Generation of quality-controlled SARS-CoV-2 variant stocks.

One of the main challenges in the fight against coronavirus disease 2019 (COVID-19) stems from the ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into multiple variants. To address this hurdle, research groups around the world have independently developed protocols to isolate these variants from clinical samples. These isolates are then used in translational and basic research-for example, in vaccine development, drug screening or characterizing SARS-CoV-2 biology and pathogenesis. However, over the course of the COVID-19 pandemic, we have learned that the introduction of artefacts during both in vitro isolation and subsequent propagation to virus stocks can lessen the validity and reproducibility of data. We propose a rigorous pipeline for the generation of high-quality SARS-CoV-2 variant clonal isolates that minimizes the acquisition of mutations and introduces stringent controls to detect them. Overall, the process includes eight stages: (i) cell maintenance, (ii) isolation of SARS-CoV-2 from clinical specimens, (iii) determination of infectious virus titers by plaque assay, (iv) clonal isolation by plaque purification, (v) whole-virus-genome deep-sequencing, (vi and vii) amplification of selected virus clones to master and working stocks and (viii) sucrose purification. This comprehensive protocol will enable researchers to generate reliable SARS-CoV-2 variant inoculates for in vitro and in vivo experimentation and will facilitate comparisons and collaborative work. Quality-controlled working stocks for most applications can be generated from acquired biorepository virus within 1 month. An additional 5-8 d are required when virus is isolated from clinical swab material, and another 6-7 d is needed for sucrose-purifying the stocks.

A comparative study of in vitro air-liquid interface culture models of the human airway epithelium evaluating cellular heterogeneity and gene expression at single cell resolution.

BACKGROUND: The airway epithelium is composed of diverse cell types with specialized functions that mediate homeostasis and protect against respiratory pathogens. Human airway epithelial (HAE) cultures at air-liquid interface are a physiologically relevant in vitro model of this heterogeneous tissue and have enabled numerous studies of airway disease. HAE cultures are classically derived from primary epithelial cells, the relatively limited passage capacity of which can limit experimental methods and study designs. BCi-NS1.1, a previously described and widely used basal cell line engineered to express hTERT, exhibits extended passage lifespan while retaining the capacity for differentiation to HAE. However, gene expression and innate immune function in BCi-NS1.1-derived versus primary-derived HAE cultures have not been fully characterized. METHODS: BCi-NS1.1-derived HAE cultures (n = 3 independent differentiations) and primary-derived HAE cultures (n = 3 distinct donors) were characterized by immunofluorescence and single cell RNA-Seq (scRNA-Seq). Innate immune functions were evaluated in response to interferon stimulation and to infection with viral and bacterial respiratory pathogens. RESULTS: We confirm at high resolution that BCi-NS1.1- and primary-derived HAE cultures are largely similar in morphology, cell type composition, and overall gene expression patterns. While we observed cell-type specific expression differences of several interferon stimulated genes in BCi-NS1.1-derived HAE cultures, we did not observe significant differences in susceptibility to infection with influenza A virus and Staphylococcus aureus. CONCLUSIONS: Taken together, our results further support BCi-NS1.1-derived HAE cultures as a valuable tool for the study of airway infectious disease.

Aetiology of Type 2 diabetes in people with a 'normal' body mass index: testing the personal fat threshold hypothesis.

Weight loss in overweight or obese individuals with Type 2 diabetes (T2D) can normalize hepatic fat metabolism, decrease fatty acid oversupply to ß cells and restore normoglycaemia. One in six people has BMI <27 kg/m2 at diagnosis, and their T2D is assumed to have different aetiology. The Personal Fat Threshold hypothesis postulated differing individual thresholds for lipid overspill and adverse effects on ß-cell function. To test this hypothesis, people with Type 2 diabetes and body mass index <27kg/m2 (n = 20) underwent repeated 5% weight loss cycles. Metabolic assessments were carried out at stable weight after each cycle and after 12 months. To determine how closely metabolic features returned to normal, 20 matched normoglycemic controls were studied once. Between baseline and 12 months: BMI fell (mean ± SD), 24.8 ± 0.4 to 22.5 ± 0.4 kg/m2 (P<0.0001) (controls: 21.5 ± 0.5); total body fat, 32.1 ± 1.5 to 27.6 ± 1.8% (P<0.0001) (24.6 ± 1.5). Liver fat content and fat export fell to normal as did fasting plasma insulin. Post-meal insulin secretion increased but remained subnormal. Sustained diabetes remission (HbA1c < 48 mmol/mol off all glucose-lowering agents) was achieved by 70% (14/20) by initial weight loss of 6.5 (5.5-10.2)%. Correction of concealed excess intra-hepatic fat reduced hepatic fat export, with recovery of ß-cell function, glycaemic improvement in all and return to a non-diabetic metabolic state in the majority of this group with BMI <27 kg/m2 as previously demonstrated for overweight or obese groups. The data confirm the Personal Fat Threshold hypothesis: aetiology of Type 2 diabetes does not depend on BMI. This pathophysiological insight has major implications for management.

