A Push-Button Molecular Switch

The preparation, characterization, and switching mechanism of a unique single-station mechanically switchable hetero[2]catenane are reported. The facile synthesis utilizing a “threading-followed-by-clipping” protocol features Cu^(2+)-catalyzed Eglinton coupling as a mild and efficient route to the tetrathiafulvalene-based catenane in high yield. The resulting mechanically interlocked molecule operates as a perfect molecular switch, most readily described as a “push-button” switch, whereby two discrete and fully occupied translational states are toggled electrochemically at incredibly high rates. This mechanical switching was probed using a wide variety of experimental techniques as well as quantum-mechanical investigations. The fundamental distinctions between this single-station [2]catenane and other more traditional bi- and multistation molecular switches are significant

Synthesis and Characterization of Ruthenium and Rhenium Nucleosides

We report the synthesis and characterization of new ruthenium and rhenium nucleosides [Ru(tolyl-acac)_2(IMPy)-T] (tolyl-acac = di(p-methylbenzonatemethane), IMPy = 2‘-iminomethylpyridine, T = thymidine) (5) and [Re(CO)_3(IMPy)-T]Cl (9), respectively. Structural analysis of 9 shows that the incorporation of this metal complex causes minimal perturbation to the sugar backbone and the nucleobase. Eletrochemical (5, E_(1/2) = 0.265 V vs NHE; 9, E_(1/2) = 1.67 V vs NHE), absorption (5, λ_(max) = 600, 486 nm; 9, λ_(max) = 388 nm), and emission (9, λ_(max) = 770 nm, π = 17 ns) data indicate that 5 and 9 are suitable probes for DNA-mediated ground-state electron-transfer studies. The separation and characterization of diastereoisomers of 5 and bipyridyl-based ruthenium nucleoside [Ru(bpy)_2(IMPy)-T]^(2+) (7) are reported

Crystallographic Education in the 21st Century

There are many methods that can be used to incorporate concepts of crystallography into the learning experiences of students, whether they are in elementary school, at university or part of the public at large. It is not always critical that those who teach crystallography have immediate access to diffraction equipment to be able to introduce the concepts of symmetry, packing or molecular structure in an age- and audience-appropriate manner. Crystallography can be used as a tool for teaching general chemistry concepts as well as general research techniques without ever having a student determine a crystal structure. Thus, methods for younger students to perform crystal growth experiments of simple inorganic salts, organic compounds and even metals are presented. For settings where crystallographic instrumentation is accessible (proximally or remotely), students can be involved in all steps of the process, from crystal growth, to data collection, through structure solution and refinement, to final publication. Several approaches based on the presentations in the MS92 Microsymposium at the IUCr 23rd Congress and General Assembly are reported. The topics cover methods for introducing crystallography to undergraduate students as part of a core chemistry curriculum; a successful short-course workshop intended to bootstrap researchers who rely on crystallography for their work; and efforts to bring crystallography to secondary school children and non-science majors. In addition to these workshops, demonstrations and long-format courses, open-format crystallographic databases and three-dimensional printed models as tools that can be used to excite target audiences and inspire them to pursue a deeper understanding of crystallography are described

A Radically Configurable Six-State Compound

Most organic radicals possess short lifetimes and quickly undergo dimerization or oxidation. Here, we report on the synthesis by radical templation of a class of air- and water-stable organic radicals, trapped within a homo[2]catenane composed of two rigid and fixed cyclobis (paraquat-p-phenylene) rings. The highly energetic octacationic homo[2]catenane, which is capable of accepting up to eight electrons, can be configured reversibly, both chemically and electrochemically, between each one of six experimentally accessible redox states (0, 2+, 4+, 6+, 7+, and 8+) from within the total of nine states evaluated by quantum mechanical methods. All six of the observable redox states have been identified by electrochemical techniques, three (4+, 6+, and 7+) have been characterized by x-ray crystallography, four (4+, 6+, 7+, and 8+) by electron paramagnetic resonance spectroscopy, one (7+) by superconducting quantum interference device magnetometry, and one (8+) by nuclear magnetic resonance spectroscopy

Communications Biophysics

Contains research objectives and summary of research on five research projects, with ten sub-topics.National Institutes of Health (Grant 1 RO1 NS10916-01)National Institutes of Health (Grant 5 RO1 NS11000-03)National Institutes of Health (Grant 1 RO1 NS11153-01)Harvard-M.I.T. Rehabilitation Engineering CenterU. S. Department of Health, Education, and Welfare (Grant 23-P-55854)National Institutes of Health (Grant 1 RO1 NS11680-01)National Institutes of Health (Grant 5 ROI NS11080-02)M.I.T. Health Sciences FundNational Aeronautics and Space Administration (Grant NSG-2032)National Institutes of Health (Grant 5 TO1 GM01555-09)Massachusetts General Hospital Purchase Order F63853Boston City Hospital Purchase Order 4338-7543

