5 years, the mean Charlson Comorbidity Index was 4.21 (±3.09), 52% were male, and 48% were admitted to medicine, whereas 52% were admitted to surgery. Thirty-three percent of patients were SGA C, 44% were SGA B, and 19% were SGA A. Twenty-seven percent of patients had cancer. The average length of hospital stay was 22 days. The main indications for PPN were gastrointestinal tract dysfunction (72%) and postsurgical status (16%). PPN provided an average of 1296 kcal (±191) and 46 g of protein (±7). Intravenous access complications in patients receiving PPN did not occur in excess of expected. Almost 40% of patients required transition to central PN. CONCLUSIONS: PPN is a safe, effective way to deliver supplemental protein, energy, and micronutrients to malnourished patients and supports transition to other modes of nutrition care.

Effects of Dietary Supplementation of Lactobacillus acidophilus on Blood Parameters and Gut Health of Rabbits.

This study aimed to evaluate the effects of Lactobacillus acidophilus D2/CSL (L-1 × 109 cfu/kg feed/day) on biochemical parameters, faecal score (FS), cecal pH, gut morphometry, microbiota and cecal short-chain fatty acid (SCFAs) in rabbits. Three zootechnical trials were performed and in each trial 30 rabbits were allotted to two groups; a probiotic group (L) and a control group (C). At slaughter (day 45), samples of blood, duodenum, jejunum, ileum, liver and spleen were collected and submitted to histomorphometric analyses. Blood biochemical analyses, cecal microbiota and SCFAs determination were also performed. In trial 1 and 3, L. acidophilus D2/CSL did not affect productive parameters (p > 0.05). However, L group of trial 1 showed a lower morbidity and mortality compared to the control. In trial 2, C group showed a higher daily feed intake (p = 0.018) and a positive statistical tendency for live weight and average daily gain (p = 0.068). On the contrary, albumin was higher and ALFA-1 globulin was lower in the C group compared to L (p < 0.05). In all the trials, FS, cecal pH, histomorphometry, microbiota and SCFAs were unaffected. In conclusion, L. acidophilus D2/CSL did not impair growth performances, gut and rabbit's health, reducing morbidity and mortality.

Identification of novel matrix metalloproteinase inhibitors by screening of phenol fragments library.

In the last 20 years, a great variety of synthetic, low molecular weight MMP inhibitors (MMPIs) have been synthesized and tested, although none has reached clinical utility. Exploration of novel ZBGs and development of non-hydroxamate MMPI has become a focus in current research. It's well-known that polyphenols can produce beneficial effects on human health by their antioxidant properties as well as they have the ability to block gelatinase activity. In this work we tested a series of selected phenols as MMP inhibitors. The most interesting hit (B6) shows sub-micromolar activity against MMP-2 (IC(50) 0.59 ± 0.05 µM, LE = 1.07) and a fairly good selectivity spectrum.

Dicopper(II)-EDTA Chelate as a Bicephalic Receptor Model for a Synthetic Adenine Nucleoside.

In the extensive field of metal ions, their interactions with nucleic acids, and their constituents, the main aim of this work is to develop a metal chelate suitable to recognize two molecules of an adenine nucleoside. For this purpose, the dinuclear chelate Cu2 (µ-EDTA) (ethylenediaminetetraacetate(4-) ion (EDTA)) is chosen as a bicephalic receptor model for N9-(2-hydroxyethyl)adenine (9heade). A one-pot synthesis is reported to obtain the compound [Cu2(µ2-EDTA)(9heade)2(H2O)4]·3H2O, which has been characterized by single-crystal X-ray diffraction and various spectral, thermal, and magnetic methods. The complex unit is a centro-symmetric molecule, where each Cu (II) center is chelated by a half-EDTA, and is further surrounded by an N7-dentate 9heade nucleoside and two non-equivalent trans-O-aqua molecules. The metal chelate-nucleoside molecular recognition is referred to as an efficient cooperation between the Cu-N7(9heade) coordination bond and a (9heade)N6-H···O(carboxyl, EDTA) interligand interaction. Theoretical calculations are also made to account for the relevance of this interaction. The extreme weakness with which each water molecule binds to the metal center disturbs the thermal stability and the infrared (FT-IR) and electron spin resonance (ESR) spectra of the compound.

Covalent Immobilization of Antibodies through Tetrazine-TCO Reaction to Improve Sensitivity of ELISA Technique.