A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8.

Small animal models have been a challenge for the study of SARS-CoV-2 transmission, with most investigators using golden hamsters or ferrets. Mice have the advantages of low cost, wide availability, less regulatory and husbandry challenges, and the existence of a versatile reagent and genetic toolbox. However, adult mice do not robustly transmit SARS-CoV-2. Here we establish a model based on neonatal mice that allows for transmission of clinical SARS-CoV-2 isolates. We characterize tropism, respiratory tract replication and transmission of ancestral WA-1 compared to variants Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Omicron BA.1 and Omicron BQ.1.1. We identify inter-variant differences in timing and magnitude of infectious particle shedding from index mice, both of which shape transmission to contact mice. Furthermore, we characterize two recombinant SARS-CoV-2 lacking either the ORF6 or ORF8 host antagonists. The removal of ORF8 shifts viral replication towards the lower respiratory tract, resulting in significantly delayed and reduced transmission in our model. Our results demonstrate the potential of our neonatal mouse model to characterize viral and host determinants of SARS-CoV-2 transmission, while revealing a role for an accessory protein in this context.

A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8.

Small animal models have been a challenge for the study of SARS-CoV-2 transmission, with most investigators using golden hamsters or ferrets 1, 2 . Mice have the advantages of low cost, wide availability, less regulatory and husbandry challenges, and the existence of a versatile reagent and genetic toolbox. However, adult mice do not robustly transmit SARS-CoV-2 3 . Here we establish a model based on neonatal mice that allows for transmission of clinical SARS-CoV-2 isolates. We characterize tropism, respiratory tract replication and transmission of ancestral WA-1 compared to variants Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Omicron BA.1 and Omicron BQ.1.1. We identify inter-variant differences in timing and magnitude of infectious particle shedding from index mice, both of which shape transmission to contact mice. Furthermore, we characterize two recombinant SARS-CoV-2 lacking either the ORF6 or ORF8 host antagonists. The removal of ORF8 shifts viral replication towards the lower respiratory tract, resulting in significantly delayed and reduced transmission in our model. Our results demonstrate the potential of our neonatal mouse model to characterize viral and host determinants of SARS-CoV-2 transmission, while revealing for the first time a role for an accessory protein in this context.

In silico docking screen identifies airway host protease targets for human SERPINs.

Proteases play key roles in viral replication cycles. They can provide cleavage maturation of viral glycoproteins, processing of viral polyproteins, or disassembly of viral capsids. Thus, proteases constitute ideal targets for antiviral intervention â€" pharmaceutically, by small molecule inhibitors, or naturally, by host immune responses. Indeed, we and others have shown that individual members of the Serine protease inhibitor (SERPIN) family have specific antiviral function by blocking proteolytic steps inherent to viral replication cycles. Whether additional members of the large SERPIN family possess antiviral activity and whether SERPINs function as part of the antiviral cell-intrinsic immune response, is currently unknown. Here, we found that specific SERPINs are produced upon infection with clinically relevant respiratory viruses in vitro and in vivo , and in concert with classical interferon-stimulated genes. We next developed a structure-based in silico screen to uncover non-canonical SERPIN-protease pairs. We identified several SERPINs with potential antiviral function, including: SERPINE1 targeting cathepsin L, required for SARS-CoV-2 entry; SERPINB8 targeting furin, required for glycoprotein maturation cleavage of numerous viruses; and SERPINB2 targeting adenovirus protease, which suggests the first direct-acting antiviral SERPIN. Our study demonstrates how proteolysis is modulated for antiviral defense and how this process could inform antiviral targets against clinically relevant respiratory pathogens.

