Evaluation of virucidal activity of residual quaternary ammonium-treated surfaces on SARS-CoV-2.

BACKGROUND: The COVID-19 pandemic has had an unprecedented impact on global health and the world's economies. Proliferation of virulent and deadly SARS-CoV-2 variants require effective transmission mitigation strategies. Under reasonable environmental conditions, culturable and infectious SARS-CoV-2 can survive on contaminated fomites from hours to months. In the present study we evaluated a surface-anchored polymeric quaternary ammonium antimicrobial to help reduce fomite transmission of SARS-CoV-2 from contaminated surfaces. METHODS: Two studies were performed on antimicrobial pre-treated metal disks in March 2020 by two independent Biosafety Level III (BSL-3) equipped laboratories in April 2020. These facilities were in Belgium (the Rega Medical Research Institute) and Australia (the Peter Doherty Institute) and independently applied quantitative carrier-based methodologies using the authentic SARS-CoV-2 isolates (hCoV-19/Australia/VIC01/2020, hCoV-19/Belgium/GHB-03021/2020). RESULTS: Residual dry tests were independently conducted at both facilities and demonstrated sustained virion destruction (108.23 TCID50/carrier GHB-03021 isolate, and 103.66 TCID50/carrier VIC01 isolate) 1 hour (drying) + 10 minutes after inoculation. Reductions are further supported by degradation of RNA on antimicrobial-treated surfaces using qRT-PCR. CONCLUSIONS: Using a polymeric quaternary ammonium antimicrobial (EPA/PMRA registered) the results independently support a sustained antiviral effect via SARS-CoV-2 virion destruction and viral RNA degradation. This indicates that silane-anchored quaternary ammonium compound (SiQAC-18) treated surfaces could play an important role in mitigating the communicability and fomite transmission of SARS-CoV-2.

Site- and Stereoselective C-H Alkylations of Carbohydrates Enabled by Cooperative Photoredox, Hydrogen Atom Transfer, and Organotin Catalysis.

Diorganotin dihalides act as cocatalysts for site-selective and stereoselective couplings of diol-containing carbohydrates with electron-deficient alkenes in the presence of an Ir(III) photoredox catalyst and quinuclidine, a hydrogen atom transfer mediator. Quantum-chemical calculations support a proposed mechanism involving the formation of a cyclic stannylene acetal intermediate that shows enhanced reactivity toward hydrogen atom abstraction by the quinuclidinium radical cation. Addition of the carbon-centered radical to the alkene partner results in C-alkylation of the carbohydrate substrate.

Access to thermally robust and abrasion resistant antimicrobial plastics: synthesis of UV-curable phosphonium small molecule coatings and extrudable additives.

The threat of antibiotic-resistant, biofilm-forming bacteria necessitates a preventative approach to combat the proliferation of robust, pathogenic strains on "high touch surfaces" in the food packaging, biomedical, and healthcare industries. The development of both biocide-releasing and tethered, immobilized biocide surface coatings has risen to meet this demand. While these surface coatings have demonstrated excellent antimicrobial efficacy, there are few examples of antimicrobial surfaces with long-term durability and performance. To this end, UV-curable phosphoniums bearing benzophenone anchors with either an alkyl, aryl, or fluoroalkyl group were synthesized and their efficacy as thermally stable antimicrobial additives in extruded plastics or as surface attached coatings probed. The surface topology and characteristics of these materials were studied to gain insight into the mechanism of their antimicrobial activity. Efficacy against both Gram negative and Gram positive bacteria as either a coating or additive showed compete reductions of the initial bacterial load. Crucially, the materials maintained the ability to kill biofilm-forming bacteria even after being subject to several cycles of abrasion.

UV-Curable Surface-Attached Antimicrobial Polymeric Onium Coatings: Designing Effective, Solvent-Resistant Coatings for Plastic Surfaces.

