Large-scale evaluation of microorganism inactivation by bipolar ionization and photocatalytic devices.

The COVID-19 pandemic has raised awareness in the spread of disease via airborne transmission. As a result, there has been increasing interest in technologies that claim to reduce concentrations of airborne pathogens in indoor environments. The efficacy of many of these emerging technologies is not fully understood, and the testing that has been done is often conducted at a small scale and not representative of applied settings. There is currently no standard test method for evaluating air treatment technologies, making it difficult to compare results across studies or technology types. Here, a consistent testing approach in an operational-scale test chamber with a mock recirculating heating, ventilation, and air conditioning (HVAC) system was used to evaluate the efficacy of bipolar ionization and photocatalytic devices against the non-enveloped bacteriophage MS2 in the air and on surfaces. Statistically significant differences between replicate sets of technology tests and control tests (without technologies active) are apparent after 1 h, ranging to a maximum of 0.88 log10 reduction for the bipolar ionization tests and 1.8 log10 reduction for the photocatalytic device tests. It should be noted that ozone concentrations were elevated above background concentrations in the test chamber during the photocatalytic device testing. No significant differences were observed between control and technology tests in terms of the amount of MS2 deposited or inactivated on surfaces during testing. A standardized, large-scale testing approach, with replicate testing and time-matched control conditions, is necessary for contextualizing laboratory efficacy results, translating them to real-world conditions, and for facilitating technology comparisons.

Impact of test methodology on the efficacy of triethylene glycol (Grignard Pure) against bacteriophage MS2.

The COVID-19 pandemic has raised interest in using chemical air treatments as part of a strategy to reduce the risk of disease transmission, but more information is needed to characterize their efficacy at scales translatable to applied settings and to develop standardized test methods for characterizing the performance of these products. Grignard Pure, a triethylene glycol (TEG) active ingredient air treatment, was evaluated using two different test protocols in a large bioaerosol test chamber and observed to inactivate bacteriophage MS2 in air (up to 99.9% at 90 min) and on surfaces (up to 99% at 90 min) at a concentration of approximately 1.2 - 1.5 mg/m3. Introducing bioaerosol into a TEG-charged chamber led to overall greater reductions compared to when TEG was introduced into a bioaerosol-charged chamber, although the differences in efficacy against airborne MS2 were only significant in the first 15 min. Time-matched control conditions (no TEG present) and replicate tests for each condition were essential for characterizing treatment efficacy. These findings suggest that chemical air treatments could be effective in reducing the air and surface concentrations of infectious pathogens in occupied spaces, although standard methods are needed for evaluating their efficacy and comparing results across studies. The potential health impacts of chronic exposure to chemicals should also be considered, but those were not evaluated here.

Evaluation of electrostatic sprayers and foggers for the application of disinfectants in the era of SARS-CoV-2.

Although research has shown that the COVID-19 disease is most likely caused by airborne transmission of the SARS-CoV-2 virus, disinfection of potentially contaminated surfaces is also recommended to limit the spread of the disease. Use of electrostatic sprayers (ESS) and foggers to rapidly apply disinfectants over large areas or to complex surfaces has emerged with the COVID-19 pandemic. ESSs are designed to impart an electrostatic charge to the spray droplets with the goal of increasing deposition of the droplets onto surfaces, thereby promoting more efficient use of the disinfectant. The purpose of this research was to evaluate several spray parameters for different types of sprayers and foggers, as they relate to the application of disinfectants. Some of the parameters evaluated included the spray droplet size distribution, the electrostatic charge, the ability of the spray to wrap around objects, and the loss of disinfectant chemical active ingredient due to the spray process. The results show that most of the devices evaluated for droplet size distribution had an average volume median diameter ≥ 40 microns, and that four out of the six ESS tested for charge/mass produced sprays of at least 0.1 mC/kg. A minimal wrap-around effect of the spray deposition onto a cylindrical object was observed. The loss of disinfectant active ingredient to the air due to spraying was minimal for the two disinfectants tested, and concurrently, the active ingredient concentrations of the liquid disinfectants sprayed and collected 3 feet (1 meter) away from the spray nozzle do not decrease.

Highly durable, coking and sulfur tolerant, fuel-flexible protonic ceramic fuel cells.

