Quarternary α-cyanobenzylsulfonamides: A new subclass of CAA fungicides with excellent anti-Oomycetes activity.

A bioisosteric carboxamide - sulfonamide replacement explored during the optimization of an insecticide lead compound led to the surprising discovery of a formerly unknown subclass of the Carboxylic Acid Amide (CAA) fungicides, which is the very first CAA fungicide group without a carboxamide function. In this paper we present invention pathway, racemic and stereoselective synthesis routes, structure-activity relationship studies as well as resistance profile of this novel family of fungicides.

Batch versus flow photochemistry: a revealing comparison of yield and productivity.

The use of flow photochemistry and its apparent superiority over batch has been reported by a number of groups in recent years. To rigorously determine whether flow does indeed have an advantage over batch, a broad range of synthetic photochemical transformations were optimized in both reactor modes and their yields and productivities compared. Surprisingly, yields were essentially identical in all comparative cases. Even more revealing was the observation that the productivity of flow reactors varied very little to that of their batch counterparts when the key reaction parameters were matched. Those with a single layer of fluorinated ethylene propylene (FEP) had an average productivity 20% lower than that of batch, whereas three-layer reactors were 20% more productive. Finally, the utility of flow chemistry was demonstrated in the scale-up of the ring-opening reaction of a potentially explosive [1.1.1] propellane with butane-2,3-dione.

Direct laser induced writing of high precision gold nanosphere SERS patterns.

The high sensitivity and molecular fingerprint capability of Surface-Enhanced Raman Spectroscopy (SERS) have lead to a wide variety of applications ranging from classical physics, chemistry over biology to medicine. Equally, there are numerous methods to fabricate samples owing to the desired properties and to create the localized surface plasmon resonances (LSPRS). However, for many applications the LSPRs must be specifically localized on micrometer sized areas and multiple steps of lithography are needed to achieve the desired substrates. Here we present a fast and reliable direct laser induced writing (DIW) method to produce SERS substrates with active areas of interest in any desired size and shape in the micrometer regime. Afterwards, the SERS substrates have been functionalized with phthalocyanines. The DIW fabricated samples realize sub-monolayer sensitivity and an almost uniform enhancement over the entire area, which make this production method suitable for many sensing applications.

Nanometer Sized Direct Laser-Induced Gold Printing for Precise 2D-Electronic Device Fabrication.

Flexible electronics manufacturing technologies are essential and highly favored for future integrated photonic and electronic devices. Direct laser induced writing (DIW) of metals has shown potential as a fast and highly variable method in adaptable electronics. However, most of the DIW procedures use silver structures, which tend to oxidize and are limited to the micrometer regime. Here, a DIW technique is introduced that not only enables electrical gold wiring of 2D van-der-Waals materials with sub-µm structures and 100 nm interspacing resolution but is also capable of fabricating photo switches and field effect transistors on various rigid and elastic materials. Light sensitive metalloid Au32 -nanoclusters serve as the ink that allows for low-power cw-laser exposure without further post-treatment. With a simple lift-off procedure, the unexposed ink can be removed. The technique realizes ultrafast, high resolution, and high precision production of integrated electronics and may pave the way for personalized circuits even printed on curved surfaces.

Probing the bioactivity-relevant chemical space of robust reactions and common molecular building blocks.

In the search for new bioactive compounds, there is a trend toward increasingly complex compound libraries aiming to target the demanding targets of the future. In contrast, medicinal chemistry and traditional library design rely mainly on a small set of highly established and robust reactions. Here, we probe a set of 58 such reactions for their ability to sample the chemical space of known bioactive molecules, and the potential to create new scaffolds. Combined with ~26,000 common available building blocks, the reactions retrieve around 9% of a scaffold-diverse set of compounds active on human target proteins covering all major pharmaceutical target classes. Almost 80% of generated scaffolds from virtual one-step synthesis products are not present in a large set of known bioactive molecules for human targets, indicating potential for new discoveries. The results suggest that established synthesis resources are well suited to cover the known bioactivity-relevant chemical space and that there are plenty of unexplored regions accessible by these reactions, possibly providing valuable "low-hanging fruit" for hit discovery.

Picosecond electrical response in graphene/MoTe2 heterojunction with high responsivity in the near infrared region.

Understanding the fundamental charge carrier dynamics is of great significance for photodetectors with both high speed and high responsivity. Devices based on two-dimensional (2D) transition metal dichalcogenides can exhibit picosecond photoresponse speed. However, 2D materials naturally have low absorption, and when increasing thickness to gain higher responsivity, the response time usually slows to nanoseconds, limiting their photodetection performance. Here, by taking time-resolved photocurrent measurements, we demonstrated that graphene/MoTe2 van der Waals heterojunctions realize a fast 10 ps photoresponse time owing to the reduced average photocurrent drift time in the heterojunction, which is fundamentally distinct from traditional Dirac semimetal photodetectors such as graphene or Cd3As2 and implies a photodetection bandwidth as wide as 100 GHz. Furthermore, we found that an additional charge carrier transport channel provided by graphene can effectively decrease the photocurrent recombination loss to the entire device, preserving a high responsivity in the near-infrared region. Our study provides a deeper understanding of the ultrafast electrical response in van der Waals heterojunctions and offers a promising approach for the realization of photodetectors with both high responsivity and ultrafast electrical response.

A collection of robust organic synthesis reactions for in silico molecule design.

A focused collection of organic synthesis reactions for computer-based molecule construction is presented. It is inspired by real-world chemistry and has been compiled in close collaboration with medicinal chemists to achieve high practical relevance. Virtual molecules assembled from existing starting material connected by these reactions are supposed to have an enhanced chance to be amenable to real chemical synthesis. About 50% of the reactions in the dataset are ring-forming reactions, which fosters the assembly of novel ring systems and innovative chemotypes. A comparison with a recent survey of the reactions used in early drug discovery revealed considerable overlaps with the collection presented here. The dataset is available encoded as computer-readable Reaction SMARTS expressions from the Supporting Information presented for this paper.

A bioinformatics framework for genotype-phenotype correlation in humans with Marfan syndrome caused by FBN1 gene mutations.

Mutations in the human FBN1 gene are known to be associated with the Marfan syndrome, an autosomal dominant inherited multi-systemic connective tissue disorder. However, in the absence of solid genotype-phenotype correlations, the identification of an FBN1 mutation has only little prognostic value. We propose a bioinformatics framework for the mutated FBN1 gene which comprises the collection, management, and analysis of mutation data identified by molecular genetic analysis (DHPLC) and data of the clinical phenotype. To query our database at different levels of information, a relational data model, describing mutational events at the cDNA and protein levels, and the disease's phenotypic expression from two alternative views, was implemented. For database similarity requests, a query model which uses a distance measure based on log-likelihood weights for each clinical manifestation, was introduced. A data mining strategy for discovering diagnostic markers, classification and clustering of phenotypic expressions was provided which enabled us to confirm some known and to identify some new genotype-phenotype correlations.

Facile and mild synthesis of linear and cyclic peptides via thioesters.

Thioester-mediated peptide bond formation has recently garnered a lot of attention, most notably in its relevance to condensation of large peptide fragments. Herein, a simple and general ligation method for the preparation of linear and cyclic peptides, starting from peptide thioester, mainly p-chlorophenyl, precursors is reported. The inherent advantages of this method are the low epimerization, reduced dimerization, use of mild reaction conditions, and elimination of superfluous coupling reagents.