Contact-active ammonium and phosphonium antimicrobial polymeric coatings grafted to plastic surfaces by UV treatment are described. Robust, antimicrobial styrenic polymeric scaffolds copolymerized with a low loading of UV-curable benzophenone were prepared by nitroxide-mediated polymerization (NMP). Similar reversible addition-fragmentation chain-transfer (RAFT)-controlled radical polymerizations were attempted for comparison. These random styrenics were further functionalized into partially quaternarized water-soluble cationic polymers. UV-cured polymeric thin film coatings possessing cationic groups with n-alkyl substituents of n ≤ 2 demonstrate antimicrobial properties against both Gram-positive and Gram-negative bacteria, while species containing bulkier or longer substituents were biologically inactive. The UV-cured cationic antimicrobial polymeric onium thin films also demonstrate enhanced abrasion and chemical resistance.

Surface-attached sulfonamide containing quaternary ammonium antimicrobials for textiles and plastics.

With the risks associated with healthcare-associated infections and the rise of antibiotic resistant microorganisms, there is an important need to control the proliferation of these factors in hospitals, retirement homes and other institutions. This work explores the development and application of a novel class of sulfonamide-based quaternary ammonium antimicrobial coatings, anchored to commercially and clinically relevant material surfaces. Synthesized in high yields (60-97%), benzophenone-anchored antimicrobials were spray-coated and UV grafted onto plastic surfaces, while silane-anchored variants were adhered to select textiles via dip-coating. Surface modified samples were characterised by advancing contact angle, anionic dye staining, X-ray photoelectron spectroscopy and atomic force microscopy. After verifying coating quality through the above characterization methods, microbiological testing was performed on batch samples in conditions that simulate the natural inoculation of surfaces and objects (solid/air) and water containers (solid/liquid). Using the previously established Large Drop Inoculum (LDI) protocol at solid/air interfaces, all treated samples showed a full reduction (105-107 CFU) of viable Arthrobacter sp., S. aureus, and E. coli after 3 h of contact time. Additional testing of the walls of plastic LDPE vials treated with a UV-cured sulfonamide antimicrobial at a solid/liquid interface using the newly developed Large Reservoir Inoculum (LRI) protocol under static conditions revealed a complete kill (>106 reduction) of Gram-positive Arthrobacter sp., and a partial kill (>104 reduction) of Gram-negative E. coli within 24-48 h of contact.

Synthesis and Characterization of Readily Modified Poly(aryl)(alkoxy)stannanes by use of Hypercoordinated Sn Monomers.

The synthesis and solid-state molecular structures of two dichlorido(aryl)(alkyl) tin compounds, 5 and 8, both key intermediates to tunable polystannane architectures, are reported. The materials were further investigated by single-crystal XRD and a DFT analysis of their preferential "open and closed" geometries. Conversion of said compounds to their dihydride analogues was undertaken, followed by their application as monomers for polystannane polymer synthesis. The properties of two asymmetrical polystannanes prepared by transition-metal-catalyzed dehydropolymerization of dihydrido(aryl)alkylstannanes (6 and 9) were investigated. The first product was the structurally simple, modest molecular weight, semi-crystalline light- and moisture-stable polystannane 10 with NMR (119 Sn) evidence of prominent Sn←O hypercoordination along the polymer backbone. The second was the lower molecular weight, tosylated four-coordinate polystannane 11 with no evidence of hypercoordination. Differential scanning calorimetry (DSC) of polymer 10 revealed a reversible semi-crystalline nature, whereas an amorphous character was detected for polymer 11. Polystannane 10 was also found to be exceptionally stable to both moisture and light (>6 months) and a promising candidate for the design of readily modified (i.e., tunable) polystannane materials.

Proof of Concept Studies Directed Towards Designed Molecular Wires: Property-Driven Synthesis of Air and Moisture-Stable Polystannanes.

Polystannanes with azobenzene moieties designed to protect the Sn-Sn backbone from light- and moisture-induced degradation are described. The azo-stannyl precursor 3 (70 %) is converted in good yields (88-91 %) to the mono- (4), and dichlorostannanes (5), by sequential chlorination, followed by further reduction of 5 to the dihydride (6) using NaBH4 (78 %). All stannanes were characterised by NMR (1 H, 13 C, 119 Sn) spectroscopy and HRMS; in addition, 3, 4 and 5 were structurally elucidated using X-ray diffraction analysis. Metal-free dehydrocoupling of 6 at RT leads exclusively to homopolymer (7-i) displaying an initial solution 119 Sn NMR signal (δ=-196 ppm) that migrates to -235 ppm after 10 days (7-f). In contrast, metal-catalyzed dehydrocoupling of 6 in toluene at RT leads directly 7-f. Random co-polymers formed from 6 and (nBu)2 SnH2 at 4:1 (8 a) and 1:1 (8 b) ratios were compared to the alternating polystannane (9) prepared by the reaction of 6 with (nBu)2 Sn(NEt2 )2 . DFT calculations of 3-6 indicate that hypercoordination at Sn is influenced by substituents and by solvation. Homopolymer 7 was found to have unprecedented moisture and light stability in the solid state for >6 months.