Enzyme-linked immunosorbent assay (ELISA) is routinely used to detect biomolecules related to several diseases facilitating diagnosis and monitoring of these, as well as the possibility of decreasing their mortality rate. Several methods have been carried out to improve the ELISA sensitivity through antibodies immobilization on the microtiter plates. Here, we have developed a strategy of antibodies immobilization to improve the ELISA sensitivity increasing the antibody density surface through the tetrazine (Tz)-trans-cyclooctene (TCO) reaction. For this, we prepared surfaces with tetrazine groups while the captured antibody was conjugated with TCO. The tetrazine surfaces were prepared in two different ways: (1) from aminated plates and (2) from Tz-BSA-coated plates. The surfaces were evaluated using two sandwich ELISA models, one of them using the low-affinity antibody anti-c-myc as a capture antibody to detect the c-myc-GST-IL8h recombinant protein, and the other one to detect the carcinoembryonic human protein (CEA). The sensitivity increased in both surfaces treated with tetrazine in comparison with the standard unmodified surface. The c-myc-GST-IL8h detection was around 10-fold more sensible on both tetrazine surfaces, while CEA ELISA detection increased 12-fold on surfaces coated with Tz-BSA. In conclusion, we show that it is possible to improve the ELISA sensitivity using this immobilization system, where capture antibodies bond covalently to surfaces.

Investigation on the phototransformation of tadalafil in aqueous media. 6-Epimerization vs. solvent trapping reaction.

Irradiation of tadalafil at lambda > 290 nm in aqueous solutions leads to 6-epimer and/or water adducts depending on concentration and pH. A rationalization of the results involves the heterolytic cleavage of C6-N5 bond via a well-stabilized zwitterionic intermediate. The drug is stable in the dark except under strongly basic conditions where it undergoes C12a-epimerization.

Interaction of nanoclay-reinforced packaging nanocomposites with food simulants and compost environments.

The production of engineered nanomaterials (ENMs) has increased exponentially over the last few decades. ENMs, made from use of engineered nanoparticles (ENPs), have been applied to the food, agriculture, pharmaceutical, and automobile industries. Of particular interest are their applications in packaging nanocomposites for consumer and non-consumer goods. ENPs in nanocomposites are of interest as a packaging material because they reduce the amount of polymer needed, while improving the physical properties. However, the transformation of ENPs in nanocomposite production, their fate, and their toxicity remain unknown while in contact with the package content or after the end of life. The objectives of this chapter are (a) to provide an overview of the main nanoclays used in packaging; (b) to categorize the main polymeric packaging nanocomposites; (c) to provide an overview of the fate and mass transport of ENPs, especially nanoclays; (d) to describe the mass transfer of nanoclays in food simulants and in compost environments; and (e) to identify current and future research needs.

Probing the effect of N-alkylation on the molecular recognition abilities of the major groove N7-binding site of purine ligands.

The study of the metal binding pattern of N-methyladenines (1-, 3-, 7- or 9-Meade) towards CuII-iminodiacetate-like chelates is addressed on the basis of XRD crystal structures of sixteen novel ternary compounds. Except for three compounds, all others feature an square-based Cu(II) coordination, type 4 + 1, and the efficient cooperation of a CuN7 bond with an intra-molecular N6-H⋯O(coord. carboxylate) interligand interaction as the major metal-binding pattern. The three referred exceptions to this behavior are: (1) the compound [Cu(MIDA)(7Meade)(H2O)]·4H2O, which evidence the CuN3 binding pattern; the (2) [Cu(IDA)(1Meade)(H2O)2]·4H2O, which molecular recognition consist in the CuN9 bond and a (distal aqua)⋯⋯N3(1Meade) intra-molecular interaction, within an octahedral Cu(II) center; and (3) [Cu(IDA)(9Meade)(H2O)2]·3H2O, also with a 4 + 1 + 1 Cu(II) coordination, where the CuN7 bond exists along with an extremely weak N6-H⋯O(coord. carboxylate) interaction (3.33 Å, 140.2°). This former interaction is determined by packing forces that promote the participation of the N6H group in a 'trifurcated' H-bond. In conclusion, the cooperation between the CuN7 bond (not possible for 7Meade) and the intra-molecular N6-H⋯O interaction is clearly favored (a) by the H-accepting role of the O-coordinated carboxylate atoms from the iminodiacetate ligands in mer-NO2 conformation and (b) in compounds where the Cu(II) atom exhibits an elongated square-base pyramidal coordination, type 4 + 1.

Assessment of aliphatic-aromatic copolyester biodegradable mulch films. Part II: laboratory simulated conditions.

