Free energy barrier for molecular motions in bistable [2]rotaxane molecular electronic devices

Donor−acceptor binding of the π-electron-poor cyclophane cyclobis(paraquat-p-phenylene) (CBPQT^(4+)) with the π-electron-rich tetrathiafulvalene (TTF) and 1,5-dioxynaphthalene (DNP) stations provides the basis for electrochemically switchable, bistable [2]rotaxanes, which have been incorporated and operated within solid-state devices to form ultradense memory circuits (ChemPhysChem 2002, 3, 519−525; Nature 2007, 445, 414−417) and nanoelectromechanical systems. The rate of CBPQT^(4+) shuttling at each oxidation state of the [2]rotaxane dictates critical write-and-retention time parameters within the devices, which can be tuned through chemical synthesis. To validate how well computational chemistry methods can estimate these rates for use in designing new devices, we used molecular dynamics simulations to calculate the free energy barrier for the shuttling of the CBPQT^4+ ring between the TTF and the DNP. The approach used here was to calculate the potential of mean force along the switching pathway, from which we calculated free energy barriers. These calculations find a turn-on time after the rotaxane is doubly oxidized of ~10^9−7) s (suggesting that the much longer experimental turn-on time is determined by the time scale of oxidization). The return barrier from the DNP to the TTF leads to a predicted lifetime of 2.1 s, which is compatible with experiments

Evaluating Multiple Arthropod Taxa as Indicators of Invertebrate Diversity in Old Fields

Biodiversity, often quantified by species richness, is commonly used to evaluate and monitor the health of ecosystems and as a tool for conservation planning. The use of one or more focal taxa as surrogates or indicators of larger taxonomic diversity can greatly expedite the process of biodiversity measurement. This is especially true when studying diverse and abundant invertebrate fauna. Before indicator taxa are employed, however, research into their suitability as indicators of greater taxonomic diversity in an area is needed. We sampled invertebrate diversity in old fields in southern Michigan using pitfall trapping and morphospecies designations after identification to order or family. Correlation analysis was used to assess species richness relationships between focal arthropod taxa and general invertebrate diversity. Relationships were assessed at two fine spatial scales: within sampling patches, and locally across four sampling patches. Cumulative richness of all assessed taxa increased proportionately with cumulative invertebrate richness as sampling intensity increased within patches. At the among-patch scale, we tentatively identified Hemiptera and Coleoptera as effective indicator taxa of greater invertebrate richness. Although Hymenoptera, Araneae and Diptera exhibited high species richness, their total richness within patches was not associated with overall invertebrate richness among patches. Increased sampling throughout the active season and across a greater number of habitat patches should be conducted before adopting Hemiptera and Coleoptera as definitive indicators of general invertebrate richness in the Great Lakes region. Multiple sampling techniques, in addition to pitfall trapping, should also be added to overcome capture biases associated with each technique

Kinetic and Thermodynamic Approaches for the Efficient Formation of Mechanical Bonds

Among the growing collection of molecular systems under consideration for nanoscale device applications, mechanically interlocked compounds derived from electrochemically switchable bistable [2]rotaxanes and [2]catenanes show great promise. These systems demonstrate dynamic, relative movements between their components, such as shuttling and circumrotation, enabling them to serve as stimuli-responsive switches operated via reversible, electrochemical oxidation−reduction rather than through the addition of chemical reagents. Investigations into these systems have been intense for a number of years, yet limitations associated with their synthesis have hindered incorporation of their mechanical bonds into more complex architectures and functional materials. We have recently addressed this challenge by developing new template-directed synthetic protocols, operating under both kinetic and thermodynamic control, for the preparation of bistable rotaxanes and catenanes. These methodologies are compatible with the molecular recognition between the π-electron-accepting cyclobis(paraquat-p-phenylene) (CBPQT4+) host and complementary π-electron-donating guests. The procedures that operate under kinetic control rely on mild chemical transformations to attach bulky stoppering groups or perform macrocyclizations without disrupting the host−guest binding of the rotaxane or catenane precursors. Alternatively, the protocols that operate under thermodynamic control utilize a reversible ring-opening reaction of the CBPQT4+ ring, providing a pathway for two cyclic starting materials to thread one another to form more thermodynamically stable catenaned products. These complementary pathways generate bistable rotaxanes and catenanes in high yields, simplify mechanical bond formation in these systems, and eliminate the requirement that the mechanical bonds be introduced into the molecular structure in the final step of the synthesis. These new methods have already been put into practice to prepare previously unavailable rotaxane architectures and novel complex materials. Furthermore, the potential for utilizing mechanically interlocked architectures as device components capable of information storage, the delivery of therapeutic agents, or other desirable functions has increased significantly as a result of the development of these improved synthetic protocols

