Accelerated SuFEx Click Chemistry for Modular Synthesis

Click chemistry is a method for the rapid synthesis of functional molecules with desirable properties. We report the development of accelerated SuFEx, a powerful click reaction for the efficient coupling of aryl and alkyl alcohols directly with SuFExable hubs catalyzed by 2-tert-butyl-1,1,3,3-tetramethylguanidine (BTMG, Barton\u27s base). The new method circumvents the need to synthesize silyl ether substrates while allowing the use of sub-stoichiometric catalyst loadings. This is made possible through a synergistic effect between BTMG and hexamethyldisilazane (HMDS) additive. The powerful combination drives the in situ formation of reactive TMS-ether intermediates while exploiting the silicon-fluoride bond formation\u27s thermodynamic driving force. Comparatively, the required BTMG base\u27s catalyst loading is generally low (1.0–20 mol%) compared to the dominant SuFEx catalyst, DBU (10–30 mol%). In line with click chemistry principles, the scalable reaction only requires simple evaporation of the volatile side products (NH3, Me3Si-F, TMS-OH, BTMG) under reduced pressure instead of extensive purification. The new SuFEx protocol is tolerant of a wide selection of functional groups and meets all the demands of a click reaction, thereby dramatically shortening reaction times and delivering products in excellent yield

Accelerated SuFEx Click Chemistry For Modular Synthesis

SuFEx click chemistry is a powerful method designed for the selective, rapid and modular synthesis of functional molecules. Classical SuFEx reactions form stable S-O linkages upon exchange of S-F bonds with aryl silyl-ether substrates, and while near-perfect in their outcome, are sometimes disadvantaged by relatively high catalyst loadings and prolonged reaction times. We herein report the development of 'Accelerated SuFEx Click Chemistry' (ASCC), an improved SuFEx method for the efficient and catalytic coupling of aryl and alkyl alcohols with a range of SuFExable hubs. We demonstrate Barton's hindered guanidine base (2- tert -butyl-1,1,3,3-tetramethylguanidine; BTMG) as a superb SuFEx catalyst that, when used in synergy with silicon additive hexamethyldisilazane (HMDS), yields stable S-O bond linkages in a single step; often within minutes. The powerful combination of BTMG and HMDS reagents allows for catalyst loadings as low as 1.0 mol% and, in congruence with click-principles, provides a scalable method that is safe, efficient, and practical for modular synthesis. ASSC expands the number of accessible SuFEx products and will find significant application in organic synthesis, medicinal chemistry, chemical biology, and materials science

Diversity Oriented Clicking (DOC): Divergent Synthesis of SuFExable Pharmacophores from 2-Substituted-Alkynyl-1-Sulfonyl Fluoride (SASF) Hubs

Diversity Oriented Clicking (DOC) is a unified click-approach for the modular synthesis of lead-like structures through application of the wide family of click transformations. DOC evolved from the concept of achieving "diversity with ease" by combining classic C-C �-bond click chemistry with recent developments in connective SuFEx-technologies. We showcase 2-Substituted-Alkynyl-1-Sulfonyl Fluorides (SASFs) as a new class of connective hub in concert with a diverse selection of click-cycloaddition processes. Through the stereoselective DOC of SASFs with a range of dipoles and cyclic dienes, we report a diverse click-library of 173 unique functional molecules in minimal synthetic steps. The SuFExable library comprises 10 discrete heterocyclic core structures derived from 1,3- and 1,5-dipoles; while reaction with cyclic dienes yields several three-dimensional bicyclic Diels-Alder adducts. Growing the library to 278 discrete compounds through late-stage modification was made possible through SuFEx click derivatization of the pendant sulfonyl fluoride group in 96 well-plates-demonstrating the versatility of the DOC approach for the rapid synthesis of diverse functional structures. Screening for function against MRSA (USA300) revealed several lead hits with improved activity over methicillin

Guidelines for diverse citizen science recruitment

Abstract The CSI-COP project will engage citizen scientists to investigate GDPR compliance through exploring cookies in websites and in apps. This document is the second of two deliverables in CSI-COP project work package 2 (WP2) that investigate the best practices that have been used Europe-wide and in international citizen science projects. The previous deliverable D2.1 conducted an exhaustive exploration of literature in order to find the best practices and the most efficient methods in citizen science engagement (CSI-COP, 2020). In the present deliverable D2.2 we explore the means that have been adopted to achieve balanced and diverse participation in citizen science, taking into consideration gender, socio-economic and geographic factors. To this end, we covered three main factors affecting inclusive citizen science projects, and we present our findings in this report. First, we review a large number of citizen science projects regarding the demographic and socio-economic characteristics of their participants and we draw conclusions about the typical characteristics of those involved in such activities. Secondly, we describe in detail the digital divide phenomenon and its effects on the social participation of different individuals and groups. Finally, we present the diversity factors that influence participation in citizen science projects and explain the identified methods to access different target audiences

Medical expert support tool (MEST): a person-centric approach for healthcare management

The Medical Expert Support Tool (MEST) is aimed at helping the clinician in recognizing risk factors in the patient status by offering a multiparametric overview, and by highlighting the individual situation using meaningful colors (green, yellow and red) in order to compare the person physiological parameters with the computed profile. The medical professionals will configure the conditions (relevant parameters, thresholds, rules and alerts) setting the values to the decision support modules and receiving the risk assessment results. Finally, interventions should be done depending on the evaluation of the patient. The tool has been designed along with the clinician involved in the project and it will be fully tested and evaluated during the observational study (100 patients) starting on June 2012