A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8

Summary paragraphSmall animal models have been a challenge for the study of SARS-CoV-2 transmission, with most investigators using golden hamsters or ferrets 1,2. Mice have the advantages of low cost, wide availability, less regulatory and husbandry challenges, and the existence of a versatile reagent and genetic toolbox. However, adult mice do not transmit SARS-CoV-2 3. Here we establish a model based on neonatal mice that allows for transmission of clinical SARS-CoV-2 isolates. We characterize tropism, respiratory tract replication and transmission of ancestral WA-1 compared to variants alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2) and omicron (B.1.1.529). We identify inter-variant differences in timing and magnitude of infectious particle shedding from index mice, both of which shape transmission to contact mice. Furthermore, we characterize two recombinant SARS-CoV-2 lacking either the ORF6 or ORF8 host antagonists. The removal of ORF8 shifts viral replication towards the lower respiratory tract, resulting in significantly delayed and reduced transmission. Our results demonstrate the potential of our neonatal mouse model to characterize viral and host determinants of SARS-CoV-2 transmission, while revealing for the first time a role for an accessory protein this context.

SARS-CoV-2 Portrayed against HIV: Contrary Viral Strategies in Similar Disguise.

SARS-CoV-2 and HIV are zoonotic viruses that rapidly reached pandemic scale, causing global losses and fear. The COVID-19 and AIDS pandemics ignited massive efforts worldwide to develop antiviral strategies and characterize viral architectures, biological and immunological properties, and clinical outcomes. Although both viruses have a comparable appearance as enveloped viruses with positive-stranded RNA and envelope spikes mediating cellular entry, the entry process, downstream biological and immunological pathways, clinical outcomes, and disease courses are strikingly different. This review provides a systemic comparison of both viruses' structural and functional characteristics, delineating their distinct strategies for efficient spread.

Degradable Polymer Structures from Carbon Dioxide and Butadiene.

The utilization of carbon dioxide as a polymer feedstock is an ongoing challenge. This report describes the catalytic conversion of carbon dioxide and an olefin comonomer, 1,3-butadiene, into a polymer structure that arises from divergent propagation mechanisms. Disubstituted unsaturated δ-valerolactone 1 (EVL) was homopolymerized by the bifunctional organocatalyst 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) to produce a hydrolytically degradable polymer. Isolation and characterization of reaction intermediates using 1H, 13C, COSY, HSQC, and MS techniques revealed a vinylogous 1,4-conjugate addition dimer forms in addition to polymeric materials. Polymer number-average molecular weights up to 3760 g/mol and glass transition temperatures in the range of 25-52 °C were measured by GPC and DSC, respectively. The polymer microstructure was characterized by 1H, 13C, FTIR, MALDI-TOF MS, and ESI tandem MS/MS. The olefin/CO2-derived materials depolymerized by hydrolysis at 80 °C in 1 M NaOH. This method and the observed chemical structures expand the materials and properties that can be obtained from carbon dioxide and olefin feedstocks.

Viperin binds STING and enhances the type-I interferon response following dsDNA detection.

Viperin is an interferon-inducible protein that is pivotal for eliciting an effective immune response against an array of diverse viral pathogens. Here we describe a mechanism of viperin's broad antiviral activity by demonstrating the protein's ability to synergistically enhance the innate immune dsDNA signaling pathway to limit viral infection. Viperin co-localized with the key signaling molecules of the innate immune dsDNA sensing pathway, STING and TBK1; binding directly to STING and inducing enhanced K63-linked polyubiquitination of TBK1. Subsequent analysis identified viperin's necessity to bind the cytosolic iron-sulfur assembly component 2A, to prolong its enhancement of the type-I interferon response to aberrant dsDNA. Here we show that viperin facilitates the formation of a signaling enhanceosome, to coordinate efficient signal transduction following activation of the dsDNA signaling pathway, which results in an enhanced antiviral state. We also provide evidence for viperin's radical SAM enzymatic activity to self-limit its immunomodulatory functions. These data further define viperin's role as a positive regulator of innate immune signaling, offering a mechanism of viperin's broad antiviral capacity.

Tenth Scientific Biennial Meeting of the Australasian Virology Society-AVS10 2019.

