As Similar As Possible, As Different As Necessary On-Site Laboratory Teaching during the COVID-19 Pandemic

Most of the available information on studying under the challenging conditions brought about by the COVID-19 pandemic emphasizes a variety of aspects on how to digitalize the whole teaching process. Thus, several useful and potentially game-changing strategies have been reported recently. In contrast to the digitalization of teaching, in this article, we focus on the reverse process: transitioning back to offline teaching, which is unavoidable especially for the acquisition of practical skills during chemistry studies. In this work, we describe our own experience acquired during the Organic Chemistry practical course at the University of Vienna, which was held in June 2020 and onwards. The article contains descriptions of precautions and measures that were taken, additional materials, and necessary changes made in order to safely continue on-site course teaching. We anticipate that this set of precautions can be used in an adapted fashion for any type of laboratory course. Further, we offer a critical analysis of students’ and instructors’ opinions concerning the changes and well-being during the course. Those opinions were collected via a detailed survey. From our experience, with careful planning and responsible behavior, a return to on-site education is possible and warmly welcomed by all involved participants. The detailed description of our course may also be useful for those who need to start a new organic laboratory course or want to improve an existing one

As Similar As Possible, As Different As Necessary On-Site Laboratory Teaching during the COVID-19 Pandemic

Most of the available information on studying under the challenging conditions brought about by the COVID-19 pandemic emphasizes a variety of aspects on how to digitalize the whole teaching process. Thus, several useful and potentially game-changing strategies have been reported recently. In contrast to the digitalization of teaching, in this article, we focus on the reverse process: transitioning back to offline teaching, which is unavoidable especially for the acquisition of practical skills during chemistry studies. In this work, we describe our own experience acquired during the Organic Chemistry practical course at the University of Vienna, which was held in June 2020 and onwards. The article contains descriptions of precautions and measures that were taken, additional materials, and necessary changes made in order to safely continue on-site course teaching. We anticipate that this set of precautions can be used in an adapted fashion for any type of laboratory course. Further, we offer a critical analysis of students’ and instructors’ opinions concerning the changes and well-being during the course. Those opinions were collected via a detailed survey. From our experience, with careful planning and responsible behavior, a return to on-site education is possible and warmly welcomed by all involved participants. The detailed description of our course may also be useful for those who need to start a new organic laboratory course or want to improve an existing one

C–H Bond Cleavage Is Rate-Limiting for Oxidative C–P Bond Cleavage by the Mixed Valence Diiron-Dependent Oxygenase PhnZ

PhnZ utilizes a mixed valence diiron­(II/III) cofactor and O2 to oxidatively cleave the carbon–phosphorus bond of (R)-2-amino-1-hydroxyethylphosphonic acid to form glycine and orthophosphate. The active site residues Y24 and E27 are proposed to mediate induced-fit recognition of the substrate and access of O2 to one of the active site Fe ions. H62 is proposed to deprotonate the C1-hydroxyl of the substrate during catalysis. Kinetic isotope effects (KIEs), pH–rate dependence, and site-directed mutagenesis were used to probe the rate-determining transition state and the roles of these three active site residues. Primary deuterium KIE values of 5.5 ± 0.3 for D(V) and 2.2 ± 0.4 for D(V/K) were measured with (R)-2-amino­[1-2H1]-1-hydroxyethylphosphonic acid, indicating that cleavage of the C1–H bond of the substrate is rate-limiting. This step is also rate-limiting for PhnZ Y24F, as shown by a significant deuterium KIE value of 2.3 ± 0.1 for D(V). In contrast, a different reaction step appears to be rate-limiting for the PhnZ E27A and H62A variants, which exhibited D(V) values near unity. A solvent KIE of 2.2 ± 0.3 for D2O(V) is observed for PhnZ. Significant solvent KIE values are also observed for the PhnZ Y24F and E27A variants. In contrast, the PhnZ H62A variant does not show a significant solvent KIE, suggesting that H62 is mediating proton transfer in the transition state. A proton inventory study with PhnZ indicates that 1.5 ± 0.6 protons are in flight in the rate-determining step. Overall, the rate-determining transition state for oxidative C–P bond cleavage by PhnZ is proposed to involve C–H bond cleavage that is coupled to deprotonation of the substrate C1-hydroxyl by H62