UV-Curable Contact Active Benzophenone Terminated Quaternary Ammonium Antimicrobials for Applications in Polymer Plastics and Related Devices.

A series of UV active benzophenone ([C6H5COC6H4-O-(CH2)n-N+Me2R][X-]; 4, R = C12H25, n = 3, X- = Br-; 5a-c, R = C18H37, n = 3, X- = Cl-, Br-, I-; 6a-c, R = C18H37, n = 4, X- = Cl-, Br-, I-; 7a-c, R = C18H37, n = 6, X- = Cl-, Br-, I-) terminated C12 and C18 quaternary ammonium salts (QACs) were prepared by thermal or microwave-driven Menshutkin protocols of the appropriate benzophenone alkyl halide (1a-c, 2a-c, 3a-c) with the corresponding dodecyl- or octadecyl N,N-dimethylamine. All new compounds were characterized by NMR spectroscopy, HRMS spectrometry, and, in one instance (4), by single-crystal X-ray crystallography. Representative C12 and C18 benzophenone QACs were formulated into 1% (w/v) water or water/ethanol-based aerosol spray coatings and then UV-cured onto plastic substrates (polypropylene, polyethylene, polystyrene, polyvinyl chloride, and polyether ether ketone) with exposure to low to moderate doses of UV (20-30 J cm-2). Confirmation as to the presence of the coatings was detected by advancing water contact angle measurements, which revealed a more hydrophilic surface after coating. Further confirmation was gained by X-ray photoelectron spectroscopy analysis, time of flight secondary ion mass spectrometry, and bromophenol blue staining, all of which showed the presence of the attached quaternary ammonium molecule. Analysis of surfaces treated with the C18 benzophenone 5b by atomic force microscopy and surface profilometry revealed a coating thickness of ∼350 nm. The treated samples along with controls were then evaluated for their antimicrobial efficacy against Gram-positive (Arthrobacter sp., Listeria monocytogenes) and Gram-negative (Pseudomonas aeruginosa) bacteria at a solid/air interface using the large drop inoculum protocol; this technique gave no evidence for cell adhesion after a 3 h time frame. These antimicrobial materials show promise for their use as coatings on plastic biomedical devices with the aim of preventing biofilm formation and preventing the spread of hospital acquired infections.

Alternating polystannanes: syntheses and properties.

A new condensation polymerization route leading to alternating polystannanes is presented. The stoichiometric reaction of tin dihydrides and tin diamides in diethyl ether or toluene under mild reaction conditions afforded three new moderate molecular weight alternating polystannanes, -[Ph2Sn-alt-Sn(n-Bu)2]n-, -[Ph2Sn-alt-SnMe2]n-, -[Me2Sn-alt-Sn(n-Bu)2]n-, in addition to a known homopolymer, -[(n-Bu)2]n-.

Crystal structure of (E)-(benzyl-idene)(pyridin-2-ylmeth-yl)amine.

In the title mol-ecule, C13H12N2, all non-H atoms, except for those of the pyridine ring, are essentially coplanar, with an r.m.s. deviation of 0.025 Å. The mean plane of these atoms forms a dihedral angle of 80.98 (4)° with the pyridine ring. In the crystal, weak C-H⋯π inter-actions link the mol-ecules, forming a three-dimensional network.

Organometallic macromolecules with piano stool coordination repeating units: chain configuration and stimulated solution behaviour.

Theoretical calculations illustrate that organometallic macromolecules with piano stool coordination repeating units (Fe-acyl complex) adopt linear chain configuration with a P-Fe-C backbone surrounded by aromatic groups. The macromolecules show molecular weight-dependent and temperature stimulated solution behaviour in DMSO.