Severity of Visual Field Loss at First Presentation to Glaucoma Clinics in England and Tanzania

Purpose: To compare severity of visual field (VF) loss at first presentation in glaucoma clinics in England and Tanzania. Methods: Large archives of VF records from automated perimetry were used to retrospectively examine vision loss at first presentation in glaucoma clinics in Tanzania (N = 1,502) and England (N = 9,264). Mean deviation (MD) of the worse eye at the first hospital visit was used as an estimate of detectable VF loss severity. Results: In Tanzania, 44.7% {CI95%: 42.2, 47.2} of patients presented with severe VF loss (< −20 dB), versus 4.6% {4.1, 5.0} in England. If we consider late presentation to also include cases of advanced loss (-12.01 dB to -20 dB), then the proportion of patients presenting late was 58.1% {55.6, 60.6} and 14.0% {13.3, 14.7}, respectively. The proportion of late presentations was greater in Tanzania at all ages, but the difference was particularly pronounced among working-age adults, with 50.3% {46.9, 53.7} of 18–65-year-olds presenting with advanced or severe VF loss, versus 10.2% {9.3, 11.3} in England. In both countries, men were more likely to present late than women. Conclusions: Late presentation of glaucoma is a problem in England, and an even greater challenge in Tanzania. Possible solutions are discussed, including increased community eye-care, and a more proactive approach to case finding through the use of disruptive new technologies, such as low-cost, portable diagnostic aids

Efficient Templated Synthesis of Donor−Acceptor Rotaxanes Using Click Chemistry

The mild reaction conditions, remarkable functional group compatibility, and complete regioselectivity of the Cu-catalyzed Huisgen 1,3-dipolar cycloaddition (“click chemistry”) between organic azides and terminal alkynes have led to a threading-followed-by-stoppering approach to the synthesis of donor−acceptor rotaxanes incorporating cyclobis(paraquat-p-phenylene) (CBPQT^(4+)) as the π-accepting ring component. Rotaxane formation is initiated by reacting azide-functionalized pseudorotaxanes containing π-donating 1,5-dioxynaphthalene (DNP) recognition units with appropriate alkyne-functionalized stoppers. The high yields obtained in this efficient, kinetically controlled post-assembly covalent modification, as well as the excellent convergence of the synthetic protocol, are demonstrated by the preparation of [2]-, [3]-, and [4]rotaxanes containing multiple DNP/CBPQT^(4+) donor−acceptor recognition motifs

Oligorotaxane radicals under orders

A strategy for creating foldameric oligorotaxanes composed of only positively charged components is reported. Threadlike components-namely oligoviologens-in which different numbers of 4,4'-bipyridinium (BIPY(2+)) subunits are linked by p-xylylene bridges, are shown to be capable of being threaded by cyclobis(paraquat-p-phenylene) (CBPQT(4+)) rings following the introduction of radical-pairing interactions under reducing conditions. UV/vis/NIR spectroscopic and electrochemical investigations suggest that the reduced oligopseudorotaxanes fold into highly ordered secondary structures as a result of the formation of BIPY(\u2022+) radical cation pairs. Furthermore, by installing bulky stoppers at each end of the oligopseudorotaxanes by means of Cu-free alkyne-azide cycloadditions, their analogous oligorotaxanes, which retain the same stoichiometries as their progenitors, can be prepared. Solution-state studies of the oligorotaxanes indicate that their mechanically interlocked structures lead to the enforced interactions between the dumbbell and ring components, allowing them to fold (contract) in their reduced states and unfold (expand) in their fully oxidized states as a result of Coulombic repulsions. This electrochemically controlled reversible folding and unfolding process, during which the oligorotaxanes experience length contractions and expansions, is reminiscent of the mechanisms of actuation associated with muscle fibers

Structural and Co-conformational Effects of Alkyne-Derived Subunits in Charged Donor−Acceptor [2]Catenanes