Data_Sheet_1_In vitro Radiopharmaceutical Evidence for MCHR1 Binding Sites in Murine Brown Adipocytes.docx

[11C]SNAP-7941 and its radiofluorinated, fluoro-ethyl derivative [18F]FE@SNAP have been developed as the first positron emission tomography tracers for melanin-concentrating hormone receptor 1 (MCHR1) imaging. Accumulation of these MCHR1 PET-tracers in rat brown adipose tissue (BAT) in vivo provided first indication of MCHR1 expression in rodent BAT. To rule out off-target binding, affinity of both MCHR1 ligands toward adrenergic beta-3 receptors (ADRB3) was examined. Further, specific binding of [11C]SNAP-7941 to brown adipocytes and effects of MCHR1 ligands on brown adipocyte activation were investigated. SNAP-7941 and FE@SNAP evinced to be highly selective toward MCHR1. [11C]SNAP-7941 binding to brown adipocytes was shown to be mainly MCHR1-specific. This data strongly indicates MCHR1 expression in rodent BAT and moreover, a peripheral, anti-obesity effect of MCHR1 antagonists directly exerted in BAT is proposed. Moreover, MCHR1 expression in murine brown adipocytes was confirmed by protein and mRNA analysis. We conclude that MCHR1 PET imaging contributes to basic research in endocrinology by elucidating the involvement of the MCH system in peripheral tissues, such as BAT.</p

Development and <i>In Vivo</i> Evaluation of Small-Molecule Ligands for Positron Emission Tomography of Immune Checkpoint Modulation Targeting Programmed Cell Death 1 Ligand 1

A substantial portion of patients do not benefit from programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) checkpoint inhibition therapies, necessitating a deeper understanding of predictive biomarkers. Immunohistochemistry (IHC) has played a pivotal role in assessing PD-L1 expression, but small-molecule positron emission tomography (PET) tracers could offer a promising avenue to address IHC-associated limitations, i.e., invasiveness and PD-L1 expression heterogeneity. PET tracers would allow for improved quantification of PD-L1 through noninvasive whole-body imaging, thereby enhancing patient stratification. Here, a large series of PD-L1 targeting small molecules were synthesized, leveraging advantageous substructures to achieve exceptionally low nanomolar affinities. Compound 5c emerged as a promising candidate (IC50 = 10.2 nM) and underwent successful carbon-11 radiolabeling. However, a lack of in vivo tracer uptake in xenografts and notable accumulation in excretory organs was observed, underscoring the challenges encountered in small-molecule PD-L1 PET tracer development. The findings, including structure–activity relationships and in vivo biodistribution data, stand to illuminate the path forward for refining small-molecule PD-L1 PET tracers

Development and <i>In Vivo</i> Evaluation of Small-Molecule Ligands for Positron Emission Tomography of Immune Checkpoint Modulation Targeting Programmed Cell Death 1 Ligand 1

A substantial portion of patients do not benefit from programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) checkpoint inhibition therapies, necessitating a deeper understanding of predictive biomarkers. Immunohistochemistry (IHC) has played a pivotal role in assessing PD-L1 expression, but small-molecule positron emission tomography (PET) tracers could offer a promising avenue to address IHC-associated limitations, i.e., invasiveness and PD-L1 expression heterogeneity. PET tracers would allow for improved quantification of PD-L1 through noninvasive whole-body imaging, thereby enhancing patient stratification. Here, a large series of PD-L1 targeting small molecules were synthesized, leveraging advantageous substructures to achieve exceptionally low nanomolar affinities. Compound 5c emerged as a promising candidate (IC50 = 10.2 nM) and underwent successful carbon-11 radiolabeling. However, a lack of in vivo tracer uptake in xenografts and notable accumulation in excretory organs was observed, underscoring the challenges encountered in small-molecule PD-L1 PET tracer development. The findings, including structure–activity relationships and in vivo biodistribution data, stand to illuminate the path forward for refining small-molecule PD-L1 PET tracers