A new technique to improve the mechanical and biological performance of ultra high molecular weight polyethylene using a nylon coating.

A new patent pending technique is proposed in this study to improve the mechanical and biological performance of ultra high molecular weight polyethylene (UHMWPE), i.e., to uniformly coat nylon onto the UHMWPE fiber (Firouzi et al., 2012). Mechanical tests were performed on neat and new nylon coated UHMWPE fibers to examine the tensile strength and creep resistance of the samples at different temperatures. Cytotoxicity and osteolysis induced by wear debris of the materials were investigated using (MTT) assay, and RT-PCR for tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) osteolysis markers. Mechanical test results showed substantial improvement in maximum creep time, maximum breaking force, and toughness values of Nylon 6,6 and Nylon 6,12 coated UHMWPE fibers between average 15% and 60% at 25, 50, and 70°C. Furthermore, cytotoxicity studies have demonstrated significant improvement in cell viability using the nylon coated UHMWPE over the neat one (72.4% vs 54.8%) for 48h and (80.7 vs 5%) for 72h (P<0.01). Osteolysis test results have shown that the expression levels of TNFα and IL-6 markers induced by the neat UHMWPE fiber were significantly higher than those induced by the Nylon 6,6 coated UHMWPE (2.5 fold increase for TNFα at 48h, and three fold increase for IL-6 at 72h (P<0.01)). This study suggests that UHMWPE coated with nylon could be used as a novel material in clinical applications with lower cytotoxicity, less wear debris-induced osteolysis, and superior mechanical properties compared to neat UHMWPE.

Synthesis, structures and properties of self-assembling quaternary ammonium dansyl fluorescent tags for porous and non-porous surfaces.

A series of H2O and/or EtOH soluble, self-assembling quaternary ammonium salts containing a dansyl (DNS) fluorescent moiety suitable for attachment to both porous ([DNS-NH-(CH2)3-NMe2-R+][X-] (2; R = -Si(OMe)3, X- = Cl-) and non-porous (3a; R = -PO(OEt)2, 3b; -PO(Oi-Pr)2, 3c; -(PO(OH)2, X- = Br-), 4; ([DNS-NH-(CH2)3-NMe2-(CH2)3-NH(CH2PO(OEt)2)2 +][Br-], 5; R = -((CH2)3SCOCH3, X- = Cl-), 6a; (R = -(CH2)nO(C6H4)CO(C6H5), n = 3, X- = Br-, 6b; n = 3, X- = Cl-, 6c; n = 3, X- = I-, 6d; n = 4, X- = Br-, 6e; n = 4, X- = I-, 6f; n = 6, X- = Br-, 6g; n = 6, X- = Cl-, 6h; n = 6, X- = I-), 7; (R = -CH2-CH[double bond, length as m-dash]CH2, X- = Br-) surfaces were prepared from the precursor dansyl amine (1; DNS-NH-(CH2)3-NMe2). Compounds 1-7 were characterized by NMR (1H, 13C, 29Si (2), 31P (3a-c, 4)) spectroscopy, HRMS, UV-Vis and fluorescence spectroscopy. Additional characterization of compounds 1 and 7 were carried out by X-ray structure determinations. Physical attachment of compound 2 to cotton surfaces after immersion in solutions containing fluorescent dyes was verified by exposure to UV light and by complexation with bromo-phenol blue that rendered the surfaces visibly blue in colour. Phosphorus containing dansyl fluorescent dye, 3c, was attached to a stainless steel surface by exposure to an aqueous solution containing this dye, resulting in the formation of a self-assembled fluorescent monolayer. UV cure of plastic surfaces (polypropylene, silicon medical tubing) coated with compound 6a resulted in the covalent attachment of the dyes.

Pd-catalysed reactions of alkynes with model distannanes and poly[di-(n-butyl)]stannane.