The Australasian Virology Society (AVS) aims to promote, support and advocate for the discipline of virology in the Australasian region. The society was incorporated in 2011 after 10 years operating as the Australian Virology Group (AVG) founded in 2001, coinciding with the inaugural biennial scientific meeting. AVS conferences aim to provide a forum for the dissemination of all aspects of virology, foster collaboration, and encourage participation by students and post-doctoral researchers. The tenth Australasian Virology Society (AVS10) scientific meeting was held on 2-5 December 2019 in Queenstown, New Zealand. This report highlights the latest research presented at the meeting, which included cutting-edge virology presented by our international plenary speakers Ana Fernandez-Sesma and Benjamin tenOever, and keynote Richard Kuhn. AVS10 honoured female pioneers in Australian virology, Lorena Brown and Barbara Coulson. We report outcomes from the AVS10 career development session on "Successfully transitioning from post-doc to lab head", winners of best presentation awards, and the AVS gender equity policy, initiated in 2013. Plans for the 2021 meeting are underway which will celebrate the 20th anniversary of AVS where it all began, in Fraser Island, Queensland, Australia.

Pollinator effectiveness in a composite: a specialist bee pollinates more florets but does not move pollen farther than other visitors.

PREMISE: Variation in pollinator effectiveness may contribute to pollen limitation in fragmented plant populations. In plants with multiovulate ovaries, the number of conspecific pollen grains per stigma often predicts seed set and is used to quantify pollinator effectiveness. In the Asteraceae, however, florets are uniovulate, which suggests that the total amount of pollen deposited per floret may not measure pollinator effectiveness. We examined two aspects of pollinator effectiveness-effective pollen deposition and effective pollen movement-for insects visiting Echinacea angustifolia, a composite that is pollen limited in small, isolated populations. METHODS: We filmed insect visits to Echinacea in two prairie restorations and used these videos to quantify behavior that might predict effectiveness. To quantify effective pollen deposition, we used the number of styles shriveled per visit. To quantify effective pollen movement, we conducted paternity analysis on a subset of offspring and measured the pollen movement distance between mates. RESULTS: Effective pollen deposition varied among taxa. Andrena helianthiformis, a Heliantheae oligolege, was the most effective taxon, shriveling more than twice the proportion of styles as all other visitors. Differences in visitor behavior on a flowering head did not explain variation in effective pollen deposition, nor did flowering phenology. On average, visitors moved pollen 16 m between plants, and this distance did not vary among taxa. CONCLUSIONS: Andrena helianthiformis is an important pollinator of Echinacea. Variation in reproductive fitness of Echinacea in fragmented habitat may result, in part, from the abundance of this species.

Lipid droplet density alters the early innate immune response to viral infection.

The cellular localisation of many innate signalling events following viral infection has yet to be elucidated, however there has been a few cases in which membranes of certain cellular organelles have acted as platforms to these events. Of these, lipid droplets (LDs) have recently been identified as signalling platforms for innate TLR7 and 9 signalling. Despite their wide range of similar roles in various metabolic pathways, LDs have been overlooked as potential platforms for antiviral innate signalling events. This study established an in vitro model to evaluate the efficiency of the early innate immune response in cells with reduced LD content to the viral mimics, dsDNA and dsRNA, and Sendai viral infection. Using RT-qPCR, the expression of IFN-ß and IFN-λ was quantified following stimulation along with the expression of specific ISGs. Luciferase based assays evaluated the combined expression of ISRE-promoter driven ISGs under IFN-ß stimulation. Cellular LD content did not alter the entry of fluorescently labelled viral mimics into cells, but significantly decreased the ability of both Huh-7 and HeLa cells to produce type I and III IFN, as well as downstream ISG expression, indicative of an impeded innate immune response. This observation was also seen during Sendai virus infection of HeLa cells, where both control and LD reduced cells replicated the virus to the same level, but a significantly impaired type I and III IFN response was observed in the LD reduced cells. In addition to altered IFN production, cells with reduced LD content exhibited decreased expression of specific antiviral ISGs: Viperin, IFIT-1 and OAS-1 under IFN-ß stimulation; However the overall induction of the ISRE-promoter was not effected. This study implicates a role for LDs in an efficient early innate host response to viral infection and future work will endeavour to determine the precise role these important organelles play in induction of an antiviral response.

Interferon-Stimulated Genes as Enhancers of Antiviral Innate Immune Signaling.

The ability of a host to curb a viral infection is heavily reliant on the effectiveness of an initial antiviral innate immune response, resulting in the upregulation of interferon (IFN) and, subsequently, IFN-stimulated genes (ISGs). ISGs serve to mount an antiviral state within a host cell, and although the specific antiviral function of a number of ISGs has been characterized, the function of many of these ISGs remains to be determined. Recent research has uncovered a novel role for a handful of ISGs, some of them directly induced by IFN regulatory factor 3 in the absence of IFN itself. These ISGs, most with potent antiviral activity, are also able to augment varying arms of the innate immune response to viral infection, thereby strengthening this response. This new understanding of the role of ISGs may, in turn, help the recent advancement of novel therapeutics aiming to augment innate signaling pathways in an attempt to control viral infection and pathogenesis.