Protonic ceramic fuel cells, like their higher-temperature solid-oxide fuel cell counterparts, can directly use both hydrogen and hydrocarbon fuels to produce electricity at potentially more than 50 per cent efficiency1,2. Most previous direct-hydrocarbon fuel cell research has focused on solid-oxide fuel cells based on oxygen-ion-conducting electrolytes, but carbon deposition (coking) and sulfur poisoning typically occur when such fuel cells are directly operated on hydrocarbon- and/or sulfur-containing fuels, resulting in severe performance degradation over time3-6. Despite studies suggesting good performance and anti-coking resistance in hydrocarbon-fuelled protonic ceramic fuel cells2,7,8, there have been no systematic studies of long-term durability. Here we present results from long-term testing of protonic ceramic fuel cells using a total of 11 different fuels (hydrogen, methane, domestic natural gas (with and without hydrogen sulfide), propane, n-butane, i-butane, iso-octane, methanol, ethanol and ammonia) at temperatures between 500 and 600 degrees Celsius. Several cells have been tested for over 6,000 hours, and we demonstrate excellent performance and exceptional durability (less than 1.5 per cent degradation per 1,000 hours in most cases) across all fuels without any modifications in the cell composition or architecture. Large fluctuations in temperature are tolerated, and coking is not observed even after thousands of hours of continuous operation. Finally, sulfur, a notorious poison for both low-temperature and high-temperature fuel cells, does not seem to affect the performance of protonic ceramic fuel cells when supplied at levels consistent with commercial fuels. The fuel flexibility and long-term durability demonstrated by the protonic ceramic fuel cell devices highlight the promise of this technology and its potential for commercial application.

Helices and other secondary structures of beta- and gamma-peptides.

The principal secondary structural motifs adopted by peptides assembled from beta-amino acid units are discussed: the 14-, 12-, 10-, 12/10-, and 8-helices, as well as the hairpin turn, extended structures, stacks, and sheets. Features that promote a particular folding propensity are outlined and illustrated by structures determined in solution (NMR) and in the solid-state (x-ray). The N-C(beta)-C(alpha)-CO dihedral angles from molecular dynamics simulations, which are indicative of a particular secondary structure, are presented. A brief description of a helix and a turn of gamma-peptides is also given.

N-linked glycosylated beta-peptides are resistant to degradation by glycoamidase A.

Beta-peptides are resistant to degradation by a variety of proteolytic enzymes that rapidly degrade natural alpha-peptides. This is one of many characteristics that make beta-peptides an attractive class of compounds for drug discovery efforts. To further understand the molecular recognition properties of beta-peptides and the ability of enzymes to degrade them, we have synthesized a series of N-linked glycosylated beta- and alpha-peptides, and tested their stability towards a glycosidase. We found that glyco-beta-peptides that contain N-acetylglucosamine (1) or N,N-diacetylchitobiose (2) are completely stable to degradation by glycoamidase A. In comparison, the glyco-alpha-peptides 3 and 4 containing N-acetylglucosamine or N,N-diacetylchitobiose are degraded. Inhibition experiments using increasing concentrations of a glyco-beta-peptide fail to inhibit degradation of the corresponding glyco-alpha-peptide, even when the glyco-beta-peptide is at a 128-fold higher concentration than the glyco-alpha-peptide. Evidently, the glyco-beta-peptides have a much weaker affinity for the active site of the glycosidase than the corresponding glyco-alpha-peptide. These and the results with proteolytic enzymes suggest that the additional CH(2) group introduced into the alpha-amino acid residues causes beta-peptides not to be recognized by hydrolytic enzymes. The results described herein suggest the potential of beta-peptides that are functionalized with carbohydrates for biological and biomedical investigations, without having to be concerned about the carbohydrate being removed.

Exploring the antibacterial and hemolytic activity of shorter- and longer-chain beta-, alpha,beta-, and gamma-peptides, and of beta-peptides from beta2-3-aza- and beta3-2-methylidene-amino acids bearing proteinogenic side chains--a survey.

The antibacterial activities of 31 different beta-, mixed alpha/beta-, and gamma-peptides, as well as of beta-peptides derived from beta2-3-aza- and beta3-2-methylidene-amino acids were assayed against six pathogens (Enterococcus faecalis, Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa), and the results were compared with literature data. The interaction of these peptides with mammalian cells, as modeled by measuring the hemolysis of human erythrocytes, was also investigated. In addition to those peptides designed to fold into amphiphilic helical conformations with positive charges on one face of the helix, one new peptide with hemolytic activity was detected within the sample set. Moreover, it was demonstrated that neither cationic peptides used for membrane translocation (beta3-oligoarginines), nor mixed alpha/beta- or gamma-peptides with somatostatin-mimicking activities display unwanted hemolytic activity.