Reexamination of Lead(II) Coordination Preferences in Sulfur-Rich Sites: Implications for a Critical Mechanism of Lead Poisoning

Recent studies suggest that the developmental toxicity associated with childhood lead poisoning may be attributable to interactions of Pb(II) with proteins containing thiol-rich structural zinc-binding sites. Here, we report detailed structural studies of Pb(II) in such sites, providing critical insights into the mechanism by which lead alters the activity of these proteins. X-ray absorption spectroscopy of Pb(II) bound to structural zinc-binding peptides reveals that Pb(II) binds in a three-coordinate Pb(II)-S3 mode, while Zn(II) is known to bind in a four-coordinate mode in these proteins. This Pb(II)-S_3 coordination in peptides is consistent with a trigonal pyramidal Pb(II)-S_3 model compound previously reported by Bridgewater and Parkin, but it differs from many other reports in the small molecule literature which have suggested Pb(II)-S_4 as a preferred coordination mode for lead. Reexamination of the published structures of these “Pb(II)-S_4” compounds reveals that, in almost all cases, the coordination number of Pb is actually 5, 6, or 8. The results reported herein combined with this new review of published structures suggest that lead prefers to avoid four-coordination in sulfur-rich sites, binding instead as trigonal pyramidal Pb(II)-S_3 or as Pb(II)-S_(5-8). In the case of structural zinc-binding protein sites, the observation that lead binds in a three-coordinate mode, and in a geometry that is fundamentally different from the natural coordination of zinc in these sites, explains why lead disrupts the structure of these peptides and thus provides the first detailed molecular understanding of the developmental toxicity of lead

Communications Biophysics

Contains reports on four research projects.National Institutes of Health (Grant 5 P01 NS13126-02)National Institutes of Health (Grant 5 K04 NS00113-03)National Institutes of Health (Grant 2 ROI NS11153-02A1)National Science Foundation (Grant BNS77-16861)National Institutes of Health (Grant 5 RO1 NS10916-03)National Institutes of Health (Fellowship 1 F32 NS05327)National Institutes of Health (Grant 5 ROI NS12846-02)National Institutes of Health (Fellowship 1 F32 NS05266)Edith E. Sturgis FoundationNational Institutes of Health (Grant 1 R01 NS11680-01)National Institutes of Health (Grant 2 RO1 NS11080-04)National Institutes of Health (Grant 5 T32 GIM107301-03)National Institutes of Health (Grant 5 TOI GM01555-10

Communications Biophysics

Contains research objectives and summary of research on nine research projects split into four sections.National Institutes of Health (Grant 5 ROI NS11000-03)National Institutes of Health (Grant 1 P01 NS13126-01)National Institutes of Health (Grant 1 RO1 NS11153-01)National Institutes of Health (Grant 2 R01 NS10916-02)Harvard-M.I.T. Rehabilitation Engineering CenterU. S. Department of Health, Education, and Welfare (Grant 23-P-55854)National Institutes of Health (Grant 1 ROl NS11680-01)National Institutes of Health (Grant 5 ROI NS11080-03)M.I.T. Health Sciences Fund (Grant 76-07)National Institutes of Health (Grant 5 T32 GM07301-02)National Institutes of Health (Grant 5 TO1 GM01555-10

Dopaminergic D1 receptor signalling is necessary, but not sufficient for cued fear memory destabilisation

Rationale. Pharmacological targeting of memory reconsolidation is a promising therapeutic strategy for the treatment of fear memory-related disorders. However, the success of reconsolidation-based approaches depends upon the effective destabilisation of the fear memory by memory reactivation. Objectives. Here, we aimed to determine the functional involvement of dopamine D1 receptors in cued fear memory destabilisation, using systemic drug administration. Results. We observed that direct D1 receptor agonism was not sufficient to stimulate tone fear memory destabilisation to facilitate reconsolidation disruption by the glucocorticoid receptor antagonist mifepristone. Instead, administration of the nootropic nefiracetam did facilitate mifepristone-induced amnesia, in a manner that was dependent upon dopamine D1 receptor activation, although. Finally, while the combined treatment with nefiracetam and mifepristone did not confer fear-reducing effects under conditions of extinction learning, there was some evidence that mifepristone reduces fear expression irrespective of memory reactivation parameters. Conclusions. The use of combination pharmacological treatment to stimulate memory destabilisation and impair reconsolidation has potential therapeutic benefits, without risking a maladaptive increase of fear