Electrocatalytic Water Oxidation by a Homogeneous Copper Catalyst Disfavors Single-Site Mechanisms.

Deployment of solar fuels derived from water requires robust oxygen-evolving catalysts made from earth abundant materials. Copper has recently received much attention in this regard. Mechanistic parallels between Cu and single-site Ru/Ir/Mn water oxidation catalysts, including intermediacy of terminal Cu oxo/oxyl species, are prevalent in the literature; however, intermediacy of late transition metal oxo species would be remarkable given the high d-electron count would fill antibonding orbitals, making these species high in energy. This may suggest alternate pathways are at work in copper-based water oxidation. This report characterizes a dinuclear copper water oxidation catalyst, {[(L)Cu(II)]2-(µ-OH)2}(OTf)2 (L = Me2TMPA = bis((6-methyl-2-pyridyl)methyl)(2-pyridylmethyl)amine) in which water oxidation proceeds with high Faradaic efficiency (>90%) and moderate rates (33 s-1 at ∼1 V overpotential, pH 12.5). A large kinetic isotope effect (kH/kD = 20) suggests proton coupled electron transfer in the initial oxidation as the rate-determining step. This species partially dissociates in aqueous solution at pH 12.5 to generate a mononuclear {[(L)Cu(II)(OH)]}+ adduct (Keq = 0.0041). Calculations that reproduce the experimental findings reveal that oxidation of either the mononuclear or dinuclear species results in a common dinuclear intermediate, {[LCu(III)]2-(µ-O)2}2+, which avoids formation of terminal Cu(IV)═O/Cu(III)-O• intermediates. Calculations further reveal that both intermolecular water nucleophilic attack and redox isomerization of {[LCu(III)]2-(µ-O)2}2+ are energetically accessible pathways for O-O bond formation. The consequences of these findings are discussed in relation to differences in water oxidation pathways between Cu catalysts and catalysts based on Ru, Ir, and Mn.

Improved time to treatment failure with an intermittent oxaliplatin strategy: results of CONcePT.

BACKGROUND: Oxaliplatin is an integral component of colorectal cancer treatment, but its use is limited by neurotoxicity. The Combined Oxaliplatin Neurotoxicity Prevention Trial (CONcePT) tested intermittent oxaliplatin (IO) administration and the use of concurrent calcium and magnesium salts (Ca/Mg), two modifications intended to reduce neurotoxicity and extend the duration of treatment. PATIENTS AND METHODS: In this trial involving double randomization, 140 patients were randomized to receive modified FOLFOX7 plus bevacizumab with IO (eight-cycle blocks of oxaliplatin treatment) versus continuous oxaliplatin (CO); and Ca/Mg versus placebo (pre- and postoxaliplatin infusion). The primary end point was time-to-treatment failure (TTF). RESULTS: One hundred thirty-nine patients were entered and treated up to the point of early study termination due to concerns by the data-monitoring committee (DMC) that Ca/Mg adversely affected tumor response. Tumor response was not a study end point. Given DMC concerns, an additional independent, blinded radiology review of all images showed no adverse effect of treatment schedule or Ca/Mg on response by Response Evaluation Criteria In Solid Tumors. The IO schedule was superior to CO [hazard ratio (HR) = 0.581, P = 0.0026] for both TTF and time-to-tumor progression (TTP) (HR = 0.533, P = 0.047). CONCLUSIONS: An IO dosing schedule had a significant benefit on both TTF and TTP versus CO dosing in this trial despite the very attenuated sample. There was no effect of Ca/Mg on response.

Identifying individuals at risk for fracture in Guatemala.

