Rachel C. Steinhardt

The academic and industrial communities have proposed two-dimensional (2D) transition metal dichalcogenide (TMD) semiconductors as a future option to supplant silicon transistors at sub-10nm physical gate lengths. In this Comment, we share the recent progress in the fabrication of complementary metal-oxide-semiconductor (CMOS) devices based on stacked 2D TMD nanoribbons and specifically highlight issues that still need to be resolved by the 2D community in five crucial research areas: contacts, channel growth, gate oxide, variability, and doping. While 2D TMD transistors have great potential, more research is needed to understand the physical interactions of 2D materials at the atomic scale. 2D semiconductors have been proposed as a potential option to replace or complement silicon electronics at the nanoscale. Here, the authors discuss the recent progress and remaining challenges that need to be addressed by the academic and industrial research communities towards the commercialization of 2D transistors.

Bioluminescence imaging with luciferase enzymes requires access to light-emitting, small-molecule luciferins. Here, we describe a rapid method to synthesize d-luciferin, the substrate for firefly luciferase (Fluc), along with a novel set of electronically modified analogues. Our procedure utilizes a relatively rare, but synthetically useful dithiazolium reagent to generate heteroaromatic scaffolds in a divergent fashion. Two of the luciferin analogues produced with this approach emit light with Fluc in vitro and in live cells. Collectively, our work increases the number of substrates that can be used for bioluminescence imaging and provides a general strategy for synthesizing new collections of luciferins.

Bioluminescence imaging with luciferase-luciferin pairs is commonly used for monitoring biological processes in cells and whole organisms. Traditional bioluminescent probes are limited in scope, though, as they cannot be easily distinguished in biological environments, precluding efforts to visualize multicellular processes. Additionally, many luciferase-luciferin pairs emit light that is poorly tissue penetrant, hindering efforts to visualize targets in deep tissues. To address these issues, we synthesized a set of π-extended luciferins that were predicted to be red-shifted luminophores. The scaffolds were designed to be rotationally labile such that they produced light only when paired with luciferases capable of enforcing planarity. A luciferin comprising an intramolecular "lock" was identified as a viable light-emitting probe. Native luciferases were unable to efficiently process the analog, but a complementary luciferase was identified via Rosetta-guided enzyme design. The unique enzyme-substrate pair is red-shifted compared to well-known bioluminescent tools. The probe set is also orthogonal to other luciferase-luciferin probes and can be used for multicomponent imaging. Four substrate-resolved luciferases were imaged in a single session. Collectively, this work provides the first example of Rosetta-guided design in engineering bioluminescent tools and expands the scope of orthogonal imaging probes.