The proteolytic stability of 'designed' beta-peptides containing alpha-peptide-bond mimics and of mixed alpha,beta-peptides: application to the construction of MHC-binding peptides.

Whereas alpha-peptides are rapidly degraded in vivo and in vitro by a multitude of peptidases, substrates constructed entirely of or incorporating homologated alpha-amino acid (i.e., beta-amino acid) units exhibit a superior stability profile. Efforts made so far to proteolytically hydrolyze a beta-beta peptide bond have not proved fruitful; a study aimed at breaching this proteolytic stability is discussed here. A series of such bonds have been designed with side-chain groups similar in relative positions (constitution) and three-dimensional arrangements (configuration) as found about alpha-peptidic amide bonds. Increasing the prospect for degradation would permit the tuning of beta-peptide stability; here, however, no cleavage was observed (1, 2, 4-6, Table 1). Peptides comprised of alpha- and beta-amino acids (mixed alpha,beta-peptides, 8-11) are expected to benefit from both recognition by a natural receptor and a high level of proteolytic stability, ideal characteristics of pharmacologically active compounds. Beta3-peptides containing alpha-amino acid moieties at the N-terminus are degraded, albeit slowly, by several peptidases. Of particular interest is the ability of pronase to cleave an alpha-beta peptide bond, namely that of alphaAla-beta3 hAla. Significantly, successful hydrolysis is independent of the configuration of the beta-amino acid. Some of the alpha,beta-peptides discussed here are being investigated for their binding affinities to class I MHC proteins. The computer-programming steps required to prepare alpha,beta-peptides on an automated peptide synthesizer are presented.

Probing the proteolytic stability of beta-peptides containing alpha-fluoro- and alpha-hydroxy-beta-amino acids.

One of the benefits of beta-peptides as potential candidates for biological applications is their stability against common peptidases. Attempts have been made to rationalize this stability by altering the electron availability of a given amide carbonyl bond through the introduction of polar substituents at the alpha-position of a single beta-amino acid. Such beta-amino acids (beta-homoglycine, beta-homoalanine), containing one or two fluorine atoms or a hydroxy group in the alpha-position, were prepared in enantiopure form. A versatile method for preparing these alpha-fluoro-beta-amino acids by the homologation of appropriate alpha-amino acids and C-OH->C-F or C=O-->CF(2) substitution with DAST, is described. Consequently, a series of beta-peptides possessing an electronically modified residue at the N terminus or embedded within the chain was synthesized, and their proteolytic stability was investigated against a selection of enzymes. All ten beta-peptides tested were resilient to proteolysis. Introducing a polar, sterically undemanding group, into the alpha-position of beta-amino acids in a beta-peptide chain does not appear to facilitate localized or general enzymatic degradation.

A practical and efficient synthesis of the C-16-C-28 spiroketal fragment (CD) of the spongistatins.

A practical and efficient route to the CD spiroketal (C-16-C-28) of the spongistatins is reported. Two stereocenters are introduced from chiral building blocks with the remainder introduced by substrate-controlled transformations. The key beta-keto-1,3-dithiane intermediate is generated by a dithiol conjugate addition to an ynone and the 1,3-dithiane unit in the C-ring plays a key role in the spiroketalization and subsequent epimerization. The synthesis requires 24 steps, with a longest linear sequence of 19 steps in an overall yield of 14.5% (for the longest linear sequence). [reaction: see text]

Synthesis of the C-1-C-28 ABCD unit of spongistatin 1.

The synthesis of the C-1-C-28 ABCD fragment of spongistatin is described. Anti-selective boron-mediated aldol coupling of a CD spiroketal ketone fragment to an AB spiroketal aldehyde unit forms the desired C1-C28 advanced intermediate. Other features include the double conjugate addition of a dithiol to an ynone to generate the key beta-keto-dithiane unit required for the synthesis of the AB spiroketal fragment. [reaction: see text]

Development of beta-keto 1,3-dithianes as versatile intermediates for organic synthesis.

beta-Keto 1,3-dithianes can be generated by the double conjugate addition of dithiols to propargylic ketones, esters and aldehydes in excellent yields. As masked 1,3-dicarbonyl systems these substrates can be converted to a range of functionalised oxygen-containing heterocycles that can be used in natural product synthesis.