In a previous paper, we demonstrated that the main mechanism of degradation of poly(butylene adipate-co-terephthalate) (PBAT) biodegradable mulch films when exposed to field conditions was crosslinking due to the photodegradation from solar radiation. The aim of this work was to determine the effect of crosslinking on the biodegradability of PBAT samples. PBAT films were subjected to UV photodegradation in laboratory simulated conditions to investigate the effects of crosslinking and other major changes in the structure and mechanical properties of the films. Crosslinking caused the films to become more brittle and produced a reduction of the tensile strength and percent elongation. Besides the crosslinking degradation mechanism, chain scission also occurred in the samples. After 45d of biodegradation test, the non-crosslinked PBAT sample reached 60% of mineralization. However, the percent mineralization was reduced when samples were crosslinked. The percent mineralization of samples with 10%, 30%, 50%, and 70% gel content was 36%, 43%, 21%, and 24%, respectively. Our results indicate that crosslinking is a key process underlying the degradation of the PBAT film and did affect the biodegradability of the films, since the samples with greater amount of gel content generally showed less percent mineralization in the biodegradation tests.

Assessment of aliphatic-aromatic copolyester biodegradable mulch films. Part I: field study.

The objective of this work was to study the use of new biodegradable films in agriculture under open field conditions. Three biodegradable mulch films made from modified biodegradable polyester of different thicknesses and colors (black and white) and a conventional low density polyethylene (LDPE) mulch film were used to cover the beds of tomato plants. Changes in physical appearance of the films were recorded as well as changes in their mechanical, optical, and physical properties. Once tomato harvest was completed, the conventional LDPE mulch film was removed and all the tomato plants were cut using a mower. The biodegradable mulch films were plowed into the soil. The change in the appearance of the film was recorded and samples of each film after plowing were characterized according to the properties mentioned above. After the biodegradable films photodegraded, cross-link formation occurred within the films which promoted brittleness. Titanium dioxide, an additive used to produce white color in the films, catalyzed the photodegradation, while carbon black used for black color stabilized the photodegradation. The white films started to degrade after two weeks while it took about eight weeks for the black films to significantly degrade. The black biodegradable film seems to be a more promising alternative as a mulch film because of the comparable yields and weed suppression ability to conventional mulch film.

Postharvest shelf life extension of blueberries using a biodegradable package.

Small berries are commonly packaged and sold to consumers in vented petroleum-based clamshell containers. Biodegradable and compostable packages may be used as an alternative package to reduce waste generation and landfill disposal. In addition, the current clamshell container design does not allow the development of a modified atmosphere that could prolong berry shelf life. Thus, in this study, a non-ventilated biodegradable container was evaluated as a possible alternative to the containers normally used in commercial distribution of small berries. To determine the potential of biodegradable containers for small berries, highbush blueberries were packaged in polylactide (PLA) containers and stored at 10°C for 18 days and at 23°C for 9 days. Commercial vented clamshell containers were used as controls. Physicochemical and microbiological studies were carried out in order to compare the efficacy of both packages. Results showed that the PLA containers prolonged blueberry shelf life at different storage temperatures.

Toughening of Poly(lactic acid) and Thermoplastic Cassava Starch Reactive Blends Using Graphene Nanoplatelets.

Poly(lactic acid) (PLA) was reactively blended with thermoplastic cassava starch (TPCS) and functionalized with commercial graphene (GRH) nanoplatelets in a twin-screw extruder, and films were produced by cast-film extrusion. Reactive compatibilization between PLA and TPCS phases was reached by introducing maleic anhydride and a peroxide radical during the reactive blending extrusion process. Films with improved elongation at break and toughness for neat PLA and PLA-g-TPCS reactive blends were obtained by an addition of GRH nanoplatelets. Toughness of the PLA-g-TPCS-GRH was improved by ~900% and ~500% when compared to neat PLA and PLA-g-TPCS, respectively. Crack bridging was established as the primary mechanism responsible for the improvement in the mechanical properties of PLA and PLA-g-TPCS in the presence of the nanofiller due to the high aspect ratio of GRH. Scanning electron microscopy images showed a non-uniform distribution of GRH nanoplatelets in the matrix. Transmittance of the reactive blend films decreased due to the TPCS phase. Values obtained for the reactive blends showed ~20% transmittance. PLA-GRH and PLA-g-TPCS-GRH showed a reduction of the oxygen permeability coefficient with respect to PLA of around 35% and 50%, respectively. Thermal properties, molecular structure, surface roughness, XRD pattern, electrical resistivity, and color of the films were also evaluated. Biobased and compostable reactive blend films of PLA-g-TPCS compounded with GRH nanoplatelets could be suitable for food packaging and agricultural applications.

Impact of Nanoclays on the Biodegradation of Poly(Lactic Acid) Nanocomposites.