Four donor−acceptor [2]catenanes with cyclobis(paraquat-p-phenylene) (CBPQT^(4+)) as the π-electron-accepting cyclophane and 1,5-dioxynaphthalene (DNP)-containing macrocyclic polyethers as π-electron donor rings have been synthesized under mild conditions, employing Cu^+-catalyzed Huisgen 1,3-dipolar cycloaddition and Cu^(2+)-mediated Eglinton coupling in the final steps of their syntheses. Oligoether chains carrying terminal alkynes or azides were used as the key structural features in template-directed cyclizations of [2]pseudorotaxanes to give the [2]catenanes. Both reactions proceed well with precursors of appropriate oligoether chain lengths but fail when there are only three oxygen atoms in the oligoether chains between the DNP units and the reactive functional groups. The solid-state structures of the donor−acceptor [2]catenanes confirm their mechanically interlocked nature, stabilized by [π···π], [C−H···π], and [C−H···Ο] interactions, and point to secondary noncovalent contacts between 1,3-butadiyne and 1,2,3-triazole subunits and one of the bipyridinum units of the CBPQT^(4+) ring. These contacts are characterized by the roughly parallel orientation of the inner bipyridinium ring system and the 1,2,3-triazole and 1,3-butadiyne units, as well as by the short [π···π] distances of 3.50 and 3.60 Å, respectively. Variable-temperature ^1H NMR spectroscopy has been used to identify and quantify the barriers to the conformationally and co-conformationally dynamic processes. The former include the rotations of the phenylene and the bipyridinium ring systems around their substituent axes, whereas the latter are confined to the circumrotation of the CBPQT^(4+) ring around the DNP binding site. The barriers for the three processes were found to be successively 14.4, 14.5−17.5, and 13.1−15.8 kcal mol^(-1). Within the limitations of the small dataset investigated, emergent trends in the barrier heights can be recognized:  the values decrease with the increasing size of the π-electron-donating macrocycle and tend to be lower in the sterically less encumbered series of [2]catenanes containing the 1,3-butadiyne moiety

Heterogeneity in the Frequency and Characteristics of Homologous Recombination in Pneumococcal Evolution

The bacterium Streptococcus pneumoniae (pneumococcus) is one of the most important human bacterial pathogens, and a leading cause of morbidity and mortality worldwide. The pneumococcus is also known for undergoing extensive homologous recombination via transformation with exogenous DNA. It has been shown that recombination has a major impact on the evolution of the pathogen, including acquisition of antibiotic resistance and serotype-switching. Nevertheless, the mechanism and the rates of recombination in an epidemiological context remain poorly understood. Here, we proposed several mathematical models to describe the rate and size of recombination in the evolutionary history of two very distinct pneumococcal lineages, PMEN1 and CC180. We found that, in both lineages, the process of homologous recombination was best described by a heterogeneous model of recombination with single, short, frequent replacements, which we call micro-recombinations, and rarer, multi-fragment, saltational replacements, which we call macro-recombinations. Macro-recombination was associated with major phenotypic changes, including serotype-switching events, and thus was a major driver of the diversification of the pathogen. We critically evaluate biological and epidemiological processes that could give rise to the micro-recombination and macro-recombination processes

Assessing the reliability of eBURST using simulated populations with known ancestry

BACKGROUND: The program eBURST uses multilocus sequence typing data to divide bacterial populations into groups of closely related strains (clonal complexes), predicts the founding genotype of each group, and displays the patterns of recent evolutionary descent of all other strains in the group from the founder. The reliability of eBURST was evaluated using populations simulated with different levels of recombination in which the ancestry of all strains was known. RESULTS: For strictly clonal simulations, where all allelic change is due to point mutation, the groups of related strains identified by eBURST were very similar to those expected from the true ancestry and most of the true ancestor-descendant relationships (90–98%) were identified by eBURST. Populations simulated with low or moderate levels of recombination showed similarly high performance but the reliability of eBURST declined with increasing recombination to mutation ratio. Populations simulated under a high recombination to mutation ratio were dominated by a single large straggly eBURST group, which resulted from the incorrect linking of unrelated groups of strains into the same eBURST group. The reliability of the ancestor-descendant links in eBURST diagrams was related to the proportion of strains in the largest eBURST group, which provides a useful guide to when eBURST is likely to be unreliable. CONCLUSION: Examination of eBURST groups within populations of a range of bacterial species showed that most were within the range in which eBURST is reliable, and only a small number (e.g. Burkholderia pseudomallei and Enterococcus faecium) appeared to have such high rates of recombination that eBURST is likely to be unreliable. The study also demonstrates how three simple tests in eBURST v3 can be used to detect unreliable eBURST performance and recognise populations in which there appears to be a high rate of recombination relative to mutation