INTRODUCTION: The FRAX calculator combines a set of clinical risk factors with country-specific incidence rates to determine the ten-year absolute risk of major osteoporotic fracture. However, regional or country-specific databases from Central American countries are not available. We compared the use of various FRAX databases and the Pluijm algorithm in determining risk of fracture. METHODS: We collected clinical risk factor data needed for the FRAX calculator and Pluijm algorithm of Hispanic women in Guatemala and calculated the FRAX absolute risk measures of major osteoporotic fracture and hip fracture. Subjects were postmenopausal women greater than age 40 with no history of using medication that affect bone. A random sample of 204 women in 34 different regions women in Guatemala City was visited in their homes to complete the surveys. The Pluijm risk score and FRAX risk score using the US Hispanic, Spain, and Mexican databases were calculated. RESULTS: We used the US NOF guidelines for treatment which suggest a treatment threshold for patients with a 10-year hip fracture probability ≥ 3% or a 10-year major osteoporotic fracture risk ≥ 20%. The number of patients meeting the suggested threshold limits for treatment using the Spain and Mexico calculators were identical. There was 100% conformity in threshold limits for both hip and major osteoporotic fracture risk. The mean conformity for any fracture risk between US Hispanic and the other two databases was 97.5%. Conformity was 99.0% based on major osteoporotic fracture and 97.5% based on risk of hip fracture. The Pluijm evaluation shows conformity of 87.2% and 83.3%, respectively, when compared to the US Hispanic and Spain/Mexico FRAX thresholds for risk of fracture. DISCUSSION: Although the different FRAX databases provide variations in the absolute risk of fracture, the overall conformity to treatment thresholds amongst the US Hispanic, Spain, and Mexico databases show the database used would have little effect as to the decision to treat. The Pluijm tool conforms to the FRAX thresholds and can be used as well. It does not matter which country-specific calculator or assessment tool is used, as there are a similar number of patients that would meet the intervention threshold.

Comparison of FRAX Scores of Southern California Females of Mexican Descent Using US Hispanic and Mexico Database.

Introduction. Regional differences for fracture risk of US Hispanics may vary by national origin. In California, where a majority of the Hispanic population is of Mexican descent, it is of interest to compare the FRAX absolute risk using the US Hispanic and Mexico databases. Methods. We collected FRAX risk factor data from 134 women of Mexican descent in southern California. The FRAX risk score was calculated using the US Hispanic and Mexican databases, using the NOF guidelines for osteoporosis to compare the number of patients that would be selected for treatment. Results. The 10-year absolute risk of major osteoporotic fracture among women of Mexican descent using the US Hispanic database was 4.82 ± 5.03 (95% CI 3.97-5.67) compared to 4.86 ± 4.72 (CI 3.98-5.44) using the Mexico database (P = .94). The 10-year risk for hip fracture was 0.86 ± 1.78 (CI .56-1.16) compared to 1.12 ± 1.97 (CI .79-1.45, P = .26). The mean conformity for meeting the interventional threshold by either risk score was 94.8%. Conclusion. The comparison between the FRAX databases demonstrates a similarity in the absolute risk of major osteoporotic fracture. Differences are noted in the absolute number of hip fracture subjects at risk, but there is a high rate of conformity.

Self-assembly of SbCl3 and 1,4-dioxane: cubic structure connected by very weak bonds.

The self-assembly of SbCl(3) and 1,4-dioxane in a 2:3 ratio leads to an interpenetrating extended cubic structure from X-ray crystallography. The structure is held together by very weak Sb-O bonds ( approximately 7 kcal/mol each), which still maintain strong directionality. Parameterization and subsequent simulation of the system using a reactive force field (ReaxFF) gives us insight into the key interactions necessary for self-assembly from a completely random configuration of molecules into the experimentally observed cubic structure. We explain why the porous structure (with no interpenetration of lattices) is not observed, and we trace the important intermediate substructures formed en route to the crystal.

Computational study of multiple-decker sandwich and rice-ball structures of neutral titanium-benzene clusters.

Density functional theory calculations were applied to systematically and directly compare the relative energetic stability of multiple-decker sandwich and rice-ball structures for a variety of neutral Ti(m)Bz(n) clusters (m = 1-4, n = 1-5). Almost all structures favored the multiple-decker sandwich structure, as observed experimentally for early transition metals. The strength of each metal-benzene interaction averages 37 kcal/mol and remains relatively constant for sandwiches with three or more Ti atoms. The most stable smaller rice-ball structures did not have eta(6)-Bz bound to a single metal atom. Instead, the preferred coordination was having the plane of the benzene molecule parallel to a Ti(2) bond or a Ti(3) face, leading to some distortion of the benzene ring. The larger rice-ball structures, on the other hand, preferred to weaken the metal-metal bonds and retain eta(6)-Bz bound to a single metal atom, a structural motif shared with sandwiches.