Poly(lactic acid) (PLA), a well-known biodegradable and compostable polymer, was used in this study as a model system to determine if the addition of nanoclays affects its biodegradation in simulated composting conditions and whether the nanoclays impact the microbial population in a compost environment. Three different nanoclays were studied due to their different surface characteristics but similar chemistry: organo-modified montmorillonite (OMMT), Halloysite nanotubes (HNT), and Laponite® RD (LRD). Additionally, the organo-modifier of MMT, methyl, tallow, bis-2-hydroxyethyl, quaternary ammonium (QAC), was studied. PLA and PLA bio-nanocomposite (BNC) films were produced, characterized, and used for biodegradation evaluation with an in-house built direct measurement respirometer (DMR) following the analysis of evolved CO2 approach. A biofilm formation essay and scanning electron microscopy were used to evaluate microbial attachment on the surface of PLA and BNCs. The results obtained from four different biodegradation tests with PLA and its BNCs showed a significantly higher mineralization of the films containing nanoclay in comparison to the pristine PLA during the first three to four weeks of testing, mainly attributed to the reduction in the PLA lag time. The effect of the nanoclays on the initial molecular weight during processing played a crucial role in the evolution of CO2. PLA-LRD5 had the greatest microbial attachment on the surface as confirmed by the biofilm test and the SEM micrographs, while PLA-QAC0.4 had the lowest biofilm formation that may be attributed to the inhibitory effect also found during the biodegradation test when the QAC was tested by itself.

Migration of antioxidants from polylactic acid films: A parameter estimation approach and an overview of the current mass transfer models.

Migration studies of chemicals from contact materials have been widely conducted due to their importance in determining the safety and shelf life of a food product in their packages. The US Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA) require this safety assessment for food contact materials. So, migration experiments are theoretically designed and experimentally conducted to obtain data that can be used to assess the kinetics of chemical release. In this work, a parameter estimation approach was used to review and to determine the mass transfer partition and diffusion coefficients governing the migration process of eight antioxidants from poly(lactic acid), PLA, based films into water/ethanol solutions at temperatures between 20 and 50°C. Scaled sensitivity coefficients were calculated to assess simultaneously estimation of a number of mass transfer parameters. An optimal experimental design approach was performed to show the importance of properly designing a migration experiment. Additional parameters also provide better insights on migration of the antioxidants. For example, the partition coefficients could be better estimated using data from the early part of the experiment instead at the end. Experiments could be conducted for shorter periods of time saving time and resources. Diffusion coefficients of the eight antioxidants from PLA films were between 0.2 and 19×10-14m2/s at ~40°C. The use of parameter estimation approach provided additional and useful insights about the migration of antioxidants from PLA films.

A new technique to prevent the main post harvest diseases in berries during storage: inclusion complexes beta-cyclodextrin-hexanal.

Natural occurring volatiles such as hexanal have a well know antifungal capacity but limited post harvest use due to their volatility. Taking this into consideration, hexanal was inserted into beta-cyclodextrins (beta-CD) to develop a controlled release mechanism and then evaluated in vitro against Colletotrichum acutatum, Alternaria alternata and Botrytis cinerea, the three main causes of post harvest diseases in berries. Different concentrations of both pure volatile hexanal and its inclusion complexes (IC) were analyzed for their fungistatic and fungicidal effects for 7 days at 23 degrees C. Hexanal has fungistatic effect on all fungi tested, however, fungicidal activity was only observed on C. acutatum. Results showed that hexanal's effectiveness was greater against C. acutatum than A. alternata and B. cinerea. Concentrations of 1.1, 2.3 and 1.3 microL hexanal/L air respectively were necessary to prevent C. acutatum, A. alternata and B. cinerea growth. Lower concentrations reduced fungal growth depending on the included amount and type of fungus. Same amount of hexanal released from beta-cyclodextrin had a lower antifungal effect on C. acutatum. Thus, ICs beta-cyclodextrin-hexanal can be used to reduce or avoid post harvest berry diseases because of their capacity to provide an antifungal volatile during storage, distribution, and consumer purchasing.

Release of acetaldehyde from beta-cyclodextrins inhibits postharvest decay fungi in vitro.

Many naturally occurring plant volatiles are known to have antifungal properties. However, they have limited use because they diffuse rapidly in air. In this in vitro study, acetaldehyde was chosen as a prototype volatile in order to study the controlled release of antifungal volatiles from cyclodextrins (CD). The major postharvest pathogens Alternaria alternata, Botrytis cinerea, and Colletotrichum acutatum were exposed to the pure volatile for 7 days at 23 degrees C. Acetaldehyde was most effective against A. alternata, followed by C. acutatum, and B. cinerea, with 0.12, 0.56, and 1.72 microL/L in air being required to inhibit fungal growth, respectively, according to the bioassay developed. Second, the effectiveness of the new beta-CD-acetaldehyde release system was evaluated against A. alternata for 7 days at 23 degrees C. Sufficient volatile was released from 0.7 g of beta-CD-acetaldehyde to prevent fungal growth in vitro.