A reinvestigation of Pd-catalysed alkyne (R'-C≡CH; R' = H, Ph) insertion chemistry involving R(3)SnSnR(3) (3a: R = Me; 3b: R = n-Bu) was undertaken. Model distannyl ethylenes 4a-b (Me(3)SnCH=CR'SnMe(3)) and 5a-b ((n-Bu)(3)SnCH=CR'Sn(n-Bu)(3)) were reproduced and further characterized by NMR ((119)Sn, (13)C, (1)H) and UV-Vis spectroscopy. In the presence of an excess of phenylacetylene, dimerization-carbostannylation of compound 4b yielded the new conjugated butadiene, (Z,Z)-1,4-bis(trimethylstannyl)-1,4-diphenyl-buta-1,3-diene (9). An X-ray structure determination of 9 reveals a symmetrical double-bond Z confirmation. Compound 9 was further characterized by NMR, UV-Vis spectroscopy, and MS. A DFT analysis of model compounds (4a-b, 5a-b, 9) and the experimental and theoretical λ(max) values from the UV-Vis spectra were also compared. Acetylene and phenylacetylene Pd-catalysed insertion into the backbone of poly[di-(n-butyl)]stannane 12 resulted in new, modest molecular weight, partially inserted alkene tin polymers (13a-b) that were also characterized by GPC, NMR, UV-Vis spectroscopy and elemental analysis.

Assessment of the working range and effect of sodium dichloroisocyanurate on Pseudomonas aeruginosa biofilms and planktonic cells.

Sodium dichloroisocyanurate (NaDCC) is a chemical agent that acts against microorganisms in a manner similar to that of sodium hypochlorite by releasing free available chlorine. NaDCC has been approved by the WHO for the emergency treatment of water and by the US EPA for routine treatment of water. Previous studies assessing the effectiveness of NaDCC for the treatment of water implied that NaDCC should have a wide array of disinfecting effects beyond the treatment of planktonic cells in potable water. In this study the biocidal effects of NaDCC against Pseudomonas aeruginosa cells in different growth modes including planktonic cells and biofilms were explored. The data showed that a 60% dilution of the standard NaDCC solution was effective in the treatment of both P. aeruginosa planktonic cells and biofilms.

Unusual cationic trinuclear nickel clusters incorporating oxazolines or N,N,N',N'-tetramethylethylene-1,2-diamine: applications in olefin polymerization.

The synthesis and characterization of two rare examples of the nickel(II)-containing trinuclear clusters of the general formula µ(3)-halido-µ(3)-hydroxotris(µ-halido)tris(L) trinickel(II) halide [halide = Cl (2), Br (3); L = 4,4-dimethyl-2-(o-anilinyl)-2-oxazoline] are described. These materials are compared and contrasted to the "parent" chloride salt (1) of this series (L = N,N,N',N'-tetramethylethylene-1,2-diamine and halide = Cl) and its congeners; 2 and 3 represent the first oxazoline-containing clusters of this structural class. Both 1 and 2 are shown to be active catalysts for the polymerization of olefins (styrene, methyl methacrylate, etc.) using a stoichiometric equivalent of methylaluminoxane as the copromoter, a situation that gives good yields of syndiotactic rich polymers. Density functional theory (B3LYP/6-31G*/LANL2DZ) is employed to hypothesize the likely origin of the activity demonstrated by these compounds.

3-Amino-1-methyl-pyrazin-1-ium iodide.

In the cation of the title compound, C(5)H(8)N(3) (+)·I(-), the C-N(H(2)) bond distance [1.338 (8) Å] is at the lower end of the range for aryl amines. In the crystal structure, cations and anions are linked via N-H⋯I hydrogen bonds, forming centrosymmetric four-component clusters.

3-Amino-1-methyl-pyrazin-1-ium chloride.

In the cation of the title compound, C(5)H(8)N(3) (+)·Cl(-), the C-N(H(2)) bond distance [1.348 (3) Å] is at the lower end of the range for aryl amines. In the crystal structure, cations and anions are linked via N-H⋯Cl hydrogen bonds, forming one-dimensional chains along [100].

Tetra-kis[3,5-bis-(trifluoro-meth-yl)phenyl]tin(IV).

The title mol-ecule, [Sn(C(8)H(3)F(6))(4)], lies on a twofold rotation axis with the Sn(IV) ion in a distorted tetra-hedral coordination environment. Both -CF(3) groups attached to one of the unique benzene rings are disordered over two sets of sites, with the ratios of refined occupancies being 0.719 (14):0.281 (14) and 0.63 (5):0.37 (5).