Dataset Information

Hydroelementation and Phosphinidene Transfer: Reactivity of Phosphagermenes and Phosphastannenes Towards Small Molecule Substrates.

ABSTRACT: We describe the facile synthesis of [(Me₃ Si)₂ CH]₂ E=PMes* (E=Ge, Sn) from the reaction of the tetrylenes with the phospha-Wittig reagent, Me₃ P-PMes*. Their reactivity towards a range of substrates with protic and hydridic E-H bonds (E=N, O, Si) is described. In addition to hydroelementation reactions of the E=P bonds, we show that these compounds, particularly [(Me₃ Si)₂ CH]₂ Sn=PMes*, also act as base-stabilized phosphinidenes, allowing phosphinidene transfer to other nucleophiles.

SUBMITTER: Reveley MJ

PROVIDER: S-EPMC10946619 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Hydroelementation and Phosphinidene Transfer: Reactivity of Phosphagermenes and Phosphastannenes Towards Small Molecule Substrates.

Reveley Matthew J MJ Feld Joey J Temerova Diana D Yang Eric S ES Goicoechea Jose M JM

Chemistry (Weinheim an der Bergstrasse, Germany) 20231009 68

We describe the facile synthesis of [(Me3 Si)2 CH]2 E=PMes* (E=Ge, Sn) from the reaction of the tetrylenes with the phospha-Wittig reagent, Me3 P-PMes*. Their reactivity towards a range of substrates with protic and hydridic E-H bonds (E=N, O, Si) is described. In addition to hydroelementation reactions of the E=P bonds, we show that these compounds, particularly [(Me3 Si)2 CH]2 Sn=PMes*, also act as base-stabilized pho ...[more]

PMID: 37589485

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Project description:Scientists rely on high-throughput screening tools to identify promising small-molecule compounds for the development of biochemical probes and drugs. This study focuses on the identification of promiscuous bioactive compounds, which are compounds that appear active in many high-throughput screening experiments against diverse targets but are often false-positives which may not be easily developed into successful probes. These compounds can exhibit bioactivity due to nonspecific, intractable mechanisms of action and/or by interference with specific assay technology readouts. Such "frequent hitters" are now commonly identified using substructure filters, including pan assay interference compounds (PAINS). Herein, we show that mechanistic modeling of small-molecule reactivity using deep learning can improve upon PAINS filters when modeling promiscuous bioactivity in PubChem assays. Without training on high-throughput screening data, a deep learning model of small-molecule reactivity achieves a sensitivity and specificity of 18.5% and 95.5%, respectively, in identifying promiscuous bioactive compounds. This performance is similar to PAINS filters, which achieve a sensitivity of 20.3% at the same specificity. Importantly, such reactivity modeling is complementary to PAINS filters. When PAINS filters and reactivity models are combined, the resulting model outperforms either method alone, achieving a sensitivity of 24% at the same specificity. However, as a probabilistic model, the sensitivity and specificity of the deep learning model can be tuned by adjusting the threshold. Moreover, for a subset of PAINS filters, this reactivity model can help discriminate between promiscuous and nonpromiscuous bioactive compounds even among compounds matching those filters. Critically, the reactivity model provides mechanistic hypotheses for assay interference by predicting the precise atoms involved in compound reactivity. Overall, our analysis suggests that deep learning approaches to modeling promiscuous compound bioactivity may provide a complementary approach to current methods for identifying promiscuous compounds.

Dataset Information

Hydroelementation and Phosphinidene Transfer: Reactivity of Phosphagermenes and Phosphastannenes Towards Small Molecule Substrates.

Publications

Hydroelementation and Phosphinidene Transfer: Reactivity of Phosphagermenes and Phosphastannenes Towards Small Molecule Substrates.

Similar Datasets

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