Cyclic Thiosulfinates and Cyclic Disulfides Selectively Cross-Link Thiols While Avoiding Modification of Lone Thiols.

This work addresses the need for chemical tools that can selectively form cross-links. Contemporary thiol-selective cross-linkers, for example, modify all accessible thiols, but only form cross-links between a subset. The resulting terminal "dead-end" modifications of lone thiols are toxic, confound cross-linking-based studies of macromolecular structure, and are an undesired, and currently unavoidable, byproduct in polymer synthesis. Using the thiol pair of Cu/Zn-superoxide dismutase (SOD1), we demonstrated that cyclic disulfides, including the drug/nutritional supplement lipoic acid, efficiently cross-linked thiol pairs but avoided dead-end modifications. Thiolate-directed nucleophilic attack upon the cyclic disulfide resulted in thiol-disulfide exchange and ring cleavage. The resulting disulfide-tethered terminal thiolate moiety either directed the reverse reaction, releasing the cyclic disulfide, or participated in oxidative disulfide (cross-link) formation. We hypothesized, and confirmed with density functional theory (DFT) calculations, that mono- S-oxo derivatives of cyclic disulfides formed a terminal sulfenic acid upon ring cleavage that obviated the previously rate-limiting step, thiol oxidation, and accelerated the new rate-determining step, ring cleavage. Our calculations suggest that the origin of accelerated ring cleavage is improved frontier molecular orbital overlap in the thiolate-disulfide interchange transition. Five- to seven-membered cyclic thiosulfinates were synthesized and efficiently cross-linked up to 104-fold faster than their cyclic disulfide precursors; functioned in the presence of biological concentrations of glutathione; and acted as cell-permeable, potent, tolerable, intracellular cross-linkers. This new class of thiol cross-linkers exhibited click-like attributes including, high yields driven by the enthalpies of disulfide and water formation, orthogonality with common functional groups, water-compatibility, and ring strain-dependence.

Development of an open technology sensor suite for assisted living: a student-led research project.

Many countries have a rapidly ageing population, placing strain on health services and creating a growing market for assistive technology for older people. We have, through a student-led, 12-week project for 10 students from a variety of science and engineering backgrounds, developed an integrated sensor system to enable older people, or those at risk, to live independently in their own homes for longer, while providing reassurance for their family and carers. We provide details on the design procedure and performance of our sensor system and the management and execution of a short-term, student-led research project. Detailed information on the design and use of our devices, including a door sensor, power monitor, fall detector, general in-house sensor unit and easy-to-use location-aware communications device, is given, with our open designs being contrasted with closed proprietary systems. A case study is presented for the use of our devices in a real-world context, along with a comparison with commercially available systems. We discuss how the system could lead to improvements in the quality of life of older users and increase the effectiveness of their associated care network. We reflect on how recent developments in open source technology and rapid prototyping increase the scope and potential for the development of powerful sensor systems and, finally, conclude with a student perspective on this team effort and highlight learning outcomes, arguing that open technologies will revolutionize the way in which technology will be deployed in academic research in the future.